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Biomedical subjects

H Shen

Publications and source records attributed to H Shen.

At least 109 records · Page 6Linked to original sources

Analytic approaches for assessing long-term treatment effects. Examples of empirical applications and findings.

Analytic approaches, including the structural equation model (autoregressive panel model), hierarchical linear model, latent growth curve model, survival/event history analysis, latent transition model, and time-series analysis (interrupted time series, multivariate time-series analysis) are discussed for their applicability to data of different structures and their utility in evaluating temporal effects of treatment. Methods are illustrated by presenting applications of the various approaches in previous studies examining temporal patterns of treatment effects. Recent advancements in these longitudinal modeling approaches and the accompanying computer software development offer tremendous flexibility in examining long-term treatment effects through longitudinal data with varying numbers and intervals of assessment and types of measures. A multimethod assessment will contribute to a more complete understanding of the complex phenomena of the long-term courses of substance use and its treatment.

Alcoholism↗

Development and evaluation of high throughput functional assay methods for HERG potassium channel.

Three functional hERG channel assay methods have been developed and evaluated. The methods were tested against five known hERG channel inhibitors: dofetilide, terfenadine (Seldane), sertindole (Serdolect), astemizole (Hismanal), and cisapride (Propulsid). The DiBAC4(3)-based assays were found to be the most economical but had high false-hit rates as a result of the interaction of dye with the test compounds. The membrane potential dye assay had fewer color-quenching problems but was expensive and still gave false hits. The nonradioactive Rb+ efflux assay was the most sensitive of all the assays evaluated and had the lowest false-hit rate.

Animals↗

Developmental expression of PEPT1 and PEPT2 in rat small intestine, colon, and kidney.

Mammalian peptide transporters (PEPT1 and PEPT2) play a pivotal role in the absorption of small peptides from the intestine and kidney, respectively, and in the disposition and targeting of peptide or mimetic drugs. However, there are few reports on the molecular basis of their regulation, especially in the young. The aim of this study was to determine the developmental expression of intestinal and renal oligopeptide transporters in rats from embryonic to adult ages. Intestinal segments were collected (i.e. duodenum, jejunum, ileum, and colon) along with whole kidney, and their mRNA and protein levels were measured. Expression levels of PEPT1 were maximal 3-5 d after birth in the duodenum, jejunum, and ileum, and then declined rapidly. Expression was increased transiently at d 24, most notably in the ileum. Adult protein levels were approximately 70% of that observed on d 3-5. Significant PEPT1 expression was observed in colon during the first week of life, but levels were undetectable shortly thereafter through adulthood. PEPT1 and PEPT2 expression is less regulated in rat kidney and more pronounced in older animals. Peptide transporters were also present as early as d 20 of fetal life for all tissues tested. These results are unique in providing the developmental expression of peptide transporter mRNA and protein in distinct regions of the small intestine, colon, and kidney in rat. Our findings suggest that intestinal expression of PEPT1 is induced postpartum, possibly by suckling, and again at the time of weaning, and that the colon may participate in peptide transport early in life.

Animals↗

[Cloning the differentially expressed genes in the retina of rds mouse during the development of retinitis pigmentosa].

OBJECTIVE: To clone the differentially expressed genes in the retina of rds mouse (the animal model of congenital retinitis pigmentosa) during the disease development. METHODS: The retinal mRNA of rds mouse during the development of retinitis pigmentosa was analyzed by the mRNA differential display. The differentially expressed mRNA fragments were cloned and sequenced. RESULTS: There was obvious difference of gene expression between rds mouse and the control during the development of retinitis pigmentosa. Five differentially expressed bands were cloned and sequenced. One of those had 86% identity (132/154) with the sequence of the human cDNA DKFZp434D1227 from adult testis in GenBank, which was submitted lately (15-Oct-1999) and without much information. The other had lower identity with the sequences in GenBank. A highly expressed clone in the rds mouse on postnatal day 25 had the same length as another clone in the normal on postnatal day 37, which was not expressed in the rds mouse on day 37. The sequences of the two clones were identical in all but two base pairs. CONCLUSION: These results indicate that there are a lot of novel differentially expressed genes in the chronic processing diseases, such as retinitis pigmentosa.

