Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 631 records · Page 35Linked to original sources

PubMed1998

A preliminary analysis of incidence of dementia in Shanghai, China.

The incidence of dementia based on DSM-III criteria and the impact of age and education on the development of dementia using the data of a longitudinal community population survey is discussed. Study subjects were randomly sampled from the community and were assessed by a two-stage procedure twice during a 5-year period. The screening instrument was the Mini-Mental State Examination and the second stage measures include a medical history and physical examination, a neurological examination and an intensive neuropsychiatric interview and testings (i.e. Blessed Dementia Scale, Activity of Daily Living, Fuld Object Memory Test and Block Design Test. All identified cases from the second stage interview were further verified by computed tomographic scan and laboratory tests. A total of 1970 subjects of non-dementia aged 65 or older in 1987 were re-surveyed after 5 years, of whom 114 new cases of dementia were identified. The incidence of dementia in total was 1.15% annually, 0.98% for males and 1.27% for females. The incidence for Alzheimer's disease, vascular dementia and dementia by other causes was 0.74, 0.33 and 0.08%, respectively. The highest rate (2.02%) was found in illiterate individuals. The incidence of dementia in the Shanghai cohort is similar to that from other countries. Age and education are closely related to the occurrence of dementia. While age increases by each 5 years for those aged 65 and over the likelihood of developing dementia increases nearly one-fold (74%). Education shows great protective effect on the development of dementia. The non-educated has a higher risk of suffering from dementia than does the educated.

Aged↗

PubMed1998

Group psychoeducation of relatives of schizophrenic patients: two-year experiences.

In order to assess the feasibility and acceptability of group psychosocial education for the relatives of schizophrenics in the community, a 2-year project was carried out in two cities: Jinan and Shanghai, China. The completed sample included 682 cases in the experimental group and 366 cases in the control group. The experimental group received group psychotherapy including 14 lectures and five group discussions with conventional services, and the control group had conventional services only. The annual relapse rate in the experimental group was much lower than that in the control group (17.6 and 23.2%, P < 0.01) and the rate of regular work in the experimental group was higher than that in the control group (37.5 and 30.0%, P < 0.05). At the end of the second year, the relatives in the experimental group had less care burden, better mental and physical health status and more knowledge of caring for schizophrenics than those in the control group. This approach was well accepted by both mental health workers and relatives of schizophrenics and the rate of drop-out was 18.4% only during the 2-year period.

Adult↗

PubMed1998

Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation.

Several studies were performed in female rats to determine dose and time course changes in mRNA levels for matrix proteins in bone after a single administration of ethanol. As expected, dose-dependent transient increases in blood ethanol were measured. Additionally, there was mild hypocalcemia with no change in immunoreactive parathyroid hormone. Coordinated dose-dependent increases in mRNA for type 1 collagen, osteonectin, and osteocalcin were noted in the proximal tibial metaphysis 6 hr after ethanol was given, with the peak values occurring at a dose of 1.2 g/kg (0.4 ml). Similar increases in mRNA levels for matrix proteins were noted in lumbar vertebrae after ethanol treatment. The changes were specific for bone; ethanol had no effect on mRNA levels for matrix proteins in the uterus or liver, although the mRNA concentrations tended to be reduced in uterus. Message levels for several cytokines implicated in the regulation of bone turnover were also assayed; mRNA levels for transforming growth factor-beta1, transforming growth factor-beta2, interferon-gamma, and interleukin-6 were unchanged at doses ranging from 0.14 to 1.7 g/kg. At the highest dose of ethanol, the mRNA level for tumor necrosis factor-alpha was elevated while the level for insulin-like growth factor-1 was reduced. The time course effects of ethanol (0.4 ml dose) were determined in a separate experiment. Ethanol resulted in a transient increase in mRNA levels for the three bone matrix proteins assayed. However, matrix protein synthesis, as determined by incorporation of 3H-proline into the proximal tibial metaphysis, was not changed after 6 hr. The changes in mRNA levels for the matrix proteins were preceded by brief, transient decreases in mRNA levels for interleukin-1beta, interferon-gamma, and migration inhibitory factor, and followed by a more prolonged decrease in the mRNA level for insulin-like growth factor-1. A subsequent study was performed to determine the effects of repetitive daily treatment with ethanol on rat bone. After 7 days, there were highly significant decreases in the mRNA level for type 1 collagen, as well as decreased bone formation. These results suggest that ethanol may alter bone metabolism by disturbing signal transduction pathways that regulate the expression of genes for bone matrix proteins, skeletal growth factors, and cytokines.

