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Kindle Money Mastery

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Preface to the Third Edition

Our thanks go to our colleagues at the VU University Medical Center and to those in other hospitals who referred their patients to us. We are indebted to all colleagues who allowed us to use their MR images, published or unpublished, making it possible for us to present illustrations of nearly all known white matter disorders. Two colleagues were particularly helpful and provided us with essential and unpublished figures our friends Susan Blaser, from the Hospital for Sick Children in Toronto, and Zoltan Patay, from the King Faisal Hospital in Riyadh.

How to Chase a Red Herring and Come up with a Smallmouth Bass

The project, when the collaboration between Alick Isaacs (1921-1967) and me started in midsummer 1956, was the following we knew that influenza virus particles, inactivated by heat and irreversibly attached to red cells, were capable of inducing interference against challenge with live influenza virus in chick embryos. I had finished this work before I reached Mill Hill in July 1956, but it was still unpublished (Mooser and Lindenmann 1957). Alick thought that we could use this technique to ask the following question how do the influenza virus particles, with one of their sides firmly attached to the carrier red cells, leaving only their opposite side free to interact with the host cells, induce interference One possibility was that something was being transferred from the virus to the host. What could that be From bacteriophage work, it was known that the phages inject their nucleic acid into the host bacterium, the rest of the phage remaining outside. If something similar went on in...

Posttranscriptional Control of Interferon Production

Similar paradoxical effects of metabolic inhibitors on interferon production were also seen in cell cultures. My first graduate student at NYU, Toby Rossman, observed that the addition of actinomycin D to chick embryo cells 10-14 h after inoculation with Chikungunya virus (an RNA-containing alphavirus) slightly increased subsequent interferon release when compared to cells not treated with the inhibitor of RNA synthesis (T. Rossman, unpublished observations). We then examined the effects of metabolic inhibitors on poly(I).poly(C)-induced interferon production in cultures of rabbit kidney cells (Vilcek et al. 1969). Actinomycin D addition before poly(I).poly(C) blocked interferon production, but when added 3.5 h after poly(I).poly(C), the inhibitor markedly enhanced the interferon yield. Rather than simply invoking the existence of preformed interferon, we proposed that the increased release of interferon from cells treated with actinomycin several hours after exposure double-stranded...

The Time Course of Acute Respiratory Failure

In a prospective study of 182 patients with ARF in our institution (unpublished observations), we separated 133 patients who had early ARF (an onset < 48 hours after ICU admission) and 49 with late ARF (an onset < 48 hours after ICU admission). On admission, the cardiovascular SOFA score was higher in early than in late ARF, whereas the neurologic score was higher in late than in early ARF. In early ARF, a high SOFA score and low Glasgow Coma Score were predictors of mortality, and in late ARF, a low Glasgow Coma Score at 48 hours predicted mortality. These findings suggest that there may be important differences in the epidemiology and outcome of ARF that are dependent on the time of onset.

CD4 Regulatory T Cells Constitutively Expressing CD25

Direct confirmation of the importance of interactions between Treg and DCs has come from recently published studies using intravital microscopy to track Treg in living lymphoid tissue, in which Treg formed stable associations not with conventional T cells but with DCs (107). Our own unpublished studies of the interaction between Treg and DCs in vivo indicate that Treg control expression of costimulatory molecules by DCs (Koh, W. -P., Power, C., and Fazekas de St. Groth, B., unpublished observations). Evidence for this model also comes from in vitro studies in which Treg were able to reduce expression of CD86 by DCs isolated from the spleen (108). By reducing the level of costimulation, Treg have a relatively greater effect on low affinity responses such as those to self-antigen, as the requirement for costimulation is greater when antigen availability and affinity are low. Thus the function of Treg may be differentially

Roles of Mast Cells in Immediate Type Hypersensitivity

Ports that mast cells are players in immediate-type hypersensitive responses only after the adaptive immune response is established (33). In many respects, an allergic response is very similar to responses to conventional antigens. T cells must be primed (sensitized) via antigen presentation by dendritic cells in the lymph nodes. In allergic responses, this process is thought to be dominated by the generation of Th2 cells, which express IL-4, IL-5, and IL-10 among other cytokines. This Th2 milieu has effects on developing B cells, inducing class switching to IgE production, primarily by IL-4 and IL-13. Allergen-specific IgE binds to mast cells and only upon secondary exposure to allergen are the mast cells triggered. However, new findings suggest that mast cells can have a more direct influence on very early events and thus contribute to shaping the character of the adaptive immune response. Evidence to support this comes from studies showing that B cells can undergo isotype...

Properties of human growthtransformed T cells

When peripheral blood mononuclear cells (PBMCs) are used as antigen-presenting cells (APCs) to study the activation of HVS-transformed T cells, antigen-specific activation may be obscured because the transformed T cells are activated by PBMCs through CD2 without antigen. This problem can be overcome by using mouse L cells (stably-transfected with the appropriate HLA molecule) as APCs, since mouse CD58 binds poorly to human CD2 autocrine activation of the T cells can be simultaneously reduced using antibodies to CD2 or CD58 (60). An alternative is to use EBV-transformed B cells as APCs in the presence of mAbs to CD58 (59). T cell-depleted (2) or unseparated PBMCs (58) have also been used as APCs to elicit an antigen-specific response without blocking mAbs. Withdrawal of IL-2 for a few days before culturing with antigen can enhance the antigen-specific response (2). HVS-transformed T cells from Rhesus monkeys (36) and man (unpublished observations) are both effective APCs. Measuring the...

Mass As A High Throughput Screen

DNA-ligand interactions, and RNA-ligand interactions 39-53 . Typically, the mass spectrometric results are in good agreement with those derived from more conventional solution-phase techniques. Several groups have shown that dissociation constants can be derived directly from ESI-MS measurements 39-41,46,49,50 . Traditional solution phase methods, such as radioimmunoassays, filter assays, and surface plasmon resonance assays, provide little to no information about the binding stoichiometry and can only measure the equilibrium concentration of one component 54 . In contrast, mass spectrom-etry can directly determine the binding stoichiometry by measuring the masses of the complexes formed, as well as detect all the components of the equilibrium mixture (i.e., free ligand, free target, and ligand-target complexes). In addition, with appropriate solution conditions, it is possible to simultaneously measure the Kd values for several ligands against a single target 15 , and it is possible...

Sporadic Bl In Temperate Climates

Young and Miller and then Levine et al. showed that non-Hodgkin's lymphomas (NHL) histopathologically similar to BL as described in Africa also occurred in the United States, with a yearly incidence rate averaging 0.06-0.10 100,000 children (28,29). International registry data showed that Iraq, Israel, and Algeria were intermediate risk areas for BL incidence (30-32). In these areas, the predominant clinical feature is abdominal involvement. On a global scale, the association with EBV appears to depend upon the socioeconomic level, ranging from a weak association (10-15 ) in BL arising in European children (Lenoir, unpublished data) to 85 in Algerian cases (32) and 98 in Uganda (see below and refs. 41,42). These international patterns suggested a critical role of breast feeding and saliva in the transmission of EBV from a mother to her young infant.

Data analysis in ecological genomics

Table 2.4 and Fig. 2.15 give an example of a BLAST search. D. Roelofs (unpublished data), using suppression subtractive hybridization (see Section 2.1), found a partial cDNA in the springtail O. cincta (Collembola) that had a differential expression between two populations, one metal-tolerant and the other not. The sequence was BLASTed to GenBank, which produced high similarities to genes annotated as ATP-binding cassette (ABC) transporters in D. melanogaster, Anopheles gambiae (mosquito, Diptera), and Apis mellifera (honey bee, Hymenoptera). The fact that the most significant hits were all insects and all hits indicated the same type of gene put great confidence in the conclusion that the unknown cDNA was a collembolan version of an ABC transporter. The ABC transporters are a large family of proteins involved in the transport of a Table 2.4 Example of a table in a BLAST report, showing the eight most significant alignments of a query sequence of an SSH clone from O. cincta...

Antilymphangiogenic Therapies in the Cornea

Besides the approaches targeting primarily hem- and lymphangiogenesis, anti-angiogenic strategies targeting the immune effects of angiogenic growth factors have recently been shown to be very effective. Blocking antibodies against VEGFR3-mediated migration of dendritic cells to the regional lymph nodes significantly improves corneal graft survival 14 . Likewise, the beneficial effect of local macrophage depletion on corneal graft survival, which has previously been attributed to 'immunologic ignorance' 26 , can also be explained by the antihem- and antilymphangiogenic effects of the liposome-depleting agent clodronate 10 . Furthermore, this clodronate-based, macrophage-depleting anti-angiogenic approach could even prolong graft survival in animal models of xenotransplantation Borges et al., unpublished findings .

Multiple Dose Protocol

In the multiple-dose protocol, there is a small incidence of LH surge (between 1 and 2.5 ). These surges were often associated with a lack of compliance by the patients, forgetting one antagonist administration. This point is important to stress to the patients. More recently, some centers have observed a higher incidence of LH surge in poor responders using the multiple-dose protocol (unpublished data). These reports should be confirmed and documented. The dose of 0.25 mg might not be always sufficient. This dose might also have to be adapted to the weight of the patients.

Remaining Questions On GnRHnt Pregnancy Rates

There is a trend in most of the controlled studies using GnRH-nt (with both compounds and protocols) to find slightly lower pregnancy rates as compared to the GnRH-a long protocol. This led to the questioning of IVF-ET results of GnRH-nts. A meta-analysis concluded there were significantly lower pregnancy rates in GnRH-nt cycles as compared to GnRH agonists (48). However, the difference was very close to being nonsignificant (OR 0.79 95 CI 0.630.99). Adding one study, Ludwig et al. (49) did not find a significant difference in pregnancy rates for Cetrorelix. A recent meta-analysis presented by Daya did not find a difference in ongoing pregnancy rate (unpublished data). Care should be taken in drawing conclusions on these observations. Some population factors were not equivalent in the groups despite randomization. In addition, the learning curve, inherent to the use of new treatment schemes, could have influenced some of the studied outcome. The trend towards higher pregnancy rate...

