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Biomedical subjects

R Zhang

Publications and source records attributed to R Zhang.

At least 325 records · Page 18Linked to original sources
PubMed1997

Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats.

Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption. We examined the bone sparing effect of NO on prevention of corticosteroid-induced bone loss in older male rats. Recently, we demonstrated that NO donor nitroglycerin (NG) can alleviate ovariectomy-induced bone loss, and the protective effects of estrogens on bone are mediated through NO [Bone 18(4):301-304; 1996]. Therefore, we chose to study a different model (i.e., steroid-induced osteoporosis in males) to evaluate whether NG can inhibit the bone loss associated with corticosteroid therapy. Twenty-five 32-week-old male Wistar rats were randomly assigned to five groups (n = 5/group). They received either vehicle, methylprednisolone (7 mg/kg per week), NO synthase inhibitor L-NAME (25 mg/kg per day), NO donor nitroglycerin (NG, 0.2 mg twice daily), a combination of prednisolone+NG, or prednisolone plus L-NAME, respectively. Prior to treatment and at the end of the 6 week treatment period, bone mineral density (BMD) of the lumbar spine was measured by dual energy X-ray absorptiometry scanning. Administration of prednisolone significantly decreased BMD (-9.50%, p < 0.05). The group receiving NG with prednisolone (-2.34%) and the group treated with NG alone (-0.36%) were not statistically different from the control group (-0.11%). Similar to the changes in BMD, femur weights were also significantly lower in prednisolone-treated rats (1.09 +/- 0.01 g vs. 1.17 +/- 0.03 in controls; p < 0.05). However, the rats receiving prednisolone together with NG were able to maintain their femur weights (1.13 +/- 0.02). There was a reduction of 9.5% of BMD (p < 0.05) and 7.8% of femoral weight (p < 0.05) in rats treated with L-NAME. A 50%-70% reduction of the percentage trabecular bone volume in the proximal tibia and distal femur and a 50% reduction of the midshaft cortical area was seen after corticosteroid therapy, and these too were prevented by administration of NG. Here, we demonstrate, for the first time, that supplementation with a NO donor compound can counteract prednisolone-induced bone loss.

Absorptiometry, Photon↗
PubMed1997

Effects of interferon and PKC modulators on human glioma protein kinase C, cell proliferation, and cell cycle.

The in-vitro effects of human interferon alpha-2b (HuIFN alpha-2b), protein kinase C (PKC) agonist [TPA (12-0-tetra-decanoyl-phorbol-13-acetate)] and PKC inhibitor (calphostin C) on human glioma (U-373 MG) PKC activity, cell proliferation and cell cycle were compared. HuIFN alpha-2b and TPA increased PKC activity, elevated the number of cells in DNA synthesis (S) phase and decreased cell proliferation by similar magnitudes. Calphostin C inhibited PKC activity, increased the number of cells in S phase and produced strong cytotoxic effects (IC50 150 nM). Higher concentrations of calphostin C with or without serum induced an additional block in gap2 and mitosis. We conclude that HuIFN alpha-2b's mode of action may be directly or indirectly affecting PKC. The response produced by HuIFN alpha-2b is similar to TPA (potent PKC activation and S phase arrest).

Antineoplastic Agents↗
PubMed1997

Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the spider Selenocosmia huwena: 2. Three-dimensional structure in solution.

The three-dimensional structure in aqueous solution of native huwentoxin-I, a neurotoxin from the venom of the spider Selenocosmia huwena, has been determined from two-dimensional H NMR data recorded at 500 and 600 MHz. Structural constraints consisting of interproton distances inferred from NOEs and dihedral angles from spin-spin coupling constants were used as input for distance geometry calculation with the program XPLOR 3.1. The best 10 structures have NOE violations < 0.3 A, dihedral violations < 2 degrees, and pairwise root-mean-square differences of 1.08 (+/- 0.20) A over backbone atoms (N, C alpha, C). The molecule adopts a compact structure consisting of a small triple-stranded antiparallel beta-sheet and five beta-turns. A small hydrophobic patch consisting of Phe 6, Trp 28, and Trp 31 is located on one side of the molecule. All six lysine residues are distributed on the molecular surface. The three disulfide bridges are buried within the molecule. The structure contains an "inhibitor cystine knot motif" which is adopted by several other small proteins, such as omega-conotoxin, agatoxin IVA, and gurmarin.

Amino Acid Sequence↗
PubMed1997

Enhancement of immune function in mice fed high doses of soy daidzein.

