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Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 271 records · Page 15Linked to original sources
PubMed2000

Elastic property of single double-stranded DNA molecules: theoretical study and comparison with experiments.

This paper aims at a comprehensive understanding of the novel elastic property of double-stranded DNA (dsDNA) discovered very recently through single-molecule manipulation techniques. A general elastic model for double-stranded biopolymers is proposed, and a structural parameter called the folding angle straight phi is introduced to characterize their deformations. The mechanical property of long dsDNA molecules is then studied based on this model, where the base-stacking interactions between DNA adjacent nucleotide base pairs, the steric effects of base pairs, and the electrostatic interactions along DNA backbones are taken into account. Quantitative results are obtained by using a path integral method, and excellent agreement between theory and the observations reported by five major experimental groups are attained. The strong intensity of the base stacking interactions ensures the structural stability of DNA, while the short-ranged nature of such interactions makes externally stimulated large structural fluctuations possible. The entropic elasticity, highly extensibility, and supercoiling property of DNA are all closely related to this account. The present work also suggests the possibility that negative torque can induce structural transitions in highly extended DNA from the right-handed B form to left-handed configurations similar to the Z-form configuration. Some formulas concerned with the application of path integral methods to polymeric systems are listed in the Appendixes.

Base Pairing↗
PubMed2000

Apoptosis and regeneration of hepatocytes during recovery from transient hepadnavirus infections.

It is well known that hepatitis B virus infections can be transient or chronic, but the basis for this dichotomy is not known. To gain insight into the mechanism responsible for the clearance of hepadnavirus infections, we have performed a molecular and histologic analysis of liver tissues obtained from transiently infected woodchucks during the critical phase of the recovery period. We found as expected that clearance from transient infections occurred subsequent to the appearance of CD4(+) and CD8(+) T cells and the production of interferon gamma and tumor necrosis factor alpha in the infected liver. These events were accompanied by a significant increase in apoptosis and regeneration of hepatocytes. Surprisingly, however, accumulation of virus-free hepatocytes was delayed for several weeks following this initial influx of lymphocytes. In addition, we observed that chronically infected animals can exhibit levels of T-cell accumulation, cytokine expression, and apoptosis that are comparable with those observed during the initial phase of transient infections. Our results are most consistent with a model for recovery predicting replacement of infected hepatocytes with regenerated cells, which by unknown mechanisms remain protected from reinfection in animals that can be cured.

Animals↗
PubMed2000

Elevated levels of hepatocyte nuclear factor 3beta in mouse hepatocytes influence expression of genes involved in bile acid and glucose homeostasis.

The winged helix transcription factor, hepatocyte nuclear factor-3beta (HNF-3beta), mediates the hepatocyte-specific transcription of numerous genes important for liver function. However, the in vivo role of HNF-3beta in regulating these genes remains unknown because homozygous null HNF3beta mouse embryos die in utero prior to liver formation. In order to examine the regulatory function of HNF-3beta, we created transgenic mice in which the -3-kb transthyretin promoter functions to increase hepatocyte expression of the rat HNF-3beta protein. Postnatal transgenic mice exhibit growth retardation, depletion of hepatocyte glycogen storage, and elevated levels of bile acids in serum. The retarded growth phenotype is likely due to a 20-fold increase in hepatic expression of insulin-like growth factor binding protein 1 (IGFBP-1), which results in elevated levels in serum of IGFBP-1 and limits the biological availability of IGFs required for postnatal growth. The defects in glycogen storage and serum bile acids coincide with diminished postnatal expression of hepatocyte genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase and glycogen synthase) and sinusoidal bile acid uptake (Ntcp), respectively. These changes in gene transcription may result from the disruptive effect of HNF-3beta on the hepatic expression of the endogenous mouse HNF-3alpha,-3beta, -3gamma, and -6 transcription factors. Furthermore, adult transgenic livers lack expression of the canalicular phospholipid transporter, mdr2, which is consistent with ultrastructure evidence of damage to transgenic hepatocytes and bile canaliculi. These transgenic studies represent the first in vivo demonstration that the HNF-3beta transcriptional network regulates expression of hepatocyte-specific genes required for bile acid and glucose homeostasis, as well as postnatal growth.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

G(i-1)/G(i-2)-dependent signaling by single-transmembrane natriuretic peptide clearance receptor.