Role of the Endothelium in Ca2 Sensitization During HPV

Sufficient to generate enough EDCF to stimulate Rho-kinase activity in the vast number of neighboring smooth muscle cells is unclear. Wang et al. (55) also demonstrated that HPV in intrapulmonary arteries was inhibited by Y-27632, but they did not detail whether the sustained HPV in their arteries was endothelium-dependent. However, both the translocation of RhoA, a causal event in the activation of Rho-kinase (9), and the activation of Rho-kinase in rat small intrapulmonary arteries during HPV appear to be endothelium-dependent (Robertson T, unpublished observations).

Programmation of GnRHnt Cycles

The programmation of GnRH-nt cycles is important to organize the work load of large IVF centers. Programmation could be obtained with progesterone administration in the late luteal phase or oral contraceptive pill (74). A more original way of programming the cycle was proposed by Fanchin et al. (75). The authors proposed luteal administration of estradiol in the late luteal phase as proposed by de Ziegler (76). The administration of estradiol prevents the FSH rise induced by the luteolysis and could synchronize the follicular cohort (75). Some authors (Kolibianakis et al., unpublished data) found lower pregnancy rates when an estro-progestative pill is used. The results of this study are not yet confirmed by other authors. In poor respon-ders, the use of contraceptive pills to program GnRH-nt cycle was found to be associated with increased cancellation rate (77).

Distribution of Spores in Foods

Clostridia are rarely present in raw milk. However, when the hygienic conditions of harvesting are poor and milk cows are fed on silage, their number increases considerably. The clostridia affecting the organoleptic quality of cheese have been widely studied, but little is known about the occurrence of C. botulinum spores in raw milk, probably because milk-derived products have rarely been associated with cases of botulism. The level of contamination of raw milk has been estimated at < 1 spore kg in Canadian milk (172) 1 spore type B 100 mL has been detected in 5.5 of the lots furnished by 35 Italian dairies (P. Aureli and G. Franciosa, 1998, unpublished data). Their milk produced the mascarpone (typical Italian spread process cheese) that was responsible for a botulism outbreak in Italy in 1996 (10).

Life in industrial barrens

In industrial barrens near Monchegorsk the number of vascular plant species ranged 0-25 of the number recorded in unpolluted (control) sites if censuses were made by using small plots (1-25 m2). However, if larger plots (100-10,000 m2) were surveyed, the decrease in species richness was around one-third, suggesting that pollution effects were expressed in decline of population densities rather than in selective removal of certain species (Kozlov et al. 1998, and unpublished). Population structure of both plants and animals is considerably changed in industrial barrens. Populations of some woody species (mountain birch and willows in Monchegorsk, white birch in Sudbury) become more continuos due to elimination of pollution-sensitive competitors, while ground layer vegetation is highly fragmented (Zvereva and Kozlov 2004, 2007). In Sudbury, the dimension of patches of 'micro-deserts' and 'micro-oases' varies typically between 5 m and 15 m (Courtin 1994). In Monchegorsk, patches of...

The Use of Phosphotransferase System Carbohydrates

Glucose and other PTS sugars such as fructose, mannose, and cellobiose are preferred carbon sources for L. monocytogenes, when growing in defined liquid minimal media (Tsai and Hodgson, 2003 our own unpublished results). The L. monocytogenes genome contains an unusually large number of genes (> 40) encoding PTSs (Glaser et al., 2001). Among those, four PTS (determined by lmo0096-0098, lmo0781-0784, and lmo1997-2002) are specific for mannose transport, nine PTS for fructose (determined by fruAB, lmo0021-0023, lmo0358, lmo0399-0400, lmo0426-0428, lmo0503, lmo0631-0633, lmo2135-2137, and lmo2733), and seven PTS for cellobiose (lmo0034, lmo0901, lmo1095, lmo2683-2685, lmo2708, lmo2762, 2763, 2765, lmo2780, 2782, and 2783). Surprisingly, however, ptsG which encodes the PTS-dependent glucose transport in many low G+C Gp bacteria, including B. subtilis (Gonzy-Treboul et al., 1991), is incomplete in L. monocytogenes, and only the gene (lmo1017) for the EIIA component of the PTS-G system is...

Variability among Patients

Breathing patterns vary widely among normal subjects at rest, with Vt ranging from 5 to 17 ml kg and RR ranging from 6 to 25 min-1 56 . Until the advent of PAV 57 it was not possible to determine the breathing pattern desired by ventilator dependent patients since, with conventional modes, breathing pattern is to a considerable extent determined by ventilator settings. When patients are placed on PAV at a high level of assist (i.e., in the absence of distress), the breathing pattern is found to be as variable among patients as it is among normal subjects. Data on a limited number of patients have been published 24, 58 . In a much larger group (n 80, unpublished observations) the range of patient-selected Vt was 0.23-0.891

Characteristics of Computational Methods

It is worthwhile performing multiple runs of CHEMTAX using a range of initial marker pigment Chl a ratio matrices. CHEMTAX works by iteratively minimizing the pigment residual (i.e. the difference between observed and calculated concentrations of the pigment to be optimized, usually Chl a). It is apt to find a local minimum rather than the overall minimum for the data set, particularly if there is a poor signal-to-noise ratio in the data. During testing of CHEMTAX Version 2, Wright (unpublished) performed multiple CHEMTAX runs on pigment data from Antarctic picoplankton using 28 pigment ratio tables that had been multiplied by a scaled random number to adjust each ratio up to 50 . Each calculation produced a slightly different result. When the results were sorted in order of decreasing pigment residual, the tax-onomic estimates were found to converge towards stable values. So although CHEMTAX was encountering local minima, it was tending towards the overall minimum in the data....

The Role of Dynamin in Caveolar Function

From the sections above, it is clear that dynamin is central in the discussions on caveolar endocytosis, and this GTP-binding protein therefore warrants further attention in this chapter. It is well established that dynamin plays a role in the final scission of clathrin-coated vesicles to form free endocytic vesicles 94,95 , and it has also been reported to be important for the fission of caveolae 28,29 . However, the role of dynamin associated with caveolae can be complex. Dynamin is an actin-interacting protein which, for example, binds to cortactin. Indeed, recently dynamin was found to be involved in the regulation of actin polymerization during micropinosome comet formation - that is, the formation of rapidly moving vesicles propelled forward by an actin treadmilling machine 96 . Additionally, caveolin interacts with the actin cytoskeleton via filamin, and reorganization of the actin cytoskeleton leads to redistribution of caveolae 39 . Depolymerization of the actin cytoskeleton...

Transcription Factors

Alterations of the chromatin structure at various sites across the ifng locus have also been linked with the recruitment of DNA-binding proteins, often to regions of chromatin remodeling, thus serving as genomic substrates in establishing competency for acute IFN-y transcription. For many years, it was thought that a single transcription factor (TF) or TF family would ultimately account for IFN-y transcription profiles and function as a master regulator of IFN-y expression. In fact, reports have accumulated over time, implicating a variety of TF in controlling IFN-y transcription, focusing primarily in the proximal IFN-y promoter and intronic regions. Notably, the NFAT, AP-1, and NF-kB families are known to have prominent roles in regulating IFN-y expression (Aune et al. 1997 Kiani et al. 2001 Penix et al. 1993, 1996 Rao and Avni 2000 Sica et al. 1997 Sweetser et al. 1998 Tato et al. 2003 Thierfelder et al. 1996 Zhou et al. 2004). This paper, however, will not focus on these TFs, as...

Iron Storage in S cerevisiae

Despite extensive efforts, it has proved extremely difficult to find evidence for iron storage proteins like the ferritins found in bacteria, plants, animals and almost every other living organism (see Chapter 6). Scrutiny of the S. cerevisiae genome fails to reveal any gene with convincing homology to consensus sequences for ferritins. We did obtain small amounts of a protein of molecular weight around 270-280 kD, with a subunit molecular weight of 12-13 kD from substantial quantities of bakers' yeast (1-2 kg) using classical protein chemical techniques (Raguzzi et al., 1988 Raguzzi, 1989). Subsequent efforts to obtain further information by microsequencing techniques were unsuccessful (Crichton, unpublished data). We did find that growth of S. cerevisiae on iron-rich medium led to iron accumulation in the vacuole (Raguzzi et al., 1988), and that this iron could subsequently be utilized for mitochondrial haem synthesis. It has been pointed out that the concentrations of iron used...

Microenvironment to Immunotherapy Clinical Trials

With 19 metastatic melanoma patients participating in a multipeptide melanoma vaccine trial. A small subset of transcriptional differences in the tumor biopsies was found to distinguish clinical responders from non-responders. Interestingly, among these was a set of chemokine genes more highly expressed in the responding patients (Gajewski et al., unpublished data). While this is a small sample size that will require confirmation, it is beginning to connect the biology of melanoma and the antitumor immune response with clinically relevant information.

Tumor Associated and Pathogen Induced Expression of MIC

MIC are strongly induced in fibroblast and endothelial cells by cy-tomegalovirus (CMV) and by Mycobacterium tuberculosis infection in dendritic and epithelial cells (Das et al. 2001 Groh et al. 2001). MICB is induced by Sendai and influenza A virus infection in macrophages (Siren et al. 2004). Skin lesions of lepromatous lepra patients are marked by large amounts of MIC (V. Groh and T. Spies, unpublished data). Intestinal epithelial expression of MIC may be inducible by bacteria, because adhesion of diarrheagenic Escherichia coli strains to the intestinal epithelial Caco-2 cell line induces a rapid increase of MICA (Tieng et al. 2002). This effect has been related to an interaction of the bacterial AfaE-III adhesin with the cellular CD55 receptor, a glycosylphosphatidylinositol (GPI)-anchored protein that is expressed on most human cells and inhibits complement C3b deposition. However, how this interaction might result in MIC induction has remained unclear. So far, these are the only...

