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Biomedical subjects

G Pan

Publications and source records attributed to G Pan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Requirement of calmodulin binding by HIV-1 gp160 for enhanced FAS-mediated apoptosis.

Accelerated apoptosis is one mechanism proposed for the loss of CD4+ T-lymphocytes in human immunodeficiency virus type 1 (HIV-1) infection. The HIV-1 envelope glycoprotein, gp160, contains two C-terminal calmodulin-binding domains. Expression of gp160 in Jurkat T-cells results in increased sensitivity to FAS- and ceramide-mediated apoptosis. The pro-apoptotic effect of gp160 expression is blocked by two calmodulin antagonists, tamoxifen and trifluoperazine. This enhanced apoptosis in response to FAS antibody or C(2)-ceramide is associated with activation of caspase 3, a critical mediator of apoptosis. A point mutation in the C-terminal calmodulin-binding domain of gp160 (alanine 835 to tryptophan, A835W) eliminates gp160-dependent enhanced FAS-mediated apoptosis in transiently transfected cells, as well as in vitro calmodulin binding to a peptide corresponding to the C-terminal calmodulin-binding domain of gp160. Stable Tet-off Jurkat cell lines were developed that inducibly express wild type gp160 or gp160A835W. Increasing expression of wild type gp160, but not gp160A835W, correlates with increased calmodulin levels, increased apoptosis, and caspase 3 activation in response to anti-FAS treatment. The data indicate that gp160-enhanced apoptosis is dependent upon calmodulin up-regulation, involves the activation of caspase 3, and requires calmodulin binding to the C-terminal binding domain of gp160.

Alanine↗
PubMed2000

Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.

OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes.

OBJECTIVE: This study investigates the effect of multiple factors, including exposure to polycyclic aromatic hydrocarbons (PAHs), lifestyle, genetic polymorphism of cytochrome P450 (CYP)1A1, glutathione transferase (GST)M1, GSTP1, N-acetyltransferase (NAT)2 and gene p53, as well as any family history of cancer, on DNA adduct levels in coke-oven workers. METHODS: Sixty-five coke-oven workers employed at the largest iron-steel factory in China were recruited for the study. Personal data were collected at the interview. DNA adduct levels in total white blood cells (WBCs) were detected using 32P-postlabeling techniques. Genetic polymorphisms were analyzed by polymerase chain reaction (PCR) methods. RESULTS: The subjects were divided into low and high exposure groups, according to personal exposure to PAHs. The mean adduct value was 1.57 (range 0.54 to 4.35) per 10(8) nucleotides. A tendency for increased levels of DNA adducts in the high exposure group was observed, compared with the low exposure group (P = 0.07). In the low exposure group, DNA adducts were found to be positively associated with urinary cotinine (r = 0.44, P = 0.01). The rare allele homozygotes of CYP1A1 showed significantly higher DNA adduct levels than those of other CYP1A1 genotypes. Individuals with the NAT2 wild type had significantly increased DNA adduct levels than those with other NAT2 genotypes in the high exposure group. The p53 genetic polymorphism revealed a significantly positive effect on DNA adducts formation. There was a significantly higher adduct level in the subjects with a family history of cancer than those without, in the high exposure category. CONCLUSIONS: Effects of several variables, such as smoking, genetic polymorphism of 2 CYP1A1, NAT2, and gene p53, and a family history of cancer on DNA adduct levels were found, suggesting that these variables should be considered when evaluating the genotoxic effect of occupational exposure to PAHs using WBCs DNA adducts.

Arylamine N-Acetyltransferase↗
PubMed2000

Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.

