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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 487 records · Page 27Linked to original sources
PubMed1999

Macrophages expressing heat-shock protein 65 play an essential role in protection of mice infected with Plasmodium yoelii.

C57BL/6 (B6) mice are resistant to infection with the non-lethal (NL) strain of Plasmodium yoelii 17X, while being susceptible to that with the lethal (L) strain. The 65 000 MW heat-shock protein (hsp 65) was strongly expressed in splenic adherent cells of B6 mice 10 days after infection with the NL strain of P. yoelii but only slightly in those from mice infected with the L strain. Mice which had survived infection with the NL strain were resistant to challenge with the L strain and hsp 65 was strongly expressed in splenic adherent cells of these mice. Severe combined immunodeficient mice and nude mice were susceptible to malaria infection even with the NL strain and did not express hsp 65 after infection, suggesting that T cells are required for the expression of hsp 65 as well as for protective immunity. B6 mice treated intraperitoneally with carrageenan, which impairs the macrophage function, became susceptible to NL strain infection, indicating that macrophages play an important role as the final effectors in protective immunity. These results demonstrate that the hsp 65 expressed by macrophages correlates closely with protection against P. yoelii infection.

Animals↗
PubMed1999

Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells.

Dendritic cells (DCs) are the most powerful of all antigen-presenting cells and play a critical role in the induction of primary immune responses. DC-based vaccination represents a potentially powerful strategy for cancer immunotherapy. In this study, a new approach for a DC-based melanoma vaccine was described. Splenic DCs from C57BL/6 mice were fused with B16 melanoma cells, and the resultant B16/DC hybrid cells expressed major histocompatibility complex (MHC) molecules - B7 as well as the B16 tumour marker M562 - which were enriched by Ia-mediated positive selection with a MiniMACS column. The fusion rates were 12.7-26.8%. To generate hybrid tumour vaccines with potentially greater potent therapeutic efficacy, we genetically engineered DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to cell fusion. Recombinant adenovirus vector was used to mediate gene transfer into DCs with high efficiency and DCs expressed GM-CSF at 96-138 ng/105 cells/ml 24 hr after GM-CSF gene transfer. GM-CSF gene-modified DCs (DC.GM) exhibited higher expression of B7 and co-stimulatory capacity in mixed lymphocyte reaction (MLR). Fusion of DC.GM with B16 cells generated B16/DC.GM hybrid cells secreting GM-CSF at 59-63 ng/105 cells/ml. Immunization of C57BL/6 mice with the B16/DC hybrid vaccine elicited a specific cytotoxic T-lymphocyte (CTL) response and protected the immunized mice from B16 tumour challenge, reduced pulmonary metastases and extended the survival of B16 tumour-bearing mice. The B16/DC.GM hybrid vaccine was able to induce a CTL response and protective immunity more potently and tended to be therapeutically more efficacious than the B16/DC vaccine. In vivo depletion of T-cell subsets demonstrated that both CD8+ and CD4+ T cells were essential for the therapeutic effects of B16/DC and B16/DC.GM hybrid vaccines. Additionally, other non-specific effector cells may also contribute to tumour rejection induced by the B16/DC.GM hybrid vaccine. These data indicate that a DC-based hybrid tumour vaccine may be an attractive strategy for cancer immunotherapy, and that GM-CSF gene-modified DCs may lead to the generation of hybrid vaccines with potentially increased therapeutic efficacy.

Animals↗
PubMed1999

Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages.

To determine whether the extent of spread of Mycobacterium tuberculosis strains in the community correlated with their capacity to replicate in human macrophages, intracellular growth rates of M. tuberculosis patient isolates were measured. Strain 210 caused disease in 43 patients in central Los Angeles, 3 "small-cluster" strains caused disease in 8-23 patients, and 5 "unique" strains each caused disease in only 1 patient who was positive by sputum acid-fast smear and spent substantial amounts of time at homeless shelters that were tuberculosis transmission sites. Strain 210 isolates grew significantly more rapidly than small-cluster and unique strains in macrophages. All strains elicited production of similar amounts of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-12 and were equally susceptible to reactive nitrogen intermediates. It was concluded that the extensive spread of an M. tuberculosis strain correlated with its capacity to replicate rapidly in human macrophages, which may be a marker of virulence.

Cells, Cultured↗
PubMed1999

Cytokine production in children with tuberculous infection and disease.

