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Biomedical subjects

J Chan

Publications and source records attributed to J Chan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Stimulation of bone formation in vitro and in rodents by statins.

Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.

Animals↗
PubMed1999

Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice.

Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ERalpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ERbeta, demanded that we examine the possible participation of ERbeta in regulation of these behaviors. In dramatic contrast to our results with ERalpha knockout (alphaERKO) males, betaERKO males performed at least as well as wild-type controls in sexual behavior tests. Moreover, not only did betaERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience. These data revealed a significant interaction between genotype and social experience with respect to aggressive behavior. Finally, females lacking a functional beta isoform of the ER gene showed normal lordosis and courtship behaviors, extending in some cases beyond the day of behavioral estrus. These results highlight the importance of ERalpha for the normal expression of natural reproductive behaviors in both sexes and also provide a background for future studies evaluating ERbeta gene contributions to other, nonreproductive behaviors.

Aggression↗
PubMed1999

Localization and activity of nitric oxide synthases in the gastrointestinal tract of Trypanosoma cruzi-infected mice.

Chagas' disease, caused by the protozoan parasite, Trypanosoma cruzi, is associated with gastrointestinal abnormalities. Since nitric oxide (NO) has been shown to be a factor influencing intestinal function we evaluated the distributions and activities of the NO synthase (NOS) isoforms, in the gut of mice infected with T. cruzi. Ca2+-dependent (NOS1/NOS3) activity was decreased, whereas Ca2+-independent (NOS2) activity was increased in infected mice. NOS2-immunoreactivity was demonstrated in cells within the muscle layers and epithelium in infected mice and NOS1 immunoreactivity was seen in nerve structures. These data indicate that alterations in the NO-system may be important in the pathogenesis of the gastrointestinal manifestations in Chagas' disease.

Animals↗
PubMed1999

Ultrastructural localization of the serotonin transporter in limbic and motor compartments of the nucleus accumbens.

Extracellular levels of serotonin [5-hydroxytryptamine (5-HT)] in the nucleus accumbens (NAc) can influence both cognitive and motor functions involving extensive connections with the frontal cortex. The 5-HT levels reflect vesicular release and plasmalemmal reuptake through the serotonin transporter (SERT). We used electron microscopic immunocytochemistry to determine the sites for SERT activation in the limbic shell and motor-associated core of the rat NAc. Of the SERT-immunoreactive profiles in each region, >90% were serotonergic axons and axon terminals; the remainder were nonserotonergic dendrites and glia. Axonal SERT immunogold labeling was seen mainly at nonsynaptic sites on plasma membranes and often near 5-HT-containing large dense core vesicles (DCVs). SERT-labeled axonal profiles were larger and had a higher numerical density in the shell versus the core but showed no regional differences in their content of SERT immunogold particles. In contrast, immunoreactive dendrites had a lower numerical density in the shell than in the core. SERT labeling in dendrites was localized to segments of plasma membrane near synaptic contacts from unlabeled terminals and/or dendritic appositions. Our results suggest that in the NAc (1) reuptake into serotonergic axons is most efficient after exocytotic release from DCVs, and (2) increased 5-HT release without concomitant increase in SERT expression in individual axons may contribute to higher extracellular levels of serotonin in the shell versus the core. These findings also indicate that SERT may play a minor substrate-dependent role in serotonin uptake or channel activity in selective nonserotonergic neurons and glia in the NAc.

Animals↗
PubMed1999

Surveillance of work-related asthma in selected U.S. states using surveillance guidelines for state health departments--California, Massachusetts, Michigan, and New Jersey, 1993-1995.