Animals↗

PubMed1998

Dependence of AT1 angiotensin receptor function on adjacent asparagine residues in the seventh transmembrane helix.

For several G protein-coupled receptors, amino acids in the seventh transmembrane helix have been implicated in ligand binding and receptor activation. The function of this region in the AT1 angiotensin receptor was further investigated by mutation of two conserved polar residues (Asn294 and Asn295) and the adjacent Phe293 residue. Analysis of the properties of the mutant receptors expressed in COS-7 cells revealed that alanine replacement of Phe293 had no major effect on AT1 receptor function. Substitution of the adjacent Asn294 residue with alanine (N294A) reduced receptor binding affinities for angiotensin II, two nonpeptide agonists (L-162,313 and L-163,491), and the AT1-selective nonpeptide antagonist losartan but not that for the peptide antagonist [Sar1, Ile8]angiotensin II. The N294A receptor also showed impaired G protein coupling and severely attenuated inositol phosphate generation. In contrast, alanine replacement of Asn295 decreased receptor binding affinities for all angiotensin II ligands but did not impair signal transduction. Additional substitutions of Asn295 with a variety of amino acids did not identify specific structural elements for ligand binding. These findings indicate that Asn295 is required for the integrity of the intramembrane binding pocket of the AT1a receptor but is not essential for signal generation. They also demonstrate the importance of transmembrane helices in the formation of the binding site for nonpeptide AT1 receptor agonists. We conclude that the Asn294 residue of the AT1 receptor is an essential determinant of receptor activation and that the adjacent Asn295 residue is required for normal ligand binding.

Alanine↗

PubMed1998

Growth of virulent and avirulent Mycobacterium tuberculosis strains in human macrophages.

Mycobacterium tuberculosis H37Rv causes progressive disease in animals, whereas the H37Ra strain does not. The relevance of this difference in virulence to human infection is uncertain because these strains have been shown to have similar growth rates in human macrophages. To evaluate the intracellular growth of M. tuberculosis strains in macrophages under conditions similar to those encountered in vivo, we infected human monocyte-derived macrophages with H37Ra, H37Rv, or one of four isolates from tuberculosis patients at a low bacillus-to-macrophage ratio. H37Rv and the patient isolates grew significantly faster than H37Ra, based on the numbers of CFU and acid-fast bacilli. These findings did not result from extracellular mycobacterial growth, differential macrophage viability, or bacillary clumping. In contrast to other published results, these findings indicate that the virulence characteristics of M. tuberculosis strains in animal models are relevant to human tuberculosis infection.

Cytokines↗

PubMed1998

Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis.

To investigate the role of chemokines during the initial local response to Mycobacterium tuberculosis in the human lung, we studied chemokine production by the human alveolar epithelial cell line A549 after infection with M. tuberculosis. M. tuberculosis-infected A549 cells produced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1beta, or IL-6. Two virulent clinical M. tuberculosis isolates, the virulent laboratory strain H37Rv, and the avirulent strain H37Ra elicited production of comparable concentrations of MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacterium avium strains did not. The three virulent M. tuberculosis strains grew more rapidly than the avirulent M. tuberculosis strain in the alveolar epithelial cell line, and the three M. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by alveolar epithelial cells but that virulence and the rate of intracellular growth do not correlate with chemokine production. Alveolar epithelial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocytes, and polymorphonuclear cells.