To determine if the manifestations of initial infection with Mycobacterium tuberculosis reflect changes in the balance of T cell cytokines, we evaluated cytokine production by M. tuberculosis-stimulated peripheral blood mononuclear cells (PBMCs) from 24 children with tuberculosis and 22 children who were healthy tuberculin reactors. PBMCs from patients with tuberculosis had lower production and mRNA expression of interferon gamma (IFN-gamma) than did PBMCs from healthy tuberculin reactors. IFN-gamma production was most severely depressed in patients with moderately advanced and far-advanced pulmonary disease and in malnourished patients. Production of IL-12, IL-4, and IL-10 was similar in tuberculosis patients and healthy tuberculin reactors. These results indicate that, during the initial immune response to M. tuberculosis, development of tuberculosis is associated with diminished IFN-gamma production, which is not due to reduced production of IL-12 or enhanced production of IL-4 or IL-10.

Child↗
PubMed1999

Effect of nimesulide on glucocorticoid receptor activity in human synovial fibroblasts.

Fibroblasts from human synovial membranes were cultured with nimesulide, naproxen or dexamethasone. Nimesulide, but not naproxen, showed effects on the glucocorticoid system that may contribute importantly to its anti-inflammatory activity. Nimesulide at therapeutically relevant concentrations induced the intracellular phosphorylation and activation of glucocorticoid receptors, and activated their binding to the target genes. Naproxen or dexamethasone markedly reduced the number of glucocorticoid receptor binding sites, in contrast to nimesulide, which had no significant effect.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Dysphagia after head trauma: the effect of cognitive-communicative impairments on functional outcomes.

This article discusses the impact of cognitive-communicative and behavior problems on oral intake. Data on the swallowing outcomes of a group of patients in an acute rehabilitation facility are presented. These data illustrate the relationships among severity of dysphagia, admission and discharge Functional Independence Measure (FIM) scores, admission and discharge cognitive FIM scores and length of stay. Two case studies that describe the effect of cognitive-communicative disorders on dysphagia are provided.

Activities of Daily Living↗
PubMed1999

The impact of geographic accessibility on the intensity and quality of depression treatment.

OBJECTIVES: For depression, this research measures the impact of travel time on visit frequency and the probability of receiving treatment in concordance with AHCPR guidelines. METHODS: The medical, insurance, and pharmacy records of a community-based sample of 435 subjects with current depression were abstracted to identify those treated for depression, to determine the number of depression visits made over a 6-month period, and to ascertain whether treatment was provided in concordance with AHCPR guidelines. A Geographic Information System was used to calculate the travel time from each patient to their preferred provider. Poisson and logistic regression analyses were used to estimate the impact of travel time on visit frequency and guideline-concordance, controlling for patient casemix. RESULTS: In the community-based sample, 106 subjects were treated for depression by 105 different preferred providers. About one-third (30.7%) were treated by a mental health specialist. One average, patients made 2.8 depression visits over the 6-month period. One-third (28.9%) of the patients received guideline-concordant treatment for depression. The average number of visits for those receiving guideline-concordant care was significantly greater than for those not receiving guideline-concordant care (P < 0.01). Travel time to the preferred provider was significantly associated with making fewer visits (P < 0.0001) and having a lower likelihood of receiving guideline-concordant care (P < 0.05). DISCUSSION: For depression, both pharmacotherapy and psychotherapy treatment regimens require frequent provider contact to be effective. This study suggests that travel barriers may prevent rural patients from making a sufficient number of visits to receive effective guideline-concordant treatment.

Adult↗
PubMed1999

Association of HIV viral load with oral diseases.

OBJECTIVE: The measurement of HIV viral load as a predictor of disease progression has revolutionized the medical management of HIV patients. In this study, oral diseases as measured by DMFT (decayed, missing and filled teeth), periodontal assessment and oral Candidacolonization, were related to HIV viral load. Also correlated was HIV status assessments, including CD4+ count, a history of intravenous drug abuse (IVDA) and the use of protease inhibitor drugs. MATERIALS AND METHODS: Oral and periodontal examination, dental radiographs, and tongue swab for fungal culture was accomplished over a 2-month period on 39 HIV positive patients attending the University of Maryland Dental School. Twenty-eight (71. 8%) of these patients had a history of IVDA. Viral load was measured by a quantitative RT-PCR. RESULTS: Among the patients with high viral load (>10 000 copies ml-1), 92.3% were found to have a history of IVDA. Also, patients with high viral load demonstrated average CD4+ counts of 136 mm-3 while moderate viral load (400-10 000 copies ml-1) corresponded to average counts of 271 mm-3. Periodontal pocket depths (PPD) of >5 mm at a minimum of two oral sites were found in 76.9% of the patients with high viral load. Among the high viral load patients, 69.2% had DMFT >20, 69.2% were culture positive for Candida and 81.5% of patients on protease inhibitors demonstrated moderate or low viral loads. CONCLUSION: These data demonstrated that elevated viral load levels correlate well with oral disease prevalence in this predominantly IVDA population of HIV-infected dental patients.

