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Biomedical subjects

Min Shen

Publications and source records attributed to Min Shen.

At least 19 recordsLinked to original sources
PubMed2026

Ampyrone is a direct agonist of human tyrosinase and a potential therapeutic for hypopigmentation disorders.

Significant loss of pigmentation can increase visual disability, skin cancer risk, and psychosocial stress. Tyrosinase (TYR) catalyzes the first and rate-limiting step of melanin synthesis. Inhibitors of TYR are well established and are currently used in clinical settings; however, there is a dearth of direct activators of TYR. Here, using a human TYR construct, we developed high-throughput screening methods, in cell confirmatory assays employing 13C-tyrosine tracing, and computational analysis techniques, and identified ampyrone (4-aminoantipyrine) as a TYR activator. Ampyrone increased the in vitro catalytic activity of the human recombinant intramelanosomal domain of TYR (hTYR) and its hypomorphic variant, Pro406Leu (P406L), a cause of oculocutaneous albinism type 1B (OCA1B). Moreover, ampyrone induced melanin synthesis in both WT and OCA1B human melanocytes, mouse OCA2 melanocytes, as well as 3-dimensional (3D) human skin cultures. Computational studies provided additional insight into the effects of direct TYR agonists on enzyme activity. Our results identify ampyrone as a lead candidate for TYR activation, potentially supporting the development of therapies for patients with genetic and acquired diseases of hypopigmentation.

Humans↗
PubMed2006

Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma.

Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in a number of pathological conditions including cancer. In a population-based case-control study of non-Hodgkin lymphoma (NHL) (n = 518 cases, 597 controls) among women in Connecticut, we analyzed one or more single nucleotide polymorphisms (SNPs) in ten candidate genes (AKR1A1, AKR1C1, AKR1C3, CYBA, GPX1, MPO, NOS2A, NOS3, OGG1, and SOD2) that mediate oxidative stress directly or indirectly in the NADPH oxidase-dependent respiratory burst. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and race. Polymorphisms in AKR1A1 and CYBA were significantly associated with increased risk of NHL. There was a 1.7-fold (95% CI = 1.2-2.4, P = 0.0047) increased risk of NHL for individuals who were variant homozygous for the AKR1A1 (IVS5 + 282T > C) SNP. The effect was most pronounced for risk of diffuse large B-cell lymphoma, but risk estimates were non-significantly elevated for other common B-cell histologies and T-cell lymphomas as well. In addition, individuals variant homozygous for the CYBA (Ex4 + 11C > T) SNP had a 1.6-fold (95% CI = 1.1-2.4, P = 0.019) increased risk of NHL that was particularly pronounced for T-cell lymphoma (OR = 3.5, 95% CI = 1.3-9.6, P = 0.013), but was also associated with non-significant increased risks for each of the common B-cell histologies. These results suggest that SNPs in genes related to the oxidative stress pathway may be associated with increased risk of NHL.

Adult↗
PubMed2006

Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma.

The caspase proteins are essential for the regulation of normal B cell development and regulation of apoptosis. We investigated five single nucleotide polymorphisms in four key caspase genes, CASP3 [Ex8-280C>A (rs6948) and Ex8+567T>C (rs1049216)], CASP8 Ex14-271A>T (rs13113), CASP9 Ex5+32G>A (rs1052576) and CASP10 Ex3-171A>G (rs3900115) to determine whether they alter risk for non-Hodgkin lymphoma (NHL) in a population-based case-control study of women in Connecticut (461 cases and 535 controls). Variants in CASP3 and CASP9 were significantly associated with a decreased risk for NHL, particularly follicular lymphoma [e.g. CASP3 Ex8+567T>C odds ratio (OR)(CC+TC) = 0.4, 95% confidence interval (CI) = 0.3-0.7; and CASP9 Ex5+32G>A OR(AA+AG) = 0.6, 95% CI = 0.4-1.0]. Further, variants in CASP3, CASP8 and CASP10 were associated with a decreased risk of marginal zone lymphoma and variants in CASP3 and CASP10 were associated with a lower risk of chronic lymphocytic leukemia and related subtypes. The striking protective associations observed for polymorphisms in all four genes for NHL and/or one or more subtypes suggest that genetic variation in CASP genes may play an important role in the etiology of NHL.