Single-transmembrane natriuretic peptide clearance receptor (NPR-C), which is devoid of a cytoplasmic guanylyl cyclase domain, interacts with pertussis toxin (PTx)-sensitive G proteins to activate endothelial nitric oxide synthase (eNOS) expressed in gastrointestinal smooth muscle cells. We examined the ability of NPR-C to activate other effector enzymes in eNOS-deficient tenia coli smooth muscle cells; these cells expressed NPR-C and NPR-B but not NPR-A. Atrial natriuretic peptide (ANP), the selective NPR-C ligand cANP-(4-23), and vasoactive intestinal peptide (VIP) inhibited (125)I-ANP and (125)I-VIP binding to muscle membranes in a pattern indicating high-affinity binding to NPR-C. Interaction of VIP with NPR-C was confirmed by its ability to inhibit (125)I-ANP binding to membranes of NPR-C-transfected COS-1 cells. In tenia muscle cells, all ligands selectively activated G(i-1) and G(i-2); VIP also activated G(s) via VIP(2) receptors. All ligands stimulated phosphoinositide hydrolysis, which was inhibited by ANP-(1-11), PTx, and antibodies to phospholipase C-beta3 (PLC-beta3) and Gbeta. cANP-(4-23) contracted tenia muscle cells; contraction was blocked by U-73122 and PTx and by antibodies to PLC-beta3 and Gbeta in intact and permeabilized muscle cells, respectively. VIP and ANP contracted muscle cells only after inhibition of cAMP- and cGMP-dependent protein kinases. ANP and cANP-(4-23) inhibited forskolin-stimulated cAMP in a PTx-sensitive fashion. We conclude that NPR-C is coupled to activation of PLC-beta3 via betagamma-subunits of G(i-1) and G(i-2) and to inhibition of adenylyl cyclase via alpha-subunits.

Adenylyl Cyclase Inhibitors↗
PubMed2000

Population pharmacokinetics/toxicodynamics (PK/TD) relationship of SAM486A in phase I studies in patients with advanced cancers.

SAM486A (previously termed CGP 48664), a potent inhibitor of S-adenosylmethionine decarboxylase, is under clinical development for the treatment of advanced refractory malignancies. Hematological toxicity manifested by dose-dependent neutropenia has been observed in phase I studies. Population methods were used to investigate pharmacokinetics (PK) as a prognostic factor for safety end point (hematological toxicity) in patients with advanced cancers. SAM486A plasma concentrations and neutrophil counts were collected from three ascending-dose tolerability and PK studies (study 1: single 5-day continuous intravenous (IV) infusion with doses ranging from 24-700 mg/m2/cycle; study 2: 10-minute to 3-hour IV infusion once weekly with doses ranging from 16-325 mg/m2/week; study 3: 1-hour IV infusion once daily for 5 days with doses ranging from 3.6-202.8 mg/m2/day). The PK of SAM486A were best estimated by a population linear three-compartment model with NONMEM (version 5) using data from 9 patients in studies 1 through 3. The population pharmacokinetic parameters (SD) were CL = 6.2 (0.4) l/h/m2, Q2 = 15.4 (1.5) l/h/m2, Q3 = 33.6 (5.3) l/h/m2, V1 = 9.5 (1.6) l/m2, V2 = 672 (52) l/m2, and V3 = 39.9 (8.3) l/m2, and the corresponding intersubject variability was 45.4%, 74.0%, 85.3%, 80.1%, 37.0%, and 103%, respectively, where CL is total body clearance, Q2 and Q3 are intercompartmental clearances, and V1, V2, and V3 are the volumes of distribution in central and peripheral compartments, respectively. The intrasubject variability was 24.0%. The cumulative AUC before the onset of neutrophil nadir count (AUC) and the duration of exposure over threshold SAM486A concentrations in the range of 0.05 to 0.1 microM based on Bayesian PK parameter estimates significantly correlated with absolute neutrophil count nadir (< 5 x 10(9)/l). AUC showed the best correlation (R2 = 0.72) with absolute neutrophil count nadir by an inhibitory sigmoid Emax model and also correlated with percent decrease in neutrophil count from baseline to nadir by a simple Emax model (R2 = 0.53). Logistic regression analysis indicated that AUC and the duration of exposure over 0.05 to 0.1 microM, but not Cmax, were strong predictors of grade 4 neutropenia (< 0.5 x 10(9)/l). Drug exposure parameters such as AUC derived from population analysis may be used clinically as a useful predictor of drug-induced neutropenia.