Modeling and Source Reconstruction

Some examples for inverse solutions based on MEG and EEG data. Left Source locations in the auditory cortex found by spatio-temporal dipole modeling of MEG data from an auditory mismatch paradigm (Knosche et al., 2002). Middle MEG-based brain surface current density (BSCD) reconstructions of motor activity in musicians listening to piano music (Haueisen and Knosche, 2001). Right Multiple signal classification (MUSIC) reconstruction based on an averaged epileptic spike in EEG (T.R. Knosche, unpublished data). Fig. 2.46. Some examples for inverse solutions based on MEG and EEG data. Left Source locations in the auditory cortex found by spatio-temporal dipole modeling of MEG data from an auditory mismatch paradigm (Knosche et al., 2002). Middle MEG-based brain surface current density (BSCD) reconstructions of motor activity in musicians listening to piano music (Haueisen and Knosche, 2001). Right Multiple signal classification (MUSIC) reconstruction based on an averaged...

Albiancenomanian Into Santonian

The discontinuous record, limited geographic distribution, and in most cases scant sampling of these faunas, together with the preliminary nature of much of the tax-onomic information available about them, severely limit interpretation of mammalian biochronology of these older strata. Accordingly, we limit ourselves in this summary to general observations on pre-Campanian mammals of North America. Members of Triconodontidae, represented by an endemic North American clade (Alti-conodontinae), are reasonably abundant in the Albian-Cenomanian (Cifelli and Madsen 1998). However, they are lacking from all later faunas except an Aquilan assemblage from Canada (Fox 1976a). Spalacotheriid sym-metrodonts are present in all pre-Campanian faunas (Cifelli and Gordon 1999). Multituberculate assemblages are dominated by species of the Paracimexomys group. Relictual plagiaulacidans may be present in the Albian-Cenomanian, when Neoplagiaulacidae first appear (Eaton and Cifelli, unpublished data)....

Diagnostics and therapy

Parameter far more easily than traditional methods of lipid analysis, and potentially also allows one to monitor the therapeutic effects of fatty acid supplementation 60 . MS-lipidomics is also helpful in diagnosis and therapy of other hereditary diseases like Fabry disease based on increased levels of, e.g., trihexosyl and lactosylceramides found in the urine due to lack of the lysosomal a-galactosidase 130,131 . Also, some peroxisomal disorders like X-linked adrenoleykodystrophy and Zellweger syndrome could be diagnosed based on MS analysis of long-chain fatty acids 132 , ceramides 133 , or PE plasmalogens (our unpublished data). MS-lipidomics may also allow one to diagnose the Lowe syndrome based on altered polyphosphoinositol lipid composition 65 . MS analysis of ascitic fluid from patients with ovarian cancer has revealed increased levels of some lysophospholipids, which could thus provide useful biomarkers for this disease 134,135 . Yet, MS-lipidomics has significant potential...

Adhesionblockade effect

The ability of LF to inhibit in vivo colonization of E. coli has been examined (Naidu et al., unpublished). Infection with E. coli strain F18 was established in streptomycin-treated mice by gastric intubation and bacterial excretion was estimated as colony forming units per gram (CFU g) feces. The excretion of strain F18 in feces reached a steady-state (108 CFU g) within 7 days, independent of challenge (dose 8 x 108 or 103 CFU). Oral administration of bLF (20 mg ml in 20 sucrose solution) caused a 1- to > 3-log reduction in CFU g feces with high and low dosages of strain F18. The bacterial multiplication in vivo was markedly affected during the early 24 hours of infection, reflecting > 3-log lower number of bacteria in the feces (2 x 103 CFU g) than the control group. Oral administration of LF prior to infection reduced fecal excretion of E. coli from mouse intestine. In vitro effects of bLF on the molecular interactions of E. coli with subepithelial matrix proteins were...

Non Receptor Tyrosine Kinases and Insulin Induced Caveolin Phosphorylation

Significant data had linked activation of Src-family kinases to caveolin phosphor-ylation. Therefore, it was initially hypothesized that a Src-family kinase was the insulin-stimulated caveolin-tyrosine kinase in adipocytes. Consistent with this, treatment of isolated caveolar fractions with Src-family kinase inhibitors blocked caveolin phosphorylation in vitro, indicating that the caveolin kinase activity that co-purifies with caveolin is a Src-family kinase (CCM, unpublished observation 16 ). (These inhibitors did not block Src-family kinase activation in intact adipocytes as measured by kinase autophosphorylation. In contrast, inhibition of autophosphorylation was readily detectable in fibroblasts. This is a common problem in adipocytes. Compounds that are sufficiently lipophilic to cross membranes are often sequestered within the prominent fat droplets in these cells.) The most An additional line of evidence suggested that a second non-receptor tyrosine kinase may be involved in...

Vector biology and vectorpathogen interactions

RNAi is not only a tool for gene characterization, it is also an important component of the innate immune response of vectors 46, 80 . Vectors mount an RNAi response upon infection with RNA viruses. Initial in vitro studies demonstrated that mosquito cells, which had been stably transformed with constructs expressing DENV sequences in sense, antisense, or in a fold-back sequence, were resistant to DENV, with the most resistant lines being ones that had been transformed with the fold-back construct 2 . The expressed fold back sequence presents a double-stranded RNA target that facilitates Dicer recognition of the aberrant RNA species 80 . In addition, infection of mosquito cells or midguts with Sindbis virus, DEN virus (family Flaviviridae), or La Crosse virus (family Bunyaviridae) induces an RNAi response, as evidenced by the accumulation of small interfereing RNA species. Finally, silencing of certain RNAi response genes makes resistant vectors susceptible to infection with...

Structural Organisation Of Human Collectins

Intranasal administration of SP-D or rhSP-D in a murine model of IPA, where mice are immunosuppressed with hydrocortisone and challenged intranasally with A. fumigatus spores, has been shown to have a protective effect. Untreated IPA mice showed 100 mortality at seven days, whereas SP-D or rhSP-D treatment rescued about 80 of the IPA mice. SP-A did not have a significant effect on survival (Madan et al. 2001a). Subsequent studies have revealed that the protective effects of SP-D or rhSP-D in the IPA model coincides with reduced colony forming units, lack of hyphal growth, and raised levels of the protective cytokines, TNF-a and IFN-7, in BALF. (U. Kishore, unpublished).

Hivhcv Knowledge Among People With Severe Mental Illness and Their Providers

Preliminary findings from qualitative interviews with medical and mental health care providers show widespread consensus that HCV is a major public healthcare issue (P. Mendel and G. Ryan, unpublished data, February 2002). Interviews with providers at 32 agencies in New York City and Los Angeles showed adequate knowledge about how to identify HCV-antibody-positive clients, at least among agencies with

Susceptibility Of Collectin Genedeficient Mice To Fungal Pathogens

Immunosuppressed SP-A- - mice, when subjected to IPA, show greater resistance to A. fumigatus conidia challenge (40 mortality) than the WT hydrocortisone treated mice (100 mortality). Interestingly, intranasal delivery of SP-A to the SP-A- - IPA mice increases the mortality to 60 . The overall mortality in immuno-suppressed SP-D- - IPA mice is similar to WT-IPA mice 60 ), however, SP-D- - IPA mice tend to die significantly sooner, display a higher hyphal density and have tissue injury in the lungs. Intranasal treatment with SP-D, or rhSP-D, has been found to reduce the mortality of SP-D- - IPA mice, from 100 , to 50 and 33 , respectively (Madan et al. unpublished). It is interesting to note that SP-A- - and SP-D- - mice show distinct immune responses to corticosteroid-induced immunosuppression. Immunosuppressed SP-A- - mice had significantly lower levels of TNF-a, IL-4, IL-5 and IL-10, and an increased IFN-7 to IL-4 ratio (2.7 fold) in lung cell suspension, compared to...

Standardization Initiatives In Proteomics

Standardization of the data is an indispensable step in collaborative proteomics studies, crucial to successful integration of the results. A good data standard should facilitate access to the data, being extensible enough to exchange data with a high level of detail. Many users require only simple access to the data via an easy data search interface. Requirements of others may be more complex and should not be limited by unavoidable simplicity of the common interface. Wherever possible, the data should be generated in the standard form straight away in the producing laboratories, rather than converted in the data collection centers. Such work flow helps to avoid conversion errors and facilitate quality control, but may generate additional work for laboratories that do not have sufficient informatics support. The problem is especially important in high-throughput mass spectrometry studies. As noted above, the instruments produce huge amounts of data not yet standardized among the...

TCR and Activating NKRs The TCR Primacy Rule

Effector CTLs, although they can express a broad panoply of NKRs, usually lack NKRs that signal through a immunomodulatory tyrosine-based activating motif (ITAM) (Table 1). These ITAMs can recruit kinases from the ZAP70 Syk family and induce alone full cellular activation. Instead, the NKRs expressed by CTLs are characterized by their capacity to modulate, positively or negatively, TCR activation. This ensures that T cell activation remains under the control of the TCR (the TCR primacy rule). For example, NKp46 protein (Moretta and Moretta 2004 Pessino et al. 1998), which associates with CD3Z and therefore could be potentially expressed on the cell surface of CTL, is not present in CTLs, including in intracellular compartments (unpublished data). Similarly, NKG2C protein is absent in normal conditions, even though transcripts are detected (Jabri et al. 2002 and unpublished data). In addition, CTLs do not express transcripts of the ITAM-bearing adaptor Some important exceptions to the...

IP and Confidentiality the Impact on Knowledge Sharing

In a study of Queensland biotech companies (Frahm and Hine, unpublished) a number of case respondents spoke of the need to secure CDAs (confidentiality disclosure agreements) before communicating with external stakeholders. This then acts as abarrier to innovation, specifically knowledge transfer that naturally occurs in social networks and loose ties. In this study, the concern about confidentiality differed depending on the case concerned. Fortwo companies, the fact that they were post patent meant there were little costs associated with open communication with external collaborators. This supports Ledwith's (2000) contention that external communication is a high-risk activity for small firms with few patents. Another company's solution was to be selective in who to communicate with and 'wrap them so tight in CDAs' that the exchange of information can then be quite free. Yet another company was more strategic in approach preferring to distribute small parcels of work to multiple...