Adult↗
PubMed2006

Assessment of dermal exposure to benzene and toluene in shoe manufacturing by activated carbon cloth patches.

OBJECTIVES: The aim of this investigation was to use activated carbon cloth (ACC) patches to study the probability and extent of dermal exposure to benzene and toluene in a shoe factory. METHODS: Inhalation and dermal exposure loading were measured simultaneously in 70 subjects on multiple days resulting in 113 observations. Dermal exposure loading was assessed by ACC patches attached to likely exposed skin areas (e.g. the palm of the hand and abdomen). A control patch at the chest and an organic vapor monitor (OVM) were used to adjust the hand and abdomen patches for the contribution from the air through passive absorption of benzene and toluene on the ACC patches. Systemic exposure was assessed by quantification of unmetabolized benzene (UBz) and toluene (UTol) in urine. RESULTS: Mean air concentrations for the study population were 1.5 and 7.5 ppm for benzene and toluene, respectively. Iterative regression analyses between the control patch, OVM and the dermal patches showed that only a small proportion of the ACC patches at the hand had likely benzene (n = 4; mean 133 microg cm(-2) h(-1)) or toluene (n = 5; mean 256 microg cm(-2) h(-1)) contamination. Positive patches were exclusively observed among subjects performing the task of gluing. Significant dermal exposure loading to the abdomen was detected only for toluene (n = 2; mean 235 microg cm(-2) h(-1)). No relation was found between having a positive hand or abdomen ACC patch and UBz or UTol levels. In contrast a strong association was found between air levels of benzene (p = 0.0016) and toluene (p < 0.0001) and their respective urinary levels. CONCLUSIONS: ACC patches are shown to be a useful technique for quantifying the probability of dermal exposure to organic solvents and to provide estimates of the potential contribution of the dermal pathway to systemic exposure. Using ACC patches we show that dermal exposure to benzene and toluene in a shoe manufacturing factory is probably rare, and when it occurred exposures were relatively low and did not significantly contribute to systemic exposure.

Abdomen↗
PubMed2006

Hair analysis for ketamine and its metabolites.

A rapid and sensitive method was developed for the simultaneous identification and quantitation of ketamine (K) and its major metabolite, norketamine (NK) in hair. After decontamination, the hair sample was incubated and extracted, and analyzed by gas chromatography-mass spectrometry (GC-MS). Limits of quantitation were found to be 0.05 ng/mg. Hair segments in black color were collected from 15 K abusers. Based on an experiment with 15 cavies with black, white, and brown hair, the mechanism of incorporation of K into hair was investigated. After shaving hair on the back of the cavies (8 cm x 4 cm), they were separated into three groups and administered intraperitoneally once a day for 7 successive days with high, medium, and low doses of K, respectively. Two days after this, hair segments with different colors were shaved. There was a direct correlation between the concentration of K in cavy hair and the dose and DHNK was detected only in high dosage group. The concentration of K increased in the order of white, brown, and black hair. The possible factors responsible for the incorporation of K and its metabolites in hair were discussed.

Anesthetics, Dissociative↗
PubMed2006

Cardioprotective effect of resvaratrol pretreatment on myocardial ischemia-reperfusion induced injury in rats.

OBJECTIVE: The major objective of the present study was to examine the cardioprotective effect of resveratrol, an antioxidant presents in red wine, in the rat after ischemia-reperfusion (I/R). DESIGN: The left coronary artery was in occlusion for 30 min followed by a 120 min reperfusion in anesthetized rats. Animals were pretreated with and without resveratrol before occlusion. The post-ischemic ventricular function (left ventricle maximum systolic pressures and the maximal first derivative of developed pressure) and myocardial infarct size and myocardial nitric oxide (NO) and malonaldehyde (MDA) content were compared. RESULTS: Resveratrol pretreatment had dramatic cardioprotective effects on post-ischemic ventricular functional recovery and decreasing myocardial infarct size. Resveratrol pretreatment also increased NO and decreased MDA content in myocardium. CONCLUSIONS: Resveratrol has cardioprotective properties in I/R rats. The cardioprotective effects in the I/R rats may be correlated with its antioxidant activity and upregulation of NO production.

