Phase I imaging study of Hodgkin's disease and non-Hodgkin's lymphomas with radiolabeled antibody to eosinophil peroxidase.
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Biomedical subjects
Publications and source records attributed to F Wang.
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Fibroblast growth factor-7 (FGF-7) and a specific splice variant of the FGF tyrosine kinase receptor family (FGFR2IIIb) constitute a paracrine signaling system from stroma to epithelium. Different effects of the manipulation of cellular heparan sulfates and heparin on activities of FGF-7 relative to FGF-1 in epithelial cells suggest that pericellular heparan sulfates may regulate the activity of FGF-7 by a different mechanism than other FGFs. In this report, we employ the heparan sulfate-binding protein, protamine sulfate, to reversibly block cellular heparan sulfates. Protamine sulfate, which does not bind significantly to FGF-7 or FGFR2IIIb, inhibited FGF-7 activities, but not those of epidermal growth factor. The inhibition was overcome by increasing the concentrations of FGF-7 or heparin. Heparin was essential for binding of FGF-7 to recombinant FGFR2IIIb expressed in insect cells or FGFR2IIIb purified away from cell products. These results suggest that, similar to other FGF polypeptides, heparan sulfate within the pericellular matrix is required for activity of FGF-7. Differences in response to heparin and alterations in the BULK heparan sulfate content of cells likely reflect FGF-specific differences in the cellular repertoire of multivalent heparan sulfate chains required for assembly and activation of the FGF signal transduction complex.
Among Caucasians, it is well known that 75-95% of primary glaucoma is due to open-angle glaucoma (POAG), with angle-closure (PACG) comprising only a very small minority of cases. These figures are reversed among other groups such as Asians and Eskimos, where PACG makes up 80-90% of primary glaucoma. Among Eskimos, the prevalence of PACG has been reported as 2-8%, as compared to 0.1% among Caucasians. It appears that a population tendency toward shallow anterior chambers may explain the excess burden of PACG morbidity. Among Asians, the prevalence of PACG is intermediate between Caucasians and Eskimos. Existing biometrical data do not show a clear tendency toward shallower anterior chambers among Asians. PACG may be screened for on a population basis by means of various techniques that estimate axial or limbal anterior chamber depth, measure intraocular pressure, or evaluate the optic disc or visual fields. Demographic information and medical and family history will also be of great importance in screening for PACG in large populations. Groups at increased risk for the disease include women, individuals over 50, first-degree relatives of PACG probands, and hyperopes.
It has been suggested that progressive pathophysiologic modifications of endothelium are associated with aging. Aging has been shown to influence some specific functions at the cellular level. In the present study, the effects of aging on levels of prostacyclin (PGI2) production were examined in cultured rat aortic endothelial cells from young (six-week-old) and old (100-week-old) Wistar rats. The level of PGI2 production from rat aortic endothelial cells decreased significantly with increasing age, suggesting decreased function of the endothelial cells. The production of PGI2 stimulated by thrombin was decreased in old rat aortic endothelial cells compared to young rat aortic endothelial cells, whereas there was no difference in the rate of intracellular calcium mobilization caused by thrombin. These data indicate that aging nonuniformly affects both basal and agonist-induced levels of PGI2 production in rat aortic endothelial cells, and that this diminution in PGI2 production may be related to the age-related potentiation of various thrombotic events.
Acetylcholine (ACh) in the vertebrate retina affects the response properties of many ganglion cells, including those that display directional selectivity. Three beta and eight alpha subunits of neuronal nicotinic acetylcholine receptors (nAChRs) have been purified and antibodies have been raised against many of them. Here we describe biochemical and immunocytochemical studies of nAChRs in the rabbit retina. Radioimmunoassay and Western blot analysis demonstrated that many of the nAChRs recognized by a monoclonal antibody (mAb210) contain beta2 subunits, some of which are in combination with alpha3 and possibly other subunits. MAb210-immunoreactive cells in the inner nuclear layer (INL) were 7-14 microm in diameter and were restricted to the innermost one or two tiers of cells, although occasional cells were found in the middle of the INL. At least 60% of the cells in the ganglion cell layer (GCL) in the visual streak displayed mAb210 immunoreactivity; these neurons ranged from 7-18 microm in diameter. The dendrites of cells in both the INL and GCL could sometimes be followed until they entered one of two dense, poorly defined, bands of processes in the inner plexiform layer (IPL) that overlap the arbors of the cholinergic starburst cells. Parvalbumin and serotonin-positive neurons did not exhibit nAChR immunoreactivity. Although the level of receptor expression appeared to be low, mAb210 immunoreactivity was observed in some of the ChAT-positive (starburst) amacrine cells.
