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Biomedical subjects

D Zhou

Publications and source records attributed to D Zhou.

At least 91 records · Page 5Linked to original sources
PubMed2000

Leptin and metabolic control of reproduction.

Leptin treatment prevents the effects of fasting on reproductive processes in a variety of species. The mechanisms that underlie these effects have not been elucidated. Progress in this area of research might be facilitated by viewing reproductive processes in relation to mechanisms that maintain fuel homeostasis. Reproduction, food intake, and fuel partitioning can be viewed as homeostatic responses controlled by a sensory system that monitors metabolic signals. These signals are generated by changes in intracellular metabolic fuel availability and oxidation rather than by changes in the amount of body fat or by changes in any aspect of body composition. Leptin might be viewed as either a mediator or as a modulator of the intracellular metabolic signal. Consistent with its purported action as a mediator of the metabolic signal, leptin synthesis and secretion are influenced acutely by changes in metabolic fuel availability, and these changes might lead to changes in reproductive function. The effects of leptin treatment on reproduction are blocked by treatments that inhibit intracellular fuel oxidation. Metabolic signals that inhibit reproduction in leptin-treated animals might act via neural pathways that are independent of leptin's action. Alternatively, both leptin and metabolic inhibitors might interact at the level of intracellular fuel oxidation. In keeping with the possibility that leptin modulates the metabolic signal, leptin treatment increases fuel availability, uptake, and oxidation in particular tissues. Leptin might affect reproduction indirectly by altering fuel oxidation or other peripheral processes such as gastric emptying. Reproductive processes are among the most energetically expensive in the female repertoire. Because leptin increases energy expenditure while simultaneously inhibiting energy intake, it may have limited use as a long-term treatment for infertility.

Adipose Tissue↗
PubMed2000

Changes of nitric oxide and its relationship with clinical features, intracranial pressure and outcome in acute head injury.

To investigate the content and dynamics of nitric oxide (NO) in the cerebrospinal fluid (CSF) of patients with acute head injury and to clarify the relationship of NO with clinical features and intracranial pressure (ICP) as well as outcomes, 38 adults with acute head injury were studied. Glasgow Coma Scale (GCS) obtained at admission and Glasgow Outcome Scale (GOS) 3 months after injury was assessed. ICP was surveyed via intraventricular catheter and lumbar puncture and CSF samples were obtained simultaneously. NO was determined with Griess reagents. Results showed that NO peak content in the head injury group was significantly higher than that of the control group. During dynamic research, no peak content of mildly injured cases and severely injured ones appeared in different time windows respectively. The peak value of NO was distinctly higher in the severe group than in the mild group. NO peak value of the raised ICP group was remarkably higher than that of the normal ICP group. The peak value of NO was considerately higher in the poor outcome group than in the good outcome group. When the content of NO was over 6.5 mumol/L, the rate of poor outcome was increased. There existed a correlation between NO and GCS, ICP and GOS. It is concluded that the content of NO was increased in patients with acute head injury and the changes of NO had different time windows in severely injured patients and mildly injured ones. The more sever the injury, the higher the NO content; and the more serious the secondary brain injury and brain edema, the worse the outcomes. When NO is combined with GCS, GOS and ICP, it increases the accuracy of judgement to the degree of head injury and outcome.

Adolescent↗
PubMed2000

Cytochrome P-450 2C9 sensitizes human prostate tumor cells to cyclophosphamide via a bystander effect.

The goal of the present study was to examine the ability of cytochrome P450-2C9 (CYP2C9) to activate cyclophosphamide (CPA) and elicit tumor cell death. A CYP2C9-deficient human lymphoblastoid cell line (AHH-1 cells) and a derivative cell line (H2C9 cells) stably transfected with a cDNA encoding CYP2C9 were used. The catalytic activity present in cell lines was examined by measuring the conversion of diclofenac, a CYP2C9-specific substrate, to its 4'-hydroxy metabolite by high-pressure liquid chromatography. Initial rate plots were constructed and the maximal rate of formation (V(max)) and the Michaelis-Menten constant (K(m)) for diclofenac metabolism were determined. Cytotoxicity was studied by exposing the cells to 0.01 to 4 mM CPA in the presence or absence of sulfaphenazole, a CYP2C9-specific inhibitor. Cell survival was quantitated by determination of the level of tritiated thymidine incorporation. H2C9 cells quickly metabolized diclofenac, indicating the presence of high levels of CYP2C9. Kinetic experiments demonstrated a V(max) and K(m) of 0.62+/-0.012 pmol/min/10(6) cells and 6.16+/-0.62 microM, respectively, for diclofenac metabolism. Diclofenac 4'-hydroxylase activity was undetectable in AHH-1 cells. H2C9 cells were more sensitive to the cytotoxic effects of CPA (50% inhibitory concentration [IC(50)], 0.80+/-0.03 mM) than AHH-1 cells (IC(50), 4.07+/-0.35 mM). The cytotoxicity (IC(50), 1.99+/-0.14 mM) of CPA to H2C9 cells was blocked by sulfaphenazole, demonstrating that the chemosensitivity of these cells is a consequence of intracellular prodrug activation. H2C9 cells mediated a bystander killing effect for CYP2C9-negative PPC-1 cells, reducing the IC(50) of CPA from about 14 to 3.62+/-0.73 mM in PPC-1 cells when they were cocultured with H2C9 cells. These results suggest that the enzyme-prodrug system of CYP2C9 and CPA may be an effective combination for gene-directed enzyme prodrug therapy. Ongoing studies are examining the utility of this system for use in prostate cancer cells.