PROBLEM/CONDITION: Cases of work-related asthma (WRA) are sentinel health events that indicate the need for preventive intervention. WRA includes new-onset asthma caused by workplace exposure to sensitizers or irritants and preexisting asthma exacerbated by workplace exposures. REPORTING PERIOD: This report reviews cases of WRA identified by state health departments from January 1, 1993, through December 31, 1995, as well as follow-up investigations of cases and associated workplaces conducted through June 30, 1998. DESCRIPTION OF THE SYSTEMS: State-based surveillance and intervention programs for WRA are conducted in California, Massachusetts, Michigan, and New Jersey as part of the Sentinel Event Notification Systems for Occupational Risks (SENSOR) cooperative agreement program, initiated by CDC's National Institute for Occupational Safety and Health (NIOSH). RESULTS: From 1993 through 1995, a total of 1,101 cases of WRA were identified by SENSOR surveillance staff members in California, Massachusetts, Michigan, and New Jersey. Of these 1,101 cases, 19.1% were classified as work-aggravated asthma, and 80.9% were classified as new-onset asthma. Objective evidence substantiating asthma work-relatedness was documented in the medical records of 3.4% of WRA cases identified in the two states (Michigan and New Jersey) where medical records are routinely reviewed for this information. Indoor air pollutants, dusts, cleaning materials, lubricants (e.g., metalworking fluids), and diisocyanates were among the most frequently reported causes of WRA. In addition, a well-recognized cause of occupational asthma - natural rubber latex - was identified in a new setting, the healthcare industry. The most common industries associated with WRA cases included transportation equipment manufacturing (19.3%), health services (14.2%), and educational services (8.7%). Air sampling for agents known to induce occupational asthma was performed in Michigan for comparison with established federal time-weighted average exposure limits. Sixteen (13.4%) of 119 workplaces tested had airborne concentrations exceeding NIOSH recommended exposure limits (RELs); 11 (9.1%) of 121 workplaces had concentrations exceeding permissible exposure limits (PELs) of the Michigan Occupational Safety and Health Act (MIOSHA) program. INTERPRETATION: The surveillance data findings confirm well-recognized causes of asthma and have identified new putative causes (e.g., cleaning materials and metalworking fluids). Because the surveillance program depends on physicians' recognizing asthma work-relatedness and reporting diagnosed cases, the data are considered an underestimate of the magnitude of the WRA problem. The data also indicate that physicians are not commonly performing objective physiologic tests to substantiate a WRA diagnosis. Workplace findings suggest a need to evaluate existing exposure standards for specific agents known to induce occupational asthma (e.g., diisocyanates). Case-based surveillance can help improve the recognition, control, and prevention of WRA. The SENSOR model also provides a mechanism for workers and physicians to request workplace investigations aimed at primary prevention for other workers. PUBLIC HEALTH ACTION: NIOSH and state health department representatives are working to establish a long-term agenda for state-based surveillance of work-related conditions and hazards. The results from the SENSOR WRA programs described in this report support inclusion of WRA as a priority condition warranting surveillance at the state level.

Asthma↗
PubMed1999

Regional and subcellular distribution of a neutral and basic amino acid transporter in forebrain neurons containing nitric oxide synthase.

The neutral and basic amino acid transporter (NBAT) facilitates sodium-independent transport of L-amino acids in renal and intestinal epithelial cells and has been postulated to play a similar role in neurons. In previous studies, NBAT has been detected within enteric and brainstem autonomic neurons in a distribution similar to that of constitutive nitric oxide synthase (cNOS). Furthermore, L-arginine, the required precursor for nitric oxide synthesis, is an excellent NBAT substrate. Together, these findings suggest that NBAT may play a role in the regulation of nitric oxide synthesis, through the control of precursor availability. To gain insight into the potential physiological role of NBAT in central neurons, we used an antipeptide antiserum to examine the light and electron microscopic immunocytochemical localization of NBAT in the rat forebrain and to compare this distribution with that of cNOS. Immunolabeling for NBAT was detected within perikarya and dendrite-like processes that were most numerous in the frontal and cingulate cortex, the ventral striatum, the central amygdala, and the bed nucleus of the stria terminalis. Labeled varicose axonal processes were distributed most densely in the agranular insular cortex and the paraventricular nuclei of the thalamus and hypothalamus (PVH). Electron microscopy showed that immunogold labeling for NBAT was distributed along plasmalemmal and vacuolar membranes within somata, dendrites, and axonal profiles. Many of the NBAT-containing somata and dendrites contained detectable cNOS. Our results suggest that expression of NBAT may provide specific populations of cNOS-containing forebrain neurons with a unique mechanism for regulating somatodendritic synthesis of nitric oxide.