Regulation of NKG2D and CD94NKG2 Expression and Function in CTLs

Like CTLA-4, NKG2A may therefore participate in a negative feedback loop in which TCR stimulation upregulates NKG2A expression and, in turn, NKG2A downmodulates TCR activation. This property may explain why some NKG2A induction could be induced in vitro on TCR stimulation on a limited subset of peripheral blood T lymphocytes, representing less than 25 of total T cells (Bertone et al. 1999 Derre et al. 2002 Mingari et al. 1998). Importantly, IL-15, TGF-p, and IL-12 could induce CD94, but not NKG2A, in the absence of concomitant TCR stimulation (Bertone et al. 1999 Derre et al. 2002 Jabri et al. 2000 Jabri et al. 2002 Mingari et al. 1998), further suggesting control of TCR over NKG2A expression. The regulation of NKG2C, NKG2E, and H is still poorly understood. Although transcripts of these genes are found in most memory T cells (Jabri et al. 2002), NKG2C proteins do not seem to be expressed under physiological conditions by human CTLs, as determined by staining with...

Inducible Defensive Responses In Plants

Every flowering plant appears to be able to accumulate low molecular weight, antimicrobial compounds locally at the sites of attempted pathogen invasion. These phytoalexins tend to fall within the same chemical class within plant families, but a wide range of compounds including phenylpropanoid derivatives, sesquiterpenes, and polyketides, involving several biosynthetic pathways, can be found among various plant groups (43). In addition to phytoalexins, which by definition are generally not detectable in uninfected plants, some preformed antimicrobial secondary metabolites also increase in concentration following infection. Phytoalexin accumulation is typically elicited by nonspecific elicitors (35), and it seems reasonable to assume that they play a role in at least some examples of nonhost resistance, particularly when the pathogen cannot detoxify or otherwise tolerate the compounds. Nevertheless, a role may not be universal, as a phytoalexin-deficient mutant of the weed Arabidopsis...

Role of g proteincoupled receptor kinase type

In humans with essential hypertension, the uncoupling of the D like receptor from its G protein effector complex has been shown to be a consequence of an activating variant in a member of the G protein-coupled receptor kinase (GRK) family of kinases that are responsible for G protein receptor inactivation following agonist stimulation. (79,120,132,144-153). The complex of phosphorylated D1 receptor, arrestin, and adaptor proteins undergo internalization, via clathrin-coated pits into an endosome in which the GPCR can be degraded by lysosomes or proteasomes, or dephosphorylated by phosphatases (e.g., GRK2A) (28,33) to be recycled back to the plasma membrane. Dephosphorylation can also occur directly at the plasma membrane (154), and desensi-tization may be clathrin-independent (133). Uncoupling of the D1 like receptor in essential hypertension involves the D1 receptor and not the D5 receptor in hypertension (155,156) and unpublished studies . The D1 receptor is...

Pathogenic Mechanisms

The low efficiency of HPV immortalization, but even more so the recessive nature of immortalized cells, frequently complementing each other to senescence when cells of different clones are subjected to somatic cell hybridization (94,95), strongly suggests that E6 E7 gene expression is necessary but not sufficient for immortalization. The same accounts for malignant conversion as previously discussed, viral oncogene expression appears to be necessary for the malignant phenotype of HPV-positive cells. Yet, somatic cell hybridization of cells from different HPV-positive lines reveals three possible modes of outcome (96) besides the failure to complement as seen for some lines (e.g., the HPV-18-positive HeLa and SW 756 cells), some complement each other for senescence (Rosl and zur Hausen, unpublished data), and still others complement each other for a nonmalignant phenotype (e.g., HeLa cells and the HPV 16-positive Caski line). Complementation to senescence on the one hand and...

Evidence that Other Factors Trigger Differentiation

Although the stringent response is the most well-characterized mechanism by which L. pneumophila controls differentiation, several lines of evidence indicate that other signals are likely to be involved. By phenotypic analysis, relA mutants appear less defective for transmissive traits than other known regulators of differentiation, suggesting additional factors may act in concert with RelA (Hammer and Swanson 1999 Zusman et al. 2002). Also, letA mutants (discussed below) can express traits that are normally impaired if certain growth conditions are altered, such as aeration, temperature, or media composition (Fernandez-Moreia and Swanson, unpublished). Furthermore, broth cultures of letA and letS mutants are defective in their ability to infect mouse macrophages, but surviving bacteria can initiate secondary and tertiary infections as efficiently as wild-type (Hammer et al. 2002). Additionally, L. pneumophila letA mutants are more infectious when harvested from cultures of bone...

General Physical Health

Nevertheless, researchers in San Diego (Jeste et al. 1996 Lacro andJeste 1994) found that middle-aged and older schizophrenic persons had fewer medical illnesses (mean 1.0) than persons with Alzheimer's disease (mean 1.4) and major depression (mean 2.4), with a comparable severity index on the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) compared with an older normal comparison group. Similarly, a study in New York City of 117 schizophrenic persons age 55 and over, with a mean age of 63 years (C.I. Cohen, unpublished data), found that 33 of the schizophrenia sample and 48 of the community sample reported 2 or more physical disorders the mean number of disorders was 1.35 and 1.66 for the schizophrenia and community groups, respectively. In the latter studies, the annual rate of hospitalization was comparable between the groups (21 community group, 22 schizophrenia group), although more than half the hospitalizations among the schizophrenia group had been for psychiatric...

Tel Aviv Sourasky Medical Center Experience

The localization ratio with RIGS was 86 . As part of the study, lymph nodes that were RIGS-positive but H& E-negative (type III) were submitted to a central laboratory for multiple cuts and immunohistochemistry with anticytokera-tin antibody. Regional lymph nodes resected with the primary specimen were included in this approach. These nodes were also tested with the probe in the pathology laboratory. Twenty-three patients with stage II disease underwent a full pathology evaluation (H& E and immunohistochemistry). Eleven patients had at least one positive lymph node by immunohistochemistry, upstaging 48 of the patients. Twenty-nine patients with rectal cancer had a complete evaluation. Twelve of these patients had stage II disease, and eight of them were upstaged (67 ). A total of 146 regional lymph nodes were submitted for serial sectioning and immunohistochemistry. Ninety-one of these lymph nodes were RIGS-positive, and 55 were RIGS-negative. Twenty of the RIGS-positive lymph...

Does the Cellular Redox State Play a Role in the Regulation of cADPR Accumulation in Pulmonary Artery Smooth Muscle

Subsequent investigations have, however, brought into question the idea that inhibition of P-NADPH oxidase by hypoxia, and subsequent P-NADPH accumulation represent the primary 02-sensing pathway. In fact, Marshall et al. (58) demonstrated that the activity ofNADPH oxidase may actually be increased by hypoxia in pulmonary artery smooth muscle. In addition, in knock-out mice lacking the neutrophil NADPH oxidase, HPV remained unaffected (7). Moreover, direct extraction and measurement of P-NADPH and P-NADP+, respectively, in pulmonary artery smooth muscle has revealed that the P-ratio is high under normoxic conditions and remains fairly constant in the presence of hypoxia (79). Given the above, it may not be surprising to discover that extremely high concentrations (10 mM) of P-NADPH are without effect on cADPR synthesis from a fixed concentration of P-NAD+ in pulmonary artery smooth muscle homogenates (unpublished observation). near anoxic conditions (5-8 Torr), to a level not...

Anal Cancer And Its Precursors

Several studies have examined anal HPV infection in women (44,113). Surprisingly, these studies demonstrate that anal HPV infection is found at a similar or higher rate as cervical HPV infection, and the spectrum of HPV types is similar in the anal canal and cervix. Notably, the same HPV types were found in the anus and cervix in only 50 of the women who were infected at both sites. The mode of acquisition of anal HPV infection was not clearly linked to receptive anal intercourse in these studies, but a more recent study of a larger number of women did show an association with receptive anal intercourse (JM Palefsky, unpublished data). However, insertion of inert objects or fingers exposed to other HPV-infected tissues of the individual or their sexual partner may also result in anal HPV infection.

What can the transcriptome tell us about the immunome

Overlap with the coding sequence (Schonbach C, Nagashima T, Silva DG, unpublished data). How much splice variation is attributable to repeats and may have disease implications is under investigation. The distribution of repeat element is not random. For example, SINEs (short interspersed nucleotide elements) occur less frequently in imprinted regions (Greally et al 2002). Depending on the location of the insertion SINE B2 may affect the transcription of neighbouring genes by acting as a pol II promoter (Ferrigno et al 2001). Endogenous retrovirus insertion (ERV) in complement C4 affects expression of C4A and C4B by antisense inhibition (Schneider et al 2001). The TOLL-like receptor 4 cDNA (AK014533) of a C57BL6 J mouse contains a MaLR longterminal repeat and an in-frame B2 repeat in the CDS that result in a premature termination codon and possibly a truncated (1 146 aa) form of TLR4 that lacks the cytoplasmic domain and most of the extracellular region and therefore lead to...

Perforin Alleles Encoding Partial Loss of Function

Function of more than 30 missense mutations has been analyzed in surrogate cytotoxicity assays. Typically, perforin function in a cellular context can be assessed by expressing it in rat basophil leukemia (RBL-2H4) cells (which are equipped to process, store, and secrete perforin upon conjugation with a target cell) (Shiver and Henkart 1991 Voskoboinik et al. 2004), or by complementing perforin function in lymphocytes isolated from perforin-deficient mice (our unpublished data). We have also pioneered the use of perforin purified from baculovirus-infected insect cells, providing a source of perforin whose lytic and proapoptotic capacities can be assessed by direct application to target cells in the presence or absence of granzyme B, respectively (Voskoboinik et al. 2004 Waterhouse et al. 2005). We have found that while the majority (about 80 ) of missense mutations lead to protein instability and degradation, some lack function due to an inability to lyse the target cell membrane...

Ala91Val a Common Hypomorphic Perforin Allele

A number of independent population studies have found 9-17 of subjects to possess at least one perforin allele encoding the apparently conservative Ala91Val (A91V) substitution (Mehta et al. 2006 Zur Stadt et al. 2004). This high-frequency and the semiconservative nature of the substitution had led most to predict that the function of A91V would be equivalent to wild-type (Mehta et al. 2006). However, two recent studies have shown the A91V allele to impose a considerable loss of function. First, the NK cells of homozygous subjects have reduced cytotoxicity (Mancebo et al. 2006), and secondly, A91V-perforin expressed in RBL cells or primary mouse lymphocytes showed a similar reduction in function (Trambas et al. 2005 Voskoboinik et al. 2005b). We have recently found that while wild-type per-forin expressed in baculovirus-infected insect cells is strongly lytic and remains potent with storage, A91V perforin has markedly reduced function (our unpublished observations). These findings...