Mitochondrial uncoupling proteins have been implicated in the maintenance of metabolic rate and adaptational thermoregulation. We recently reported the identification of a brain-specific mitochondrial uncoupling protein homologue, UCP4. Here we characterized another newly described member of the uncoupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in multiple human and mouse tissues, with an especially high abundance in the brain and testis. Expression of UCP5 in mammalian cells reduces the mitochondrial membrane potential. Multiple isoforms of UCP5 were identified and exhibited tissue-specific distribution and different potency in reduction of membrane potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by nutritional status or temperature in a tissue-specific manner in mice. Brain UCP4 and UCP5 mRNA transcripts rose by 1.5- and 1.7-fold, respectively, and liver UCP5 expression increased by 1.8-fold in response to acute cold exposure. A high-fat diet increased UCP5 mRNA in liver by 1.6-fold selectively in the obesity-resistant A/J but not in the obesity-prone C57BL/6J mouse strain. Liver UCP5 expression decreased significantly with a 24 h fast and was restored to the normal level after refeeding. In contrast, brain transcripts for both genes were not significantly altered by fasting or high-fat diet. These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific thermoregulation and metabolic changes associated with nutritional status.

Amino Acid Sequence↗
PubMed2000

Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and mitochondrial proton leak kinetics.

Linking tissue uncoupling protein (UCP) homolog abundance with functional metabolic outcomes and with expression of putative genetic regulators promises to better clarify UCP homolog physiological function. A murine endotoxemia model characterized by marked alterations in thermoregulation was employed to examine the association between heat production, UCP homolog expression, and mitochondrial proton leak ("uncoupling"). After intraperitoneal lipopolysaccharide (LPS, approximately 6 mg/kg) injection, colonic temperature (T(c)) in adult female C57BL6/J mice dropped to a nadir of approximately 30 degrees C by 8 h, preceded by a four- to fivefold drop in liver UCP2 and UCP5/brain mitochondrial carrier protein 1 mRNA levels, with no change in their hindlimb skeletal muscle (SKM) expression. SKM UCP3 mRNA rose fivefold during development of hypothermia and was correlated with an LPS-induced increase in plasma free fatty acid concentration. UCP2 and UCP5 transcripts recovered about three- to sixfold in both tissues starting at 6-8 h, preceding a recovery of T(c) between 16 and 24 h. SKM UCP3 followed an opposite pattern. Such results are not consistent with an important influence of UCP3 in driving heat production but do not preclude a role for UCP2 or UCP5 in this process. The transcription coactivator PGC-1 displayed a transient LPS-evoked rise (threefold) or drop (two- to fivefold) in SKM and liver expression, respectively. No differences between control and LPS-treated mouse liver or SKM in vitro mitochondrial proton leak were evident at time points corresponding to large differences in UCP homolog expression.

Animals↗
PubMed2000

[Distribution and transferring of carbon in kast soil system of peak forest depression in humid subtropical region].

Taking Guilin Yaji Karst Experiment Site as an exemple and with the methods of field monitoring and laboratory analysis, this paper studied the distribution and transferring of carbon in the karst soil system of peak forest depression in the humid subtropical region of China. The carbon pools in biomass, litters and soil organic matter(SOM) and their mobility as expressed by oxidizability and decomposition rate of SOM, the concentration of soil CO2 and the emission rate of CO2 from soil were investigated. The mobile carbon pool in the system supplied a rich source of CO2, which drived the karst process. When active karst process happened in Spring and Summer, over 60% of carbon in the output water was derived from soil CO2, as traced by delta 13 C distribution in the system. Therefore, owing to the carbon transfer in the pathway of air-plant-soil-water, karst process took place rather under soil-rock-water interface than under air-rock-water interface. Thus, the epigenetic karst process was driven and accelerated by soil as an interface of carbon environmental geochemistry.

Carbon↗
PubMed2000

Epidemiologic study of the irritable bowel syndrome in Beijing: stratified randomized study by cluster sampling.

