Biomedical subjects

B Zhang

Publications and source records attributed to B Zhang.

At least 181 records · Page 10Linked to original sources

PubMed2000

Lactation reduces breast cancer risk in Shandong Province, China.

Results from studies of western populations investigating lactation and breast cancer risk have been inconsistent. To examine this issue, the authors conducted a hospital-based case-control study in Shandong Province, China, in 1997-1999. A total of 404 cases and an equal number of controls were included. Detailed information regarding lactation, menstruation, and reproduction was collected through in-person interview. The authors found a significant inverse association between duration of lactation and breast cancer risk. For women who breastfed for more than 24 months per child, the odds ratio was 0.46 (95% confidence interval (CI): 0.27, 0.78) when compared with those who breastfed for 1-6 months per child. A significantly reduced risk of breast cancer was also found for those whose lifetime duration of lactation totaled 73-108 months (odds ratio = 0.47, 95% CI: 0.23, 0.95) and for those who breastfed for > or =109 months (odds ratio = 0.24, 95% CI: 0.11, 0.53). The test for trend was statistically significant for both mean duration of lactation per child (p = 0.02) and lifetime duration of lactation (p = 0.00). Further stratification by menopausal status resulted in the same conclusion. These data suggest that prolonged lactation reduces breast cancer risk.

Adolescent↗

PubMed2000

Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w.

The non-essential amino acids L-serine (Ser) and glycine (Gly) have recently been shown to exhibit specific actions in the nervous system. In the present study, L-Ser and Gly promoted the survival of cultured rat cerebrocortical neurons in a concentration-dependent manner as revealed by Alamar blue assay and microtubule-associated protein-2 (MAP2) immunoblotting. The maximum effects of the amino acids were detected at the concentrations of 30-100 microM. L-Ser was more effective than Gly. D-Ser failed to promote neuronal survival. L-Ser and Gly upregulated expression of the anti-apoptotic gene product Bcl-w, while they did not affect the expression of Bcl-xL. The promotion of neuronal survival by L-Ser and Gly may be, at least in part, attributable to the upregulated Bcl-w.

Animals↗

PubMed2000

Structure of the BH domain from graf and its implications for Rho GTPase recognition.

Cellular signaling by small G-proteins is down-regulated by GTPase-activating proteins (GAPs), which increase the rate of GTP hydrolysis. The GTPase regulator associated with focal adhesion kinase (Graf) exhibits GAP activity toward the RhoA and Cdc42 GTPases, but is only weakly active toward the closely related Rac1. We determined the crystal structure of a 231-residue fragment of Graf (GrafGAP), a domain containing the GAP activity, at 2.4-A resolution. The structure clarifies the boundaries of the functional domain and yields insight to the mechanism of substrate recognition. Modeling its interaction with substrate suggested that a favorable interaction with Glu-95 of Cdc42 (Glu-97 of RhoA) would be absent with the corresponding Ala-95 of Rac1. Indeed, GrafGAP activity is diminished approximately 40-fold toward a Cdc42 E95A mutant, whereas a approximately 10-fold increase is observed for a Rac1 A95E mutant. The GrafGAP epitope that apparently interacts with Glu-95(Glu-97) contains Asn-225, which was recently found mutated in some myeloid leukemia patients. We conclude that position 95 of the GTPase is an important determinant for GrafGAP specificity in cellular function and tumor suppression.

Amino Acid Sequence↗

PubMed2000

Renal toxicity caused by cisplatinum in glutathione-depleted metallothionein-null mice.