High soy consumption leading to high exposures of soy isoflavones has been associated with a reduced risk of cancers at many sites. As part of a study focusing on the chemopreventive mechanisms, we have investigated the modulating effects of daidzein, a prominent and more bioavailable isoflavone in soy foods, on murine immune function. Swiss mice were fed daidzein at various doses daily for seven consecutive days. At high doses (20 and 40 mg/kg), daidzein exerted a stimulatory effect on nonspecific immunity, as shown by increases in the phagocytic response of peritoneal macrophages and thymus weight, in a dose-dependent manner. Augmentation of spleen immunoglobulin M-producing cells against sheep red blood cells demonstrated an-activation of humoral immunity. Enhanced cell-mediated immunity was also observed as increases in lymphocyte proportion of peripheral blood. However, no significant immunoregulatory effect was found when mice were fed 10 mg/kg daidzein. These results demonstrate for the first time that daidzein at high doses enhances several immunologic functions and suggest a novel approach to understanding the mechanism(s) by which soy foods may contribute to observed cancer prevention.

Animals↗
PubMed1997

Individual and combinatory effects of soy isoflavones on the in vitro potentiation of lymphocyte activation.

Daidzein and genistein are two prominent soy isoflavones that have been reported as promising protectors against cancers at many sites. In a study focusing on the chemopreventive mechanisms, we previously demonstrated that daidzein was an effective immune stimulator in an in vivo murine system. In this study we further evaluated the effects of daidzein and genistein, individually and in combination, on in vitro mitogen-stimulated activation of murine lymphocytes. At physiologically relevant concentrations (0.01-10.0 microM), daidzein significantly potentiated proliferation of mixed splenocyte cultures activated with concanavalin A or lipopolysaccharide in a dose-dependent manner in comparison with vehicle control, whereas genistein had no influence on the response. Although a significant cooperativity with genistein (1 microM) was observed at low concentrations of daidzein (0.01 microM) in comparison with daidzein alone, genistein failed to augment or counteract the effects of high concentrations of daidzein on lymphocyte proliferation. The secretion of cytokine interleukins-2 and -3 from concanavalin A-activated lymphocytes was significantly increased again by daidzein and was unaffected or mildly decreased by genistein. Taken together, these results demonstrate that daidzein, rather than genistein, is able to enhance in vitro activation of murine lymphocytes and suggest that more studies focusing on the immunoregulatory mechanism of soy daidzein and the potential clinical relevance are warranted.

Animals↗
PubMed1997

Probing the substrate specificity of hepatitis C virus NS3 serine protease by using synthetic peptides.

We probed the substrate specificity of a recombinant noncovalent complex of the full-length hepatitis C virus (HCV) NS3 serine protease and NS4A cofactor, using a series of small synthetic peptides derived from the three trans-cleavage sites of the HCV nonstructural protein sequence. We observed a distinct cleavage site preference exhibited by the enzyme complex. The values of the turnover number (k(cat)) for the most efficient NS4A/4B, 4B/5A, and 5A/5B peptide substrates were 1.6, 11, and 8 min(-1), respectively, and the values for the corresponding Michaelis-Menten constants (Km) were 280, 160, and 16 microM, providing catalytic efficiency values (k(cat)/Km) of 92, 1,130, and 8,300 M(-1) s(-1). An alanine-scanning study for an NS5A/5B substrate (P6P4') revealed that P1 Cys and P3 Val were critical. Finally, substitutions at the scissile P1 Cys residue by homocysteine (Hcy), S-methylcysteine (Mcy), Ala, S-ethylcysteine (Ecy), Thr, Met, D-Cys, Ser, and penicillamine (Pen) produced progressively less efficient substrates, revealing a stringent stereochemical requirement for a Cys residue at this position.

Amino Acid Sequence↗
PubMed1997

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress.

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Adult↗
PubMed1997

Monoclonal antibodies to rat calcitonin: their use in antigenic mapping and immunohistochemistry.

A library of monoclonal antibodies (mAbs) to rat calcitonin (rCT) was raised from several fusions. Antibodies were screened by enzyme-linked immunosorbent assay with solid phase rCT. Affinities for rCT ranged from 10(9)-10(11) M(-1). Some mAbs reacted preferentially with solid phase rCT, but not with liquid phase, 125I-labeled rCT. Cross-reactivity with human CT (hCT) was assessed using solid phase hCT. Although there are only two amino acid differences, at least nine of the mAbs do not cross-react with solid phase hCT. Several cross-reactive mAbs were chosen for immunohistochemical studies of human medullary thyroid carcinoma samples and showed strong positive staining. A 33 x 33 matrix solid-liquid mAb inhibition assay was carried out to probe the rCT molecule. Five different clusters of mAb were distinguished and interpreted as reflecting five distinct antigenic regions on the surface of the rCT molecule.