Cell Line↗

PubMed1998

Production of monocyte chemoattractant protein 1 in tuberculosis patients.

To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the immune response to Mycobacterium tuberculosis, we studied MCP-1 production in tuberculosis patients. CD14+ blood monocytes from tuberculosis patients spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+ monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from tuberculosis patients was also markedly increased. These findings suggest that MCP-1 can contribute to the antimycobacterial inflammatory response by attracting monocytes and T lymphocytes.

Chemokine CCL2↗

PubMed1998

Mutations in rotavirus nonstructural glycoprotein NSP4 are associated with altered virus virulence.

Rotaviruses are major pathogens causing life-threatening dehydrating gastroenteritis in children and animals. One of the nonstructural proteins, NSP4 (encoded by gene 10), is a transmembrane, endoplasmic reticulum-specific glycoprotein. Recently, our laboratory has shown that NSP4 causes diarrhea in 6- to 10-day-old mice by functioning as an enterotoxin. To confirm the role of NSP4 in rotavirus pathogenesis, we sequenced gene 10 from two pairs of virulent and attenuated porcine rotaviruses, the OSU and Gottfried strains. Comparisons of the NSP4 sequences from these two pairs of rotaviruses suggested that structural changes between amino acids (aa) 131 and 140 are important in pathogenesis. We next expressed the cloned gene 10 from the OSU virulent (OSU-v) and OSU attenuated (OSU-a) viruses by using the baculovirus expression system and compared the biological activities of the purified proteins. NSP4 from OSU-v virus increased intracellular calcium levels over 10-fold in intestinal cells when added exogenously and 6-fold in insect cells when expressed endogenously, whereas NSP4 from OSU-a virus had little effect. NSP4 from OSU-v caused diarrhea in 13 of 23 neonatal mice, while NSP4 from OSU-a caused disease in only 4 of 25 mice (P < 0.01). These results suggest that avirulence is associated with mutations in NSP4. Results from site-directed mutational analyses showed that mutated OSU-v NSP4 with deletion or substitutions in the region of aa 131 to 140 lost its ability to increase intracellular calcium levels and to induce diarrhea in neonatal mice, confirming the importance of amino acid changes from OSU-v NSP4 to OSU-a NSP4 in the alteration of virus virulence.

Amino Acid Sequence↗

PubMed1998

A non-isotopic method for the detection of telomerase activity in tumour tissues: TRAP-silver staining assay.

Telomerase activity has been observed in a high proportion of specimens from a wide variety of human malignant tumours, but not in non-neoplastic tissues. Measurement of telomerase activity is a possible diagnostic maker for malignant tumours. A non-isotopic telomeric repeat amplification protocol (TRAP) silver staining method for the detection of telomerase activity in human bone tumour tissues is described. The TRAP-silver staining method was quick, safe, and effective, and can be used as a routine diagnostic method for the detection of telomerase activity in bone tumours.

Biomarkers, Tumor↗

PubMed1998

Molecular mechanisms of calmodulin's functional versatility.