Animals↗

Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study.

Previous studies have suggested that low folate intake is associated with increased risk of lung cancer. Methylene-tetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and is thought to influence DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Therefore, we hypothesized that these variant genotypes may play a role in the etiology of lung cancer. To test this hypothesis, we investigated the association between two common MTHFR polymorphisms (C677T and A1298C) and risk of lung cancer in a non-population-based case-control study of 550 histologically confirmed lung cancer cases and 554 healthy controls. The subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+ or -5 years), sex, and smoking status (ever or never). Folate intake and alcohol consumption were estimated from a self-administered food-frequency questionnaire. The cases consumed significantly less folate (162 microg/day/1000 kcal) than the controls did (172 microg/day/1000 kcal; P = 0.033). However, we found no evidence for an association between the MTHFR C677T and A1298C polymorphisms and risk of lung cancer in either all of the subjects or the low folate intake subgroup; nor did we find evidence for an interaction between these two MTHFR polymorphisms and dietary folate intake or alcohol use. In multivariate logistic regression analysis, the adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 1.1 (0.8-1.4) for 677CT versus 677CC wild type and 1.1 (0.7-1.7) for 677TT versus 677CC, and for MTHFR A1298C, they were 1.0 (0.8-1.3) for 1298AC versus 1298AA wild type and 1.1 (0.7-1.8) for 1298CC versus 1298AA. These results suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play an important role in the etiology of lung cancer.

Aged↗

Binding of the aminothiol WR-1065 to transcription factors influences cellular response to anticancer drugs.

The aminothiol WR-1065 (the active form of amifostine) protects normal tissues from the toxic effects of certain cancer drugs, while leaving their antitumor effects unchanged. The present data address the mechanism of action of this dichotomous effect. (35)S-Labeled WR-1065 bound directly to the transcription factors nuclear factor-kappaB, activator protein-1, and p53, resulting in enhanced binding of these proteins to target regulatory DNA sequences and subsequent transactivation of a number of downstream genes. Since other small molecular thiols could mimic WR-1065, the redox potential of the sulfhydryl is an important determinant of its activity. In nontransformed cells, WR-1065 protected cells from the cytotoxic effects of paclitaxel in a p53-dependent manner. However, in a transformed human tumor cell line, there was no cytoprotectivity by WR-1065, consistent with the premise that p53-dependent growth arrest is the basis for the protective effect of this compound, and that this pathway is abrogated in human tumors. The combined data support the principle that the cellular effects of the aminothiol WR-1065 are mediated through an impact on transcriptional regulation and are not only a consequence of radical scavenging.

Animals↗

Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures.

The objective of this study was to delineate the transepithelial transport mechanisms of fosinopril in cultured cell lines expressing the intestinal and renal peptide transporters. Lineweaver-Burk, Dixon, and dose-response analyses revealed that GlySar uptake was competitively inhibited by fosinopril in both Caco-2 (K(i), 35.5 microM) and SKPT cells (K(i), 29.6 microM). Intracellular accumulations of fosinopril were 3 to 4 times higher from apical versus basolateral surfaces of the membrane, as was the apical-to-basal flux of the drug. The apical peptide transporter had a significantly greater affinity for fosinopril than did the basolateral peptide transporter in Caco-2 cells (K(m), 154 versus 458 microM, respectively; p < 0.001) and SKPT cells (K(m), 22 versus 104 microM, respectively; p < 0.001). Moreover, fosinopril uptake by the basolateral peptide transporter was less sensitive to changes in medium pH than the apical peptide transporter in both cell lines. Although Caco-2 cells are known to express PEPT1 protein (and not PEPT2), our immunoblot analyses provide definitive evidence that SKPT cells express PEPT2 protein (and not PEPT1). Taken as a whole, our findings demonstrate that fosinopril is transported intact by PEPT2 and PEPT1, with high-affinity and by a proton-coupled, saturable process. Our results also suggest that distinct peptide transporters exist at the basolateral and apical membranes and that they play an important role in modulating the intestinal absorption and renal reabsorption of peptides and peptide-like drugs.