Animals↗
PubMed1997

A monoclonal antibody against rat calcitonin inhibits the growth of a rat medullary thyroid carcinoma cell line in vitro.

Medullary thyroid carcinoma (MTC) cells synthesize large amounts of calcitonin (CT), which serves clinically as a useful tumor marker. To examine the possibility of CT serving as a target in immunotherapy for MTC, we raised and characterized more than 40 monoclonal antibodies (mAbs) against rat CT (rCT). The affinity constants for the mAbs were between 2.8 x 10(9) and 1.8 x 10(11) M(-1). Some mAbs react preferentially with solid phase rat CT, but not with liquid phase 125I-labeled rCT. Thirty-nine mAbs cross-react with human CT. We evaluated the antitumor effect of the mAbs in vitro by analysis of [3H]thymidine incorporation into the rat MTC cell line CRL-1607. Some antibodies show an antiproliferative effect, but most are inactive. One mAb (2E5G5, IgG2b), which preferentially reacts with solid phase rCT, but not with liquid phase 125I-labeled rCT, exerts an antiproliferative activity on CRL-1607. At 6.25 x 10(-7) M, 2E5G5 killed all of the tumor cells independently of complement in a cytotoxicity assay. We explored the cytotoxic mechanisms by assays for cell cycle arrest and DNA fragmentation. The antitumor effect was manifested by apoptosis and cell cycle arrest. Hence, a secreted peptide may serve as a target in tumor immunotherapy. Therapeutically antibodies may exert antitumor activity by a variety of mechanisms. The antitumor effect of this mAb in a rat animal tumor model is being tested.

Animals↗
PubMed1997

Quality control of spirometry testing in the registry for patients with severe alpha1-antitrypsin deficiency. alpha1-Antitrypsin Deficiency Registry Study Group.

As part of the multicenter National Heart, Lung, and Blood Institute registry of patients with severe deficiency of alpha1-antitrypsin with 1,129 enrollees, this report describes measures undertaken to achieve high-quality FEV1 measurements, the rates of satisfying reproducibility and acceptability criteria, and clinical features of participants unable to achieve reproducible FEV1 values at baseline. Spirograms were performed both before and after an inhaled bronchodilator in enrollees followed up at 37 participating clinical centers. Using a reproducibility criterion of < 100 mL or 5% (whichever greater), high reproducibility rates for FEV1 measurements at baseline were observed for both prebronchodilator (95.0% of 1,090 sessions) and postbronchodilator measurements (95.7% of 1,077 sessions). Using the more recently published reproducibility criterion of < or = 200 mL, reproducibility rates were even higher. Eighty-four percent of clinical centers submitted FEV1 values that satisfied reproducibility criteria for at least 90% of spirograms. Also, the mean coefficient of variation for prebronchodilator FEV1 values measured over serial visits separated by up to 9 months was 5.6% for participants with baseline FEV1 55 to 90% predicted. This degree of reproducibility is similar to that observed in the Lung Health Study. Rates of satisfying acceptability criteria for prebronchodilator spirograms were lower, almost universally (98% of tests) due to failure to achieve end-of-test criteria (which usually required 15 s of expiration in this population with mean FEV1 = 42.6+/-29.6% [SD] predicted). Multivariate logistic regression models show that clinical correlates of failure to achieve reproducible prebronchodilator FEV1 efforts include symptoms of chronic wheeze, chronic cough, and chronic phlegm, and the degree of airflow obstruction. We conclude that highly reproducible FEV1 measurements are achievable in a population with severe airflow obstruction despite the additional challenges posed by testing in multiple centers on a variety of spirometers. Furthermore, the difficulty of satisfying end-of-test criteria in a large cohort with severe airflow obstruction did not preclude achieving high rates of reproducibility for FEV1 measurements. Finally, our study confirms prior observations that failure to achieve reproducible efforts is associated with the presence of pulmonary symptoms and the degree of airflow obstruction. Thus, excluding patients with nonreproducible FEV1 efforts from epidemiologic studies would bias results by including only healthier participants.

Female↗
PubMed1997

[Clinical investigation on 42 cases of pulmonary tuberculoma].

OBJECTIVE: For the purpose to find the possible reasons causing pulmonary tuberculoma been misdiagnosed as lung cancer. METHODS: Clinical symptoms, chest X ray films, tomographic and CT manifestations as well as laboratory data of 42 cases of pulmonary tuberculoma pathologically proved were thoroughly reviewed. All the radiological appearances were compared with pathological findings. RESULTS: Shallow lobulated contour, spurlike shadow formation, vacoule sign, satellite lesions, pleural involvement, calcified spots were found very important for differential diagnosis of these 2 diseases. CONCLUSIONS: It is difficult to differentiate pulmonary tuberculoma from lung cancer. By paying special attention to the above mentioned appearance, evaluating them very carefully and considering them with positive laboratory findings, it might be possible to avoid misdiagnosis before surgical operation.