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) in Beijing and its risk factors. METHODS: Phase I: a screening for IBS in Beijing area according to symptoms using both Manning (modified including constipation) and Rome criteria. 2486 subjects were studied by cluster sampling of the inhabitant groups according to a stratified design of urban, suburban and rural areas, and sample size of each area studied was in proportion to the population of the area. Selection of the inhabitant groups was made by simple random sampling. Age of subjects enrolled in the study was 18-70 years. All subjects fulfilling the selection criteria were requested to fill in a questionnaire assisted by trained doctors or medical students during the visit to their families. Phase II: an aliquot of patients who fulfilled at least the Manning criteria were further selected according to their scoring series to undergo detail clinical examination in the hospital including laboratory examination, abdominal ultrasonography, colonoscopy or/and barium enema to exclude organic disease of the colon. Prevalence of IBS of the population was then adjusted by the rate of correct diagnosis during Phase II study. Study using Minnesota Multi-Personality Indices (MMPI) was done in some cases. Probable risk factors were explored by comparing their frequencies among IBS group and non-IBS group using chi 2 and logistic analysis of multifactors. RESULTS: The adjusted point prevalence of IBS in Beijing is 7.26% according to Manning criteria, and is 0.82% according to Rome criteria. There is a higher prevalence rate in city (10.50%) than in rural areas (6.14%) by stratified analysis (P < 0.001). Male to female ratio is 1:1.15. And IBS is more common in people aged between 18-40 years (51.6%), and among the intellectuals. Our study indicated that history of dysentery (OR 3.00), exposure to cool (OR 1.55) and ingestion of cold food and raw materials (OR 1.24) may be the most important risk factors (P < 0.001), and IBS patients may have a higher tendency of psychological abnormalities. CONCLUSION: IBS is a common disorder in Beijing and should be taken into consideration in the human welfare strategy.

Adolescent↗
PubMed2000

[An epidemiologic study of irritable bowel syndrome in Beijing - a stratified randomized study by clustering sampling].

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its risk factors in Beijing. METHODS: Phase I: a screening program for IBS was carried out in Beijing area according to symptoms using both Manning (modified including constipation) and Rome criteria. Random clustered sampling involving 2 486 subjects of the inhabitants was carried out under stratification of city, suburban and rural areas. Sample size of each studied area was in proportion to the population of the area. The range of age was 18 - 70. All subjects studied were requested to fill in a questionnaire assisted by trained doctors or medical students during the visit to their families. Phase II: a small number of patients who fulfilled the Manning criteria were further selected to undergo detail clinical examination in the hospital including laboratory examination, abdominal ultrasonography, colonoscopy or/and barium enema to exclude organic disease of the colon. Prevalence of IBS of the population was then adjusted by the rate of correct diagnosis during phase II study. Minnesota Multi - Personality Indices was used in some cases. Potential risk factors were explored by comparing frequencies among IBS group and non - IBS group using chi(2) and logistic analysis of multifactors. RESULTS: The adjusted point prevalence of IBS in Beijing according to Manning criteria was 7.26%, in contrast to Rome criteria - 0.82%. Higher prevalence rate of IBS in the city (10.50%) than in rural areas (6.14%) (P < 0.001) was noticed. Male to female ratio was 1:1.15 with majority of IBS fell in age 18 - 40 (51.6%), and among intellectuals. Our study indicated that history of dysentery (OR = 3.00), exposure to coldness (OR = 1.55), ingestion of cold food and raw materials (OR = 1.24) might serve as the most important risk factors (P < 0.001). Patients with IBS seemed to have a higher tendency of abnormal personalities. CONCLUSION: IBS is a common disorder in Beijing which deserves greater care.

Adolescent↗
PubMed1999

Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis.

Apoptosis is a very general phenomenon, but only a few reports concern astrocytes. Indeed, astrocytes express receptors for tumor necrosis factor (TNF) alpha, a cytokine demonstrated on many cells and tissues to mediate apoptosis after recruitment of adaptor proteins containing a death effector domain (DED). PEA-15 is a DED-containing protein prominently expressed in the CNS and particularly abundant in astrocytes. This led us to investigate if PEA-15 expression could be involved in astrocytic protection against deleterious effects of TNF. In vitro assays evidence that PEA-15 may bind to DED-containing protein FADD and caspase-8 known to be apical adaptors of the TNF apoptotic signaling. After generation of PEA-15 null mutant mice, our results demonstrate that PEA-15 expression increases astrocyte survival after exposure to TNF.

Amino Acid Sequence↗
PubMed1999

TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege.