Administration, Oral↗

[Treatment of the wound on donor site after great toe-nail flap grafting].

OBJECTIVE: To investigate the method of improving the vitality of skin graft on donor site of the great toe-nail skin flap. METHODS: From June 1982 to April 1998, 252 cases of the great toe-nail flaps with piece of phalangeal bone and 18 cases of the simple great toe-nail flap were repaired with thin skin graft and packed under proper pressure. The stitches were removed two weeks later in common situation. It should be postponed on split thickness or partial survival skin flap avoiding early mobilization. RESULTS: Sixty-six cases of skin graft were necrotic after operation. Among them, 38 cases needed second skin grafting and 28 cases were healed after changing dressing. The survival rate of skin grafting was obviously higher on phalangeal marrow surface than on periosteum of the naked phalange. Contracture of the skin graft after operation made the retained skin flap expanding from medial side to lateral side and covered the whole plantar surface of the great toe. CONCLUSION: The survival rate of the skin graft on donor foot is improved after adopting the improved measures on taking the flap from great toe and paying attention to skin graft planting and packing. Free flap grafting is advocated for repairing of the wound on donor area of the great toe nail flap.

Adolescent↗

[A preliminary study on translocation of the immunoglobulin heavy chain gene in KM3 myeloma cell line].

OBJECTIVE: To identify the IgH translocation in KM3 myeloma cell line established from a Chinese patients. METHODS: Southern blotting was performed with dig-labeled probes specific for IgH switch regions to identify and distinguish IgH switch recombination events. RESULTS: Besides a 10.0 kb Hind III fragment being able to hybridize with both 5' S mu and 3' S mu probes as that in placenta genome DNA. There was a 5.6 kb Hind III fragment in KM3 genome DNA could only hybridize with the 3' S mu probe. CONCLUSION: There was an illegitimate switch recombination fragment containing 3' S mu region in the KM3 myeloma cell line, which was caused by the IgH translocation involving the IgH S mu region.

Blotting, Southern↗

[Study on the correlation of estrogen receptor gene polymorphism to bone mineral density of radius in Chinese Han postmenopausal women in Beijing].

OBJECTIVE: To investigate the distribution of estrogen receptor (ER) gene polymorphism in postmenopausal Han women in Beijing as well as its correlation with bone mineral density (BMD) of radius. METHODS: Xba I, and Pvu II polymorphism of ER gene were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 99 healthy postmenopausal Han women. BMD of distal (spongy bone) and proximal (compact bone) radius were determined by dual-energy X-ray absorptiometry (DEXA) as well. The relationship between BMD and polymorphism of ER gene was analyzed by variance analysis. RESULTS: Pvu II polymorphism of ER gene is not associated with BMD of both sites of radius (P > 0.05); while Xba I polymorphism of ER gene is significantly associated with BMD spongy and compact bone of radius (P < 0.05). Women with XX genotype have the lowest BMD T-score of -1.55 +/- 0.37 for the compact and -2.54 +/- 0.38 for the spongy, and those with xx genotype have the highest BMD T-score of -0.95 +/- 0.24 for compact and -1.74 +/- 0.16 for spongy. CONCLUSION: There is a significant correlation of Xba I polymorphism of ER gene with BMD of distal and proximal radius. It is indicated that the difference in ER genotypes among individuals might influence the development of osteoporosis.

Asian People↗

Expression of exon 13 from the Ki-67 gene in human cells and tissues by digoxigenin-labelled mRNA in situ hybridization.

OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study the Ki-67 gene transcription and translation in various human cells and tissues. HeLa cells and fresh colon cancer cells, tonsil, normal pancreas and pancreatic cancer tissues were used in this study. A 435 bp cDNA fragment located in exon 13 of the Ki-67 antigen gene was amplified by polymerase chain reaction (PCR). Digoxigenin-labelled antisense and sense RNA probes were prepared for detecting Ki-67 mRNA, combined with MIB-1 immunohistochemistry. RESULTS: Successful localization of Ki-67 mRNA in human HeLa cells, colon cancer cells, tissues specimen of the tonsil and pancreatic cancer tissue sections was accomplished by digoxigenin-labelling in situ hybridization technique. ISH to colon cancer cells and pancreatic cancer tissue slides showed that much stronger cytoplasm and perinuclear mRNA signals of the Ki-67 gene were present in malignant cells than in normal cells, which was in accordance with MIB-1 nuclear protein signals. CONCLUSIONS: A sensitive and practical in situ hybridization method for the analysis of Ki-67 antigen mRNA in human cell and tissue was developed. Abnormal transcription of exon 13 of Ki-67 gene might be responsible for malignant cell proliferation in colon and pancreatic cancer.

Digoxigenin↗

[Effects of copper mine tailings on growth and development and physiological function of wheat].

Through pot culture experiments, the effects of Tonling copper mine tailings on growth and development and physiological function of wheat were investigated in this paper. The results showed that the seeds of wheat could germinate in copper mine tailings, but seed germination percentage and germination rate were lower than that in control. High ratio tailings decreased seedling height. Tailings decreased chlorophyll contents, but didn't effect on chlorophyll a/b. Compared with control, tailings significantly inhibited root growth and decreased root number. Tailings increased root and shoot biomass and significantly increased root/shoot ratio of wheat. The permeability of cell membrane and the free proline content in leaves of wheat increased with the increase of the ratio of tailings, they were relative tolerance index of wheat to copper tailings stress.

Biomass↗

[Quantitative measurement on degradation degree of ecosystem in hilly region of western Liaoning Province].

Exactly measuring the degradation degree of ecosystems is the basis and precondition of restoring ecosystems. At present, degradation degree is usually analyzed qualitatively. In this paper, quantitative classification method was used to study the degradation degree of ecosystem in hilly region of western Liaoning, which was measured by the degradation degree of habitat. The result shows that the habitat in the northern slope of mountains has been degraded to certain stage between shrubbery and pioneer tree forest, which provides theoretical basis for vegetation restoration practice. Moreover, the result is beneficial for studying the degradation degree of ecosystems in other regions or of other types.

China↗

Trauma-related xanthogranulomatous interstitial nephritis: a clinicopathological analysis.

OBJECTIVE: To investigate the pathogenesis, exact nature, histologic feature of xanthogranulomatous interstitial nephritis (XGIN) as well as its significance in clinical medicine. METHODS: The medical histories concerned were collected with diagnostic images including CT scanning, ultrasonography, intravenous urography (IVU) and laboratory data being synthesized by comparison with what was discover ed during operations and pathologic examinations. RESULTS: All patients were ever struck on their loins or backs by blunt violence over 4-12 years. The diseases were clinically diagnosed as "renal cancer" before, during and after operations, and treated with ra dic al nephrectomy. Located at cortical parts, the tumor focus had penetrated the renal capsules and invaded other organs. However, immunohistochemistry demonstrated that the lesions were xanthogranulomas, not tumors, in which there were stacks of foam cells and lymphocytes with vast extends of fibrotic tissues obliterating the cortical interstitial structures. Urinary tracts yielded no bacterium, obstruction or calculus. CONCLUSIONS: XGIN is likely to be one kind of immunologic mediated granuloma following blunt renal trauma. It is imperative to clarify pathogenesis and character of this lesion so as to find out any approach to diagnosis and cure of such an unusual nephropathy.

Adult↗

[The associations between concentration of selenium in semen and sperm parameters as well as oxidative DNA damage in human sperm].

