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Biomedical subjects

S Yin

Publications and source records attributed to S Yin.

At least 91 records · Page 5Linked to original sources
PubMed1996

Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI.

The aim of this study was to examine the role of TNF receptor I (TNF-RI) in the pathogenesis of heat-killed Corynebacterium parvum- and live bacillus Calmette-Guerin (BCG)-induced granulomas. Granuloma formation was analyzed in TNF-RI knockout mice and after treatment with soluble TNF-RI (sTNF-RI). TNF-RI knockout mice injected with C. parvum or BCG developed fewer and smaller granulomas than wild-type control mice. Mice treated with sTNF-RI from days 7 to 13 after injection of C. parvum or BCG developed fewer and smaller granulomas than saline-treated control mice. Established granulomas regressed in rats treated with sTNF-RI from days 10 to 13 after injection of C. parvum. In conclusion, TNF signaling via TNF-RI contributes to the pathogenesis of C. parvum- and BCG-induced granulomas. sTNF-RI inhibits the development of granulomas and can cause the regression of established granulomas.

Animals↗
PubMed1996

hprt mutation frequency among workers exposed to 1,3-butadiene in China.

Hypoxanthine-guanine phosphoribosyl transferase (hprt) mutation frequency (M(f)) was studied in workers at a polybutadiene rubber production facility in Yanshan, China. Exposed workers included for study were active either as process analysts, who sampled butadiene production process lines and analyzed product by gas chromatography, or as process operators, who did routine process control, minor maintenance and, as needed, major repair operations. For process analysts at the polymer and dimethyl formamide (DMF) facilities, the median air levels of BD were 1.0 and 3.5 ppm, respectively. Among process operators, air levels of 1.1 ppm were found during routine activities, while the median air level during pump repair and related operations was 45 ppm (6-h time-weighted average). Overall, M(f) was similar in unexposed (mean M(f) = 20.2 x 10(-6)) and butadiene-exposed (mean M(f) = 21.6 x 10(-6)) workers (P = 0.68). M(f) decreased with cloning efficiency, increased with age, and was moderately greater in women than in men. After adjustment by multiple regression analysis for mean age, sex, and cloning efficiency, the adjusted mean M(f)(Xadj) was 13.6 x 10(-6) in unexposed and 18.0 x 10(-6) in butadiene-exposed. This 32% difference was, however, not statistically significant (P = 0.13). Butadiene exposure was associated with a modest, if any, increase in hprt M(f) in this population of Chinese workers.

Adult↗
PubMed1996

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice.

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.

Anemia↗
PubMed1996

Radiation-induced lung injury in vivo: expression of transforming growth factor-beta precedes fibrosis.

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion. TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.

Animals↗
PubMed1996

The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.

Animals↗
PubMed1996

Interphase cytogenetics of workers exposed to benzene.

Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells. In previous studies, FISH has been used to demonstrate that the benzene metabolites hydroquinone and 1,2,4-benzenetriol induce aneuploidy of chromosomes 7 and 9 in cultures of human cells. In the present study, we used an interphase FISH procedure to perform cytogenetic analyses on the blood cells of 43 workers exposed to benzene (median = 31 ppm, 8-hr time-weighted average) and 44 matched controls from Shanghai, China. High benzene exposure (> 31 ppm, n = 22) increased the hyperdiploid frequency of chromosome 9 (p < 0.01), but lower exposure (< or = 31 ppm, n = 21) did not. Trisomy 9 was the major form of benzene-induced hyperdiploidy. The level of hyperploidy in exposed workers correlated with their urinary phenol level (r = 0.58, p < 0.0001), a measure of internal benzene dose. A significant correlation was also found between hyperdiploidy and decreased absolute lymphocyte count, an indicator of benzene hematotoxicity, in the exposed group (r = -0.44, p = 0.003) but not in controls (r = -0.09, p = 0.58). These results show that high benzene exposure induces aneuploidy of chromosome 9 in nondiseased individuals, with trisomy being the most prevalent form. They further highlight the usefulness of interphase cytogenetics and FISH for the rapid and sensitive detection of aneuploidy in exposed human populations.

Adult↗
PubMed1996

Tissue distribution of DNA adducts and their persistence in blood of mice exposed to benzene.

Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts x 10(-8) nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of "adduct B" declined linearly but mildly, while "adduct C" displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene.

Animals↗
PubMed1996

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.

Adult↗
PubMed1996

Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo.