Antineoplastic Agents, Alkylating↗
PubMed2000

Prolonged dominance of clonally restricted CD4(+) T cells in macaques infected with simian immunodeficiency viruses.

The repertoire of functional CD4(+) T lymphocytes in human immunodeficiency virus type 1-infected individuals remains poorly understood. To explore this issue, we have examined the clonality of CD4(+) T cells in simian immunodeficiency virus (SIV)-infected macaques by assessing T-cell receptor complementarity-determining region 3 (CDR3) profiles and sequences. A dominance of CD4(+) T cells expressing particular CDR3 sequences was identified within certain Vbeta-expressing peripheral blood lymphocyte subpopulations in the infected monkeys. Studies were then done to explore whether these dominant CD4(+) T cells represented expanded antigen-specific cell subpopulations or residual cells remaining in the course of virus-induced CD4(+) T-cell depletion. Sequence analysis revealed that these selected CDR3-bearing CD4(+) T-cell clones emerged soon after infection and dominated the CD4(+) T-cell repertoire for up to 14 months. Moreover, inoculation of chronically infected macaques with autologous SIV-infected cell lines to transiently increase plasma viral loads in the monkeys resulted in the dominance of these selected CDR3-bearing CD4(+) T cells. Both the temporal association of the detection of these clonal cell populations with infection and the dominance of these cell populations following superinfection with SIV suggest that these cells may be SIV specific. Finally, the inoculation of staphylococcal enterotoxin B superantigen into SIV-infected macaques uncovered a polyclonal background underlying the few dominant CDR3-bearing CD4(+) T cells, demonstrating that expandable polyclonal CD4(+) T-cell subpopulations persist in these animals. These results support the notions that a chronic AIDS virus infection can induce clonal expansion, in addition to depletion of CD4(+) T cells, and that some of these clones may be SIV specific.

Animals↗
PubMed2000

Rotating Gamma System radiosurgery for cerebral arteriovenous malformations.

One hundred and thirty-two patients with cerebral arteriovenous malformations (AVMs) were treated using the Rotating Gamma System, a new radiosurgical system between November 1996 and May 2000. The average size of the AVMs was 23 mm in diameter (range 6 to 69 mm). The mean dose delivered to the AVM margin was 19.2 Gy (range 13 to 25 Gy), and that delivered to the center of the AVMs was 37.6 Gy (range 32.5 to 50 Gy). One hundred and six patients were followed up for an average of 18.4 months (range 5 to 44 months). Five patients (4.7%) experienced rebleeding which took place between 5 and 13 months after treatment, but none of them died from hemorrhage. No bleeding took place after complete angiographic obliteration. Neuroimaging studies showed radiation-induced edema in 19 (22%) of the 87 patients, none of whom had severe permanent neurological deficits. Of the 68 patients followed up for more than one year, 57 underwent angiography at 1 year after treatment. The complete obliteration was demonstrated in 24 patients (42%) at 1 year. Of the 27 patients followed for more than 2 years, 23 patients underwent angiography 2 years after treatment, and complete obliteration was demonstrated in 18 patients (78%). These results are comparable to the results of treatment with other radiosurgical systems.

Adolescent↗
PubMed2000

Airway hyperresponsiveness to cigarette smoke in ovalbumin-sensitized guinea pigs.