OBJECTIVE: To explore the associations between concentrations of selenium (Se) in serum and semen and sperm parameters as well as oxidative DNA damage in human sperm. METHODS: Concentrations of selenium in serum and semen were determined using atomic absorption spectrophotometer (AAS). The sperm parameters were detected according to WHO laboratory manual for the examination of human sperm. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and deoxyguanosine (dG) in human sperm DNA were measured using HPLC-ECD and HPLC-UV. RESULTS: Mean semen concentration of selenium was significantly higher in fertile subjects (0.74 mumol/L) than that in infertile subjects (0.56 mumol/L), while there was no significant difference in serum concentrations of selenium between the two groups. Semen volume (3.91 ml vs. 2.79 ml), sperm density (46.4 x 10(9)/L vs. 36.5 x 10(9)/L) and sperm count (168.0 x 10(6) vs. 102.0 x 10(6)) were significantly higher in fertile subjects than those in infertile subjects. There was no significant difference in motility and viability of sperm, and proportion of deformity sperm between the two groups, Significantly positive correlation was observed between semen concentration of Se and sperm density (r = 0.48, P < 0.01 for fertile subjects and r = 0.32, P < 0.05 for infertile subjects) as well as sperm count (r = 0.32, P < 0.05 for fertile subjects and r = 0.26, P < 0.05 for infertile subjects), sperm motility (r = 0.46, P < 0.01 for fertile subjects and r = 0.65, P < 0.01 for infertile subjects) and viability (r = 0.33, P < 0.05 for fertile subjects and r = 0.64, P < 0.01 for infertile subjects). There was no correlation between serum Se concentrations and sperm parameters. Moreover, 8-OHdG levels in sperm DNA inversely correlated with semen Se concentrations in fertile (r = -0.21, P < 0.05) and infertile (r = -0.28, P < 0.05) subjects. However, no significant correlation was found between 8-OHdG levels in sperm DNA and serum Se concentrations in all subjects. CONCLUSIONS: Semen concentrations of Se were associated with sperm quality and 8-OHdG levels in human sperm. Serum concentrations of Se did not affect sperm quality and oxidative DNA damage in human sperm.

8-Hydroxy-2'-Deoxyguanosine↗

[Clinical study on effect of hewei capsule on promoting gastric dynamics].

OBJECTIVE: To investigate the effect of Hewei capsule (HWC) on gastric dynamics. METHODS: Sixty-two patients with dysmotility-like functional dyspepsia (DFD) were included in the study. The principal symptoms, electrogastrogram (EGG), plasma motilin (MTL), serum gastrin (Gas) and nitric oxide (NO) of the patients were the chief parameters observed before and after treatment. RESULTS: There were arrhythmia of EGG, deficiency of MTL, Gas and NO in the patients with DFD, and these abnormal changes could be improved significantly by treating with HWC. CONCLUSION: The abnormal gastric dynamics of the patients with DFD could be improved by HWC through multiple pathways.

Adolescent↗

[Study on donor-specific antigens in inducing immunological tolerance].

OBJECTIVE: To compare the effects of different donor-specific antigens, through different pathways, on the inducement of immunological tolerance. METHODS: After the establishment of a stable rat cervical heterotopic heart transplantation model, donor specific transfusion (DST), donor specific spolenocyte (DSSL) and donor specific bone marrow (DSBM) were given to recipients 3-14 days prior to the transplantation through peripheral vein, portal vein and intrathymic injection respectively. Low dose CsA 5 mg/(kg.d) was given from the 3rd-14th day pre-transplantation to the 28th day post-transplantation. The survival time of cardiac grafts was monitored, meanwhile, the donor specific mixed lymphocyte reaction (MLR) and the subsets of T lymphocytes CD8+ were determined. RESULTS: DSBM and the administrative pathway of intrathymic injection achieved the best effects on the inducement of immunological tolerance and the improvement of graft survival. CONCLUSION: The donor specific antigens can induce the donor-specific immunological tolerance. It may be a practicable approach for the clinical experiments in the future.

Animals↗