Calmodulin (CaM) is a primary Ca2+-binding protein found in all eukaryotic cells. It couples the intracellular Ca2+ signal to many essential cellular events by binding and regulating the activities of more than 40 different proteins and enzymes in a Ca2+-dependent manner. CaM contains two structurally similar domains connected by a flexible central linker. Each domain of the protein binds two Ca2+ ions with positive cooperativity. The binding of Ca2+ transforms the protein into its active form through a reorientation of the existing helices of the protein. The two helices in each helix-loop-helix Ca2+-binding motif are almost antiparallel in Ca2+-free CaM. The binding of Ca2+ induces concerted helical pair movements and changes the two helices in each Ca2+ binding motif to a nearly perpendicular orientation. These concerted helix pair movements are accompanied by dramatic changes on the molecular surface of the protein. Rather than exhibiting a flat, hydrophilic molecular surface as seen in Ca2+-free CaM, the Ca2+-saturated form of the protein contains a Met-rich, cavity-containing hydrophobic surface in each domain. These hydrophobic surfaces are largely responsible for the binding of CaM to its targets. The unique flexibility and high polarizability of the Met residues located at the entrance of each hydrophobic pocket together with other hydrophobic amino acid residues create adjustable, sticky interaction surface areas that can accommodate CaM's targets, which have various sizes and shapes. Therefore, CaM is able to bind to a large array of targets without obvious sequence homology. Upon binding to its target peptides, the unwinding of the central linker allows the two domains of the protein to engulf the hydrophobic face of target peptides of differing lengths. The binding of Ca2+ reduces the backbone flexibility of CaM. Formation of complexes with its target peptides further decreases the backbone motion of CaM.

Allosteric Regulation↗

PubMed1998

Effects of meal volume and composition on gastric myoelectrical activity.

The absence of a standard meal in electrogastrography may limit its clinical significance. Different meals may fail to produce the expected postprandial motility pattern. The aim of this study was to investigate the effect of meal volume and composition on postprandial myoelectrical activity. Fourteen healthy subjects were given four meals that differed from a "reference meal" in one single parameter (volume, calorie, or fiber content). Gastric myoelectrical activity was measured using surface electrogastrography. Spectral and statistical analyses were performed to investigate the effect of food properties on electrogastrogram (EGG) parameters. It was found that the reference meal produced a postprandial increase in the dominant frequency (P < 0.007), dominant power (P < 0.04), and percentage of normal 2-4 cycle/min gastric slow waves (P > 0.05). Similar changes were observed with the low-volume and high-fiber meals but not with the reduced-calorie meal. Fasting EGG parameters in all four sessions showed no significant difference. It was concluded that low-calorie meals do not result in expected postprandial physiological responses and thus are not appropriate for EGG tests. A volume reduction of down to one-half the volume of a regular meal does not affect postprandial changes of the EGG; thus a condensed test meal may be recommended for symptomatic patients.

Adult↗

PubMed1998

Development of gastric slow waves in preterm infants measured by electrogastrography.

The aim of this study was to investigate the developmental process of gastric myoelectrical activity (GMA) in preterm infants. Nineteen healthy preterm infants were studied. GMA was recorded using surface electrogastrography, and six follow-up studies were performed in each subject. Spectral analysis methods were applied to compute the parameters of the electrogastrogram (EGG). The results showed that there was a developmental process of GMA with age during the first 6 mo of life. 1) The percentage of normal slow waves showed a progressive increase after birth (36.7 +/- 6.1, 37.8 +/- 6.2, 47.0 +/- 10.0, 52.2 +/- 12.2, 55.2 +/- 9.7, and 65.8 +/- 13.5% at 1 and 2 wk and 1, 2, 4, and 6 mo, respectively); 2) there was a significant postprandial increase in the percentage of normal slow waves during the first 2 mo after birth; and 3) the percentages of normal slow waves for different gestation ages were not statistically significant. In conclusion, the percentage of normal slow waves is low at birth and there is a developmental process that may be stimulated by enteral feeding.

Electromyography↗

PubMed1998

Expenditures for the treatment of major depression.

OBJECTIVE: Health policy makers lack accurate information about per capita spending for the treatment of major depression, the distribution of those expenditures, and the proportion of the health care dollar consumed by depression treatment. METHOD: The authors recruited and followed a community cohort of individuals with major depression; the 298 subjects were either enrolled in fee-for-service insurance plans or self-insured. Charges for all health care services received during the year following baseline were abstracted from medical and insurance records. RESULTS: Over the course of 1 year, 48.1% of the subjects received depression treatment. The per capita total expenditure for inpatient and outpatient depression treatment averaged $631, with a median of $152, for the treated subjects. Just 4.9% of the treated subjects consumed 45.0% of the outpatient expenditures. Depression treatment consumed only 8 cents of every health care dollar spent on the patients treated for depression. CONCLUSIONS: Studies are needed to examine how the level and distribution of expenditures for depression treatment change under managed care and to determine whether and how any differences affect outcomes in the afflicted population. Managed care attempts to contain costs by limiting outpatient care may not affect total health care expenditures dramatically, since depression treatment consumes such a minuscule portion of the health care dollar spent on this population.