Amino Acid Transport Systems, Basic↗
PubMed1999

The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain.

The expression of a brain-specific high-affinity Na+-dependent (and Cl--dependent) L-proline transporter (PROT) in subpopulations of putative glutamatergic neurons in mammalian brain suggests a physiological role for this carrier in excitatory neurotransmission (). To gain insights into potential sites where PROT may function, we used a C-terminal domain antipeptide antibody to determine the regional distribution and subcellular localization of PROT in rat forebrain. PROT immunoreactivity was seen in processes having a regional light microscopic distribution comparable to that of known glutamatergic projections within the cortex, caudate putamen nucleus (CPN), hippocampal formation, and other forebrain regions. In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses. Immunogold labeling for PROT was detected in close contact with membranes of small synaptic vesicles (SSVs) and more rarely with the plasma membrane in these axon terminals. Subcellular fractionation studies confirmed the preferential distribution of PROT to synaptic vesicles. The topology of PROT in synaptic vesicles was found to be inverted with respect to the plasma membrane, suggesting that PROT-containing vesicles are generated by a process involving endocytosis from the plasma membrane. Because PROT lacks any of the known characteristics of other vesicular transporters, these results suggest that certain excitatory terminals have a reserve pool of PROT associated with SSVs. The delivery of PROT to the plasma membrane by exocytosis could play a critical role in the plasticity of certain glutamatergic pathways.

Amino Acid Sequence↗
PubMed1999

Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice.

Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide synthase (NOS2) expression have been implicated in the cardiac dysfunction associated with myocarditis and cardiomyopathy. Chagas' disease, caused by Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the effect of T. cruzi (Brazil strain) infection with or without verapamil treatment on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL-1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western blot analysis as well as immunohistochemistry demonstrated a significant increase in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2 protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated increases in cardiac L-citrulline were also reduced by verapamil treatment. Verapamil-treated infected mice that survived for 80 days exhibited less inflammation and fibrosis compared to untreated mice. Gated MRI and echocardiography revealed an increased right ventricular inner diameter (RVID) in untreated but not in verapamil-treated infected CD1 mice. This suggests that the infection-associated expression of cytokines and NOS2 in the heart correlate with the severity of myocarditis and the effect of verapamil. The RVID was significantly increased in infected wild-type (WT) compared to infected syngeneic NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial L-citrulline was increased in infected WT mice. These data suggest that NO generated from cardiac NOS2 may participate in the pathogenesis of murine chagasic heart disease.

Animals↗
PubMed1999

The role of diabetes mellitus in the aetiology of renal cell cancer.

To investigate the relation between diabetes mellitus and the risk of renal cell cancer we carried out a population-based retrospective cohort study. Patients identified in the Swedish Inpatient Register who were discharged from hospitals with a diagnosis of diabetes mellitus between 1965 and 1983 formed a cohort of 153852 patients (80005 women and 73847 men). The cohort members were followed up to 1989 by record linkage to three nation-wide registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using age-specific sex-specific and period-specific incidence and mortality rates derived from the entire Swedish population. After exclusion of the first year of observation, a total of 267 incidences of renal cell cancer (ICD-7:180.0) occurred in diabetic patients compared with the 182.4 that had been expected. Increased risks were observed in both women (SIR = 1.7, 95% confidence interval, CI = 1.4-2.0) and men (SIR = 1.3; 95 % CI = 1.1-1.6) throughout the duration of follow-up (1-25 years). A higher risk was seen for kidney cancer (ICD-7:180) mortality (SMR = 1.9; 95% CI = 1.7-2.2, women; SMR 1.7, 95% CI = 1.4-1.9, men). In comparison with the general population, patients with diabetes mellitus have an increased risk of renal cell cancer.

Age Factors↗
PubMed1999

Intraarterial catheter-directed thrombolysis: urokinase versus tissue plasminogen activator.