This study was carried out to determine if the bronchoconstrictive effect of cigarette smoke (CS) is enhanced when airway hyperresponsiveness is induced by ovalbumin (Ova) sensitization, and if so, whether an increase in endogenously released tachykinins is involved. The bronchoconstrictive effects of an acute CS inhalation challenge (15 ml; 50% concentration) were compared between guinea pigs sensitized with aerosolized Ova and matching control animals (receiving saline aerosol). In Ova-sensitized animals, there were marked increases in the numbers of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by an elevated bronchomotor response to acetylcholine (ACh). The baseline lung resistance (RL) and dynamic pulmonary compliance (Cdyn) were not significantly different between the two groups; however, the same CS inhalation challenge evoked a significantly more intense bronchoconstriction in the Ova-sensitized group (control group: DeltaRL = 68 +/- 8%, DeltaCdyn = -26 +/- 6%; Ova group: DeltaRL = 425 +/- 76%; DeltaCdyn = -47 +/- 8%). The levels of substance P-like immunoreactivity (SP-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) measured in the bronchoalveolar lavage (BAL) collected after CS inhalation challenge were also significantly greater in Ova-sensitized animals than in control animals. Furthermore, pretreatment with SR-48968, a selective antagonist of neurokinin-2 (NK(2)) receptor, inhibited more than 85% of the enhanced bronchomotor responses to CS challenge, but did not significantly reduce the airway hyperresponsiveness to ACh in Ova-sensitized guinea pigs. These results show that Ova sensitization induces airway hyperresponsiveness to inhaled CS, and that the endogenous tachykinins evoked by CS-induced activation of lung C fibers play a primary role in this augmented response.

Acetylcholine↗
PubMed2000

PNRC: a proline-rich nuclear receptor coregulatory protein that modulates transcriptional activation of multiple nuclear receptors including orphan receptors SF1 (steroidogenic factor 1) and ERRalpha1 (estrogen related receptor alpha-1).

PNRC (proline-rich nuclear receptor coregulatory protein) was identified using bovine SF1 (steroidogenic factor 1) as the bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. PNRC is unique in that it has a molecular mass of 35 kDa, significantly smaller than most of the coregulatory proteins reported so far, and it is proline-rich. PNRC's nuclear localization was demonstrated by immunofluorescence and Western blot analyses. In the yeast two-hybrid assays, PNRC interacted with the orphan receptors SF1 and ERRalpha1 in a ligand-independent manner. PNRC was also found to interact with the ligand-binding domains of all the nuclear receptors tested including estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), thyroid hormone receptor (TR), retinoic acid receptor (RAR), and retinoid X receptor (RXR) in a ligand-dependent manner. Functional AF2 domain is required for nuclear receptors to bind to PNRC. Furthermore, in vitro glutathione-S-transferase pull-down assay was performed to demonstrate a direct contact between PNRC and nuclear receptors such as SF1. Coimmunoprecipitation experiment using Hela cells that express PNRC and ER was performed to confirm the interaction of PNRC and nuclear receptors in vivo in a ligand-dependent manner. PNRC was found to function as a coactivator to enhance the transcriptional activation mediated by SF1, ERR1 (estrogen related receptor alpha-1), PR, and TR. By examining a series of deletion mutants of PNRC using the yeast two-hybrid assay, a 23-amino acid (aa) sequence in the carboxy-terminal region, aa 278-300, was shown to be critical and sufficient for the interaction with nuclear receptors. This region is proline rich and contains a SH3-binding motif, S-D-P-P-S-P-S. Results from the mutagenesis study demonstrated that the two conserved proline (P) residues in this motif are crucial for PNRC to interact with the nuclear receptors. The exact 23-amino acid sequence was also found in another protein isolated from the same yeast two-hybrid screening study. These two proteins belong to a new family of nuclear receptor coregulatory proteins.

Amino Acid Motifs↗
PubMed2000

Neuroprotective role for the p50 subunit of NF-kappaB in an experimental model of Huntington's disease.

Prototypical NF-kappaB consists of a transcription factor dimer of p50 and p65, and an inhibitory subunit called I-kappaB. NF-kappaB is activated in neurons in response to excitotoxic, metabolic, and oxidative stress. Cell-culture data suggest that activation of NF-kappaB can prevent neuronal apoptosis, but its role in vivo is unclear and the specific kappaB subunits involved are unknown. In Huntington's disease (HD), striatal neurons degenerate, and a similar pattern of neuronal vulnerability occurs in rats and mice following exposure to the mitochondrial toxin 3-nitropropionic acid (3NP). We report that mice lacking the p50 subunit of NF-kappaB exhibit increased damage to striatal neurons following administration of 3NP. The neuronal death occurs by apoptosis as indicated by increased caspase activation and DNA fragmentation into oligonucleosomes. NF-kappaB activity is markedly increased in striatum 24-72 h following 3NP administration in wild-type mice, but not in mice lacking p50, indicating that p50 is necessary for the vast majority of 3NP-induced NF-kappaB DNA-binding activity in striatum. Cultured striatal neurons from p50-/- mice exhibited enhanced oxidative stress, perturbed calcium regulation, and increased cell death following exposure to 3NP, suggesting a direct adverse effect of p50 deficiency in striatal neurons.