Targeting Enhanced Clearance Of The Latent Pool

The demonstration that cells containing potentially infectious, integrated provirus persist following prolonged undetectable plasma viral loads on HAART has prompted discussions about strategies that might complement HAART by stimulating the clearance of the latently infected cell pool. The population of latently infected cells appears to be established quite early in the process of HIV infection and then persists for many years regardless of therapy (11,12,90,91). In support of this general concept, in our own unpublished observations the total complement of viral DNA in a cohort of HIV-infected patients remains relatively stable for periods of follow-up of up to a decade.

Subjective Health Status

The study of older schizophrenic persons in New York City cited previously found that despite equal or lower prevalence rates of physical disorders among schizophrenic persons compared with older community persons, self-reported health differed between the two aging samples (C. I. Cohen, unpublished data). When the entire schizophrenic sample was examined, the percentage reporting excellent good health was 38 , compared with 54 of community persons. In a multivariate analysis, only activity limitations and depression were significant predictors of negative self-health ratings among older schizophrenic persons. Compared with the general older community sample, older schizophrenic persons had higher scores on the scales for depression (7.5 vs. 5.5) and activity limitations (6.0 vs. 5.0), although it is worth noting that scores on the activity scale can be affected by limitations due to mental as well as physical causes. Thus, the results of the multivariate analysis indicate that...

Electron Transport Chain Inhibition May Act as the 02 Sensor in AMC

If hypoxia is sensed by the mitochondria, how is the signal transduced to plasmalemmal K+ channels Our data suggest that hypoxia decreases ROS generation from the ETC at a site upstream of the classical 02 and CN binding site of cytochrome c oxidase (complex IV) and downstream of the rotenone binding site in complex I. We tested if alterations of ROS could account for K+ channel inhibition during hypoxia. Exogenous H202, an 02-signaling pathway second messenger, reversed the effect of hypoxia on K+ currents, and the ROS scavenger, N-acetylcysteine, mimicked and attenuated the hypoxic inhibition of K+ currents (Thompson and Nurse, unpublished data). Taken together, these data suggest that hypoxia decreases ROS generation by the ETC of AMC. A similar mechanism, involving inhibition of mitochondrial ROS generation has been proposed to explain the 02-sensitivity ofpulmonary myocytes (19).

ROS May Contribute to Insulin Resistance

If ROS participate in cardiovascular risk and disease, then benefits of antioxidants should be evident among high-risk subjects, e.g., those in the heart outcomes prevention evaluation (HOPE) study (109). In this study, vitamin E had no significant benefit, whereas the ACE inhibitor ramipril reduced risk. However, vitamin E in a wide range of concentrations of the racemic mixture as well as specific enantiomers had no effect on ROS produced by VSMCs stimulated with oleic acid and angiotensin II (unpublished observations). Consequently, vitamin E, which is lipophilic, may not block some important signaling events, many of which occur in the cytosol, in the genesis of vascular disease in humans.

Concentrationresponse Relationships

It is tempting to speculate that hcrtr-1 and -2 would display not only distinct pharmacology with respect to hypocretin-2 but also distinct signaling properties. Despite their high homology in the transmebrane segments, hcrtr-1 and -2 display clear differences in the intracellular parts, suggesting that there would be a prerequisite for distinct signaling. With the current tools, or rather the lack of some central ones, we consider that the only systems, where comparisons can be performed with high enough reliability are recombinant expression systems. Even in these systems one has to make sure that the clonal selection does not distort the results. The only report published so far on differences in signaling suggests that hcrtr-2 but not hcrtr-1 receptors are able to couple to Gj proteins in recombinant BIM cells.49 However, this is not in agreement with our results (Kukkonen et al., unpublished) with other cell lines, suggesting that either the expression profile of different Gi...

Aberrant T Cell Immunity

Support for such a T cell-mediated component of the neurodegenerative immune response in glaucoma is evidenced by abnormal T cell subsets in many glaucoma patients 14 . Recent experimental studies have also provided evidence that antigen-stimulated T cells may directly be cytotoxic to RGCs, mostly through the Fas Fas ligand-dependent pathway. Although retinal microglia are involved in the apoptotic elimination of T cells from the retina and optic nerve head, similarly via Fas Fas ligand interactions, RGCs progressively undergo apoptosis in antigen-immunized animals, which results in a pattern of neuronal damage similar to human glaucoma Tezel and Wax, unpublished data . These data suggest that T cell-mediated neurodegeneration not only depends on aberrant activation of autoreactive T cells but may also reflect a dysfunction in the

Inulintype Fructans And Lipid Homeostasis

The hypothesis that inulin-type fructans might modulate the metabolism of lipids originates in an experiment protocol to evaluate their caloric value (see Chapter 7). Indeed, at the end of the treatment period, analysis of total body composition of oligofructose-fed rats (20 w w in diet for 6 weeks) revealed a reduction in total body fat mass as compared to age-paired rats fed a control diet (Roberfroid unpublished results).

Alfred Russel Wallace

During an attack of a tropical fever, Wallace experienced a flash of insight in which he realized that natural selection could serve as the mechanism of evolution. Within a few days he completed his essay On the Tendency of Varieties to Depart Indefinitely from the Original Type and sent it to Charles Darwin for review and possible publication. Darwin was shocked to find that Wallace had developed a theory of evolution identical to that outlined in his own unpublished 1842 essay. Darwin's friends Charles Lyell and Joseph Hooker arranged for a joint presentation of the papers written by Wallace and Darwin and simultaneous publication in the August, 1858, Proceedings of the Linnean Society.

Rho Rhokinase in Vascular Smooth Muscle Cell Growth

Thrombin-induced DNA synthesis in rat aortic VSMC is associated with activation of RhoA and inhibited by C3 exoenzyme and Y-27632 (55). The activation of RhoA apparently augments the response to activated Ras by reducing the expression of the cyclin-dependent kinase (Cdk) inhibitor p27Kipl via activation of phosphatidylinositol 3-kinase (55). In human aortic and saphenous vein VSMC, RhoA mediates platelet derived growth factor (PDGF)-induced DNA synthesis by downregulating p27K'pl and stimulating Cdk-2 and the hyperphosphorylation of retinoblastoma protein (32). In this case, activation of RhoA is apparently necessary and sufficient for serum- and PDGF-induced DNA synthesis. Angiotensin II activates RhoA in rat aortic VSMC, and C3 exoenzyme and Y-27632 inhibit angiotensin II-induced protein synthesis (68). Similarly, C3 exoenzyme and Y-27632 inhibit stretch-induced activation of extracellular signal-regulated kinase (ERK) and stimulation of DNA synthesis in rat VSMC (45). Inhibition...

Selected further reading

Antimalarial drug policies data requirements, treatment of uncomplicated malaria and management of malaria in pregnancy. Report of an informal consultation, Geneva 14-18 March 1994. Geneva, World Health Organization, i994 (unpublished document WHO MAL 94.i070 available on request from Communicable Disease Prevention and Control, World Health Organization, i2ii Geneva 27, Switzerland).

Regression Of Gastric Mucosa Associated Lymphoid Tissue Lymphoma Following Eradication Of H Pylori

The stability of the regressions induced by the eradication of H. pylori is still under investigation. Of the six patients originally reported by Wotherspoon et al., three patients have remained in complete remission for 6 yr one patient who took 1 yr to obtain complete remission has maintained this for 5 yr (54). Two patients relapsed histologically during the follow-up period but returned to undetectable tumor without further therapy and continue in this state 6 yr after initial diagnosis (A.C. Wotherspoon and P.G. Isaacson, unpublished data). In a separate study Neubauer et al. found four local relapses in 40 patients achieving complete remission during a mean follow-up period of 24 mo (58).

The Use Of Mri In Current And Upcoming Stroke Trials

The benefits of arterial recanalization may be supplemented by neuronal protection (a first protocol draft including MRI in the clinical trial is underway), particularly when the two strategies are used simultaneously, and if they can be used very early following symptom onset. A further very interesting approach being tested in the clinic is ultrasound-enhanced recanalization in stroke patients under treatment with rtPA. Ultrasound can be applied via intravascular devices (EKOS, EPAR, Angiojet), or clot lysis facilitation with transcranial ultrasound is another option. Two trials examining these possibilities are underway TRUMBI is an international trial, while CLOTBUST is an oligocentric trial headed by the university medical center at Houston, Texas. Preliminary data from CLOTBUST (Alexandrov and Grotta, unpublished data) showed a significantly higher rate of early recanalization in patients treated with rtPA and ultrasound as opposed to rtPA alone. Further data are pending. Also,...

Mechanisms of Pulmonary Vasodilation at Birth

Mechanisms, such as a compensatory vasodilator mechanisms (e.g., upregulation of other NOS isoforms or dilator prostaglandins) or less constrictor tone. Interestingly, these animals are more sensitive to the development of pulmonary hypertension at relatively mild decreases in Pa02 and have higher neonatal mortality when exposed to hypoxia after birth (unpublished observations). We speculate that isolated eNOS deficiency alone may not be sufficient for the failure of postnatal adaptation, but that decreased ability to produce NO in the setting of a perinatal stress (e.g., hypoxia, inflammation, hypertension, or upregulation of vasoconstrictors) may cause PPHN.

Influence of Rotational Cues on the Neural Processing of Gravito Inertial Force

Sensory systems often provide ambiguous information. For example, otolith organs measure gravito-inertial force (GIF), the sum of gravitational force and in-ertial force due to linear acceleration. According to Einstein's equivalence principle, no set of linear accelerometers alone can distinguish gravitational force (which changes with head orientation during head tilt) from inertial force (which changes with linear acceleration of the head). Therefore, the central nervous system (CNS) must use other sensory cues to distinguish tilt from translation. For example, the CNS can use rotational cues provided by the semicircular canals and vision. Much of this chapter provides a brief review of studies showing the influence of rotational cues on the neural processing of tilt and translation. However, we also include preliminary unpublished data. We begin by discussing the underlying physics (and associated neural processes) and neural representations. We then present studies that measure...