Mechanisms accounting for protection of the fetal semiallograft from maternal immune cells remain incompletely understood. In other contexts, interactions between TRAIL (TNF-related apoptosis-inducing ligand/Apo-2L) and its receptors kill activated lymphocytes. The purpose of this study was therefore to investigate the potential of the TRAIL/TRAIL-R system to protect the placenta against immune cell attack. Analysis by Northern blotting demonstrated mRNAs encoding TRAIL as well as the four TRAIL receptors (DR4, DR5, DcR1/TRID, DcR2/TRUNDD) in human placentas. Immunohistochemical experiments demonstrated that TRAIL protein is prominent in syncytiotrophoblast, an uninterrupted placental cell layer that is continuously exposed to maternal blood, as well as in macrophage-like placental mesenchymal cells (Hofbauer cells). Studies on cell lines representing trophoblasts (Jar, JEG-3 cells) and macrophages (U937, THP-1 cells) showed that both lineages contained TRAIL mRNA and that steady state levels of transcripts were increased 2- to 11-fold by IFN-gamma. By contrast, cell lineage-specific differences were observed in expression of the TRAIL-R genes. Although all four lines contained mRNA encoding the apoptosis-inducing DR5 receptor, only trophoblast cells contained mRNA encoding the DcR1 decoy receptor and only macrophages contained DcR2 decoy receptor transcripts. DR4 mRNA was present only in THP-1 cells and was the only TRAIL-R transcript increased by IFN-gamma. Cytotoxicity assays revealed that the two trophoblast cell lines were resistant, whereas the two macrophage lines were partially susceptible to killing by rTRAIL. Collectively, the results are consistent with a role for the TRAIL/TRAIL-R system in the establishment of placental immune privilege.

Apoptosis Regulatory Proteins↗
PubMed1999

UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells.

Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.

Amino Acid Sequence↗
PubMed1999

Nested case-control study of esophageal cancer in relation to occupational exposure to silica and other dusts.

BACKGROUND: Standardized proportionate mortality ratio (SPMR) was found to be 2.2 (95% CI = 1.3-3.5) for esophageal cancer (EC) among workers exposed to refractory brick dust in a large iron-steel complex in China. METHODS: A nested case-control design within a cohort of industrial workers. One hundred and twenty-five EC cases and 250 controls were identified from the death registry file. Interviews were conducted of the next of kin for past exposure information on job, domestic, and lifestyle factors. History of occupational exposure to various dusts was reconstructed from personnel files and by interviewing colleagues utilizing a job-exposure matrix. RESULTS: After adjusting for confounders, occupational exposure to silica dust was the most important risk factor among all variables investigated, with a 2.8-fold risk and a clear dose-response by length of exposure. Alcohol drinking (OR = 1.8) and coal cooking (OR = 2.0) were risk factors and high consumption of fruit diet (OR = 0.5) and meat diet (OR = 0.6) were protective factors. CONCLUSIONS: The relationship between occupational exposure to silica dust and the risk of EC found in an earlier SPMR study was confirmed. Ingestion of silica particles after lung clearance may increase the risk of EC among workers exposed to silica.

Aged↗
PubMed1999

Apoptosis and tumorigenesis in human cholangiocarcinoma cells. Involvement of Fas/APO-1 (CD95) and calmodulin.

We have previously demonstrated that tamoxifen inhibits the growth of human cholangiocarcinoma cells in culture and inhibits tumor growth when cells are injected into nude mice. However, the mechanism of action of tamoxifen remains unknown. Here we demonstrate that tamoxifen and trifluoperazine, both potent calmodulin antagonists, induce apoptosis in vitro, probably acting via the Fas system, in human cholangiocarcinoma cells. Human cholangiocarcinoma cell lines heterogeneously express Fas antigen on their surface. Fas-negative and Fas-positive surface-expressing cells were isolated, cloned, and cultured. Fas antibody, tamoxifen, and trifluoperazine induced dose-dependent apoptosis only in Fas-positive cells; Fas-negative cells were unaffected. Furthermore, apoptosis induced by tamoxifen in Fas-positive cells was blocked by an inhibitory Fas antibody. Tamoxifen was not acting through an anti-estrogenic mechanism, because neither Fas-negative nor Fas-positive cells expressed estrogen receptors and the pure anti-estrogen compound, ICI 182780, did not induce apoptosis in either cell line. Fas-negative cells, but not Fas-positive cells, were able to produce tumors when subcutaneously injected into nude mice. These findings suggest Fas may be a candidate oncogene involved in the pathogenesis of cholangiocarcinoma. Furthermore, the similarity between the pro-apoptotic effects of tamoxifen and trifluoperazine support an underlying molecular mechanism for Fas-mediated apoptosis that involves calmodulin.