To elucidate the protective role of metallothionein (MT) and glutathione (GSH) in renal toxicity caused by cisplatinum (cis-DDP), we examined the sensitivity of GSH-depleted MT-null mice to the renal toxicity of cis-DDP. Blood urea nitrogen and creatinine values in the serum, and histopathological change in the kidney were utilized as indicators of nephrotoxicity caused by cis-DDP. Although cis-DDP exerted renal toxicity in MT-null mice and wild-type mice, the toxicity was more conspicuous in the MT-null mice than in the wild-type mice. Moreover, renal toxicity caused by cis-DDP was enhanced significantly by a decrease in the renal GSH level by buthionine sulfoximine (BSO) pretreatment in both kinds of mice. The cis-DDP-caused nephrotoxicity that was enhanced by BSO-mediated GSH depletion was much more severe in the MT-null mice than in the wild-type mice. However, preadministration of zinc sulfate cancelled the BSO-enhanced, cis-DDP-dependent renal toxicity in the wild-type mice, but not in the MT-null mice. In the present study, we found that MT and GSH play an important, cooperative role in detoxification of severe kidney damage caused by cis-DDP. Moreover, the renal MT preinduced by zinc could protect mice from cis-DDP nephrotoxicity enhanced by GSH depletion.

Animals↗

PubMed2000

Stable expression of varied levels of inducible nitric oxide synthase in primary cultures of endothelial cells.

Nitric oxide (NO*), generated by nitric oxide synthase (NOS II) from immunostimulated cells during infection, plays an important role in host immune defense against microbial invasion. The impact of different rates of NO* production on host cell function has not been defined. Herein, we describe the development of a method to express varied levels of murine NOS II in bovine pulmonary artery endothelial cells. A retroviral vector (pMFGSNOS) encoding NOS II was used to transduce primary cultures of endothelial cells. Bovine endothelial cells were susceptible to this transduction and up to 18% of the cells expressed immunodetectable murine NOS II. The NOS II-transduced endothelial cells were cultured on the three-dimensional matrix, Gelfoam, for 8-10 days. Stable expression of NOS II was assessed by measuring nitrite accumulation in media every 2 days. By day 10, endothelial cells on Gelfoam were found to secrete NO* at a rate exceeding 1.0 microM/h/10(6) cells, concomitant with an enhanced level of NOS II activity. Argininosuccinate synthetase, a key enzyme in the metabolism of l-citrulline to l-arginine, increased as well, perhaps in response to dimunition of the intracellular arginine pool corresponding to the observed high output of NO*. In spite of the continuous flux of NO*, endothelial cell viability was not effected. This system provides the opportunity to assess the impact of different levels of sustained NO* production on endothelial cell physiology.

Animals↗

PubMed2000

Relative risk of dietary components and colorectal cancer.

OBJECTIVES: To investigate the relative risk factor of dietary components for colorectal cancer in a Chinese rural area through a hospital-based study. DESIGN AND SETTING: Colorectal cancer patients diagnosed at a county cancer center, Hebei Province, China, and out-patients with similar age, sex and resident place were selected for cases and controls, respectively. All subjects were given to interview about their food intake using a foods frequency questionnaire. The intake of different dietary components and life style were compared between cases and controls. MAIN RESULTS: There were 45 colorectal cancer patients and 45 outpatients being the cases and controls in the hospital-based study. In comparison of dietary components between cases and controls, milks, vegetables, fruits and teas had protective effect, and odds ratios were 0.21 (95% CI 0.07-0.60), 0.13 (95% CI 0.03-0.49), 0.27 (95% CI 0.11-0.68) and 0.39 (95% CI 0.16-0.98), respectively. Meats and saturated fats had an increased risk for colorectal cancer, and odds ratios were 5. 13 (95% CI 1.54-17.00) and 3.61 (95% CI 1.17-11.11), respectively. CONCLUSIONS: These findings indicate that there is a similar trend of dietary factors and risk of colorectal cancer in rural areas in comparison with westem dietary pattern, and suggest that the special attention should be paid to dietary habit for prevention and control of colorectal cancer in Chinese rural area.

Adult↗

PubMed2000

Nitrogen Adsorption Studies of PAN-Based Activated Carbon Fibers Prepared by Different Activation Methods.

