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Biomedical subjects

Z Ma

Publications and source records attributed to Z Ma.

At least 199 records · Page 11Linked to original sources
PubMed1997

[Therapy for intracranial lesions by gamma knife].

The authors summarized 281 patients with intracranial lesions treated by gamma knife (GK) during Sept. 1995-Sept. 1996. The patients included 170 males and 111 females with age ranging from 5 to 85 years (average of 49.9 years). Seventy-seven patients received a follow-up 3.3-12.5 months. The average of Karnofsky Performance Status was 70.8 in pre-operation and 83.9 in post-operation; the average of tumor volume was 17.1 cm3 in pre-operation and 13.6 cm3 in post-operation; the average of lesion diameter was 2.8 cm and 2.4 cm in pre- and post-operation. respectively. GK radiosurgery has achieved the goal to improve the quality of life and to prolong the life of those patients with malignant intracranial tumors.

Adolescent↗
PubMed1996

Structural requirements of taxoids for nitric oxide and tumor necrosis factor production by murine macrophages.

Taxol (paclitaxel), a microtubule stabilizer with antitumor activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages (M phi). In the present study, a variety of synthetic analogs of paclitaxel were examined for their potencies to induce nitric oxide (NO) and tumor necrosis factor (TNF) production by peritoneal M phi from LPS-responsive C3H/HeN, and LPS-hyporesponsive C3H/HeJ mice, and by M phi-like LPS-responsive J774.1 and its mutant LPS-hyporesponsive J7.DEF3 cells. In this structure-activity relationship study, we found that (i) the benzoyl group at the C-3' position of paclitaxel is the most important site to activate C3H/HeN M phi; (ii) the phenyl group at C-3' is not a requisite for the activity; (iii) there is good correlation between NO and TNF production by the M phi in response to compounds, except for the analogs having a tert-butoxycarbonyl (10-acetyldocetaxel) or a thiophene-2-carbonyl group at C-3'-N instead of a benzoyl group, which is more dominant in TNF than in NO production; (iv) the compounds tested induce neither NO nor TNF production by C3H/HeJ M phi; (v) active compounds to C3H/He M phi induce TNF production by J7.DEF3 cells as well as J774.1 cells; and (vi) there is no correlation between the NO/TNF inducibility to C3H/HeN M phi and growth inhibitory activity against M phi-like J774.1 and J7.DEF3 cells. These data also suggest that the binding of taxoid/LPS to tubulin is not essential for the M phi activation.

Animals↗
PubMed1996

Characterization of expression of phosphofructokinase isoforms in isolated rat pancreatic islets and purified beta cells and cloning and expression of the rat phosphofructokinase-A isoform.

Phosphofructokinase (PFK) plays a key role in regulating glycolytic flux, and the mammalian enzyme is a tetramer. Three monomeric isoforms are encoded by separate genes, are differentially expressed in specific tissues, and are designated by tissues in which they are most abundant (A, muscle; B, liver; and C, brain). Glucose-induced insulin secretion from pancreatic islets requires glucose transport into islet beta-cells and glycolytic metabolism. Little is known about islet PFK isozymes, but the possibility that PFK-A is expressed in beta-cells is of interest because that isoform is thought to govern glycolytic oscillations and to interact with a metabolically activated beta-cell phospholipase A2 enzyme. Using as probe a PCR product generated from rat islet RNA with primers designed from the human PFK-A sequence, we have cloned a full-length PFK-A cDNA from a rat islet cDNA library. The rat PFK-A deduced amino-acid sequence is 96% identical to that of human PFK-A, and all residues thought to participate in substrate or allosteric effector binding are conserved between the two sequences. The rat PFK-A amino-acid sequence is 69% and 68% identical to those for rat PFK-B and rat PFK-C, respectively, and differences in residues involved in binding of allosteric effectors were observed among the three isoforms. Rat PFK-A expressed as a glutathione-S-transferase fusion protein was recognized by antibodies raised against a peptide in the PFK-A sequence. Expression of PFK isoform mRNA species was examined by RT-PCR in rat islets, in purified populations of beta-cells prepared by fluorescence-activated cell sorting (FACS), and in RIN-m5F insulinoma cells, all of which expressed mRNA species for PFK-A, -B, and -C isoforms. PFK-A mRNA was expressed at much lower levels in an islet alpha-cell-enriched population. Interleukin-1 impairs islet glucose metabolism and insulin secretion and was found to induce a specific decline in islet expression of PFK-A mRNA. These findings establish the sequence of rat PFK-A, demonstrate that it is expressed in FACS-purified islet beta-cells, and suggest that its expression is regulated by a cytokine which influences insulin secretion.