Adult↗
PubMed1997

[DNA polymorphisms of apolipoprotein A I gene in Chinese endogenous hypertriglyceridemics].

The restriction fragment length polymorphisms (RFLPs) of apolipoprotein(apo) A I gene were studied using polymerase chain reaction (PCR) in 69 endogenous hypertriglyceridemics (HTG) and 74 healthy subjects from a population of Chinese Han nationality in Chengdu area. The loci studied included Msp 1 within intron 3 of the apo A I gene; Xmn I, 5' to the apo A I gene; and Pst I, 3' to the apo A I gene. The results showed that both in HTG group and control group M1, X1 and P1 alleles were the major alleles and homozyous M1M1, X1X1 and P1P1 genotypes were the most frequent ones. The frequencies of rare M2 and X2 alleles in Chinese were significantly higher than those in European Caucasians (0.293 vs 0.111, P < 0.0006, 0.286 vs 0.130, P < 0.004), but no differences were found in the frequency of rare P2 allele (0.071 vs 0.046, P > 0.05). The frequency of rare M2 tended to increase in the HTG group when compared with the control group (0.353 vs 0.275, P > 0.05). Both in the HTG group and control group, subjects with genotype M2M2 had a higher serum mean concentration of TC, apo C II and higher serum TG/HDL-C ratio compared with the subjects with the genotypes M1M1 and M1M2 (P = 0.05, P < 0.03, P < 0.04), and the serum TG, apo C II and apo E levels had a tendency to increase. The subjects with the genotypes P1P2 and P2P2 had a higher serum apo A II levels compared with the subjects with the genotype P1P1 (P < 0.04). The data show that the only Msp I RFLP within the intron 3 of apo A I gene is associated with endogenous hypertriglyceridemia to some extent in Chinese population.

Adult↗
PubMed1997

[Successful 48-72 h cold storage of dog kidneys with HX-1 solution].

HX-1 solution was used in this study to determine its effects on long term kidney preservation. 20 female and male mongrel dogs were randomly divided into control (HC-WCU solution) and experimental (HX-1 solution) groups. Kidneys were flushed with HC-WCU or HX-1 solution and stored at 0.4 degree C for 48 or 72 h. After being preserved, the kidney was implanted in the right groin of the animal and anastomosed to the iliac vessles. This procedure was immediately followed by a contralateral nephrectomy. The experimental findings were: 1. The maximum serum creatinine levels were 642.60 +/- 158.60 mumol/L and 686.20 +/- 154.04 mumol/L respectively in HC-WCU solution subgroups for 48 or 72 h cold storage. But the maximum serum creatinine levels were 448.32 +/- 36.90 mumol/L and 524.60 +/- 109.38 mumol/L respectively in HX-1 solution subgroups. 2. 80% of the kidneys were viable after 48 h storage in HC-WCU kidney solution, but 100% viable when stored in HX-1 solution: 40% of the kidneys were viable after 72 h storage in HC-WCU solution, but 60% viable when stored in HX-1 solution. 3. Histologically the kidney of dogs that died of renal failure was damaged worse in HC-WCU solution group than that in HX-1 solution group. These results suggest that HX-1 solution is superior to HC-WCU solution for preserving kidneys and HX-1 solution may store up the kidney of dogs to 48-72 h.

Animals↗
PubMed1997

[Serum apolipoprotein C II, C III and E levels in 437 male healthy subjects aged 40-70 in Chengdu area].

Apolipoprotein (apo) C II, C III and E levels of 437 male healthy subjects aged 40-70 [with fasting serum triglyceride (TG levels < 2.26 mmol/L, total cholesterol (TC) levels < 6.21 mmol/L and plasma glucose levels < 6.10 mmol/L] in Changdu area were determined by radial immunodiffusion assay (RID). The results showed that the concentrations of apoC II, C III and E were 41.6 +/- 13.1, 112.8 +/- 31.0 and 38.7 +/- 8.2 mg/L (mean +/- s) respectively. No difference in the serum levels of apoC II, C III and E was noted between the men of different ages. The results of the linear correlation showed that there was a positive correlation of apoC II, C III, E with TG, TC, LDL-C; of apoC II, C III with BMI; and of apoE with ages.

Adult↗