Adolescent↗

PubMed1998

Clonidine-Induced Heat-Shock Protein Expression in Rat Aorta.

BACKGROUND: Restraint-stress and administration of drugs that precipitate hypertension induce heat-shock protein (HSP) expression in the aorta. The exact mechanism supporting this hypertension-related HSP response is unclear because HSP induction is blocked by receptor-selective and nonselective antihypertensive agents. METHODS AND RESULTS: To identify mechanisms contributing to the pharmacological/physiological regulation of the HSP response in cardiovascular tissues, we administered clonidine to awake and freely moving animals to determine its effect on HSP expression in vivo. Inconsistent with previous work, we found that clonidine produced a dose-dependent and transient increase in HSP70 mRNA levels in the aorta. No other tissue examined displayed an HSP response after clonidine administration. Clonidine-induced HSP expression was not restricted to the HSP70 family; HSP89alpha, HSP89beta, and HSP60 were also induced. Interestingly, no heat-shock element-binding activity was observed after clonidine administration, suggesting that unusual transcriptional regulatory mechanisms mediate this response. Yohimbine and nifedipine blocked HSP70 mRNA expression, whereas isoproterenol, mecamylamine, and reserpine had no effect. CONCLUSIONS: The functional consequence of HSP expression in cardiovascular tissues may be to alter the responsiveness of cells in these tissues to subsequent drug or stress exposures, thereby implicating the HSP response as an important component of cardiovascular homeostasis. If so, treatment of mammalian organisms with drugs capable of inducting selective HSP expression in vascular tissue may alter the progression of cardiovascular disease processes.

Journal Article↗

PubMed1998

Agonist-induced phosphorylation of the endogenous AT1 angiotensin receptor in bovine adrenal glomerulosa cells.

A polyclonal antibody was raised in rabbits against a fusion protein immunogen consisting of bacterial maltose-binding protein coupled to a 92-amino acid C-terminal fragment of the rat AT1b angiotensin II (Ang II) receptor. The antibody immunoprecipitated the photoaffinity-labeled bovine AT1 receptor (AT1-R), but not the rat AT2 receptor, and specifically stained bovine adrenal glomerulosa cells and AT1a receptor-expressing Cos-7 cells, as well as the rat adrenal zona glomerulosa and renal glomeruli. The antibody was employed to analyze Ang II-induced phosphorylation of the endogenous AT1-R immunoprecipitated from cultured bovine adrenal glomerulosa cells. Receptor phosphorylation was rapid, sustained for up to 60 min, and enhanced by pretreatment of the cells with okadaic acid. Its magnitude was correlated with the degree of ligand occupancy of the receptor. Activation of protein kinase A and protein kinase C (PKC) also caused phosphorylation of the receptor, but to a lesser extent than Ang II. Inhibition of PKC by staurosporine augmented Ang II-stimulated AT1-R phosphorylation, suggesting a negative regulatory role of PKC on the putative G protein-coupled receptor kinase(s) that mediates the majority of AT1-R phosphorylation. The antibody should permit further analysis of endogenous AT1-R phosphorylation in Ang II target cells.

Angiotensin II↗

PubMed1998

Heat-induced proteolysis of HSF causes premature deactivation of the heat shock response in Nb2 lymphoma cells.