A brief regulatory history of breast implants

In the meantime, concerns were raised about the safety of breast implants. In 1989 an unpublished study showed that polyurethane foam, which was used as a coating on some silicone gel-filled breast implants to reduce capsular contracture, would degrade and release 2-toluene diamine (TDA), a chemical known to cause cancer in animals, under conditions of high temperature and alkalinity. The manufacturer removed these from the market in 1991. Based on a study by one of the manufacturers, FDA estimated that the risk of cancer from exposure to TDA is about one in 1 million over a woman's lifetime 4,5 .

Vertebroplasty In Nonfractured Vertebrae

The last scenario is vertebroplasty of nonfractured vertebrae adjacent to a fractured level (prophylactic vertebroplasty). Experimental data suggest that treatment of one vertebra with cement infusion may place adjacent vertebrae at increased risk of spontaneous fracture, given decreased compliance of the local spinal segment (29). One clinical study (20) showed a small but statistically significant increased risk of vertebral fracture in the vicinity of a cemented level, although vicinity was not defined, and may not necessarily have been adjacent. Indeed, it remains common for patients treated with vertebroplasty to return with new fractures. The authors note that approx 17 of patients develop new fractures following vertebroplasty, at variable locations in relation to the treated level (unpublished data). These new-onset fractures may be unrelated to the vertebroplasty, as approx 20 of osteoporotic patients who suffer from one fracture and are treated conservatively will present...

Partially Overlapping Repertoire of Genes Induced by Viruses IFNanddsRNA

In order to identify the primary target genes induced by viruses, type I IFNs and dsRNA, microarray analyses have been performed by many investigators (reviewed in Sarkar and Sen 2004). However, it is important to realize that because the different inducing agents can induce one another, the results of the above analyses, unless carefully designed, are often difficult to interpret. For example, virus replication can produce both dsRNA and IFNs, and dsRNA treatment can produce IFN, thus complicating the pictures. Mutant cell lines have helped to circumvent this problem considerably. Human cell lines that cannot synthesize IFNs, because of the deletion of the type I IFN locus in their genomes, have been particularly useful to identify dsRNA-regulated genes. Such an analysis using cDNA microarray identified 175 dsRNA-stimulated genes in a human glioma cell line. On the other hand, expression of 95 other genes was repressed by dsRNA treatment of these cells (Geiss et al. 2001). A subset...

Clinical Application of Isoquinolinesulfonamide to Human Cerebral Vascular Diseases

Cerebral vasospasm is the leading cause of poor postoperative outcome of patients with subarachnoid hemorrhage due to ruptured aneurysms. Constriction of the arterial lumen begins about 4 days after the hemorrhage. Patients begin to show symptoms and signs of spasm at about the seventh day which last for 2-3 weeks. However, the spastic arteries begin to dilate by themselves after the fourth week if the patient can tolerate the ischemic insult. The primary cause of spasm is the degradation products of red blood cells in subarachnoid clot. However, further details of the mechanism have yet to be clarified. Both constriction of smooth muscle cells and inflammation seem to be involved. After the patient is secured from further bleeding by a successful neck clipping or intravascular treatment by GDC (Guglielmi detachable coil), 30 of the patients suffer from vasospasm in various forms, resulting in neurological deficits that range from mild cognitive dysfunction, sensorimotor paralysis,...

Changes in Immune Marker Expression in Response to IFN7

Data from rat brain-derived stem cells also show dynamic upregulation of MHC class I in response to rat recombinant IFN-7 38 . In addition, we obtained similar results with human brain-derived stem cells Klassen et al., unpublished data . Although class II levels are high at baseline in the human cells, levels increased even higher after 4-day exposure to human recombinant IFN-7. MHC class II was also expressed at this time, as was the adhesion marker intercellular adhesion molecule (CD54), the latter result being consistent with the behavioral changes (increased flattening of cells and increased adhesion to substrate) seen in culture during this time.

NK Cells in Autoimmune Disease

NK cells are not only found at sites of normal immune responses but have also been shown to accumulate in target organs of autoimmunity, for example, in the inflamed joints of RA (Dalbeth and Callan 2002 Tak et al. 1994), in brain lesions of MS (Traugott 1985), in psoriasis lesions (Cameron et al. 2002), and in the inflamed islets of Langerhans in IDDM (Miyazaki et al. 1985 Poirot et al. 2004 and our unpublished data). The presence of NK cells in target organs of autoimmunity, implying a role in disease at this site, is interesting in relation to findings reporting decreased NK cell numbers and impairment of NK cell function in peripheral blood in patients (Cameron et al. 2003 Yabuhara et al. 1996 and reviewed in Baxter and Smyth 2002 Flodstrom et al. 2002b Grunebaum et al. 1989). Data from us and others show that rodents with diabetes also have compromised peripheral NK cells (Johansson et al. 2004 Poulton et al. 2001). It is not clear whether the reported alterations in blood NK...

Surgical Complications

Peri- and postoperative complications have been calculated on 1164 patients followed for 4 years (13, and unpublished observations). During the primary stay at the hospital the following complications occurred bleeding 0.5 , embolus and or thrombosis 0.8 , wound complications 1.8 , deep infections (leakage, abscess) 2.1 , pulmonary 6.1 , other complications 4.8 . The number of complications was 193 and the number of patients with complications 151 (13 ). In 26 patients (2.2 ) the postoperative complications were serious enough to cause a reoperation.

RH mapping in different mammals

Four WGRH panels generated using different dosages of irradiation are currently available for genome mapping in cattle (5000 rad cattle-hamster, Womack et al., 1997 3000 rad cattle-hamster, Williams et al., 2002 12,000 rad cattle-hamster, Rexroad et al., 2000 7000 rad cattle-hamster, unpublished, see Liu et al., 2002). Published literature shows that the 5000 rad panel (Womack et al., 1997) has been most extensively used, and has served as the key contributor to genome mapping efforts in cattle. A large assortment of medium to high density RH maps for several individual bovine chromosomes are all based on this panel among which the first parallel RH map between BTA19 and HSA17 is worth mentioning (Yang and Womack, 1998 Yang et al., 1998). Over the years, the panel has been widely used to integrate physical and genetic linkage maps of various cattle chromosomes (e.g. Band et al., 1998 Rexroad and Womack, 1999 Amarante et al., 2000 Antoniou et al., 2002 Ashwell et al., 2002)....

Endocrine Actions Of Hypocretins

In addition to this anatomical evidence, physiological studies have revealed the existence of a functional link between hypocretins and the HPA axis. It has been shown that intracerebroventricular administration of both hypocretins results in the induction of c-fos activity and a depolarization of CRH-synthesizing parvocellular neurons of the paraventricular hypothalamic nucleus.96-99 Furthermore, central administration of Hcrtl increased mRNA levels of CRH and arginine vasopressin (AVP) in this neuronal population100 (our unpublished data). Central administration of Hcrtl also raised the circulating levels of adrenocorticotropin hormone (ACTH) and corticosterone.98101102 Despite all the evidence linking hypocretins and the HPA axis, the actions of glucocorticoids on hypocretin expression are not very well established. It has been demonstrated that bilateral adrenalectomy induces a marked reduction in prepro-Hcrt mRNA levels in the LHA, which is reversed by peripheral dexamethasone...

The DCNK Cell Interplay in the Periphery

Other sites of DC-NK cell interactions could be inflamed tissues. The chemokine receptor repertoire of CD56dimCD16+ blood NK cells (expressing CXCR1 and CX3CR1) suggests that they could migrate in response to IL-8 and soluble fractalkine 51 . A direct contact between DC and NK cells was first shown in Malassezia-induced atopic skin lesions 52 and later highlighted in imatinib mesylate (Gleevec STI571)-induced lichenoid dermatitis 53 . We recently observed aberrant PEN5+ NK cell infiltrates in tissues infiltrated with malignant Langerhans cell histiocytosis (C. Borg, unpublished data), suggesting that a dysregulation of the LC-NK cell cross-talk could participate in chronic inflammation.

Legionella Siderophores

Growth in an iron-deplete defined medium. Second, the chelating activity is subject to iron-repression i.e., the addition of iron to the CDM decreases reactivity, whereas the removal of additional iron from the CDM cultures increases CAS reactivity. Third, the CAS reactivity is less than 1 kDa and is resistant to heat and proteases. Fourth, CAS reactions are rapid and intense. Fifth, CAS-positive super-natants facilitate the growth of wild-type legionellae in BCYE agar containing otherwise inhibitory concentrations of the iron chelator 2,2'-dipyridyl (DIP) (Allard et al, 2005). The iron-chelating activity in L. pneumophila supernatants is known as legiobactin (Liles et al, 2000). CAS-reactive supernatants remain negative in the Arnow, and Csaky assays, implying that legiobactin is not a typical catecholate or hydroxamate. In support of this notion, solvents used to extract common siderophores do not extract the Legionella siderophore (Liles et al, 2000). Legiobactin has been purified...

Some Recent Novel Sensing Methods

Ruthenium Tris Diphenyl

Photonic crystals are ordered dielectric arrays that diffract light at wavelengths determined by the lattice spacing between the arrays and the average refractive index of a structure (Carlson and Asher, 1984 Asher, 1986 John, 1987 Yablonovitch, 1987). One example of a photonic crystal is a closely packed colloidal array as shown in Figure 9.26. This crystal was prepared at our Institute, using 200-nm polystyrene spheres. These spheres were floated, as a suspension, over a patterned template where they settled to form a highly ordered array (Markowicz and Prasad, unpublished). Figure 9.26. Close packing of colloidal nanospheres to form a photonic crystal of close-packed colloidal array. (Left) Atomic force microscope (AFM) image of the surface layer. (Right) Scanning electron microscope (SEM) image of a cross section (Markowicz and Prasad, unpublished). Figure 9.26. Close packing of colloidal nanospheres to form a photonic crystal of close-packed colloidal...