The purpose of this study was to evaluate the differences between tissue plasminogen activator (TPA) and urokinase (UK) in the management of ischemic limbs. A total of 58 limbs (24 in the TPA group and 34 in the UK group) in 53 patients were studied prospectively. The two groups were based on the surgeon's preference for lytic agent. The dose regimen for UK was 150,000 IU/hr over 1/2 to 2 hr followed by a continuous infusion of 50,000 IU/hr. TPA was given as a 5-mg bolus followed by 1 mg/hr. Both groups received heparin at a rate of 400 IU/hr through the side arm of the arterial sheath. There was no significant difference in efficacy between UK and TPA, but TPA acted faster and had a higher incidence of bleeding complications.

Aged↗
PubMed1999

Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.

Adult↗
PubMed1999

Evaluation of the efficacy of a hospital-based asthma education programme in patients of low socioeconomic status in Hong Kong.

BACKGROUND: Good asthma control requires optimal medical treatment in conjunction with appropriate self-management. In the West, the effectiveness of patient education on improving self-management has been well documented. However, data amongst Asian populations are lacking. We performed a pilot study to evaluate the efficacy of a hospital based education programme aimed at improving self-management skills and reducing morbidity in a Chinese population with low socioeconomic status and education level. METHODS: Our asthma education programme was a low-cost programme conducted in essence by specialist respiratory nurses. Patients attending our asthma clinic were instructed during a two-hour educational session on the pathophysiology of asthma, its potential triggers, the appropriate use of medications including proper inhaler techniques, and the self-management of their disease. These instructions were reinforced by video sessions at subsequent outpatient clinic attendance when patients' inhaler and peak flow techniques were checked by the same nurses and their self-management plan re-examined by the attending physicians. Asthma knowledge, inhaler technique, FEV1 and peak expiratory flow (PEF), and patients' self-rating of their asthma were determined at baseline, 6 months and 1 year after the intervention. Morbidity was assessed by the numbers of hospitalizations, unscheduled visits to family physicians and accident and emergency department attendance, courses of oral steroid used and days off work or school at baseline and 1 year. RESULTS: Two hundred and thirty patients were recruited for the study, 83% completing the entire assessment period. The group demonstrated significant improvements in lung function: the mean FEV1 +/- SD increased from 63.6 +/- 20.6% of predicted values at baseline to 68.5 +/- 22.3% at 6 months and 68.6 +/- 22.8% at 1 year (P < 0.05), and the mean PEF +/- SD increased from 64.6 +/- 23.0% of predicted values at baseline to 75.4 +/- 27.0% at 6 months and 76.8 +/- 24.5% at 1 year(P < 0.001). There were also significant improvements in inhaler technique (P < 0.01), asthma knowledge (P < 0.001), patients' self-rating of their asthma (P < 0.05), and reductions in the numbers of hospitalizations (P < 0.01), visits to family physicians (P < 0.001) and accident and emergency department attendance (P < 0.001) during the study period. Patients with moderate to severe asthma as defined by an FEV1 of < 80% of predicted values were most likely to benefit from the programme. CONCLUSIONS: We conclude that patient education is likely to be an essential component in the holistic approach to the management of asthma even amongst Asian populations of low socioeconomic status and education level. Further studies using randomised controlled trials are necessary to consolidate our findings.

Administration, Oral↗
PubMed1999

Helical computed tomography angiography in the evaluation of Chinese living renal donors.

OBJECTIVE: To determine the suitability of helical computed tomography angiography (CTA), recently used in the anatomical evaluation of potential living renal donors (LRDs) in the Caucasian population, for Chinese LRDs. SUBJECTS AND METHODS: Eighteen consecutive potential LRD candidates underwent both CTA and conventional renal angiography (CRA). Results from each were interpreted while unaware of the results from the other. Renal function was monitored after each radiological procedure. RESULTS: Both procedures were able to identify all four accessory renal arteries present. One prehilar branch of < 1 mm in diameter was not recognized on CTA. Renal artery ostial stenosis in one subject with normal blood pressure was identified on CTA, but not on CRA. CTA better delineated the renal venous and parenchymal anatomy and cost 60% less than CRA. There was no change in renal function after either procedure. CONCLUSION: Despite there being few subjects. CTA has potential value as an alternative to CRA for the anatomical assessment of potential LRDs in Hong Kong. Advantages include a short examination time, non-invasiveness and lower cost. CTA may provide an opportunity to living-related and unrelated renal donor transplantation in this conservative Chinese culture.

