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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 793 records · Page 44Linked to original sources

The relaxosome protein MobC promotes conjugal plasmid mobilization by extending DNA strand separation to the nick site at the origin of transfer.

The frequency of conjugal mobilization of plasmid R1162 is decreased approximately 50-fold if donor cells lack MobC, one of the plasmid-encoded proteins making up the relaxosome at the origin of transfer (oriT). The absence of MobC has several different effects on oriT DNA. Site- and strand-specific nicking by MobA protein is severely reduced, accounting for the lower frequency of mobilization. The localized DNA strand separation required for this nicking is less affected, but becomes more sensitive to the level of active DNA gyrase in the cell. In addition, strand separation is not efficiently extended through the region containing the nick site. These effects suggest a model in which MobC acts as a molecular wedge for the relaxosome-induced melting of oriT DNA. The effect of MobC on strand separation may be partially complemented by the helical distortion induced by supercoiling. However, MobC extends the melted region through the nick site, thus providing the single-stranded substrate required for cleavage by MobA.

Bacterial Proteins↗

The effect of raised inspired carbon dioxide on normal retinal vascular development in the neonatal rat.

PURPOSE: Raised arterial carbon dioxide levels have been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of raised inspired CO2 on normal postnatal vasculogenesis in the neonatal rat retina. METHODS: One hundred fifty newborn rat pups were divided among 15 mothers (n = 10 for each litter). Five litters were exposed to low CO2 (0.2%), 5 litters exposed to 6%, and 5 litters to 10% CO2. On day 7 of life the rats were sacrificed and the total retinal and vascularized retinal areas analyzed. RESULTS: The vascularized retinal area and ratio of vascularized to total retinal area were reduced in rats exposed to 6% and 10% CO2. CONCLUSIONS: Raised inspired CO2 was associated with retardation of normal retinal vascular development and increased peripheral avascular area in neonatal rats. Raised CO2 may be a risk factor for the development of abnormal neovascularization such as in ROP.

Animals↗

The effect of carbon dioxide on oxygen-induced retinopathy in the neonatal rat.

PURPOSE: Hypercarbia has been suggested as a risk factor for retinopathy of prematurity. We investigated the effect of raised inspired carbon dioxide on oxygen-induced retinopathy in the neonatal rat. METHODS: Newborn rats raised in expanded litters (n = 25 each) were exposed to cycles of hyperoxia (80% O2) and hypoxia (10% O2 for 7 days, followed by room air recovery for 5 days. During cyclic oxygen exposure, 3 litters (n = 75) were exposed to 10% CO2 (PaCO2 78 mm Hg +/- 6; mean +/- SD) and 3 litters (n = 75) were exposed to 0.2% CO2 (PaCO2 45 mm Hg +/- 7). Animals were sacrificed on day 13 and retinae were analyzed using fluorescein perfusion and ADPase staining techniques. RESULTS: Neovascularization occurred in 85% of rats exposed to high CO2 compared to 52% of rats exposed to low CO2 (p = 0.001). The severity of neovascularization, in clock hours, was also greater in the rats exposed to high CO2 (p < 0.001). CONCLUSIONS: Exposure to high CO2 results in an increased incidence and severity of neovascularization in a rat model for oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.

Administration, Inhalation↗

Differential effects of neuropeptide Y type 2 receptor activation on responses of rat ventral posteromedial thalamus neurons to surround vibrissae and trigeminal subnucleus interpolaris stimulation.

Single cell recording, receptive field analysis, and microejection techniques were used to evaluate the effects of neuropeptide Y (NPY) type 2 (Y2) receptor activation on the responses of vibrissae-sensitive ventral posteromedial thalamic (VPM) neurons. Activation of this receptor with the C-terminal fragment, NPY[13-36] had no significant effect on responses evoked by deflection of principal or surround vibrissae or electrical stimulation of the trigeminal principal sensory nucleus. However, it did significantly decrease (p < 0.01) responses evoked by electrical stimulation of subnucleus interpolaris (SpI) by a mean (+/- standard error) of -31.0 +/- 8.7%). The finding that responses to surround vibrissa stimulation were not significantly decreased by a manipulation that did significantly attenuate SpI- evoked responses suggests that this nucleus is not the sole source of surround vibrissae input to VPM neurons.