Animals↗
PubMed2006

Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity.

Benzene is a recognized hematotoxicant and carcinogen that produces genotoxic damage. DNA double-strand breaks (DSB) are one of the most severe DNA lesions caused directly and indirectly by benzene metabolites. DSB may lead to chromosome aberrations, apoptosis and hematopoietic progenitor cell suppression. We hypothesized that genetic polymorphisms in genes involved in DNA DSB repair may modify benzene-induced hematotoxicity. We analyzed one or more single nucleotide polymorphisms (SNPs) in each of seven candidate genes (WRN, TP53, NBS1, BRCA1, BRCA2, XRCC3 and XRCC4) in a study of 250 workers exposed to benzene and 140 controls in China. Four SNPs in WRN (Ex4 -16 G > A, Ex6 +9 C > T, Ex20 -88 G > T and Ex26 -12 T > G), one SNP in TP53 (Ex4 +119 C > G) and one SNP in BRCA2 (Ex11 +1487 A > G) were associated with a statistically significant decrease in total white blood cell (WBC) counts among exposed workers. The SNPs in WRN and TP53 remained significant after accounting for multiple comparisons. One or more SNPs in WRN had broad effects on WBC subtypes, with significantly decreased granulocyte, total lymphocyte, CD4(+)-T cell, CD8(+)-T cell and monocyte counts. Haplotypes of WRN were associated with decreased WBC counts among benzene-exposed subjects. Likewise, subjects with TP53 Ex4 +119 C > G variant had reduced granulocyte, CD4(+)-T cell and B cell counts. The effect of BRCA2 Ex11 +1487 A > G polymorphism was limited to granulocytes. These results suggest that genetic polymorphisms in WRN, TP53 and BRCA2 that maintain genomic stability impact benzene-induced hematotoxicity.

Adult↗
PubMed2006

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut.

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case-control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P=0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P=0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56-0.91; P=0.007) and DLBCL (OR: 0.66; 95% CI: 0.45-0.95; P=0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.

Adult↗
PubMed2006

Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.

Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.

Adult↗
PubMed2006

A pooled analysis of second primary pancreatic cancer.

Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor.

Aged↗
PubMed2006

Serum cotinine level as predictor of lung cancer risk.

BACKGROUND: No prospective studies are available on serum cotinine level as a marker of lung cancer risk. METHODS: We analyzed serum cotinine level among 1,741 individuals enrolled since the 1970s in a prospective study of Norwegian volunteers who developed lung cancer during the follow-up and 1,741 matched controls free from lung cancer. Serum cotinine was measured with a competitive immunoassay. Regression dilution was corrected for based on repeated measures on samples from 747 subjects. RESULTS: Mean serum cotinine level was higher in cases than in controls. Compared with subjects with a cotinine level of < or = 5 ng/mL, the odds ratio of lung cancer was increasing linearly, reaching 55.1 (95% confidence interval, 35.7-85.0) among individuals with a serum cotinine level of > 378 ng/mL. There was no clear suggestion of a plateau in risk at high exposure levels. Odds ratios were very similar in men and women. We found no association between serum cotinine level (range, 0.1-9.9 ng/mL) and lung cancer risk among self-reported nonsmokers and long-term quitters (79 cases and 350 controls). DISCUSSION: The association between tobacco smoking and lung cancer risk might be stronger than is estimated from questionnaire-based studies. Serum cotinine level is a predictor of risk of lung cancer among smokers. The reported plateau in risk at high doses is likely due mainly to artifacts. There is no difference between men and women in the carcinogenicity of tobacco smoking.