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Using data from the 1988 Two-Per-Thousand Survey of Fertility and Birth Control, this paper examines the effects of gender, birth order, and other correlates of childhood mortality in China. Controlling for family-level factors, childhood mortality is found to be associated with the child's gender and birth order. Among firstborn children the difference between male and female childhood mortality is not statistically significant, but among others, female children between ages 1 and 5 experience higher mortality than male children. Childhood mortality is slightly higher for children who have older brothers only than for those who have older sisters only, and it is highest for those who have both older brothers and sisters. Other factors affecting childhood mortality in China include mortality of older siblings, birth interval, urban/rural residence, mother's level of education, and mother's occupation. All interactive effects between gender and family-level characteristics are found to be statistically insignificant.
Sixteen patients with metastatic stage IV melanoma were treated with use of intravenous infusions of dendritic cells (DC) derived by incubation of plastic-adherent peripheral blood mononuclear cells (PBMC) with IL-4 and GM-CSF for 8 days in serumless AIM-V medium, followed by overnight pulsing with peptides. The tyrosinase368-376 (370D) and gp100(209-217 (210M)) peptides restricted to HLA class I A*0201 each differed from wild type by one amino acid modified to increase HLA binding. Median age was 49, with nine men and seven women. All patients, except one, had visceral disease. Patients received escalating doses of peptide-pulsed DCs at 10e7, 3 x 10e7, and 10e8 cells/dose twice at 2 weeks apart, with toxicity and clinical and immune responses as the principal endpoints. The first infusion of DCs was fresh, and frozen DCs were given for the second infusion of each cycle. Mean DC purity by flow cytometry was 49%, with a mean HLA-DR level of 57%, CD86 of 41%, CD58 of 46%, and mean CD14 cells of 0.9%. Toxicity was minimal, with two patients having transient grade III DC-related toxicity. Ten patients received one cycle of treatment and six patients received two cycles of treatment. One patient had a complete remission (CR) of lung and pleural disease after two cycles of DC therapy. Two additional patients had stable disease and two patients had mixed responses. Overall immunity was assessed by recall skin testing with peptides, gamma interferon ELISA assays of peptide specific cytolytic T cell (CTL) stimulated twice with peptide, IL-2, and IL-7 over 24 days, and peptide-specific tetramer assays performed before and after vaccination. Five of 16 patients had an immune response to gp100 or tyrosinase by gamma interferon ELISA assay; four of five were clinically stable or had tumor regression. These data suggest that melanoma antigen peptide-pulsed DC given intravenously are not toxic, and regression or stability of tumor appeared to correlate with the detection of a peptide-specific immune response in the peripheral blood.
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Recent studies have shown that patients with heart failure overexpress a class of biologically active molecules, generically referred to as pro-inflammatory cytokines. This article will review recent clinical and experimental material that suggests that pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) may play a role in the pathogenesis of congestive heart failure. In addition, we will review recent studies that suggest that antagonizing cytokines may represent a novel target for heart failure therapy.
Changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) in cultured hippocampal CA1 neurons isolated from newborn rats were measured by a confocal laser scanning microscope, using the Ca(2+) indicator Fluo-3. The results showed that exogenous adenosine (100 microM) significantly attenuated the increase of neuronal [Ca(2+)](i) induced by acute anoxia. This effect of adenosine could be suppressed by the adenosine A1 receptor antagonist 8-cyclopentyltheophylline. Moreover, potassium channel blockers, aminopyridine, and glipizide could also block the inhibitory role of adenosine, but tetraethylammonium had no effect. These results suggest that adenosine may activate 4-AP or ATP-sensitive potassium channels via an A1-receptor-mediated mechanism and consequently inhibit anoxia-induced [Ca(2+)](i) elevation in hippocampal neurons.