The Hypocretin System In Peripheral Endocrine Tissues

Hypocretin and Hcrtr1 mRNA expression, but not Hcrtr2 mRNA, has been detected in the rat testis,7,66,70,78 with presence of prepro-Hcrt signal in interstitial Leydig cells and seminiferous tubules, and predominant location of Hcrtr1 mRNA in the tubular compartment of the testis78 (our unpublished data). In contrast, in humans prepro-Hcrt is only expressed in the epididymis and penis whereas both Hcrtrs are present in testis, epididymis, seminal vesicle and penis.79 Low levels of hypocretin and hypocretin receptors have been detected in other peripheral tissues. In humans prepro-Hcrt is expressed in the stomach, kidney, colon, colorectal epithelial cells and placenta.72 In the rat, Hcrtr1 mRNA has been detected in the kidney, thyroid, ovary and placenta66 (our unpublished data). In addition, Hcrtr2 mRNA has been found in rat lung, placenta66 (our unpublished data) and pineal gland.84

Pht Family of Transporters

Pneumophila

Examination of the L. pneumophila genome reveals that strains Philadelphia 1 and Lens have 11 phtA homologs, while the Paris strain has 9 (Cazalet et al. 2004 Sauer et al. 2005). Though several of these loci are likely gene duplications, it is conceivable that L. pneumophila encodes pht homologs dedicated to transporting each of the six essential amino acids, either arginine, cysteine, methionine, serine, threonine, or valine (Ristroph et al. 1981). In support of this model, a phtJ (previously milA) mutant has a growth defect in macrophages and alveolar epithelial cells (Harb and Abu Kwaik 2000), which can be suppressed by valine supplementation (Sauer and Swanson, unpublished). Other vacuolar pathogens may also exploit transporters to evaluate nutrient availability before undergoing differentiation, since pht homologs have been identified in Coxiella burnetti and Francisella tularensis, two closely related pathogens that also efficiently parasitize both

Hormone Production Sexual Development and Activity Hormone Production

Cryptorchid Testicular Volume

Although there is no reason to expect a disturbance in sexual activity because men who were formerly cryptorchid have normal development and testosterone levels and a normal interest and abilities for sexual functioning, an early report suggested that sexual drive seemed to be diminished (130). Also, men who were formerly cryptorchid have been reported to be less sexually active as adults when judged by frequency of intercourse, although the mean age of onset of masturbation and coitus were not different than normal. It is of interest that a direct relationship was found between frequency of intercourse and both testicular volume and testosterone levels (142). Also, unpublished data from the Children's Hospital of Pittsburgh cohort of formerly cryptorchid men indicate that frequency of intercourse is lower than in control men. These data are not well substantiated.

Functional Gonadotropin Deficiency

Pulse Frequency

Spontaneous and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion in an adult man with chronic renal failure and in a normal adult man. Blood samples were obtained every 10 min for 8 h. The arrow indicates the administration of 100 ig iv GnRH. Note the scale for LH differs, and mean values are 36.5 and 5.41 mlU mL, respectively, indicating the presence of Leydig cell insufficiency. In the man with chronic renal failure there are low amplitude LH secretory episodes with a normal threefold rise in LH after GnRH stimulation, implying GnRH deficiency. The delay to peak LH and the delayed downstroke are indicative of prolonged LH clearance. (Data courtesy of F. Bruns and S.J. Winters, and are unpublished.) Fig. 1. Spontaneous and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion in an adult man with chronic renal failure and in a normal adult man. Blood samples were obtained every 10 min for 8 h. The arrow...

Ryanodine Receptors Ca2 Channels and Ca2 Sparks in Pulmonary Artery Smooth Muscle Cells

In pulmonary arteries, the expression of RyR subtypes has not been reported. Ongoing studies in our laboratory detected mRNA for all three RyR subtypes using reverse-transcription polymerase chain reaction, and RyR1 and RyR2 proteins by Western blot and immunostaining techniques (Yang and Sham, unpublished data), suggesting that multiple RyR subtypes are expressed in rat PASMCs as in systemic myocytes (11, 27, 30, 34). Even though it is unclear which RyR subtype is the major contributor for spark generation, there is no doubt that spontaneous sparks originate exclusively via RyRs in PASMCs. This is based on evidence that i) ryanodine concentration-dependently abolished Ca2+ sparks, ii) enhancement of RyR activity using a subthreshold concentration of caffeine increased spark frequency, an effect reversed by ryanodine, and iii) IP3 receptor antagonists, 2-aminoethoxy-diphenylborate (2-APB) and xestospongin C, had no effects on resting spark frequency (24, 39). These observations are in...

The current relevance of salvage cystectomy broadening the definition

Retroperitoneal Node Dissection

Looking at our report of salvage cystectomy in 1980, we performed an average of 6.2 salvage cystectomies a year between 1969 and 1979 for patients for whom definitive irradiation had failed.9 An unpublished review of our experience from 1979 to 1987 showed that we were still performing 6.1 salvage cystectomies per year, predominantly for treatment failure after radiation therapy. Looking at the years 1993 to 1998, however, we performed only 1.4 salvage cystectomies per year after definitive radiation therapy, including cystectomies on four patients who underwent planned combination therapy with irradiation and chemotherapy on so-called 'bladder preservation' protocols. During this same timespan, however, we also performed 7.2 salvage cystectomies a year for patients who had undergone definitive chemotherapy and had persistent or recurrent disease. In fact, if we were to expand the use of the term 'salvage cystectomy' to also include patients who had received non-definitive...

Internalization of human pathogens into growing plants

Donated as sax (Survival on Arabidopsis eXtract), has been identified in a range of Ps. syringae pathovars but absent from non-phytopathogenic strains. From comparative homology studies the gene shows a high level of similarity to an uncharacterized gene in E. coli O157 H7 (Crooks, unpublished data). Whether the expression of sax within E. coli O157 H7 enhances persistence within plants has yet to be established.

Spermatogenesis Stimulation

Testosterone And Prenatal Development

GnRH is not an appropriate treatment for patients with pituitary disease and will be ineffective in men with CHH resulting from GnRH receptor mutations. These mutations produce a variable degree of resistance to GnRH. According to our experience, GnRH-R mutations are rare, and we found none in approx 50 patients diagnosed as IHH or Kallmann syndrome (data unpublished). However, a few cases have been described (13-15) (see Chapter 5). Because these cases are rare, PCR testing of the GnRH receptor gene sequence is recommended only if a patient fails to respond to pulsatile GnRH treatment. In our view, screening before beginning pulsatile GnRH treatment is not currently necessary. Gordon Holmes spinocerebellar ataxia and X-linked adrenohypoplasia congenita are two other forms of inherited HH in which responsiveness to GnRH is impaired (16). The formation of antibodies to GnRH or its receptor seldom occurs but can lead to a failure of pulsatile GnRH therapy (17,18). These patients should...

Regulation of Type I Ifn Gene Expression

2005), C57BL 6 J mice express only a single , dominant transcript and very low levels of one IRF-5 splice variant in bone marrow. This variant was not express in spleen or established mouse cell lines and shows a transactivation capability similar to full-length IRF-5. Also, the mouse IRF-5, while activated by MyD88 and TBK-1, does not seem to be activated efficiently by NDV infection (P.M. Pitha, unpublished results). The differences in the IRF-5-mediated activation of human IFNA genes in vitro and in MyD88-stimulated induction in mice, as well as the discordant effect of IRF-5 on the activation of IFN genes in cells expressing ectopic IRF-5 and mouse cells lacking IRF-5 expression, are unexpected. These results indicate that in the presence of high levels of activated IRF-7, the contribution of IRF-5 to the induction of IFN genes may be negligible, and its role may be limited to the induction of inflammatory che-mokines and cytokines that are not stimulated by IRF-7. The...

Angiogenic Privilege

Developmentally, corneal angiogenic privilege is established very early already at fetal stages, the human cornea - in contrast to the adjacent conjunctiva - is devoid of lymphatic and blood vessels Cursiefen et al., unpublished findings . Whether corneal immune privilege is already fully active at these early stages is currently not known, but corneal antigen-presenting cells lacking major histocompatibility complex (MHC) class II are not present in fetal corneas before term 17 .

Structure and Regulation of MIC

Unlike that of the ubiquitous MHC class I molecules, the tissue distribution of MIC is normally restricted to variable areas of the intestinal epithelium, with limited evidence for surface expression (Groh et al. 1996). In cultured polarized epithelial cells, the proteins are sorted to basolateral epithelial membranes by an active process that is determined by two adjacent hydrophobic amino acids, leucine and valine, at the membrane-proximal ends of their cytoplasmic tails (Suemizu et al. 2002). The immunobiology and regulatory mechanisms underlying the expression of MIC in intestinal epithelium are poorly understood. Among tissue culture cell lines, expression of MIC is mostly limited to fibroblast and epithelial cells and is not inducible by interferons. Importantly, however, MIC can be heat shock-induced similar to heat shock protein 70 (hsp70) genes, presumably because of the presence of a highly conserved heat shock response element (HSE) in the 5'-flanking regions of the...

Induction of ISGs by TLR3 Signaling

Pathway Neutrophils

As mentioned above, Tyr759 of TLR3 is absolutely needed for complete signaling by this receptor. When this residue is mutated to Phe, NFkB- and IRF-3-driven genes are not induced by dsRNA. Surprisingly, in dsRNA-treated cells expressing the mutant receptor, NFkB is released from IkB and translocated to the nucleus but it does not drive gene transcription (our unpublished observation) similarly, IRF-3 is dimerized and translocated to the nucleus but it is transcriptionally inactive (Sarkar et al. 2004). Investigation of the underlying molecular mechanisms has revealed that the activation of both transcription factors, IRF-3 and NFkB, is a two-step process and the second step is defective in cells expressing the Y759F mutant of TLR3. Phosphorylated Tyr759 recruits PI3 kinase, probably indirectly, to the TLR3 complex, PI3 kinase is activated, it phosphorylates Akt, which leads to additional phosphorylation of the TBK1-activated IRF-3. The tyrosine kinase, Src, which is known to be...