Animals↗
PubMed2000

Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis.

Stroke is a major cause of long-term disability, the severity of which is directly related to the numbers of neurons that succumb to the ischemic insult. The signaling cascades activated by cerebral ischemia that may either promote or protect against neuronal death are not well understood. One injury-responsive signaling pathway that has recently been characterized in studies of non-neural cells involves cleavage of membrane sphingomyelin by acidic and/or neutral sphingomyelinase (ASMase) resulting in generation of the second messenger ceramide. We now report that transient focal cerebral ischemia induces large increases in ASMase activity, ceramide levels, and production of inflammatory cytokines in wild-type mice, but not in mice lacking ASMase. The extent of brain tissue damage is decreased and behavioral outcome improved in mice lacking ASMase. Neurons lacking ASMase exhibit decreased vulnerability to excitotoxicity and hypoxia, which is associated with decreased levels of intracellular calcium and oxyradicals. Treatment of mice with a drug that inhibits ASMase activity and ceramide production reduces ischemic neuronal injury and improves behavioral outcome, suggesting that drugs that inhibit this signaling pathway may prove beneficial in stroke patients.

Animals↗
PubMed2000

Geodesics without conjugate points and curvatures at infinity.

We study the asymptotic behavior of curvature and prove that the integral of curvature along a geodesic without conjugate points is nonpositive and some generalizations of Myers theorem and Cohn-Vossen's theorem. Some applications are also given.

Journal Article↗
PubMed2000

[Study on the p53 gene mutation and microsatellite instability of gastric carcinoma].

OBJECTIVE: To observe the relationship between p53 gene mutation and microsatellite instability (MSI) of the preoperative staging of gastric carcinoma by endoscopic ultrasonography(EUS). METHODS: A total of 73 cases of gastric carcinoma were taken for the preoperative staging with EUS. Silver staining PCR-SSCP method was used to detect mutations in exons 5, 6, 7, 8 of p53 gene and MSI at 4 loci on chromosomes 2, 5, 17 in the 73 paraffin-embedded biopsy specimens, and the relationship between them was studied further. RESULTS: The overall mutated rate of p53 gene was 54.8%, with 6.8%, 15.1%, 19.2% and 13.7% in exons 5 to 8, respectively. Analysis of the relation of the mutation with the preoperative staging by EUS showed that it was significantly higher in T3(64.3%) and T4(67.9%) than in T1(0) or T2(25.0%)(P<0.05), and it was 67.6% in cases with lymph node metastasis, which was significantly higher than that without metastasis (41.7%)(P<0.05). The overall detective rate of MSI was 37.0%. The detective rate of MSI had no relation with the depth of invasion, which was 40.0%, 33.3%, 39.3% and 34.5% at T1 to T4 stages (P<0.05), respectively, but it was significantly higher in cases with lymph node metastasis(51.4%) than those without metastasis(22.2%)(P<0.05). Although the detective rate of MSI showed an increasing trend in the mutated cases of p53 gene as compared with the no mutation cases, there was no relationship between MSI and p53 gene mutation (P<0.05). CONCLUSION: These results suggest that the gene mutation of p53 and MSI may represent the different mechanisms of carcinogenesis. They can reflect the cytobiologic malignant behavior of gastric carcinoma in varying degrees, which may be of reference significance in analysing the prognosis of the patients in clinics.

Adult↗
PubMed2000

1376G-->T mutation of G6PD gene in Han and Li nationalities in Hainan, China.