Animals↗

Genetic testing for male infertility: a postulated role for mutations in sperm nuclear matrix attachment regions.

Numerous reports have suggested that disturbances in nuclear condensation may result in male infertility. This notion has been supported by the observation of infertile individuals with a decrease or absence of the male sperm-specific chromatin packaging protamine proteins. To date, no correlation between the absence of protamine proteins and a mutation within the coding regions of the protamine genes has been documented. To address this issue, PCR-based mutation scanning analysis has been performed across the human male haploid expressed PRM1-->PRM2-->TNP2 domain in several oligozoospermic infertile individuals. This analysis identified a candidate mutation in a region of contact with the sperm nuclear matrix from 2 of 5 affected individuals. This is the first report of a mutation scan covering the entire PRM1-->PRM2-->TNP2 locus in affected individuals.

Chromosomal Proteins, Non-Histone↗

Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects.

A case-control study of the associations of retinoids and specific carotenoids with breast cancer using concentrations of these nutrients in breast adipose tissue was conducted among women attending a breast clinic in the Boston area in 1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n = 46) were women whose biopsies revealed invasive or in situ breast cancer; control subjects (n = 63) were women whose biopsies revealed benign disease. We observed inverse associations between breast adipose concentrations of retinoids and carotenoids and risk of breast cancer, although not all were statistically significant. The multivariate-adjusted odds ratio comparing women above the median value of the control group for retinol with those below or equal to the median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61 (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for beta-carotene, 0.32 (95% CI: 0.11, 0.94) for lycopene, and 0.68 (95% CI: 0.27, 1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and dietary intake of preformed vitamin A, including supplements measured by using a food-frequency questionnaire. No correlation was found between breast adipose concentrations of carotenoids and intake of dietary carotenoids. These data suggest that higher breast adipose concentrations of retinoids and some carotenoids may be associated with decreased risk of breast cancer and that further examination of these relations is warranted.

Adipose Tissue↗

Glycophorin A somatic cell mutation frequencies in residents of Tibet at high altitudes.

Since cosmic radiation is absorbed by the atmosphere surrounding the Earth, people who live at high altitude receive significantly larger amounts of cosmic radiation exposure than do those who live at low altitude. The glycophorin A-based somatic mutation assay was performed on 36 blood samples from two populations of Tibet inhabitants to determine whether residents at high altitude (4,300 m) accumulate more somatic mutations than do those who live at low altitude (1,500-1,900 m). These two populations differ in estimated cumulative lifetime cosmic radiation dose, with high altitude residents having received a mean of 111 mSv while low altitude residents received a mean of 27 mSv. Results showed no significant difference in peripheral blood variant erythrocyte frequency between these two populations and no difference from results of a previous study on Finnish workers who live at very low altitude (<500 m).

Altitude↗

Multiple modulations of action potential duration by different calcium channel blocking agents in guinea pig ventricular myocytes.

Effects of extracellular applications of different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) on action-potential duration and membrane currents were studied by the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Low concentrations of Mn2+ (1 mM) and verapamil (1 microM) prolonged action-potential duration at 90% repolarization (APD90) with a suppressed plateau phase. Increases in Mn2+ (5 mM) and verapamil (5 microM) shortened APD90 with a further depression of the plateau. Nisoldipine (0.2-1 microM) shortened APD90 without lengthening it. Applications of Mn2+ and verapamil suppressed amplitudes of the L-type Ca2+ current (ICa), the delayed outward K+ current (IK), and the inward rectifier K+ current (IK1). Furthermore, the ratios of ICa:IK inhibition were similar by low and high concentrations of Mn2+ and verapamil. Nisoldipine selectively suppressed ICa without effect on IK and IK1. A low concentration (1 mM) of Mn2+ not only decreased the peak amplitude of ICa but also delayed its decay time course, which caused an increase in late ICa amplitude at the end of a 200-ms depolarizing pulse. Both verapamil and nisoldipine suppressed peak ICa without affecting its decay. Whereas Mn2+ suppressed IBa without changing its decay time course, verapamil and nisoldipine speeded up the IBa decay with suppressed amplitude of IBa. We conclude that different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) diversely modulate APD because of their multiple modes of actions on ICa and IK.