Adult↗
PubMed1999

Toxicity of nitrogen oxides and related oxidants on mycobacteria: M. tuberculosis is resistant to peroxynitrite anion.

OBJECTIVE: To test the toxicity of reactive nitrogen intermediates (RNI), including authentic nitric oxide (NO), nitrogen dioxide (NO2), and peroxynitrite anion (ONOO-), a potent oxidant derived from NO and superoxide anion, on various mycobacterial strains including M. tuberculosis. DESIGN: Relatively avirulent mycobacteria including M. smegmatis and BCG, as well as the pathogenic M. Bovis Ravenel and M. tuberculosis Erdman and the clinical isolate M160 (also known as the C strain) were tested for their susceptibility to the toxic effects of NO, NO2, and ONOO-, Deaerated, NO-saturated solutions as well as an anaerobic in vitro system in which mycobacteria can be exposed to desired concentrations of authentic NO or NO2, were employed in these studies. An in vitro ONOO- killing assay was used to examine the adverse effects of this NO-derived oxidant on the various strains of mycobacteria. RESULTS: Both NO and NO2 exhibit antimycobacterial activity, with the former being more potent. Results obtained using ONOO- killing assay revealed that while avirulent mycobacteria including BCG and M. smegmatis are susceptible to this NO-derived oxidant, the virulent Erdman strain of M. tuberculosis and M. bovis, as well as the clinical tuberculous isolate M160, are remarkably resistant. CONCLUSION: These results suggest that the interactions between RNI and various species of mycobacteria could be highly specific. And since activated macrophages produce peroxynitrite, the significance of the ONOO- resistance of M. tuberculosis strains in relation to intracellular survival deserves further investigation.

Adult↗
PubMed1999

Recent developments in mycobacterial research.

Tuberculosis remains a major health problem in the world, which is compounded further by the alarmingly high rate of M. tuberculosis infections in AIDS patients. Thus, there is an urgent need to advance our understanding of the mycobacterium to develop new drugs. The extraordinary recent developments in mycobacterial genetic research, particularly in genomics will greatly facilitate this goal. The knowledge of the entire genome sequence of M. tuberculosis will help in designing new chemotherapeutic and immunotherapeutic interventions. This review highlights recent developments in genomics, mycobacterial genetics, novel vaccine strategies, and our understanding of tuberculous dormancy.

Journal Article↗
PubMed1999

Reactivation of latent tuberculosis: variations on the Cornell murine model.

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.

Animals↗
PubMed1999

Rapid film-based determination of antibiotic susceptibilities of Mycobacterium tuberculosis strains by using a luciferase reporter phage and the Bronx Box.

Detecting antibiotic resistance in Mycobacterium tuberculosis is becoming increasingly important with the global recognition of drug-resistant strains and their adverse impact on clinical outcomes. Current methods of susceptibility testing are either time-consuming or costly; rapid, reliable, simple, and inexpensive methods would be highly desirable, especially in the developing world where most tuberculosis is found. The luciferase reporter phage is a unique reagent well-suited for this purpose: upon infection with viable mycobacteria, it produces quantifiable light which is not observed in mycobacterial cells treated with active antimicrobials. In this report, we describe a modification of our original assay, which allows detection of the emitted light with a Polaroid film box designated the Bronx Box. The technique has been applied to 25 M. tuberculosis reference and clinical strains, and criteria are presented which allow rapid and simple discrimination among strains susceptible or resistant to isoniazid and rifampin, the major antituberculosis agents.

Antitubercular Agents↗