Amino Acid Sequence↗
PubMed1996

Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Animals↗
PubMed1996

Evidence for association of an ATP-stimulatable Ca(2+)-independent phospholipase A2 from pancreatic islets and HIT insulinoma cells with a phosphofructokinase-like protein.

Glucose-induced insulin secretion from pancreatic islets requires metabolism of glucose within islet beta-cells, and ATP has attracted interest as a messenger of glucose metabolism within beta-cells. Glucose-induced insulin secretion from islets and HIT insulinoma cells is accompanied by activation of an ATP-stimulatable Ca(2+)-independent phospholipase A2 (ASCI-PLA2) enzyme, the catalytic activity of which resides in a 40 kDa protein. An analogous PLA2 enzyme in myocardium was recently found to consist of a complex of a 40 kDa catalytic protein with a tetramer of an isoform of the glycolytic enzyme phosphofructokinase (PFK). Association of the PFK isoform with the myocardial PLA2 catalytic protein was found to confer ATP sensitivity onto the enzyme complex. Here we demonstrate that the majority of HIT cell and islet ASCI-PLA2 catalytic activity elutes from a gel filtration column in a region corresponding to 400 kDa, suggesting that the 40 kDa beta-cell ASCI-PLA2 catalytic protein exists as part of a larger molecular mass complex. Islet and HIT cell ASCI-PLA2 activities were immunoprecipitated by antibodies directed against PFK, and the immunoprecipitates contained 40 and 85 kDa proteins which correspond to the molecular masses of the PLA2 catalytic protein and of a PFK monomer, respectively. Islet and HIT cell ASCI-PLA2 activities were selectively and reversibly adsorbed to affinity matrices containing immobilized PFK but not to similar matrices containing immobilized transferrin or bovine serum albumin. Addition of free PFK prevented binding of HIT cell ASCI-PLA2 activity to immobilized PFK matrices and promoted desorption of activity previously bound to such matrices. These results suggest that beta-cell ASCI-PLA2, like the myocardial enzyme, exists as a complex comprised of a catalytic protein and a PFK-like protein and raise the possibility that the ASCI-PLA2 complex may represent a component of the beta-cell glucose sensor, which links glycolysis, phospholipid hydrolysis, and membrane electrochemical events involved in glucose-induced insulin secretion.

Animals↗
PubMed1996

Signal transduction pathways induced by heregulin in MDA-MB-453 breast cancer cells.

Heregulins (HRGs) induce tyrosine phosphorylation of several members of the erb-B family of receptors. Although originally isolated as the ligands for p185c-erb-2, recent evidence suggests that other receptors of the erbB family, including p180erbB-3 and p180erbB-4, are their true cognate receptors. Stimulation of MDA MB-453 cells with HRG beta 2 resulted in the tyrosine phosphorylation of p185c-erbB-2 and p180erbB-4 in a time- and dose-dependent fashion. This event was accompanied by the formation of multimeric complexes between the activated receptors and SH2-containing proteins. Ligand caused p120-rasGTPase activating protein (GAP), SHC and the p85 subunit of phosphatidylinositol-3'-kinase (PI3K) to be associated with both p185c-erbB-2 and p180erbB-4. In addition, tyrosine phosphorylation of p85-PI3K and SHC, but not of GAP or of its associated p62 and p190 proteins, was also detected. HRG also induced the association of GRB2 with tyrosine phosphorylated p185c-erbB-2, p180erbB-4 and SHC. Activation of mitogen-activated protein kinase (MAPK) ( > 30-fold over untreated controls) was observed upon receptor(s) activation, as it was the induction of the immediate early gene c-fos ( > 200-fold). These observations suggest that p21ras activation plays a role in the HRG pathway. Furthermore, comparative analysis of the binding of p85-PI3K to 185c-erbB-2 and p180erbB-4, revealed a preferential association with activated p180erbB-4. These findings might suggest a model of HRG action in which the relative expression of the various erb-B family members and the partitioning of signal transduction molecules between each type of receptor might determine the nature of the signal elicited by the ligand and the biological response attained.

1-Phosphatidylinositol 4-Kinase↗
PubMed1996

Characterization of the sphingomyelin content of isolated pancreatic islets. Evaluation of the role of sphingomyelin hydrolysis in the action of interleukin-1 to induce islet overproduction of nitric oxide.