Biomarkers↗
PubMed2006

Modeling human metabolism of benzene following occupational and environmental exposures.

We used natural spline (NS) models to investigate nonlinear relationships between levels of benzene metabolites (E,E-muconic acid, S-phenylmercapturic acid, phenol, hydroquinone, and catechol) and benzene exposure among 386 exposed and control workers in Tianjin, China. After adjusting for background levels (estimated from the 60 control subjects with the lowest benzene exposures), expected mean trends of all metabolite levels increased with benzene air concentrations from 0.03 to 88.9 ppm. Molar fractions for phenol, hydroquinone, and E,E-muconic acid changed continuously with increasing air concentrations, suggesting that competing CYP-mediated metabolic pathways favored E,E-muconic acid and hydroquinone below 20 ppm and favored phenol above 20 ppm. Mean trends of dose-specific levels (micromol/L/ppm benzene) of E,E-muconic acid, phenol, hydroquinone, and catechol all decreased with increasing benzene exposure, with an overall 9-fold reduction of total metabolites. Surprisingly, about 90% of the reductions in dose-specific levels occurred below about 3 ppm for each major metabolite. Using generalized linear models with NS-smoothing functions (GLM + NS models), we detected significant effects upon metabolite levels of gender, age, and smoking status. Metabolite levels were about 20% higher in females and decreased between 1% and 2% per year of life. In addition, levels of hydroquinone and catechol were greater in smoking subjects. Overall, our results indicate that benzene metabolism is highly nonlinear with increasing benzene exposure above 0.03 ppm, and that current human toxicokinetic models do not accurately predict benzene metabolism below 3 ppm. Our results also suggest that GLM + NS models are ideal for evaluating nonlinear relationships between environmental exposures and levels of human biomarkers.

Adolescent↗
PubMed2006

[Study on appraisement and determination GHB levels in hair].

OBJECTIVE: The possibility for the identification of GHB administration through hair analysis was investigated to provide method and information for toxicology examination of GHB. METHODS A GC/MS assay for GHB in hair was developed. Endogenous levels of GHB in hair, time course of GHB in hair, relationship between GHB levels in hair and hair color or administration dose were also established by guinea pig model. RESULTS: Endogenous levels of GHB in guinea pig black hair and human black hair were (3.01 +/- 1.41) ng/mg (n=28) and (1.02 +/- 0.27) ng/mg (n=20), respectively. GHB levels in black hair were increased by GHB administration and related with drug dosage, and also much higher than in brown and white hair. CONCLUSION: Analysis of GHB in hair is suitable for investigation of GHB abuse in forensic toxicology and GHB level in segmental analysis compared with endogenous level of GHB may provide useful information about GHB administration.

Animals↗
PubMed2006

[Determination of opiates in biological human samples by liquid chromatography-tandem mass spectrometry].

OBJECTIVE: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of opiates in biological samples according to the emerging problem in drugs abuse. METHODS: Opiates such as heroin, 6-acetylmorphine, morphine, codeine, acetylcodeine, hydrocodone and hydromorphone were isolated from human blood, urine, oral fluid and hair using a simple extraction and consequently analyzed using LC-MS/MS. The method was evaluated by real cases. RESULTS: The mobile phase give the optimum separation for opiates. The detection limit of morphine in urine with dilution and liquid-liquid extraction and in hair is 10ng/mL, 0.01 ng/mL and 0.01 ng/mg, respectively. CONCLUSION: The method is simple and rapid, offering superior sensitivity and selectivity for opiates. The target compounds comprising hydrocodone and hydromorphone enlarge the applied area.

Chromatography, Liquid↗
PubMed2006

[Study on determination and distribution of GHB in biological fluids and tissues of acute poisoned rats].