Polyacrylonitrile (PAN)-based activated carbon fibers (ACFs) prepared by various activation methods were characterized using low-temperature nitrogen adsorption over a wide relative pressure from 10(-6) to 1. Nitrogen adsorption is a standard tool for determination of porous structure parameters. In the present work, we carried out extensive adsorption studies of a series of PAN-ACFs activated by different methods. It was shown that the high-resolution alpha(S) plot provided valuable information about structural properties of samples under study. The pore size distributions of samples under study were calculated by employing the regularization method according to density functional theory. By these analyses, the pore development and the dominant pores of samples prepared by different methods can be clearly observed. Moreover, the adsorption measurement could provide profound insight into the structural heterogeneity of the ACFs. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214.

The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P=.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.

AIDS Vaccines↗

PubMed2000

Effects of a traditional Chinese medicine, Qing Nao Yi Zhi Fang, on glutamate excitotoxicity in rat fetal cerebral neuronal cells in primary culture.

Qing Nao Yi Zhi Fang (QNYZ), a traditional Chinese medicine, has been developed as a drug to be used for the prevention and treatment of vascular dementia. However, the mechanisms by which this drug affects vascular dementia remain unknown. We examined the effects of QNYZ serum on glutamate excitotoxicity in rat fetal cerebral neuronal cells in primary culture. Exposure of neuronal cells to glutamate leads to a decrease in the activities of cholinesterase, superoxide dismutase, and streptoavidin peroxidase, and an increase in lactate dehydrogenase release. These enzyme activities were restored to the levels in untreated cells by the addition of QNYZ serum. QNYZ serum suppressed the increased nitric oxide production induced by glutamate and prevented glutamate-mediated apoptosis. QNYZ serum also improved mitochondrial energy metabolism after glutamate exposure. These findings suggest that QNYZ has protective effects against glutamate-mediated excitotoxicity in neuronal cells during ischemic brain injury.

Animals↗

PubMed2000

The role of Mg2+ cofactor in the guanine nucleotide exchange and GTP hydrolysis reactions of Rho family GTP-binding proteins.

The biological activities of Rho family GTPases are controlled by their guanine nucleotide binding states in cells. Here we have investigated the role of Mg(2+) cofactor in the guanine nucleotide binding and hydrolysis processes of the Rho family members, Cdc42, Rac1, and RhoA. Differing from Ras and Rab proteins, which require Mg(2+) for GDP and GTP binding, the Rho GTPases bind the nucleotides in the presence or absence of Mg(2+) similarly, with dissociation constants in the submicromolar concentration. The presence of Mg(2+), however, resulted in a marked decrease in the intrinsic dissociation rates of the nucleotides. The catalytic activity of the guanine nucleotide exchange factors (GEFs) appeared to be negatively regulated by free Mg(2+), and GEF binding to Rho GTPase resulted in a 10-fold decrease in affinity for Mg(2+), suggesting that one role of GEF is to displace bound Mg(2+) from the Rho proteins. The GDP dissociation rates of the GTPases could be further stimulated by GEF upon removal of bound Mg(2+), indicating that the GEF-catalyzed nucleotide exchange involves a Mg(2+)-independent as well as a Mg(2+)-dependent mechanism. Although Mg(2+) is not absolutely required for GTP hydrolysis by the Rho GTPases, the divalent ion apparently participates in the GTPase reaction, since the intrinsic GTP hydrolysis rates were enhanced 4-10-fold upon binding to Mg(2+), and k(cat) values of the Rho GTPase-activating protein (RhoGAP)-catalyzed reactions were significantly increased when Mg(2+) was present. Furthermore, the p50RhoGAP specificity for Cdc42 was lost in the absence of Mg(2+) cofactor. These studies directly demonstrate a role of Mg(2+) in regulating the kinetics of nucleotide binding and hydrolysis and in the GEF- and GAP-catalyzed reactions of Rho family GTPases. The results suggest that GEF facilitates nucleotide exchange by destabilizing both bound nucleotide and Mg(2+), whereas RhoGAP utilizes the Mg(2+) cofactor to achieve high catalytic efficiency and specificity.

Dose-Response Relationship, Drug↗

PubMed2000

Converting a c-type to a b-type cytochrome: Met61 to His61 mutant of Pseudomonas cytochrome c-551.