Inflammatory cytokines may participate in the destruction of pancreatic islets during the pathogenesis of insulin-dependent diabetes mellitus, and the cytokine interleukin-1 (IL-1) strongly inhibits insulin secretion from rat pancreatic islets by a process which involves induction of expression of the inducible isoform of nitric oxide synthase and the overproduction of nitric oxide. The signaling events between IL-1 receptor occupancy and induction of nitric oxide synthase in rat islets involve activation of the transcriptional activator NFkappa B. Because sphingomyelin hydrolysis has been implicated as a signaling process both in NFkappa B activation and in IL-1 action in some cells, we have examined the potential involvement of sphingomyelin hydrolysis in the induction of islet nitric oxide overproduction by IL-1. Rat islet sphingomyelin pools were radiolabeled with [3H]choline, and sphingomyelin was then isolated by normal phase HPLC. Electrospray ionization-mass spectrometric analysis revealed islet sphingomyelin consists of at least 4 distinct molecular species, and the most abundant of them contained sphingosine as the long chain base and a residue of palmitic acid as the fatty acid substituent. Molecular species containing residues of stearic acid and arachidic acid were also observed. Neither interleukin-1 nor tumor necrosis factor-alpha was found to induce hydrolysis of islet sphingomyelin species, and neither an exogenous, cell-permeant ceramide species (N-acetyl-D-sphingosine) nor exogenous sphingomyelinase mimicked or potentiated the effect of IL-1 to increase rat islet nitric oxide generation, as reflected by nitrite production. Similar findings were obtained with RINm5F insulinoma cells and with mouse pancreatic islets. These findings provide the first information on the molecular species of sphingomyelin in pancreatic islets and suggest that sphingomyelin hydrolysis is not involved in the signaling pathway whereby IL-1 induces the overproduction of nitric oxide by pancreatic islets.

Animals↗
PubMed1996

Continuing increase in incidence of germ-cell testis cancer in young adults: experience from Connecticut, USA, 1935-1992.

The current study is designed to examine long-term trends by histologic types of testis cancer in Connecticut. A regression model was used to identify age, period, or cohort as determinants of the time-trend on histologic types of testis cancer. The results from this descriptive epidemiologic study show that the overall age-adjusted incidence rate of testis cancer has increased 3.5-fold in Connecticut during the past nearly 60 years of cancer registration. The rates for seminoma and non-seminoma have been increasing since the mid-1950s and increase in a similar manner for those aged 15 to 49. The largest increase was observed in the age groups 20 to 44 for seminoma and 15 to 34 for non-seminoma. The observed increase was limited to whites. The results from age-period-cohort modeling suggest that the observed increase in seminoma before 1950s could be largely attributable to a period effect, while the increase for cohorts born after about 1910 both for seminoma and for non-seminoma are mainly explained by a strong birth-cohort effect. Therefore, the observed increase in germ-cell testis cancer in this population is likely to continue in the coming years. Thus far, the proposed hypotheses, such as exposure to DES in utero, earlier lifetime exposure to viruses, trauma or unusual amounts of heat to the testis, cannot adequately explain the observed incidence patterns of testis cancer. Analytical epidemiologic studies with large sample size are urgently needed to examine the risk factors responsible for the increase.

Adolescent↗
PubMed1996

Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product generation by increasing substrate availability through a nitric oxide-dependent mechanism.

Interleukin-1 (IL-1) impairs insulin secretion from pancreatic islets and may contribute to the pathogenesis of insulin-dependent diabetes mellitus. IL-1 increases islet expression of nitric oxide (NO) synthase, and the resultant overproduction of NO participates in inhibition of insulin secretion because NO synthase inhibitors, e.g. NG-monomethyl-arginine (NMMA), prevent this inhibition. While exploring effects of IL-1 on islet arachidonic acid metabolism, we found that IL-1 increases islet production of the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid 12-(HETE). This effect requires NO production and is prevented by NMMA. Exploration of the mechanism of this effect indicates that it involves increased availability of the substrate arachidonic acid rather than enhanced expression of 12-lipoxygenase. Evidence supporting this conclusion includes the facts that IL-1 does not increase islet 12-lipoxygenase protein or mRNA levels and does not enhance islet conversion of exogenous arachidonate to 12-HETE. Mass spectrometric stereochemical analyses nonetheless indicate that 12-HETE produced by IL-1-treated islets consists only of the S-enantiomer and thus arises from enzyme action. IL-1 does enhance release of nonesterified arachidonate from islets, as measured by isotope dilution mass spectrometry, and this effect is suppressed by NMMA and mimicked by the NO-releasing compound 3-morpholinosydnonimine. Although IL-1 increases neither islet phospholipase A2 (PLA2) activities nor mRNA levels for cytosolic or secretory PLA2, a suicide substrate which inhibits an islet Ca(2+)-independent PLA2 prevents enhancement of islet arachidonate release by IL-1. IL-1 also impairs esterification of [3H8]arachidonate into islet phospholipids, and this effect is prevented by NMMA and mimicked by the mitochondrial ATP-synthase inhibitor oligomycin. Experiments with exogenous substrates indicate that NMMA does not inhibit and that the NO-releasing compound does not activate islet 12-lipoxygenase or PLA2 activities. These results indicate that a novel action of NO is to increase levels of nonesterified arachidonic acid in islets.