Animals↗
PubMed1999

Small molecule antagonists of the bradykinin B1 receptor.

Screening Pharmacopeia's encoded combinatorial libraries has led to the identification of potent, selective, competitive antagonists at the bradykinin B1 receptor. Libraries were screened using a displacement assay of [3H]-des-Arglo-kallidin ([3H]-dAK) at IMR-90 cells expressing an endogenous human B1 receptor (Bmax = 20,000 receptors/cell, K(D) = 0.5+/-0.1 nM) or against membranes from 293E cells expressing a recombinant human B1 receptor (Bmax = 8,000 receptors/cell, K(D) = 0.5 +/- 0.3 nM). Compound PS020990, an optimized, representative member from the class of compounds, inhibits specific binding of 3H-dAK at IMR-90 cells with a KI of 6 +/- 1 nM. The compound inhibits dAK-induced phosphatidyl inositol turnover (K(Bapp) = 0.4 +/- 0.2 nM) and calcium mobilization (K(Bapp) = 17 +/- 2 nM) in IMR-90 cells. Compounds from the lead series are inactive at the B2 receptor and are > 1000-fold specific for B1 vs. a variety of other receptors, ion channels and enzymes. PS020990 and other related chemotypes therefore offer an excellent opportunity to explore further the role of B1 receptors in disease models and represent a potential therapeutic avenue.

Bradykinin↗
PubMed1999

Five new triterpene saponins from Pulsatilla patens var. multifida.

Five new oleanane-type glycosides (1-5), along with two known triterpene saponins, were isolated from the roots of Pulsatilla patens var. multifida (Ranunculaceae). The structures of the new triterpene saponins were elucidated as 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-galactopyranosyl hederagenin 28-O-beta-D-glucopyranosyl ester (1), hederagenin 3-O-[beta-D-glucopyranosyl(1-->2)][beta-D-glucopyranosyl(1-->6)]-beta -D-galactopyranoside (2), 3-O-beta-D-glucopyranosyl bayogenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (3), 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-galactopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (4), and 3-O-[beta-D-glucopyranosyl(1-->2)][beta-D-glucopyranosyl(1-->6)]-beta -D-galactopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (5). Structure elucidation was accomplished by 1D and 2D NMR (HMQC, HMBC, and ROESY) methods, FABMS, and hydrolysis.

Carbohydrate Sequence↗
PubMed1999

Regional correlation between estimated UVB levels and skin cancer mortality in Japan.

Most ecological studies investigating the relationship between incidence and/or mortality of skin cancer and surrogate measures of ultraviolet radiation B (UVB) have been conducted among the Caucasian population. The objective of the present study was therefore to assess the geographical correlation between ambient UVB estimates and regional mortality rates for skin cancer in Japan. The standardized mortality ratio (SMR) for malignant melanoma and other malignant neoplasms of the skin was calculated by sex, region and time-period for all deaths occurring in the period 1973-1994. The Spearman's correlation coefficient was calculated between estimated ambient UVB and regional SMRs for the two types of skin cancer. There was no geographical correlation between UVB and skin cancer mortality, except for a significantly negative correlation in malignant melanoma among males and a significantly negative correlation in other malignant neoplasms of the skin confined to unexposed anatomic sites of the body among females. The characteristic ecological relationship adds to the importance of conducting further epidemiological studies at the individual level in Japan.

Age Distribution↗