Nb2-11 cells, a prolactin (PRL)-dependent T-lymphoma cell line, display an unusual response to heat stress characterized by the lack of expression of inducible hsp70 mRNA transcripts and a reduction in the levels of constitutively expressed heat shock protein (HSP) genes. This aberrant heat shock response appears to result from heat-induced proteolytic fragmentation of heat shock factor (HSF). In this report, we have investigated processes that promote HSF fragmentation and identified characteristics of a protease that may be responsible for this effect. Cycloheximide did not affect HSF fragmentation of heat-shocked Nb2-11 cells suggesting that proteases responsible for this proteolysis are constitutively expressed and become activated by the heat shock conditions. PRL protected Nb2-11 cells from heat-induced fragmentation whereas sodium butyrate (NaBT) rendered a fragmentation-resistant cell line (Nb2-SFJCD1 cells) sensitive to HSF proteolysis. Heat-induced HSF fragmentation in Nb2-11 cells was not affected by pretreating cultures with several serine protease inhibitors. However, a dose-dependent decrease in HSF fragmentation was achieved by pretreating cultures with iodoacetamide, a cysteine protease inhibitor that is active in apoptosis. Apparently, the heat shock response in Nb2 cells is attenuated by a mechanism that involves the premature deactivation of HSF by its selective proteolysis. Attenuation of this critical cellular stress response may be an important contributor to the progression of hormone-dependent tumors possibly by influencing apoptotic processes known to regulate the activity of these cells.

Animals↗

PubMed1998

Skeletal muscle fibre types: detection methods and embryonic determinants.

Muscle fibres used to be simply classified as either type I, IIa or IIb. Advances in molecular and histological techniques have, however, lead to the realisation that the phenotypes of muscles are more varied than this. An additional fibre type (IIX/IID) has been discovered, fibres with intermediate fibre types have been described and there is accumulating evidence that the fibres types described from the study of limb muscles are not necessarily applicable to other skeletal muscles, such as the jaw and extra-ocular muscles. Further to this has been the discovery that diversity occurs at all stages of muscle development. There are subpopulations of myoblasts and myotubes as well as various types of muscle fibres. The relationships between the different stages of development is still under study. However, it is clear that each stage of muscle development is influenced to a certain degree by prior events. Consequently, the characteristics of mature fibres reflect both their developmental origins and influences from the adult environment, such as their patterns of muscle activation.

Adenosine Triphosphatases↗

PubMed1998

Controlling for selection bias in the evaluation of Alcoholics Anonymous as aftercare treatment.

OBJECTIVE: The purpose of this research was to control for self-selection bias in the evaluation of Alcoholics Anonymous (AA) as aftercare treatment. Observational studies of alcoholism aftercare treatment are subject to selection bias whenever the self-selection process results in important differences in unobserved casemix dimensions between treatment groups. METHOD: The sample included 118 male veterans discharged from inpatient alcohol treatment, 85% of whom were followed-up at 3 months. Drinking outcomes were measured by self-reported abstinence in the third month after discharge. The aftercare treatment effect of AA was estimated using standard logistic regression analysis and instrumental variables analysis. Instruments included the subject's ability to drive oneself to AA meetings and the presence/absence of an AA meeting in the subject's town of residence. A Hausman exogeniety test was used to determine whether the standard logistic regression results were subject to self-selection bias. RESULTS: Estimates from the standard logistic regression yielded a positive (OR = 3.7) and significant (p = .018) treatment effect for AA attendance. However, the instrumental variables analysis yielded a smaller (OR* = 1.7) and insignificant treatment effect estimate (p = .782). The Hausman exogeniety test indicated that the treatment effect estimate from the standard logistic regression was subject to significant self-selection bias (chi2 = 83.9, 1 df, p <.01). CONCLUSIONS: The AA aftercare treatment effect observed in this sample was due to differences in unobserved casemix factors between the treatment groups. Results suggest that previous AA aftercare research may have also been subject to self-selection bias. Researchers of substance abuse outcomes should consider analyzing nonexperimental data using instrumental variables methodologies.

Adult↗