Adult↗
PubMed2000

Making rats rise to erect bipedal stance for feeding partially prevented orchidectomy-induced bone loss and added bone to intact rats.

The objectives of this study were to investigate the different effects on muscle mass and cancellous (proximal tibial metaphysis [PTM]) and cortical (tibial shaft [TX]) bone mass of sham-operated and orchidectomized (ORX) male rats by making rats rise to erect bipedal stance for feeding. Specially designed raised cages (RC) were used so that the rats had to rise to erect bipedal stance to eat and drink for 12 weeks. Dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computerized tomography (pQCT) were used to estimate the lean leg mass and bone mineral. Static and dynamic histomorphometry were performed on the triple-labeled undecalcified sections. We found that making the intact rats rise to erect bipedal stance for feeding increased muscle mass, cortical bone volume, and periosteal bone formation. Orchidectomy increased net losses of bone next to the marrow by increasing bone turnover. Making the ORX rats rise to erect bipedal stance increased muscle mass, partially prevented cancellous bone loss in the PTM, and prevented net cortical bone loss in TX induced by ORX by depressing cancellous and endocortical high bone turnover and stimulating periosteal bone formation. The bone-anabolic effects were achieved mainly in the first 4 weeks in the PTM and by 8 weeks in the TX. These findings suggested that making the rats rise to erect bipedal stance for feeding helped to increase muscle mass and cortical bone mass in the tibias of intact rats, increase muscle mass, and partially prevented cancellous and net cortical bone loss in ORX rats.

Animals↗
PubMed2000

Longitudinal studies of Aedes aegypti (Diptera: Culicidae) in Thailand and Puerto Rico: population dynamics.

Aspiration collections of adult Aedes aegypti (L.) were made weekly from inside and outside of houses for 3 yr in a rural Thai village (n = 9,637 females and n = 11,988 males) and for 2 yr in a residential section of San Juan, Puerto Rico (n = 5,941 females and n = 6,739 males). In Thailand, temperature and rainfall fell into distinct seasonal categories, but only temperature was correlated with fluctuations in female abundance. Average weekly temperature 6 wk before mosquitoes were collected and minimum weekly temperature during the week of collection provided the highest correlations with female abundance. Accounting for annual variation significantly improved Thai models of temperature and mosquito abundance. In Puerto Rico, temperature, but not rainfall, could be categorized into seasonal patterns. Neither was correlated with changes in female abundance. At both sites the vast majority of females were collected inside houses and most contained a blood meal. Most teneral females were collected outside. Wing length--an indicator of female size--and parity, egg development or engorgement status were not correlated, indicating that feeding success and survival were not influenced by female size. At both sites, females fed almost exclusively on human hosts (> or = 96%), a pattern that did not change seasonally. In Puerto Rico more nonhuman blood meals were detected in mosquitoes collected outside than inside houses; no such difference was detected in Thailand. Gut contents of dissected females indicated that females in the Thai population had a younger age distribution and fed more frequently on blood than did Ae. aegypti in Puerto Rico. Our results indicated that aspects of this species' biology can vary significantly from one location to another and 1 yr to the next.

Aedes↗
PubMed2000

Improved controlled release study of lomustine.

Lomustine (CCNU) microcapsules was prepared by improved recoacervation method, then mixed microcapsules with 0.7% collagen swelling solution to prepare the emulsion, spreaded the emulsion on the plate to form membrane and cross-linked it, the membrane would be planted into body and was expected to release at steady speed. The concentration of CCNU and the CCNU content of microcapsules were measured by ultraviolet spectrophotometry to observe the release of CCNU be slow and constant, approach to 0-class release approximately.

Absorbable Implants↗
PubMed2000

pH-responsive swelling behavior of collagen complex materials.