Platelet-derived growth factor (PDGF) is postulated to play a role in the pathophysiology of pulmonary fibrosis. Recombinant human PDGF-BB administered as a single intratracheal injection in rats causes an increase in peribronchial and perivascular stromal cells on days 2 and 3 after injection as evaluated by hematoxylin and eosin histology and 5-bromodeoxyuridine incorporation. Proliferation of bronchial epithelial cells and arterial smooth muscle cells, although not evident by routine histological examination alone, is detected on days 2 and 3 by increased 5-bromodeoxyuridine incorporation. A mild increase in 5-bromodeoxyuridine labeling is observed in peripheral alveolar parenchyma after injection of PDGF. The proliferative peribronchial and perivascular mesenchymal cells appear by light microscopic and ultrastructural criteria to be fibroblasts that are immunoreactive for vimentin but negative for alpha-smooth muscle actin and desmin. Daily intratracheal injection of PDGF-BB for 3 days causes a slightly more pronounced peribronchial and perivascular spindle cell proliferation accompanied by collagen deposition as evaluated by Masson's trichrome stain. PDGF-induced increases in cellularity and collagen resolve within 5 days after the last PDGF injection. In conclusion, intratracheal injection of PDGF-BB causes transient proliferation of pulmonary mesenchymal and epithelial cells accompanied by collagen deposition.

Actins↗
PubMed1996

[Evaluation of levator palpebrae superioris muscle resection in 500 cases].

We sum up the effects of levator palpebrae superioris muscle resection to correct congenital ptosis in 500 cases. The surgical results in 369 cases (73.8%) are excellent; ninety-six cases (19.2%) are good and 35 cases (7%) are poor. The operative result depends on the amount of muscle resection. We believe that the levator palpebrae superioris muscle resection is the first choice of treatment for a patient whose levator has no function. The operation method is described and the indications of the operation and related problems are discussed.

Blepharoptosis↗
PubMed1996

Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.

Alveolitis, Extrinsic Allergic↗
PubMed1996

Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality.

Keratinocyte growth factor (KGF) is a growth factor for type II pneumocytes. Type II pneumocyte hyperplasia, a common reaction to lung injury, has been postulated to play an important role in lung repair. The potential protective effect of KGF was therefore studied in rat models of radiation- and bleomycin-induced lung injury. Intratracheal instillation of KGF (5 mg/kg) 72 and 48 hours before 18 Gy of bilateral thoracic irradiation did not significantly improve survival, although histology showed less pneumonitis and fibrosis in KGF-pretreated as compared with control-irradiated rats. Intratracheal pretreatment with KGF in rats receiving intratracheal bleomycin (2.5 U) improved survival at 3 weeks to 100% (20/20 rats) from 40% (8/20 rats) in controls. All KGF-pretreated rats receiving bleomycin were well at 3 weeks and without histological evidence of pulmonary fibrosis whereas the 8 surviving control rats exhibited severe respiratory distress. Finally, in the most lethal challenge to the lung, rats pretreated with intratracheal KGF or saline were challenged with a combination of bleomycin (1.5 U) and bilateral thoracic irradiation (18 Gy). KGF-pretreated rats did not begin to die or show signs of respiratory distress until 7 weeks, whereas all saline-pretreated control rats receiving radiation and bleomycin died within approximately 4 weeks with severe respiratory distress and weight loss. In conclusion, radiation- and bleomycin-induced pulmonary injury and respiratory death are ameliorated by KGF pretreatment, suggesting a protective role for KGF-induced type II pneumocyte proliferation in lung injury.

Animals↗
PubMed1996

The glutathione S-transferase M1 (GSTM1) null genotype and benzidine-associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts.

Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer. To evaluate the impact of the GSTM1-null genotype on bladder cancer caused by occupational exposure to benzidine and to determine its influence on benzidine metabolism, we carried out three complementary investigations: a case-control study of bladder cancer among workers previously exposed to benzidine in China, a cross-sectional study of urothelial cell DNA adducts and urinary mutagenicity in workers currently exposed to benzidine in India, and a laboratory study of the ability of human GSTM1 to conjugate benzidine and its known metabolites in vitro. There was no overall increase in bladder cancer risk for the GSTM1-null genotype among 38 bladder cancer cases and 43 controls (odds ratio, 1.0; 95% confidence interval, 0.4-2.7), although there was some indication that highly exposed workers with the GSTM1-null genotype were at greater risk of bladder cancer compared to similarly exposed workers without this allele. However, the GSTM1 genotype had no impact on urothelial cell DNA adduct and urinary mutagenicity levels in workers currently exposed to benzidine. Furthermore, human GSTM1 did not conjugate benzidine or its metabolites. These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population.

Benzidines↗
PubMed1996

[Impulsive angular acceleration evoked middle and long latency potentials in guinea pigs].

