Two-photon production of charged pion and kaon pairs.
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Biomedical subjects
Publications and source records attributed to S Chan.
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Alveolar type-II cells are responsible for alveolar epithelial cell proliferation during growth and development and in response to lung injury. Based on the observation of abnormal lung development in rachitic rat pups and the expression of receptors for vitamin D by fetal alveolar epithelial cells, the present study examined the influence of 1,25-dihydroxy vitamin D (DHD) on the proliferation of primary cultures of fetal, neonatal and adult alveolar epithelial cells. The ontogony of vitamin D responsiveness was examined, using fetal (days 18, 19 and 22 = term), neonatal (days 7 and 18) alveolar epithelial cells as well as adult alveolar type-II cells. Maximal stimulation of [3H]thymidine incorporation occurred in neonatal d18 cells: (250 +/- 4.8%, n = 4, P < 0.05). Incubation of adult type-II cells, in the presence of 10(-9) M DHD increased thymidine incorporation into DNA (149.1 +/- 33.2%, mean +/- S.E., n = 3, P < 0.001) compared to control cells maintained in basal medium. Exposure to DHD also increased thymidine incorporation after stimulation with a mixture of conventional progression factors (insulin (10 micrograms/ml) (I), cholera toxin (10 micrograms/ml) (C) and EGF (20 ng/ml) (E)) (349.4 +/- 42.9% vs. 213.5 +/- 23.6%, n = 6, P < 0.005). Autoradiographic labeling indices of adult type-II cells increased from 3.1 +/- 0.6% for cells cultured in basal medium to 7.2 +/- 1.7% in cells exposed to DHD from the time of plating and I, C, E from 20-68 h in culture (n = 4, P < 0.05). Although no increase in the number of adult type-II cells was observed in these experiments, flow cytometric analysis of nuclear DNA content revealed an increased proportion of cells in the S and G2 phases of the cell cycle (basal: S = 2.6%, G2/M = 3.0%, DHD+GF: S = 4.7%, G2/M = 5.6%, P < 0.05 for each comparison). These data demonstrate that vitamin D3 is a growth factor for alveolar type-II cells and suggest the possibility that local elaboration of vitamin D may provide a novel mechanism of modulation of epithelial proliferation in the context of lung development and repair.
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Previous studies have defined specific functional relationships within monophosphoryl lipid A (MLA) preparations. To extend this understanding to all contributing entities, MLA samples have been structurally characterized using electrospray ionization, collision-induced dissociation (CID), and tandem mass spectrometry (MS/MS). MLA profiles of Salmonella minnesota Re595 have been compared with Shigella flexneri for sample type and component distribution. In excess of 20 individual structures compose each sample, which differ considerably in abundance but little in composition. Component heterogeneity can be directly related to alkane chain length, "lipid X"-type analogs, and variations in esterification to the core 2-amino-2-deoxydisaccharide, GlcNH2 beta(1-6)GlcNH2. The previously defined heptaacyl structure in S. minnesota Re595 was identified at only 15% with the most abundant species a hexaacyl analog. Profiles of S. flexneri MLA show an absence of any heptaacyl analog, with the pentaacyl component the most abundant. To confirm structural relationships, ions from both samples were fragmented by CID and separated by MS/MS. Product ion spectra proved to be identical, showing a series of acyl losses and glycosidic cleavage fragments. Since the position of each acyl group has been previously established in S. minnesota Re595 MLA, ions in the CID spectrum of S. flexneri sample could be structurally assigned. Knowledge of these structural details, their isolation, and biological testing may provide components of unique immune adjuvancy or block-selective deleterious endotoxic processes.
The improved sensitivity and soft ionization characteristics of electrospray (ES) mass spectrometry (MS) has been applied to the glycan structures of recombinant erythropoietin (rEPO). The four glycopeptides (O-126, N-24, N-38, N-83) were mapped, isolated, deglycosylated, and the glycans profiled (without desialylation) by ES-MS as their methyl derivatives. The O-linked glycopeptide was also analyzed directly. In this fraction seven glycans were identified (two previously unreported) in addition to the unglycosylated peptide. The three N-linked fractions were divided with one fraction preceded by periodate oxidation and reduction to resolve isomeric structures, linkage, and branching patterns, and confirm the overall structural motif. All were methylated and profiled. Two biantennary, 8 triantennary, and 10 tetraantennary structures were identified with approximately 13% of each N-linked glycan possessing a single N-glycolylneuraminyl analog. The minimal energies of ionization, the absence of a matrix background, and enhanced sensitivity brings an improved technology for studying carbohydrate structural detail.