Adult↗
PubMed1999

Treatment of depression in rural Arkansas: policy implications for improving care.

Policy-makers have long suspected that greater barriers to care result in depressed rural residents being less likely to receive high-quality treatment. This study recruited 470 depressed community residents in a 1992 telephone survey, followed 95 percent of them through one year, and abstracted additional data on their health care utilization from insurance claims, medical and pharmacy records. Bivariate and multivariate models demonstrated that during the year following the baseline, there were no significant rural-urban differences in the rate (probability of any outpatient depression treatment), type (probability of receiving general medical depression care only), or quality (completion of guideline-concordant acute-stage care) of outpatient depression treatment. Annual expenditures for outpatient depression treatment were lower for rural subjects compared with their urban counterparts. Rural subjects had 3.05 times the odds of being admitted to a hospital for physical problems and 3.06 times the odds of being admitted to a hospital for mental health problems during the year following baseline compared with urban subjects. Cost-offset analyses demonstrate that every dollar invested in depression treatment was associated with a $2.61 decrease in the cost of treating physical problems in depressed rural residents. Limited insurance coverage and limited availability of services were the most significant barriers to specialty and general medical outpatient treatment for depression in both rural and urban residents. More than 80 percent of depressed residents in both rural and urban areas visited a primary care provider during the year following baseline. The potential cost offset of depression treatment in rural populations plus the improvement in productivity observed in both rural and urban populations indicate that it may be economically possible to improve quality of care for depression without bankrupting an already strained health care budget.

Adult↗
PubMed1999

An open reading frame element mediates posttranscriptional regulation of tropoelastin and responsiveness to transforming growth factor beta1.

Elastin, an extracellular component of arteries, lung, and skin, is produced during fetal and neonatal growth. We reported previously that the cessation of elastin production is controlled by a posttranscriptional mechanism. Although tropoelastin pre-mRNA is transcribed at the same rate in neonates and adults, marked instability of the fully processed transcript bars protein production in mature tissue. Using RNase protection, we identified a 10-nucleotide sequence in tropoelastin mRNA near the 5' end of the sequences coded by exon 30 that interacts specifically with a developmentally regulated cytosolic 50-kDa protein. Binding activity increased as tropoelastin expression dropped, being low in neonatal fibroblasts and high in adult cells, and treatment with transforming growth factor beta1 (TGF-beta1), which stimulates tropoelastin expression by stabilizing its mRNA, reduced mRNA-binding activity. No other region of tropoelastin mRNA interacted with cellular proteins, and no binding activity was detected in nuclear extracts. The ability of the exon-30 element to control mRNA decay and responsiveness to TGF-beta1 was assessed by three distinct functional assays: (i) insertion of exon 30 into a heterologous gene conferred increased reporter activity after exposure to TGF-beta1; (ii) addition of excess exon 30 RNA slowed tropoelastin mRNA decay in an in vitro polysome degradation assay; and (iii) a mutant tropoelastin cDNA lacking exon 30, compared to wild-type cDNA, produced a stable transcript whose levels were not affected by TGF-beta1. These findings demonstrate that posttranscriptional regulation of elastin production in mature tissue is conferred by a specific element within the open reading frame of tropoelastin mRNA.

Animals↗
PubMed1999

Endothelin-1 stimulation of endothelial nitric oxide synthase in the pathogenesis of hepatopulmonary syndrome.

Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas exchange abnormalities that characterize the hepatopulmonary syndrome. This vasodilatation correlates with increased levels of pulmonary microcirculatory endothelial nitric oxide synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1). Prehepatic portal hypertension induced by portal vein ligation (PVL) does not cause similar changes, suggesting that ET-1 in cirrhosis may modulate pulmonary eNOS and vascular tone. We assessed whether ET-1 altered eNOS expression and nitric oxide production in bovine pulmonary artery endothelial cells (BPAECs) and if a 2-wk low-level intravenous ET-1 infusion in PVL animals modulated pulmonary eNOS levels, microcirculatory tone, and gas exchange. ET-1 caused a 2.5-fold increase in eNOS protein in BPAECs, inhibitable with an endothelin B receptor antagonist, and an increase in eNOS mRNA and nitrite production. ET-1 infusion in PVL animals caused increased pulmonary eNOS levels, intrapulmonary vasodilatation, and gas exchange abnormalities without increasing pulmonary arterial pressure. ET-1 produced during hepatic injury may contribute to the hepatopulmonary syndrome by modulating eNOS and inducing pulmonary microcicrulatory vasodilatation.