Animals↗
PubMed1996

Vasoactive intestinal peptide in cirrhotic rats: hemodynamic effects and mesenteric arterial receptor characteristics.

Vasoactive intestinal peptide (VIP) blood levels in cirrhosis are elevated, but its hemodynamic and receptor characteristics remain unclarified. We aimed to quantify VIP receptor characteristics in mesenteric arteries, plasma VIP concentration by radioimmunoassay (RIA), and the hemodynamic effects of VIP infusion in bile duct-ligated (BDL) cirrhotic and sham-operated control rats. Mesenteric arterial membranes were prepared by ultracentrifugation, and receptor characteristics were studied using 125I-labeled VIP as a radioligand. For the hemodynamic study, there were four groups: cirrhotic and sham-operated rats were infused with either VIP (50 ng/kg/min for 15 minutes) or equivolumic isotonic saline. Regional blood flows were measured in conscious rats with radioactive microspheres. Receptor studies showed high- and low-affinity binding sites for VIP, which had similar equilibrium dissociation constants (binding affinities) and receptor densities for both the cirrhotic and control rats. Plasma VIP concentrations were significantly elevated in the cirrhotic rats. In both cirrhotic and sham-operated rats, VIP infusion produced plasma levels approximately twofold to threefold increased over the basal levels observed in cirrhotic rats. In cirrhotic rats, VIP infusion did not affect any hemodynamic parameter, whereas in the sham-operated rats VIP infusion significantly increased the mesenteric visceral blood flow. These results show that the hyporesponsiveness to VIP in cirrhotic rats is not attributable to receptor downregulation, implying postreceptor alterations. This suggests that VIP may not play a major role in the maintenance of splanchnic hyperemia in cirrhosis.

Analysis of Variance↗
PubMed1996

Cirrhotic cardiomyopathy: getting to the heart of the matter.

In cirrhosis, cardiac contractile function has been extensively documented to be abnormal. At baseline, cardiac output is increased, and this is one of the characteristics of hyperdynamic circulation. However, when cirrhotic patients are challenged by pharmacological or physiological stress, ventricular hyporesponsiveness is revealed. Similar patterns have been noted in cirrhotic animal models. This phenomenon has been termed "cirrhotic cardiomyopathy." Although alcohol abuse may contribute to some cases of cirrhotic cardiomyopathy, it has been clearly documented to occur even in the absence of alcohol ingestion. Diminished myocardial beta-adrenergic receptor signal transduction function, possibly caused by a persistent elevation in norepinephrine content, has been shown to play an important role. Alternation in cardiac plasma membrane properties due to impaired lipid metabolism is also crucial. Other possible pathogenic factors are reviewed, including accumulation of cardiodepressant substances caused by hepatocellular insufficiency, and ventricular overload secondary to increased blood volume and hyperdynamic circulation. Because the cardiac reserve function is borderline in patients with cirrhosis, cardiovascular status should be carefully monitored, especially when patients undergo stresses such as liver transplantation or portosystemic shunting procedures.

Blood Volume↗
PubMed1996

Automated system for detailed measurement of respiratory mechanics.