OBJECTIVE: e To investigate the distribution of GHB in biological fluids and tissues and provide methodand information for detcetion of GHB in Biological Fluids and Tissues METHOD The concentrations of GHB in Biological Fluids and Tissues were analyzed by gas chromatography-mass spectrometry; Two groups of rats were fed with 1000 mg/kg of GHB and were killed at 1 hour and 3 hours post dose, respectively. RESULTS GHB concentrations of the administrated groups distributed in a degressive order of urine, stomach, blood, intestine, kidney, lung, spleen, heart, liver and brain. CONCLUSION: Urine was the best specimen for the determination of GHB concentrations in biological fluids and tissues.

Acute Disease↗
PubMed2005

[Pleuropulmonary manifestations of systemic lupus erythematosus].

OBJECTIVE: To analyze the incidence, clinical features, and prognosis of pleuropulmonary involvement in patients with systemic lupus erythematosus (SLE). METHODS: The medical records of 320 SLE inpatients hospitalized in Peking Union Medical College Hospital 2004, 50 males and 270 females, aged 33 +/- 14 (8-75), were retrospectively analyzed. RESULTS: Pleuropulmonary involvement occurred in 142 cases with an incidence rate of 44.4%. The incidence of pleural involvement was 25% (80/320) and the incidence of pulmonary parenchyma involvement was 33.8% (108/320). The mortality rate of the SLE patients with thoracic involvement was 7.0%, significantly higher than that of the SLE patients without thoracic involvement (1.0%, P = 0.006). The incidence of acute lupus pneumonitis (ALP) was 1.3% and the survival rate of ALP was 100%. The clinical manifestations of ALP included hypoxemia, dyspnea, fever, and cough and chest radiograph characteristically showed unilateral or bilateral patchy acinar infiltrates predominantly in the lower lung zone. The incidence of diffuse alveolar hemorrhage (DAH) was 1.9% with a mortality rate of 66.7%. The clinical manifestations of DAH included hemoptysis, hypoxemia, cough, anemia and bloody bronchoalveolar lavage and the chest radiographic findings included new acinar infiltrates that were typically diffuse and bilateral and might be patchy. The other common pleuropulmonary complications of SLE included pleural disease (25%), chronic interstitial pneumonitis (6.9%), pulmonary hypertension (15.3%), pulmonary embolism (1.9%), and pulmonary infection (19.1%). CONCLUSION: SLE may affect all components of the respiratory system. Thoracic involvement is an adverse prognostic sign. Life-threatening pulmonary involvement is not uncommon. The clinicoradiographic features of the SLE-associated pulmonary syndromes overlap. Aggressive diagnostic evaluations such as blood culture, sputum culture, fibreoptic bronchoscopy, and lung biopsy are very important.

Adolescent↗
PubMed2005

Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism.

Although the toxicity of benzene has been linked to its metabolism, the dose-related production of metabolites is not well understood in humans, particularly at low levels of exposure. We investigated unmetabolized benzene in urine (UBz) and all major urinary metabolites [phenol (PH), E,E-muconic acid (MA), hydroquinone (HQ) and catechol (CA)] as well as the minor metabolite, S-phenylmercapturic acid (SPMA), in 250 benzene-exposed workers and 139 control workers in Tianjin, China. Median levels of benzene exposure were approximately 1.2 p.p.m. for exposed workers (interquartile range: 0.53-3.34 p.p.m.) and 0.004 p.p.m. for control workers (interquartile range: 0.002-0.007 p.p.m.). (Exposures of control workers to benzene were predicted from levels of benzene in their urine.) Metabolite production was investigated among groups of 30 workers aggregated by their benzene exposures. We found that the urine concentration of each metabolite was consistently elevated when the group's median benzene exposure was at or above the following air concentrations: 0.2 p.p.m. for MA and SPMA, 0.5 p.p.m. for PH and HQ, and 2 p.p.m. for CA. Dose-related production of the four major metabolites and total metabolites (micromol/l/p.p.m. benzene) declined between 2.5 and 26-fold as group median benzene exposures increased between 0.027 and 15.4 p.p.m. Reductions in metabolite production were most pronounced for CA and PH<1 p.p.m., indicating that metabolism favored production of the toxic metabolites, HQ and MA, at low exposures.

Acetylcysteine↗