Animals↗
PubMed1999

Estrogen has rapid tissue-specific effects on rat bone.

The decrease in cancellous bone formation after estrogen treatment is generally thought to be coupled with a prior decrease in bone resorption. To test the possibility that estrogen has rapid tissue-specific actions on bone metabolism, we determined the time course (1-32 h) effects of diethylstilbestrol on steady-state mRNA levels for immediate-response genes, extracellular matrix proteins, and signaling peptides in the proximal tibial metaphysis and uterus by using Northern blot and RNase protection assays. The regulation of signaling peptides by estrogen, although tissue specific, followed a similar time course in bone and uterus. The observed rapid decreases in expression of insulin-like growth factor I, a growth factor associated with bone formation; decreases in mRNA levels for bone matrix proteins; evidence for reduced bone matrix synthesis; failure to detect rapid increases in mRNA levels for signaling peptides implicated in mediating the inhibitory effects of estrogen on bone resorption (interleukin-1 and -6) as well as other cytokines that can increase bone resorption; and the comparatively long duration of the bone remodeling cycle in rats indicate that estrogen can decrease bone formation by a mechanism that does not require a prior reduction in bone resorption.

Animals↗
PubMed1999

Influence of ozone and nitrogen dioxide on histamine and interleukin formation in a human nasal mucosa culture system.

There is evidence that asthma and other allergic diseases are increasing and air pollution has been considered an important contributing factor to this observation. Using a specially designed organ culture system, we examined the influence of ozone (0.06 to 0. 2 ppm) and nitrogen dioxide (NO2, 200 and 800 micrograms/m3) on nasal mucosa exposed for 24 h. Tissue was obtained from 105 patients undergoing surgical therapy (septoplasty and reduction of the inferior turbinates) for chronic nasal obstruction. The histamine content in the culture medium of ozone- and NO2-exposed samples was significantly elevated compared with the control cultures. This elevation was correlated with the number of degranulated mast cells in the tissue determined by histomorphometry (P < 0.001). Moreover, the cytokines interleukin (IL)-1beta (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.001), and tumor necrosis factor-alpha (TNF-alpha, P < 0. 001) were significantly increased (ozone 0.1 ppm). Furthermore, we found significant increases in the release of IL-4, IL-6, IL-8, and TNF-alpha of ozone-exposed (0.1 ppm) samples of atopic versus nonatopic patients and to a lesser extent for histamine following exposure to 0.15 ppm ozone. These results indicate that low ozone concentrations and NO2 lead to an inflammation of human nasal mucosa in vitro and that priming factors such as atopy or preexisting inflammation do increase the sensitivity to ozone and NO2. This organ culture system proved to be a good experimental design for studying pathophysiologic alterations of human nasal mucosa under different experimental conditions (e.g., air pollutants).

Culture Media↗
PubMed1999

Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A.

Pulmonary surfactant protein-A (SP-A) has been reported to regulate the uptake and secretion of surfactant by alveolar type II cells, to stabilize large surfactant aggregates including tubular myelin, and to protect the surface activity of surfactant from protein inhibitors. In this study we investigated the consequences of overexpression of SP-A on pulmonary homeostasis and surfactant function in transgenic mice. The human SP-C promoter was used to direct synthesis of rat surfactant protein A (rSP-A) in alveolar type II cells and nonciliated bronchiolar cells of the distal respiratory epithelium. Levels of SP-A measured through enzyme-linked immunosorbent assay were 7- to 8-fold higher in lung homogenates and alveolar lavage fluid of the rSP-A mice than in those of transgene-negative littermates. The swimming exercise tolerance and lung compliance of mice bearing the transgene were unchanged. Mean air space sizes seen in randomly selected light-microscopic fields were not significantly different in the transgene-positive and -negative mice by morphometric analysis, but 15% of transgenic animals had scattered foci containing dilated alveoli and alveolar ducts without evidence of inflammation or fibrosis. Some alveolar macrophages contained bar-shaped osmophilic inclusions that had a highly ordered ultrastructure. There were no differences between the transgene-positive and -negative mice in the tissue or alveolar pool sizes of saturated phosphatidylcholine or in the large-aggregate composition of alveolar surfactant. The surface activity of surfactant isolated from the rSP-A mice was similar to that of the controls, but in the presence of protein inhibitors, the surface tension-reducing properties of the rSP-A surfactant were better preserved (P < 0.05). We conclude that overexpression of SP-A does not affect resting surfactant phospholipid levels, but that it enhances the resistance of surfactant to protein inhibition.