Action Potentials↗

Salicylic acid activates a 48-kD MAP kinase in tobacco.

The involvement of phosphorylation/dephosphorylation in the salicylic acid (SA) signal transduction pathway leading to pathogenesis-related gene induction has previously been demonstrated using kinase and phosphatase inhibitors. Here, we show that in tobacco suspension cells, SA induced a rapid and transient activation of a 48-kD kinase that uses myelin basic protein as a substrate. This kinase is called the p48 SIP kinase (for SA-Induced Protein kinase). Biologically active analogs of SA, which induce pathogenesis-related genes and enhanced resistance, also activated this kinase, whereas inactive analogs did not. Phosphorylation of a tyrosine residue(s) in the SIP kinase was associated with its activation. The SIP kinase was purified to homogeneity from SA-treated tobacco suspension culture cells. The purified SIP kinase is strongly phosphorylated on a tyrosine residue(s), and treatment with either protein tyrosine or serine/threonine phosphatases abolished its activity. Using primers corresponding to the sequences of internal tryptic peptides, we cloned the SIP kinase gene. Analysis of the SIP kinase sequence indicates that it belongs to the MAP kinase family and that it is distinct from the other plant MAP kinases previously implicated in stress responses, suggesting that different members of the MAP kinase family are activated by different stresses.

Amino Acid Sequence↗

Teaching and assessing clinical skills: a competency-based programme in China.

The objective of this study was to develop a competency-based clinical skills teaching and assessment programme in China utilizing modern teaching techniques. Medical teachers from three schools agreed on items for inclusion in the complete physical examination of an asymptomatic adult, an outline for an adult and paediatric history, and important interviewing skills. Lesson plans, performance checklists, and written and videotape training materials were developed. Standardized patients were trained at one school to assist with the teaching at that school and with the assessment at all three schools. A national, a provincial, and a local medical school in China were used. Before beginning the new curriculum for students in their first year of clinical training, baseline data were collected on skills of students at various levels of training in the previous curriculum at all three schools. Although in the previous curriculum there was some improvement in clinical skills among advanced compared to more junior students, performance was lower than expected by staff. One year after implementation of the new curriculum, students were evaluated. These students significantly outperformed their counterparts as well as the more senior level students tested the previous year. This project has established a competency-based teaching and assessment programme in China that allows for rapid improvement in the clinical skills of students. Within a short time, a sophisticated group of medical educators has been formed, who now function as consultants to other educators in their own country. Many aspects of this programme are being adapted throughout China and are applicable to medical schools throughout the world.

Attitude↗

Immune suppression in calves with bovine immunodeficiency virus.

The present study was designed to evaluate the effect of bovine immunodeficiency virus (BIV) infection on immune functions and possible interactions between BIV and other bovine viruses in calves. Ten calves were inoculated intravenously with BIV, and five served as controls. An increased lymphocyte proliferation to BIV gag protein was demonstrated 2 to 6 weeks after BIV inoculation (P < 0.05). Lymphocyte subset differentiation revealed a decreased CD4/CD8 ratio (P < 0.05) during weeks 2 to 7, suggesting a possible immune dysfunction in BIV-infected calves. When the calves were inoculated with bovine herpesvirus type 1 (BHV-1), the antibody response to BHV-1 in BIV-infected calves was delayed and the antibody titers were significantly lower (P < 0.05). Injection of bovine viral diarrhea virus vaccine also elicited a lower neutralizing antibody response in BIV-infected calves. The results indicated that immune suppression occurred in BIV-infected calves.