OBJECTIVE: The mechanical properties of the respiratory system (i.e., elastance and resistance) depend on the frequency, tidal volume, and shape of the flow waveform used for forcing. We developed a system to facilitate accurate measurements of elastance and resistance in laboratory and clinical settings at the frequencies and tidal volumes in the physiologic range of breathing. METHODS: A personal computer (PC) is used to drive a common clinically used ventilator while simultaneously collecting measurements of airway flow, airway pressure, and esophageal pressure from the experimental subject or animal at different frequencies and tidal volumes. Analysis analogous to discrete Fourier transform at the fundamental frequency (i.e., ventilator setting) is used to calculate elastances and resistances of the total respiratory system and its components, the lungs and the chest wall. We have shown that this analysis is independent of the high-frequency harmonics that are present in the waveform from clinical ventilators. RESULTS: The system has been used successfully to make measurements in anesthetized/paralyzed dogs and awake or anesthetized human volunteers in the laboratory, and in anesthetized human volunteers in the laboratory, and in anesthetized humans in the operating room and intensive care unit. Elastances and resistances obtained with this approach are the same as those obtained during more controlled conditions, e.g., sinusoidal forcing. CONCLUSIONS: Accurate, standardized measurements of lung and chest wall properties can be obtained in many settings with relative ease with the system described. These properties, and their frequency and tidal volume dependences in the physiologic range, provide important information to aid in the understanding of changes in respiratory function caused by day-to-day conditions, clinical intervention and pathologies.

Airway Resistance↗
PubMed1996

Role of altered beta-adrenoceptor signal transduction in the pathogenesis of cirrhotic cardiomyopathy in rats.

BACKGROUND & AIMS: Attenuated ventricular contractility has been documented in cirrhosis, but the pathogenesis remains unclear. The beta-adrenergic receptor system is critical in modulating cardiac contraction. Therefore, the aim of this study was to clarify beta-adrenoceptor signaling function in a rat model of cirrhosis. METHODS: Cirrhosis was induced by bile duct ligation, whereas controls underwent a sham operation. Myocardial contractility was studied by measuring isolated left ventricular papillary muscle contraction under isoproterenol stimulation. Beta-Adrenoceptor signaling was evaluated by measuring adenosine 3',5'-cyclic monophosphate generation after stimulation with isoproterenol, sodium fluoride, and forskolin. Guanosine triphosphate-binding protein expression from ventricular plasma membranes was determined by Western blots to measure G(s)alpha, Gi2alpha, and G(common)beta, respectively. RESULTS: Maximum papillary muscle contractile responses in control and cirrhotic rats were 113% +/- 3% and 70% +/- 2% of basal, respectively (P<0.01), with no significant differences in the dose-inducing half-maximal response. Adenosine 3', 5'-cyclic monophosphate generation after stimulation with all three agents was significantly lower in cirrhotic compared with control rat membranes. G(s)alpha and Gi2alpha expression was significantly reduced in cirrhotics compared with controls, but G(common)beta expression remained unchanged. CONCLUSIONS: These data showed cardiac contractile impairment in cirrhosis, associated with altered beta-adrenergic receptor signaling function and guanine nucleotide-binding protein expression. These factors may play an important role in the pathogenesis of cirrhotic cardiomyopathy.

Adrenergic beta-Agonists↗
PubMed1996

Spousal-residence separation among Chinese young couples.

The factors affecting the residential separation of spouses in China are examined. "Based on the microdata of the 1987 National Population Survey, we find that the variation in spousal-residence separations among Chinese young couples in the mid-1980s is well explained by personal and household factors within a multivariate model. The separations were aggravated by migrations for the reasons of employment or education. Although marriage migrations reduced the number of separations, those who had been married for a short period of time...were more prone to be separated. It is ironic that the higher a person's level of education, the greater the tendency for them to suffer the pain of spousal-residence separation. Household status could also be a very important factor: the lower the household status of a married individual, the more likely that he (or she) would be separated from their spouse."

Asia↗
PubMed1996

The continuing increase in adenocarcinoma of the uterine cervix: a birth cohort phenomenon.

BACKGROUND: Adenocarcinoma of the uterine cervix has been reported to be increasing among young white women and earlier studies suggest a birth cohort pattern for the observed increase. No study, however, has examined the time trends of adenocarcinoma of the cervix by birth cohort. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) data through 1990, the current study is designed to examine the time trends of invasive adenocarcinoma by birth cohort. An age-period-cohort model was fitted to the annual-age-specific rates to identify the components of birth cohort and time period as determinants of the observed time trends. RESULTS: The results from this study clearly show that invasive adenocarcinoma of the uterine cervix has been increasing in both whites and blacks, but the increase is statistically significant only among whites, reaching 4.2 percent per year for those born since 1935. The results also show that the recent increase in invasive adenocarcinoma started among those born around the mid 1920s, and a strong birth cohort effect is largely responsible for the observed increase. CONCLUSION: Invasive adenocarcinoma of the uterine cervix is increasing among recent birth cohorts. Analytical epidemiological studies are urgently needed to explore the risk factors responsible for the increase. The time trends for adenocarcinoma of the cervix should also be carefully monitored in the coming years.

Adenocarcinoma↗