The gene nirM, coding for cytochrome c-551 in Pseudomonas stutzeri substrain ZoBell, was engineered to mutate Met61, the sixth ligand to the heme c, into His61, thereby converting the typical Met-His coordination of a c-type cytochrome into His-His, typical of b-type cytochromes. The mutant protein was expressed heterologously in Escherichia coli at levels 3-fold higher than in Pseudomonas and purified to homogeneity. The mutant retained low-spin visible spectral characteristics, indicating that the strong field ligand His 61 was coordinated to the iron. The physiochemical properties of the mutant were measured and compared to the wild-type properties. These included visible spectra, ligand binding reactions, stability to temperature and chemical denaturant, oxidation-reduction potentials, and electron-transfer kinetics to the physiological nitrite reductase of Pseudomonas. Despite a change in potential from the normal 260 mV to 55 mV, the mutant retained many of the properties of the c-551 family.

Amino Acid Substitution↗

PubMed2000

Development of multichannel devices with an array of electrospray tips for high-throughput mass spectrometry.

The basic principles of multichannel devices with an array of electrospray tips for high-throughput infusion electrospray ionization mass spectrometry (ESI-MS) have been developed. The prototype plastic devices were fabricated by casting from a solvent-resistant resin. The sample wells on the device were arranged in the format of the standard 96-microtiter well plate, with each sample well connected to an independent electrospray exit port via a microchannel with imbedded electrode. A second plastic plate with distribution microchannels was employed as a cover plate and pressure distributor. Nitrogen gas was used to pressurize individual wells for transport of sample into the electrospray exit port. The design of independent microchannels and electrospray exit ports allowed very high throughput and duty cycle, as well as elimination of any potential sample carryover. The device was placed on a computer-controlled translation stage for precise positioning of the electrospray exit ports in front of the mass spectrometer sampling orifice. High-throughput ESI-MS was demonstrated by analyzing 96 peptide samples in 480 s, corresponding to a potential throughput of 720 samples/h. As a model application, the device was used for the MS determination of inhibition constants of several inhibitors of HIV-1 protease.

Angiotensins↗

PubMed2000

In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease.

Strategies for treating Alzheimer's disease (AD) include therapies designed to decrease senile plaque (SP) formation and/or promote clearance of SPs, but clinical trials of these treatments are limited by the lack of effective methods to monitor changes in plaque burden in the brains of living AD patients. However, because SPs are extracellular deposits of amyloid-beta peptides (Abeta), it may be possible to eventually develop radioligands that cross the blood-brain barrier (BBB) and label SPs so they can be visualized by current imaging methods. As a first step toward the generation of such a radioligand, we developed a probe, [(trans,trans)-1-bromo-2, 5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB)], and we report here that BSB has the following properties essential for a probe that can detect SPs in vivo. First, BSB sensitively labels SPs in AD brain sections. Second, BSB permeates living cells in culture and binds specifically to intracellular Abeta aggregates. Third, after intracerebral injection in living transgenic mouse models of AD amyloidosis, BSB labels SPs composed of human Abeta with high sensitivity and specificity. Fourth, BSB crosses the BBB and labels numerous AD-like SPs throughout the brain of the transgenic mice after i.v. injection. Thus, we conclude that BSB is an appropriate starting point for future efforts to generate an antemortem diagnostic for AD.

Alzheimer Disease↗

PubMed2000

A minimum folding unit in the ankyrin repeat protein p16(INK4).