Middle and long latency evoked potentials have been successfully recorded in guinea pigs with impulsive angular acceleration delivered by a specially developed motor. The middle latency responses elicited by impulsive angular acceleration had peaks at about 9 ms, 15 ms and 24 ms with a mean peak to peak amplitude of about 28muV and the long latency responses after the delivering of impulsive angular acceleration in guinea pigs composed of a triphasic wave with a mean peak to peak amplitude of about 50 muV occurring during 32 ms to 130 ms with respect to the start of head stimuli. A series of experiments lead to the conclusion that the middle latency responses to impulsive angular acceleration are middle latency vestibular evoked potentials. The long latency response elicited by impulsive angular acceleration is not a specific response of auditory or vestibular pathway.

Animals↗
PubMed1995

Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines.

The instability of short repetitive sequences in tumor DNA can result from defective repair of replication errors due to mutations in any of several genes required for mismatch repair. Understanding this repair pathway and how defects lead to cancer is being facilitated by genetic and biochemical studies of tumor cell lines. In the present study, we describe the mismatch repair status of extracts of 22 tumor cell lines derived from several tissue types. Ten were found to be defective in strand-specific mismatch repair, including cell lines from tumors of the colon, ovary, endometrium, and prostate. The repair defects were independent of whether the signal for strand specificity, a nick, was 5' or 3' to the mismatch. All 10 defective cell lines exhibited microsatellite instability. Repair activity was restored to 9 of these 10 extracts by adding a second defective extract made from cell lines having known mutations in either the hMSH2 or hMLH1 genes. Subsequent analyses revealed mutations in hMSH2 (4 lines) and hMLH1 (5 lines) that could explain the observed microsatellite instability and repair defects. Overall, this study strengthens the correlation between microsatellite instability and defective mismatch repair and the suggestion that diminuition in mismatch repair activity is a step in carcinogenesis common to several types of cancer. It also provides an extensive panel of repair-proficient and repair-deficient cell lines for future studies of mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice.

Megakaryocyte growth and development factor (MGDF) administered intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis accompanied by a decrease in mean platelet volume. MGDF increases the number of megakaryocytes in the bone marrow and spleen. MGDF does not affect the circulating number of leukocytes. Carboplatin, a chemotherapeutic agent that causes thrombocytopenia in humans, administered to mice as a single IP injection at a nonlethal dose causes a significant, but reversible thrombocytopenia. The carboplatin-induced thrombocytopenia is accompanied by an increase in circulating endogenous MGDF that precedes the return of circulating platelets to a normal level. MGDF mRNA is constitutively present in the liver. After carboplatin treatment, hepatic MGDF mRNA does not increase in concordance with circulating MGDF. Circulating soluble MGDF receptor levels (c-mpl) do not change significantly during the course of carboplatin-induced thrombocytopenia. MGDF injected IP once daily beginning 1 day after injection of carboplatin reverses carboplatin-induced thrombocytopenia in a dose-dependent fashion. The normalization of circulating platelet numbers in carboplatin plus MGDF-treated mice is accompanied by a normalization of megakaryocyte numbers in the bone marrow. In conclusion, MGDF, by increasing the number of marrow megakaryocytes and circulating platelets is an effective therapy for carboplatin-induced thrombocytopenia in mice.

Animals↗
PubMed1995

Hematologic effects of stem cell factor (SCF) and leukemia inhibitory factor (LIF) in vivo: LIF-induced thrombocytosis in SCF-primed mice.

Stem cell factor (SCF) administered as daily bolus injections in dose-response experiments in mice causes a progressive and dramatic dose-dependent panleukocytosis characterized by neutrophilia, eosinophilia, monocytosis, and lymphocytosis. SCF causes circulating platelet numbers to be dose-dependently increased after 2 weeks of daily injections. Leukemia inhibitory factor (LIF) administered as daily bolus injections in mice causes a peripheral leukopenia that is largely due to peripheral lymphopenia. LIF causes thrombocytosis peaking after approximately 1 w. Coinjection of SCF and LIF for 1 to 2 wk in mice does not cause a much greater thrombocytosis than the maximum thrombocytosis achievable with SCF or LIF alone. On the other hand, daily injection of SCF for 5 days followed by daily injection of LIF for 5 to 6 d in mice causes a very substantial increase in platelets that was lineage-specific in terms of not being accompanied by a generalized leukocytosis. In contrast, only a very modest thrombocytosis was noted in SCF-primed LIF-treated rats. LIF causes a large increase in the cytoplasmic volume of splenic megakaryocytes in mice, but not in rats. In conclusion, SCF-induced priming followed by LIF-induced maturation of megakaryocytes causes a substantial selective increase in the numbers of circulating platelets in mice.

Animals↗