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An appreciation of the physiological changes and possible complications of thoracoscopic surgery is required by the medical team caring for the patient. The alteration of ventilatory and cardiac status under anesthesia can have significant impact on the morbidity and mortality of the patient. Considerations of the interaction between surgical and anesthetic effects may help to identify the problems early and avoid deleterious changes.
Flexible fiberoptic bronchoscopy (FB) is a recently available tool for the investigation of pediatric pulmonary diseases. Endobronchial tuberculosis (ETB), a common complication of primary tuberculosis, has traditionally been diagnosed by clinical findings of bronchial obstruction and roentgenographic evidence of bronchial involvement. A retrospective study was conducted to determine the incidence of endobronchial tuberculosis in children diagnosed by traditional means as having uncomplicated primary tuberculosis. Analysis of the bronchoscopic findings of 36 children with active pulmonary tuberculosis revealed that 15 (41.7%) had endobronchial involvement. Significantly 10 (28%) children who had no clinical or radiologic evidence of endobronchial involvement had endobronchial tuberculosis; 4 (11%) had early and 6 (17%) had advanced ETB by FB. There were 6 patients with radiologic evidence suggestive of ETB, which was confirmed by FB in 5 patients. One child had a obstruction of a bronchus by mucus. The mucus was removed with subsequent expansion of the distal lung segment. Complications of the procedures were mild. FB is a safe procedure and a valuable aid for the rapid diagnosis of ETB.
The purpose of this work was to define the pharmacology of an intestinal epithelial [3H]strychnine binding site. Strychnine, brucine, verapamil and desmethoxyverapamil bind to small intestinal mucosal homogenates with nanomolar affinity at a site not related to the strychnine receptor, which is in the spinal cord. The antidiarrheal agents, fluperamide and loperamide, and several alkaloids have an order of magnitude lower affinity. Agents that bind to cytochrome P450IID6 also displace [3H]strychnine binding, which implies that the binding site may have some properties similar to the catalytic site of this cytochrome P450 enzyme.
Anorexia and bulimia nervosa are eating disorders characterised by abnormal eating behaviour, a morbid concern over body weight and a distorted perception of body size. It commonly occurs in young postpubertal girls in developed societies. Aetiological factors are a complex interplay of biological, psychological and social factors. Bizarre eating patterns can lead to life-threatening medical situations which require urgent in-hospital care. Comprehensive management should be effected by a multi-disciplinary team with contributions from the internist, the psychiatrist, the nurse, the psychologist, the social worker and the teacher. There is significant psychiatric morbidity and mortality in the outcome of these eating disorders.
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To elaborate a rational approach to chemoimmunotherapy in humans, information is required as to how current cytotoxic chemotherapy regimens modulate patients' endogenous immune cells. We have studied a group of 16 advanced breast cancer patients who received cyclical cytotoxic chemotherapy (CMF-cyclophosphamide, methotrexate and 5-fluorouracil) and have documented the progressive differential effects of chemotherapy on endogenous immune cells as judged by changes in immunophenotype and absolute numbers of lymphocyte subsets, together with analysis of natural-killer-cell function. Cells with the immunophenotype of natural killer cells and lymphokine-activated killer cells (NK/LAK cells) were well retained, but their function was suboptimal. Additionally, CD8 T cells were well preserved, but the numbers of CD4 T cells decreased with succeeding cycles of chemotherapy; B-cell numbers decreased rapidly from the first cycle of chemotherapy. These cellular changes in humans indicate defined and precisely timed windows of opportunity for introducing in vivo, simple and direct immune stimulation of the cells modulated by chemotherapy, with the possibility of improving therapy and survival in this disease.
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