The ankyrin repeat is an abundant, 33 residue sequence motif that forms a consecutive beta-hairpin-helix-loop-helix (beta(2)alpha(2)) fold. Most ankyrin repeat proteins consist of four or more complete repeats, which provide stabilizing interactions between adjacent modules. The cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4) (p16) is one of the smallest ankyrin repeat proteins with a known structure. It consists of four complete repeats plus short N and C-terminal flanking regions that are unstructured in solution. On the basis of preliminary proteolysis studies and predictions using a computer algorithm for identifying autonomous folding units, we have identified a fragment consisting of the third and fourth ankyrin repeats of p16, called p16C, that can fold independently, without the rest of the protein. Far-UV circular dichroism studies showed that p16C has a significant level of alpha-helical secondary structure, and two proline substitutions that disrupt the alpha-helical secondary structure in wild-type p16 disrupt the secondary structure in p16C. The thermal denaturation of p16C is cooperative and reversible, with a midpoint of transition at 30. 5(+/-1) degrees C. From urea-induced denaturation studies, the free energy of unfolding for p16C was estimated to be 1.7(+/-0.3) kcal/mol at 20 degrees C. (1)H-(15)N 2D NMR studies suggest that the ankyrin repeats in p16C are likely to fold into a structure similar to that of full-length p16. In order to define the minimum autonomous folding unit in p16, we have further dissected p16C into two complementary peptides, each containing a single ankyrin repeat. These peptides are unstructured in solution. Thus, p16C is the smallest ankyrin repeat module that is known to fold independently and, in general, we believe that the two-ankyrin repeat fold could be the minimum structural unit for all ankyrin repeat proteins. We further discuss the significance of p16C in protein folding and engineering.

Algorithms↗

PubMed2000

The basal SAR of a novel insulin receptor activator.

The synthesis and SAR of analogues prepared from novel insulin receptor activator 1 are described. Changes to the dihydroxyquinone core were not tolerated while functionalization of the two indoles contained in 1 resulted in little effect upon activation of the insulin receptor.

Receptor, Insulin↗

PubMed2000

Exposure to electromagnetic fields from use of electric blankets and other in-home electrical appliances and breast cancer risk.

Exposure to electromagnetic fields (EMFs) from use of electric blankets and other in-home electrical appliances has been hypothesized to increase breast cancer risk. To test the hypothesis, the authors analyzed data from a case-control study of female breast cancer conducted in Connecticut in 1994-1997. A total of 608 incident breast cancer patients and 609 age frequency-matched controls, 31-85 years old, were interviewed by trained study interviewers using a standardized, structured questionnaire to obtain information on lifetime use of various in-home electrical appliances. A total of 40% of the cases and 43% of the controls reported regular use of electric blankets in their lifetime, which gave an adjusted odds ratio of 0.9 (95% confidence interval (CI): 0.7, 1.1). For those who reported using electric blankets continuously throughout the night, the adjusted odds ratio was 0.9 (95% CI: 0.7, 1.2) when compared with never users. The risk did not vary according to age at first use, duration of use, or menopausal and estrogen receptor status. The authors also did not find an association between use of other major in-home electrical appliances and breast cancer risk. In conclusion, exposure to EMFs from in-home electrical appliance use was not found to increase breast cancer risk in this study.

Adult↗

PubMed2000

High Magnetic Field Pulsars and Magnetars: A Unified Picture.

We propose a unified picture of high magnetic field radio pulsars and magnetars by arguing that they are all rotating high-field neutron stars but that their magnetic axes have different orientations with respect to their rotation axes. In strong magnetic fields where photon splitting suppresses pair creation near the surface, the high-field pulsars can have active inner accelerators while the anomalous X-ray pulsars cannot. This can account for the very different observed emission characteristics of the anomalous X-ray pulsar 1E 2259+586 and the high-field radio pulsar PSR J1814-1744. A predicted consequence of this picture is that radio pulsars having surface magnetic fields greater than about 2x1014 G should not exist.

Journal Article↗

PubMed2000

2,3,4,5-Tetrakis[(2-hydroxyethyl)thio]tetrathiafulvalene tetrafluoroborate.

The title complex, C(14)H(20)O(4)S(8)(+)(.)BF(4)(-), is a charge-transfer complex with typical charges for the donor and anion of +1 and -1, respectively. Two centrosymmetrically related donors form a face-to-face pi-dimer with a strong intermolecular S.S interaction. These pi-dimers stack along the a axis to form a donor column. The structure is extensively hydrogen bonded.

Journal Article↗