Animals↗

Expression of the poliovirus receptor in intestinal epithelial cells is not sufficient to permit poliovirus replication in the mouse gut.

Although the initial site of poliovirus replication in humans is the intestine, previously isolated transgenic mice which carry the human poliovirus receptor (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral inoculation, are not susceptible to infection by the oral route. The low levels of PVR expressed in the TgPVR mouse intestine might explain the absence of poliovirus replication at that site. To ascertain whether PVR is the sole determinant of poliovirus susceptibility of the mouse intestine, we have generated transgenic mice by using the promoter for rat intestine fatty acid binding protein to direct PVR expression in mouse gut. Pvr was detected by immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP-PVR) small intestine. Upon oral inoculation with poliovirus, no increase in virus titer was detected in the feces of TgFABP-PVR mice, and no virus replication was observed in the small intestine, although poliovirus replicated in the brain after intracerebral inoculation. The failure of poliovirus to replicate in the TgFABP-PVR mouse small intestine was not due to lack of virus binding sites, because poliovirus could attach to fragments of small intestine from these mice. These results indicate that the inability of poliovirus to replicate in the mouse alimentary tract is not solely due to the absence of virus receptor, and other factors are involved in determining the ability of poliovirus to replicate in the mouse gut.

Animals↗

Genetic redundancy between SPT23 and MGA2: regulators of Ty-induced mutations and Ty1 transcription in Saccharomyces cerevisiae.

SPT23 was isolated as a dosage-dependent suppressor of Ty-induced mutations in Saccharomyces cerevisiae. SPT23 shows considerable sequence homology with MGA2, a gene identified as a dosage-dependent suppressor of a snf2-imposed block on STA1 transcription in S. cerevisiae var. diastaticus. Although single mutations in either of these genes have only modest effects on cell growth, spt23 mga2 double mutants are inviable. Unlike SPT23, multicopy expression of a truncated form of MGA2 suppresses a narrow subset of Ty-induced mutations. SPT23/MGA2 and the SNF/SWI genes affect transcription of certain target genes in similar ways. Spt23p appears to be a rate-limiting component required for functional HIS4 expression of his4-912delta, a promoter insertion mutation induced by the Ty1-912 long terminal repeat. Furthermore, both Spt23p and Mga2p can activate transcription when fused to the Gal4p DNA-binding domain, as previously observed with Snf2p and Snf5p. A 50-amino-acid region in the N terminus of the predicted Spt23p protein is necessary and sufficient for the transactivation and necessary for suppression of Ty1-induced mutations and the essential function of Spt23p. Cell fractionation and cytological experiments suggest that Spt23p is associated with the nucleus. Our results suggest that SPT23/MGA2 affects transcription of a subset of genes in yeast, perhaps by changing chromatin accessibility.

Adenosine Triphosphatases↗

Detection of bovine immunodeficiency virus antibodies in cattle by western blot assay with recombinant gag protein.

A western blot assay using purified recombinant bovine immunodeficiency virus gag protein has been developed for detection of bovine immunodeficiency virus antibodies in bovine serum samples. The test was standardized with known bovine immunodeficiency virus positive and negative bovine serum samples and the monoclonal antibody to gag protein. Both naturally and experimentally infected cattle sera demonstrated positive test results. The result of western blot assay was compared with polymerase chain reaction test results in 134 blood samples collected from Kansas. Twenty-six samples tested positive for bovine immunodeficiency virus DNA with polymerase chain reaction (18.7%) and 25 were positive for the antibody to gag protein by western blot analysis (17.9%). Of 26 cattle testing positive using the polymerase chain reaction assay, 24 were antibody-positive by western blot assay, thus establishing a strong correlation between the two tests. The sensitivity and specificity of western blot relative to polymerase chain reaction are 0.92 and 0.99, respectively. The western blot assay proved to be a specific and sensitive test.