This article deals with an natural collagen blended with chitosan, poly(vinyl alcohol)(PVA). We investigated the swelling properties of collagen and collagen complex in the solution with different pH, and the swelling/deswelling behavior of collagen and collagen-chitosan complex when changing the pH of the medium from 5.4 to 1.8 and in the reverse. The results show that the swelling degree of collagen and collagen complex are dependent to pH of the solution, and the swelling behavior of collagen and collagen-chitosan complex are pH-responsive.

Absorption↗
PubMed2000

The effect of berberine chloride on experimental colitis in rats in vivo and in vitro.

Berberine is an isoquinoline alkaloid with multiple pharmacological actions, including anti-inflammatory activity. The aims of this study were to examine the effect of berberine on the mucosal healing process and to investigate whether berberine can inhibit the increased production of interleukin-8 in trinitrobenzene sulfonic acid-induced colitis in rats. Berberine was administered orally for 3 days or 1 week at a dosage of 7.5 or 15 mg/kg/day. Tissue damage scores, body weight, colon wet weight, and colon wall thickness were measured, and myeloperoxidase activity in colon tissue was also examined. Histological lesions, morphological damage, and myeloperoxidase activity were reduced after 1 week of treatment with berberine at a dosage of 15 mg/kg/day. Furthermore, 1 week after trinitrobenzene sulfonic acid treatment, the production of interleukin-8 by cultured rectal mucosa or cardiac blood mononuclear cells with or without stimulation of lipopolysaccharide for 24 h was also analyzed by enzyme-linked immunosorbent assay. Cardiac blood mononuclear cells and rectal mucosa of normal rats produced substantial amounts of interleukin-8, which increased strikingly with the stimulation of lipopolysaccharide. Cardiac blood mononuclear cells and rectal mucosa of trinitrobenzene sulfonic acid-treated rats secreted more interleukin-8 than those of normal rats. The addition of berberine with a concentration of 10(-5) M to the culture media resulted in an inhibition of interleukin-8 production of rectal mucosa.

Animals↗
PubMed2000

Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and has a very poor prognosis. Fifty primary HCC cases have been analyzed in the present study to explore the association between genomic alteration in primary HCC and clinical features. Several recurrent chromosomal abnormalities were identified in this study. The most frequently detected chromosomal gains involved chromosome arms 1q (33/50 cases, 66%), 8q (24/50 cases, 48%), and 20q (10/50 cases, 20%). High-copy-number amplifications involving 1q (4 cases), 8q (3 cases), and 20q (3 cases) were detected, and a minimum overlapping amplified region at 1q12-q22 was identified. The most frequently detected loss of chromosomal material involved 16q (35/50 cases, 70%), 17p (26/50 cases, 52%), 19p (21/50 cases, 42%), 4q (20/50 cases, 40%), 1p (18/50 cases, 36%), 8p (16/50 cases, 32%), and 22q (14/50 cases, 28%). The associations between genomic alterations detected in the present study and clinical features including clinical stage, tumor size, HBV infection, chronic liver disease, and liver cirrhosis were explored. Our CGH results suggest that the gain of 20q and deletion of 8p are late genetic alterations in HCC, because the incidence of these alterations was obviously increased in the advanced clinical stages. Another finding showed that loss of 8p and gain of 8q and 20q are associated with tumor size. The recurrent gain and loss of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes respectively involved in HCC development and progression.

Adult↗
PubMed2000

Toxicity associated with repeated administration of first-generation adenovirus vectors does not occur with a helper-dependent vector.

BACKGROUND: Certain gene therapy protocols may require multiple administrations of vectors to achieve therapeutic benefit to the patient. This may be especially relevant for vectors such as adenoviral vectors that do not integrate into the host chromosome. Because immunocompetent animal models used for gene transfer studies develop neutralizing antibodies to adenoviral vectors after a single administration, little is known about how repeat administrations of vectors might affect transgene expression and vector toxicity. MATERIALS AND METHODS: We used mice deficient in the membrane spanning region of immunoglobulin (IgM), which do not develop antibodies, to evaluate the effect of repeated intravenous administration of first-generation and helper-dependent adenoviral vectors expressing human alpha 1-antitrypsin (hAAT). The duration and levels of transgene expression were evaluated after repeated administration of vectors. Toxicity was assessed by measuring the level of liver enzymes in the serum and the degrees of hepatocyte hypertrophy and proliferation. RESULTS: We found that previous administration of first-generation adenoviral vectors can alter the response to subsequent doses. These alterations included an increase in transgene expression early (within 1 and 3 days), followed by a rapid drop in expression by day 7. In addition, previous administrations of first-generation vectors led to an increase in toxicity of subsequent doses, as indicated by a rise in liver enzymes and an increase in hepatocyte proliferation. In contrast to first-generation vectors, use of the helper-dependent adenovirus vector, Ad-STK109, which contained no viral coding regions, did not lead to increased toxicity after multiple administrations. CONCLUSIONS: We conclude that the response of the host to adenoviral vectors can be altered after repeated administration, compared with the response after the initial vector dose. In addition, these experiments provide further evidence for the relative safety of helper-dependent adenoviral vectors for gene therapy, compared with first-generation vectors.

