Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF)

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.     

A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing

STUDY HYPOTHESIS: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are given intravenously for the treatment of cyanide poisoning. Because OHCob solutions are intensely red and have peak light absorptions at 352 nm and 525 nm, we investigated whether the presence of OHCob in serum would interfere with various automated, colorimetric chemistry measurements. DESIGN: Selected serum chemistry colorimetric measurements were compared in seven patients, using their own serum as control, with serum containing OHCob at the following concentrations: 100 mg/L, 500 mg/L, and 1,000 mg/L. These concentrations are in the range achieved with therapeutic doses of OHCob when given for cyanide poisoning. MEASUREMENTS AND MAIN RESULTS: Statistically significant alterations in serum values for aspartate aminotransferase, total bilirubin, creatinine, magnesium, and iron were seen in the presence of OHCob. CONCLUSION: The presence of OHCob in serum interferes with several chemistry methodologies, and such interference should be anticipated when this antidote is used.     

An investigation of phase transformation behavior in sputter-deposited PtMn thin films

Sputter-deposited, equiatomic PtMn thin films have application in giant magnetoresistive spin valves, tunneling magnetoresistive spin valves, and magnetic random access memory. However, the as-deposited films are found to be a disordered A1 phase in a paramagnetic state rather than an antiferromagnetic phase with L1₀ structure, which is needed for device operation. Therefore, a postannealing step is required to induce the phase transformation from the asdeposited A1 face-centered-cubic phase to the antiferromagnetic L1₀ phase. The A1 to L1₀ metastable transformation was studied by x-ray diffraction and differential-scanning calorimetry. An exothermic transformation enthalpy of −12.1 kJ/mol of atoms was determined. The transformation kinetics were simulated using the Johnson-Mehl-Avrami analysis.     

Does oral experience terminate ingestion?

Using data from studies of ingestive behavior in developing rat pups we demonstrate how oral experience can contribute to the termination of ingestion. In rat pups, repeated oral stimulation with sweet solutions causes a decline in oral responsiveness. The diminished responsiveness is specific to the flavor of the stimulus experienced orally and can persist for several hours. We suggest that this experience-based decrement in responsiveness is best considered "oral habituation" and that oral habituation largely accounts for the onset of satiety. Post-ingestive feedback signals may have their influence through the oral habituation process or act in the context of oral habituation. Oral habituation is also shown to depend on the pattern of stimulus presentation, a phenomenon that adds considerable complexity to assessing the contributions of oral experience to satiety. The concept of oral habituation may be useful in understanding the immediate control of ingestion and the moment-to-moment expression of ingestive behavior in adult animals.     

The role of zinc in pre- and postnatal mammalian thymic immunohistogenesis

Histogenetically, the thymus is the primary lymphopoietic organ and provides an optimal microenvironment for the differentiation of T lymphocytes, independently of the influence of foreign antigens. Lymphocytes with diverse potential are produced in a protective microenvironment optimal for their maturation, whose dual cellular network is provided by endodermally derived RE cells and numerous ectomesenchymal cells derived from the neural crest. The full development of intrathymic hematopoiesis depends upon the successful completion of a series of well coordinated cellular interactions between widely divergent (in terms of origin) cells [epithelium (primitive pharynx); ectomesenchyrne (neural crest); and PHSCs (yolk sac, fetal liver)]. The cells of the thymic epithelial primordium do not proliferate in the absence of "inductive" interactions with the ectomesenchyme. Moreover, the nature of the mesenchyme determines the behavior of the thymic epithelial anlagen. The ectomesenchymal origin of chemotactic stem cell factor secretion, responsible for hemopoietic stem cell immigration, is a distinct possibility. The human thymus is a generalized hematopoietic tissue with between 7 to 9 weeks of ontogenesis. In human and dog fetuses various elements of mammalian hematopoiesis were identified intrathymically: B lymphocytes, plasma cells, erythropoietic and granulocytopoietic (neutrophils and eosinophils) cells, antigen presenting dendritic cells, and mast cells. Our light and ultrastructural (transmission and scanning), as well as immunocytochemical observations have established that during the embryonal and fetal period, the thymus is seeded by pluripotent, yolk sac derived PHSCs characterized by the following immunophenotype CD34+CD43+CD38-Lin-HLA-DR+CD69+. Stem cell c-kit tyrosine kinase (also referred to as mast cell growth factor, stem cell factor, or steel factor) in combination with autocrine and paracrine growth factors and cytokines (IL-3, IL-4, IL-5, IL-6, IL-7, G-CSF, etc.) stimulates myelopoiesis, including erythropoiesis, as well as lymphopoiesis. These hematopoietic growth factors are produced by activated lymphoblastic cells and stromal RE cells under the influence of immunoneuroendocrine regulation, supported by the finding that experimental or spontaneous, in vivo neural crest ablation during early mammalian ontogenesis always results in an abnormal development of the thymus, as well as the heart and great vessels, thyroid, and parathyroid glands.     

Influence of centrifugal pathways on forward masking of ventral cochlear nucleus neurons

When responses to one part of a sequence of auditory signals reduce the responses to a subsequent portion of the signal, "forward masking" results. Although forward masking occurs in the auditory nerve, that observed in the ventral cochlear nucleus (VCN) more closely resembles psychophysical forward masking. In contrast to the auditory nerve in which the amount of forward masking is proportional to the amount of excitation produced by the masker, most VCN neurons show a poor correlation between forward masking and excitation produced by the masker, indicating a more complex interaction between responses to adjacent signals. This study tested the hypothesis that one component of forward masking is produced by inputs from centrifugal neural connections to the VCN. The centrifugal pathways were interrupted with knife-cut lesions medial to the CN. Responses of single units obtained 60 minutes after the lesions were compared to those obtained before the lesions. In primarylike, sustained chopper and on units the lesions resulted in a reduction in forward masking and enhanced recovery. In contrast, lesions resulted in increased masking in primarylike-notch and low-intensity chopper units. The relationship between masker-elicited excitation and forward masking became more monotonic for transient choppers and on units, approaching that observed for auditory nerve fibers. These effects are probably the result of removal of both inhibitory and excitatory inputs, ultimately reflecting a balance of excitation and inhibition to each neural population in the VCN.     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Conformations and folding of lysozyme ions in vacuo

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.