Animals↗
PubMed1999

Earnings changes for depressed individuals treated by mental health specialists.

OBJECTIVE: It is unclear whether the additional benefits of receiving depression treatment from mental health specialists in routine care pays for the additional costs, compared with treatment delivered by general medical providers. This study examines the difference in lost earnings and the difference in treatment costs experienced by depressed individuals treated in these two sectors. METHOD: Representative community residents with depression were recruited and interviewed at baseline and at 6-month and 12-month follow-ups. Lost earnings were measured by lost workdays multiplied by subjects' wage rates. Treatment costs were approximated by charges abstracted from provider and insurance records. RESULTS: After controlling for sociodemographic variables, baseline severity, and baseline comorbidity, the authors found a net mean annual economic savings of $877 associated with depression treatment delivered in the mental health sector compared with the general medical sector. Sensitivity analyses in alternative scenarios indicated similar savings. CONCLUSIONS: Although it is the trend for primary care providers to provide mental health services, these analyses indicate a net economic savings if depression treatment is provided by mental health specialists, probably as a result of patients' greater functional improvement. As gatekeepers, especially in managed care, primary care providers have a unique responsibility to identify and detect patients with mental health problems. In the current structure, however, they may lack the necessary time to provide effective mental health services. Therefore, mental health specialists play a crucial role, with primary care providers' cooperation (i.e., detection, consultation, and referral), in providing the most cost-effective mental health services.

Adult↗
PubMed1999

A community study of depression treatment and employment earnings.

OBJECTIVE: Although treatment for major depression has been shown to reduce the costs of lost earnings resulting from lost work days, research has not demonstrated whether the reduction fully offsets the costs of treatment for the disorder. METHODS: A statewide cohort of community residents with recent major depression, dysthymia, or substantial depressive symptoms was recruited and interviewed at baseline and at six-month and 12-month follow-ups. The cost of lost earnings was measured by lost work days multiplied by subjects' wage rates. Cost of treatment for depression was approximated using charges abstracted from provider and insurance records. Net economic cost, defined as the sum of changes in lost earnings and depression treatment costs, was examined in multiple regression analyses. RESULTS: After the analyses controlled for sociodemographic characteristics, baseline severity of depression, and comorbidity, no statistically significant effect of depression treatment on net economic cost was found. This finding suggests that the cost of depression treatment was fully offset by savings from reduction in lost work days. Results from sensitivity analyses in multiple alternative scenarios support the same conclusion. CONCLUSIONS: The finding of a full offset of depression treatment cost is conservative because other benefits, such as reduced pain and suffering and increased productivity while at work, were not included in the analyses. Employers who bear the cost from lost work days should encourage their employees with depressive disorders to seek treatment, even if it means paying for the entire treatment cost. Self-employed individuals with depression also will benefit even if they pay for the treatment costs themselves.

Absenteeism↗
PubMed1999

Is resveratrol an estrogen agonist in growing rats?

Trans-3,4,5-trihydroxystilbene (resveratrol), a polyphenolic compound found in juice and wine from dark-skinned grape cultivars, was recently shown to bind to estrogen receptors in vitro, where it activated transcription of estrogen-responsive reporter genes. The purpose of this 6-day study in weanling rats was to determine the dose response (1, 4, 10, 40, and 100 microg/day) effects of orally administered resveratrol on estrogen target tissues. The solvent (10% ethanol) had no significant effect on any measurement or derived value. 17Beta-estradiol treatment (100 microg/day) decreased the growth rate, final body weight, serum cholesterol, and radial bone growth (periosteal bone formation and mineral apposition rates) at the tibia-fibula synostosis. In the uterus, 17beta-estradiol treatment increased wet weight, epithelial cell height, and steady state messenger RNA levels for insulin-like growth factor I. In contrast, resveratrol treatment had no significant effect on body weight, serum cholesterol, radial bone growth, epithelial cell height, or messenger RNA levels for insulin-like growth factor I. Resveratrol treatment resulted in slight increases in uterine wet weight, but significance was achieved at the 10-microg dose only. A second experiment was performed to determine whether a high dose of resveratrol (1000 microg/day) antagonizes the ability of estrogen to lower serum cholesterol. As was shown for the lower doses, resveratrol had no effect on body weight, uterine wet weight, uterine epithelial cell height, cortical bone histomorphometry, or serum cholesterol. 17Beta-estradiol significantly lowered serum cholesterol, and this response was antagonized by cotreatment with resveratrol. These in vivo results suggest, in contrast to prior in vitro studies, that resveratrol has little or no estrogen agonism on reproductive and nonreproductive estrogen target tissues and may be an estrogen antagonist.

Administration, Oral↗