Adenoviridae↗
PubMed2000

A clinical investigation on tong xin luo capsule in treatment of coronary heart disease with silent myocardial ischemia.

36 cases of coronary heart disease with silent myocardial ischemia (SMI) were treated sequentially with Tong Xin Luo (TXL) capsule and isosorbide dinitrate in random order. The results showed that both drugs were effective in decreasing episodes of SMI and shortening the duration of asymptomatic myocardial ischemia. TXL, however, was found with a better action and was superior to isosorbide dinitrate. It was also found that TXL could improve diastolic function of the left ventricle as well.

Adult↗
PubMed2000

[Scedosporiosis of the brain with fatal outcome after traumatizatio of the foot. case report].

A 33 year old German man suffered from a wound of his foot after an accident. He developed an osteomyelitis. From wound probes Scedosporium apiospermum could be isolated for several times. Some weeks later a cerebral lesion could be diagnosed. The lesion was extirpated and again S. apiospermum could be cultured from the cerebral probes. A few weeks later the patient died and some new cerebral lesions could be diagnosed by CT-scan.

Adult↗
PubMed2000

[Morphological variation of spermatogenic cell nucleus in Macrobrachium nipponense(de Haan) and its status during reproductive evolution of Caridea].

The morphological variation of nucleus during spermatogenesis in Macrobrachium nipponense and its status during the reproductive evolution of Caridean shrimp were investigated using transmission electron microscopy(TEM) technique. During the whole process of spermatogenesis, the nuclear morphology of spermatogenic cell varied from spherical or ellipsoidal to shallow-dish-like shape, and the nuclear membrane existed only in the rear part of mature sperm varied from intact to unintegrated one. The chromatin gradually varied from loosen to coacervative one, and then, developed differentially into two types of nucleus in the mature sperm, i.e., vesicular nucleus and filamental nucleus, which became an important characteristics of Macrobrachium nipponense. These nuclear morphological variations could be regarded as an important classifying property among Decapoda, on which, studies could contribute much to the analysis of the status of this species in the reproductive evolution of Caridean shrimp.

Animals↗
PubMed2000

[Physioecological characteristics of four dominant plant species in Kerqin sandy land].

The photosynthetic and water physioecological characteristics of four dominant species, Caragana microphylla, Artemisia halodendron, Artemisia frigida and Populus spp(a hybrid), in Kerqin sandy land were compared. The photosynthesis rates of C. microphylla, A. halodendron, and Populus spp. reached highest at 6:00, rapidly fall at 8:00, remained at low level from 8:00 to 16:00, then rose slowly after 16:00. The photosynthesis rate of A. frigida was comparatively low at 6:00, so the range of declining speed was small. Diurnal photosynthesis rate of Artemisia frigida decreased at 6:00-8:00, C. microphylla at 8:00-10:00, Populus spp and. A. halodendron at 6:00-10:00, and was controlled by stomatal limitation; in rest time, it was controlled by non-stomatal limitation. The four species also adapted different ways to resist drought stress. C. microphylla and A. frigida resisted drought stress through their low transpiration, low water potential and high ratio of bound water to free water(BW/FW); Populus spp. resisted drought stress through its rapid fall of stomatal conductivity to reduce its transpiration in spite of its high water potential and high BW/FW, while A. halodendron resisted drought stress weakly because of its high transpiration, high water consumption and low water use efficiency.

Artemisia↗