BACKGROUND: It has been hypothesized that infection with either herpes simplex virus (HSV) or cytomegalovirus (CMV) is associated with atherogenesis. However, prospective data relating evidence of prior exposure to these agents with risks of future myocardial infarction (MI) and stroke are sparse. METHODS AND RESULTS: In a prospective, nested case-control study of apparently healthy men, the baseline prevalence of antibodies directed against HSV or CMV was similar among 643 men who subsequently developed a first MI or thromboembolic stroke and among 643 age- and smoking-matched men who remained free of reported vascular disease over a 12-year follow-up period. Specifically, the relative risks for future MI and stroke were 0.94 (95% CI, 0.7 to 1.2) for HSV seropositivity and 0.72 (95% CI, 0.6 to 0.9) for CMV seropositivity, after adjustment for other cardiovascular risk factors. These findings were not materially altered in comparisons of early versus late events or in analyses stratified by smoking status. There was no evidence of association between HSV or CMV antibodies and plasma concentration of C-reactive protein, a marker of inflammation that predicts vascular risk in this cohort. CONCLUSIONS: Among apparently healthy middle-aged men, IgG antibodies directed against HSV or CMV do not appear to be a marker for increased atherothrombotic risk. The observed possible inverse relationship of CMV with MI and stroke was unexpected and may well be due to chance, because the direction of association is not compatible with the a priori hypothesis based on proposed biological mechanisms or previous cross-sectional and retrospective data.
BACKGROUND: Glucagon-like peptide-2 (GLP-2), a 33 amino acid, proglucagon-derived peptide with intestinotrophic activity, is secreted from enteroendocrine cells in the small and large intestine. METHODS: This review describes recent advances in our understanding of GLP-2 physiology from rodent experiments in vivo. RESULTS: GLP-2 administration induces mucosal epithelial proliferation in small and large bowel and stomach. GLP-2 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP-IV) to produce the biologically inactive form GLP-2(3-33), however, GLP-2 analogs that confer resistance to DPP-IV exhibit enhanced biologic activity in vivo. GLP-2-treated bowel retains normal to enhanced functional absorptive capacity. Furthermore, GLP-2 infusion prevents total parenteral nutrition (TPN)-associated intestinal hypoplasia, and enhances bowel adaptation and nutrient absorption in rats following small bowel resection. GLP-2 also reverses weight loss and improves histologic and biochemical parameters of disease activity in mice with experimental colitis. CONCLUSIONS: GLP-2 is an intestine-derived peptide with intestinotrophic properties that may be therapeutically useful in diseases characterized by intestinal damage or insufficiency.
To assess the significance of polymorphisms of the genes for angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2) and urotensin II (UTS2) as risk factors for essential hypertension in two populations from north-western China, we enrolled 198 patients with essential hypertension and 131 healthy controls from the Han population and 120 patients with essential hypertension and 102 healthy controls from the Dongxiang population. Polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism were used to analyse gene polymorphisms. The results provided evidence that genetic variants of UTS2 and ACE2 may play a role in the development of essential hypertension in these populations. Polymorphisms of ACE were not associated with essential hypertension in either population. This is the first report showing that the S89N single-nucleotide polymorphism of the UTS2 gene is associated with essential hypertension.
Non-reactive SLE sera in an ELISA for anticardiolipin antibody (aCL) retested positive in the immunoassay when the sera were first heat-inactivated at 56 degrees C for 30 minutes. This was not a false positive phenomenon since the positive ELISA reactivity of the heated SLE sera was markedly reduced by inhibition with the cardiolipin antigen. Furthermore, the heat-potentiated ELISA reaction was abolished by prior IgG depletion of the SLE sera with Protein A preparation. The unmasked aCL in the heat-treated SLE sera also exhibited selective binding in ELISA to other negatively-charged phospholipids, namely phosphatidylserine and phosphatidic acid but not against either phosphatidylcholine or phosphatidyl-ethanolamine. The data strongly indicate an interaction between antiphospholipid antibodies and heat-sensitive serum component(s), a reduction of the latter resulting in the ELISA detection of the autoantibody.
A recombinant Escherichia coli strain XL1-Blue harboring a stable high-copy-number plasmid pSYL107 containing the Alcaligenes eutrophus polyhydroxyalkanoate biosynthesis genes and the Escherichia coli ftsZ gene was employed for the production of poly(3-hydroxybutyrate) (PHB) by fed-batch culture in a defined medium. Suppression of filamentation by overexpressing the cell division protein FtsZ allowed production of PHB to a high concentration (77 g/L) with high productivity (2 g/L/h) in a defined medium, which was not possible with the recombinant E. coli that underwent filamentation. Further optimization of fed-batch culture condition resulted in PHB concentration of 104 g/L in a defined medium, which was the highest value reported to date by employing recombinant E. coli.