Nonrem Sleeprelated Symptoms

A complementary experiment we carried out in order to further confirm this conclusion was examination of arousal effect of i.c.v. orexin-A administration in each strain of knockout mice (unpublished observation). As previously reported in rodents, i.c.v. administration of orexin-A in wild-type mice increased wakefulness and suppressed both non-REM and REM sleep in dose-dependent manner.15 Effects of orexin-A on sleep wakefulness pattern were not significantly different in OX1R- - mice, while effects on wakefulness and non-REM sleep in OX2R- - mice were dramatically attenuated as compared to wild-type and OX1R- - mice. These data suggest that OX1R is dispensable for increase of wakefulness and suppression of non-REM sleep by orexin-A administration in the presence of OX2R, although stimulation of OX1R in the absence of OX2R is capable of promoting wakefulness and suppressing non-REM sleep with efficiency much lower than stimulation of OX2R. As for suppression of REM sleep by orexin-A...

Simultaneous Brightness Contrast

With the aid of modern computer graphics, pictorial representations of complex three-dimensional patterns with vivid impressions of shadows, transparency and shading have replaced the conventional SBC display, and with impressive results. I have provided an example of my own in Figure 3.12, a figure inspired by Adelson's (unpublished) checkerboard-shadow illusion. The allure of these new demonstrations is the sheer magnitude of their illusory brightness differences, which far surpass that found with standard SBC displays. Yet there is a negative side. For some protagonists it has meant downplaying the value of not just simple forms of SBC such as the standard display, but more importantly their explanation in terms of contrast. After all, if such stunning illusions are apparently inexplicable in terms of contrast, is contrast really that important I will argue in the next section that it is. Moreover, demonstrations suggesting that contrast may be insufficient...

Analysis of Plasma Parameters

Calcium line at 422.7 nm of a plasma on healthy tooth substance. The plasma was induced by a Nd YLF laser (pulse duration 30 ps, pulse energy 500 J). Unpublished data Fig. 3.52. Calcium line at 422.7 nm of a plasma on healthy tooth substance. The plasma was induced by a Nd YLF laser (pulse duration 30 ps, pulse energy 500 J). Unpublished data Fig. 3.53. Dependence of spectral width on plasma density and temperature according to Saha's equation (plasma temperature as labeled). Given values apply for the calcium line at 422.7 nm. Unpublished data Fig. 3.53. Dependence of spectral width on plasma density and temperature according to Saha's equation (plasma temperature as labeled). Given values apply for the calcium line at 422.7 nm. Unpublished data

The ULBP Family of NKG2D Ligands

Nkg2d Gene

Binding studies utilizing recombinant IgG Fc region fusion proteins led to the discovery that the CMV UL16 transmembrane glycoprotein, which was of unknown function, specifically interacts with cell surface proteins that were termed ULBP1 and ULBP2 (Cosman et al. 2001). Three additional ULBP sequences were identified by sequence homology (Fig. 2) (Chalupny et al. 2003 Bacon et al. 2004). ULBP3 and -4 and MICA do not interact with UL16, but MICB does. ULBP share no direct sequence relationship with MIC and are encoded outside the MHC on chromosome 6q25. As with MIC, ULBP are distant members of the MHC class I family. All ULBP lack the membrane proximal a3 domain. ULBP1-3, and ULBP4 and -5 have GPI membrane anchors and transmembrane regions, respectively. None of these molecules is associated with p2m or peptide ligands. The a1a2 domains of ULBP share about 50 -60 identical amino acids and are equidistant from those of MHC class I and MIC, with about 25 sequence homology. ULBP1-3 are...

Phenotyping of Bone Marrow MCs

Mast Cells Fsc

Correct sampling of bone marrow cells is a first critical step in MC phenotyping in patients with suspected SM (20,21). The selection of patients and pre-invasive steps in the diagnostic work-up in SM have been described in detail elsewhere (22-24). In all patients examined, a bone marrow biopsy is performed (22-24). Usually, the bone marrow is obtained from the posterior iliac crest. Aspiration can be performed with any type of bone marrow-aspiration needle. In recent years several companies have offered biopsy needles through which bone marrow can be aspirated after the biopsy cylinder has been removed (one step procedure and one needle for both the biopsy and aspiration). The quality of the aspirated marrow does not differ from that obtained with conventional aspiration needles (unpublished observation).

Assembly and Signaling Properties of NKG2D and CD94NKG2 Receptors Expressed by CTLs

CD94, NKG2D, andthe NKG2 family comprisedofA, C, E, andFare genetically and structurally related type II transmembrane proteins with a C-type lectin domain. They are encoded within the NK complex (NKC) on human chromosome 12p12.3-p13.1 (Houchins et al. 1991 Plougastel and Trowsdale 1997 Renedo et al. 1997) and overall display very low levels of polymorphism, CD94 and NKG2A being the most conserved (Shum et al. 2002). NKG2A and NKG2E have splice variants, NKG2B and NKG2E, respectively. The signaling receptors expressed on the cell surface include CD94 NKG2A (Brooks et al. 1997 Carretero et al. 1997 Lazetic et al. 1996) and CD94 NKG2C (Lazetic et al. 1996) disulfide-linked heterodimers, and NKG2D homodimers (Bauer et al. 1999), as well as a yet-undefined CD94 NKG2x adaptor immunoreceptor complex with coactivating properties (unpublished data) (Fig. 1). CD94 homodimers exist (Lazetic et al. 1996) but probably have no signaling properties. Although transcripts for NKG2E, NKG2H, and NKG2F...

Regulation of NK Cell Activation by DC

Cell Activation

Human NK cells stimulated by monocyte- or CD34+-derived DC and LPS or by peripheral blood mDC in response to TLR3 or TLR8 ligands has been formally demonstrated. Other cytokines, such as IL-18, and or cellular contacts are also involved 26,33,36 (S. Burg, F. Briere, G. Trinchieri, C. Caux, P. Garrone, unpublished results). However, NK cell activation by DC also requires direct cell-to-cell contacts and depends on the adhesion molecule LFA-1 39 . The formation of DC NK cell conjugates was found to depend on cytoskeleton remodeling and lipid raft mobilization in DC. BM-DC derived from mice with loss of function of the Wiskott Aldrich syndrome protein, a major cytoskeletal regulator expressed in hematopoietic cells, fail to promote NK cell lytic ac

Role Of Intrinsic GnRh Deficiency In Mediating Lowamplitude Lh Secretion

Pituitary Leydig Cell Axis

Simplified schema of the gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH)-testosterone (hypothalamic-pituitary-Leydig cell) axis with feedback (-, inhibitory) and feedforward (+, stimulatory) interactions mediated via specific interface (dose-response) functions. (Unpublished line drawing.) Fig. 1. Simplified schema of the gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH)-testosterone (hypothalamic-pituitary-Leydig cell) axis with feedback (-, inhibitory) and feedforward (+, stimulatory) interactions mediated via specific interface (dose-response) functions. (Unpublished line drawing.)

Ecological implicationsUVB and the structure of seaweed communities

The effect of UVB exposure on the early succession of macroalgae was also studied at a rocky intertidal platform at King George Island, Antarctica, revealing a significant reduction of species diversity based on the effects of UVB (Zacher et al. unpublished data). Species recruitment and dry weight was monitored over a period of 15 weeks on artificial substrates exposed in the intertidal zone. Natural UV-exposure was found to affect the density of the green alga Monostroma hariotii in the first 10 weeks of the experiment, whereas the density of red algal recruits decreased significantly due to UV after 8 and 15 weeks, respectively. Shannon diversity H' dropped as succession proceeded in the PAR + UVA + UVB treatment, increased slightly in the PAR + UVA treatment, and increased in the PAR treatment from the beginning until the end of the experiment. Furthermore, the treatment with PAR alone resulted in a significantly higher diversity at the end of the experiment than the treatment...

Surface Proteins Anchored Covalently

Srtb Gene Svpa Listeria

Proteins containing diverse non-LRR repeat regions preceding the C-terminal sorting region form the second class of LPXTG proteins. The EGD-e strain has 22 LPXTG proteins in this class, of which 14 have orthologs in L. innocua (Cabanes et al. 2002 our unpublished data). To date, only one protein of this group, Vip (Lmo0320), has been characterized at a functional level (Cabanes et al. 2005) (see Section 5.4.1).

Side Effects Of Pituitary Irradiation

The likelihood of developing radiation-induced pituitary deficiency is partly determined by latent or preexisting pituitary dysfunction. In patients not requiring replacement therapy in the immediate postradiotherapy period, the actuarial cumulative probability of requiring hydrocortisone and thyroxine replacement therapy is 10-30 at 10 yr and 30-50 at 20 yr (after doses of 40-50 Gy in 25-30 fractions) (51 unpublished personal data). Other studies report rates of deficiency at 10 yr of approx 80 for ACTH and 30 for TSH, with a suggestion of faster decline in hormone levels after higher radiation doses (50). From a clinical perspective, regular assessment of pituitary function after radiotherapy is the primary medical activity in the posttreatment period.

Regulatory Divide Between Agnathans And Gnathostomes

Skate Fish Infection

The PU.1 Ets domain is conserved throughout the vertebrate radiation. There is an indisputable PU.1 Spi family member even in the agnathan lamprey (Petromyzon mari-nus) (131). Cartilaginous fish have a whole family of three PU.1 Spi members, like mammals (123). By contrast, the PU.1 Ets domain cannot be detected in any invertebrate to date. No member of this subfamily of Ets factors is encoded in the Drosophila or C. elegans genome sequences, and even deuterostome invertebrates seem to lack such genes. Multiple attempts to detect a family member in sea urchin genomic DNA or cDNA have been unseccessful (M.K. Anderson, X. Sun, R. Pant, and E.V.R., unpublished data). Thus, the divergence of this PU.1 Spi subfamily from other Ets factor genes is probably a vertebrate-specific innovation.

Key Features And Patterns Of The Global Obesity Epidemic

Figure 1.2 Projected increases in obesity prevalence. The figure illustrates the rate at which obesity prevalence is increasing in selected countries. It is based on crude projections from repeated national surveys. Source IOTF unpublished Figure 1.2 Projected increases in obesity prevalence. The figure illustrates the rate at which obesity prevalence is increasing in selected countries. It is based on crude projections from repeated national surveys. Source IOTF unpublished

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