OBJECTIVE: To investigate the 1376G-->T mutation of G6PD gene in the cases of G6PD deficiency in the Han nationality and the Li nationality of Hainan, China. METHODS: DNAs were extracted from the white blood cells of G6PD deficient cases by salt-out method. Allelic specific polymerase chain reaction was used to detect the 1376G-->T mutation. RESULTS: Fifty-nine Han nationality cases and 32 Li nationality cases were analysed; the 1376G-->T mutation was found in 19 Han cases(32.2%) and 18 Li cases(56.2%). CONCLUSION: 1376G-->T is a common mutation which causes G6PD deficiency in the Han nationality and the Li nationality in Hainan, China. Based on the phylogenetic tree of populations in China, these results indicate that the mutation might occur prior to the divergence of the Han and Li nationalities. It is of significance to study the mutations of G6PD gene in different nationalities in China for elucidating the origin, migration and evolution of the nationalities.

Biological Evolution↗
PubMed2000

[Response of broadleaved Pinus koraiensis forests in Xiaoxinganling Mt. to global climate change--a dynamic modeling].

In this paper, the Forest Gap Model and four General Circulation Models (GCMs) were employed to investigate the dynamic response of broadleaved Pinus koraiensis forests in Xiaoxinganling Mountains of China to global climate change. Under CO2 doubling which was simulated by the scenarios of Oregon State University and Goddard Institute for Space Studies, the biomass of broadleaved Pinus koraiensis forest increased and the current Picea-Abies-broadleaved Pinus koraiensis forest would gradually develop to Betula costata-Tilia amurensis-Ulmus laciniata-broadleaved Pinus koraiensis forest. Under the scenarios of Geophysical Fluid Dynamics Laboratory at Princeton University and United Kingdom Meteorological Office, Pinus koraiensis and other coniferous species would be replaced by broadleaved species such as Quercus mongolica, Tilia amurensis and Ulmus laciniata, and the broadleaved Pinus koraiensis forest would change to broadleaved forest, due to the great range increasing temperature by the scenarios. The future warming rate would determine the succession of broadleaved Pinus koraiensis forest.

China↗
PubMed2000

[Some geographical features of the location and gene mutation of cancers occurring in Nantong City, China].

OBJECTIVE: To detect the location and geographical features of gene mutation of the cancer based on 30,709 clinical tumor biopsies. METHODS: Thirty thousand seven hundred and nine cases of tumor biopsy materials were collected from the Department of Pathology of Nantong Cancer Hospital between June 1974 and December 1987. The address of the village and county of patients was collected and statistical analysis was performed on data from lab examination. DNA sequencing of 31 cases of hepatocellular carcinoma (HCC) was performed at the Department of Pathology of the Medical College of Tokyo University, Japan. RESULTS: The data suggested that different carcinomas occurred predominantly in some districts and the frequency and type of mutation of the P53 gene in the HCC were different in different districts. CONCLUSION: It seems that based on the clinical biopsy materials, carcinomas of the uterus cervix (CC) and nasopharynx tend to occur in some districts of Nantong City and the frequency and type of mutation of the gene P53 of the HCC were different in different districts. The reason for this is not understood and further study will be done.

China↗
PubMed2000

[A preliminary study of viral cross-transmission in dentistry].

OBJECTIVE: To research the viral cross-transmission of a DNA virus (HBV) and a RNA virus (HCV) in dentistry. METHODS: Five plans were designed to sterilize the oral instruments that had been infected with HBV or HCV positive serum. HBsAg, HBV-DNA, anti-HCV, HCV-RNA were detected before and after sterilization. RESULTS: All methods could effectively clean the specific proteins (HBsAg/anti-HCV) and nucleic acids (HBV-DNA/HCV-RNA) of the infected virus. CONCLUSION: The instruments which have been sterilized should not be the main way of the cross-transmission of virus in dentistry.

Antigens, Viral↗
PubMed2000

[Clinical analysis of 13 infected total knee replacements].

OBJECTIVE: To investigate the cause, treatment and its result of infected total knee replacements (TKRs). METHODS: Between 1987 and 1999, 13 infected TKRs in 13 patients were treated with surgical debridement and one-stage or two-stage reimplantation. The preoperative average ROM of knees was 55 degrees and the average Hospital for Special Surgery (HSS) knee score was 36.5 points. Clinical results were evaluated after average follow-up for 3 years and 5 months. We analyzed the factors for TKR infection. RESULTS: No recurrent infection was noted, and pain was significantly alleviated in all patients. The average ROM of knees was 85 degrees and the average HSS knee score was 73.5 points. CONCLUSIONS: The high risk factors for TKR infection are rheumatoid arthritis, steroid administration, associated diabetes mellitus, hinged prosthesis and previous knee surgery. Early surgical debridement with intravenous antibiotics is necessary as soon as deep infection is detected. Two-stage reimplantation is more effective in eradicating deep infection than single debridement or one-stage reimplantation.

Adult↗