Animals↗

Relationship between Asbestos Exposures and 8-Hydroxydeoxyguanosine Levels in Leukocytic DNA of Workers at a Chinese Asbestos-material Plant.

The objective of the study was to evaluate the level of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of peripheral-blood leukocytes as a biological marker of asbestos exposure and/or its fibrotic effects in an occupational population exposed to asbestos. The setting was a large-scale asbestos plant in China producing brake linings, asbestos rubber, and textile using chrysotile. From a base population of active and retired workers with various levels of cumulative exposure to asbestos and grades of asbestosis, 39 study subjects were randomly selected to reflect incremental grades of asbestosis based on Chinese diagnostic standards. They consisted of 19 "normal" (control) and ten "suspected" and ten "definite" asbestosis-grade subjects, group-matched for age and sex. Leukocytic DNA was extracted from 5-mL samples of peripheral blood and 8-OHdG level measured by high-pressure liquid chromatography. A cumulative asbestos exposure index (CEI) was calculated for each subject as the summed product of duration and level of asbestos exposure per job, incorporating a job-exposure matrix. Geometric mean 8-OHdG levels showed a positive gradient in relation to increasing grades of asbestosis (control: 1.78, suspected: 2.21, definite: 2.58), with a significant difference between the control and definite-asbestosis subgroups (p < 0.05). The 8-OHdG level of the two subgroups combined as one "asbestosis" group was significantly higher than that of the control group (control: 1.78, asbestosis: 2.39, p = 0.01). Further, 8-OHdG levels were moderately correlated with CEIs for all subjects (r = 0.35, p < 0.05) and with grades of asbestosis for all (r = 0.47, p < 0.01) and for male subjects (r = 0.43, p < 0.05). In multiple regression analyses, grade of asbestosis explained 27% of the total variation in 8-OHdG and was a better predictor than CEI or duration of exposure. Thus, the 8-OHdG level in leukocytic DNA is related to grade of asbestosis and to individual cumulative exposure and may serve as a biologic marker reflecting the status of oxidative DNA damage by asbestos.

Journal Article↗

Visually mediated odometry in honeybees

The ability of honeybees to gauge the distances of short flights was investigated under controlled laboratory conditions where a variety of potential odometric cues such as flight duration, energy consumption, image motion, airspeed, inertial navigation and landmarks were manipulated. Our findings indicate that honeybees can indeed measure short distances travelled and that they do so solely by analysis of image motion. Visual odometry seems to rely primarily on the motion that is sensed by the lateral regions of the visual field. Computation of distance flown is re-commenced whenever a prominent landmark is encountered en route. 'Re-setting' the odometer (or starting a new one) at each landmark facilitates accurate long-range navigation by preventing excessive accumulation of odometric errors. Distance appears to be learnt on the way to the food source and not on the way back.

Journal Article↗

N-(4-hydroxyphenyl)retinamide induces apoptosis in T lymphoma and T lymphoblastoid leukemia cells.

We demonstrate that N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), a synthetic retinoic acid (RA) derivative, is a potent and selective inducer of apoptosis in malignant T lymphoid cells, but has little effect on normal lymphoid cells of the thymus or spleen. 4-HPR and its stereoisomer, 9-cis-4-HPR, are 50 to > 150 times more potent than 7 other retinoids in killing CEM-C7 human T lymphoblastoid leukemia cells and P1798-C7 murine T lymphoma cells. 4-HPR's apoptotic action requires the intact molecule bearing both the retinoid moiety and the hydroxyphenol ring; 4-HPR remains unmetabolized after uptake into CEM-C7 and P1798-C7 cells for up to 24 hours. We also show that glucocorticoid (GC)-resistant variants are equally susceptible to 4-HPR as are GC-sensitive cells. Thus, 4-HPR may be potentially important as a new chemotherapeutic drug for use as alternative to, or in combination with, conventional drugs for treating lymphoid malignancies.

Aminophenols↗