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J Chan

Publications and source records attributed to J Chan.

At least 181 records · Page 10Linked to original sources
PubMed1995

Use of quantitative ultrastructural immunoperoxidase labeling for analysis of catecholamine neurotoxicity and plasticity.

Levels of catecholamines and the synthesizing enzyme, tyrosine hydroxylase (TH) are markedly decreased in the dorsal striatum, caudate-putamen nuclei, following neurotoxic lesions with 6-hydroxy-dopamine (6-OHDA). We examined whether pre-embedding immunoperoxidase labeling of TH could be standardized for quantitatively examining the density and ultrastructure of spared dopaminergic terminals in the striatum of lesioned rats. The peroxidase-antiperoxidase (PAP) method was used to localize rabbit antiserum against TH in caudate-putamen nuclei of adult rats given unilateral nigral injections of either vehicle or 6-hydroxydopamine in the early postnatal period. Experimental differences in fixation and immunocytochemical labeling were minimized by limiting comparisons of immunoreactivity to co-processed sections from the same litters of animals. Imaging software and a Phillips CM-10 electron microscope were used to quantitatively examine immunoreactive profiles in a narrow zone of tissue in contact with the embedding resin. Under these conditions variables attributed to differences in penetration were minimized. There were no significant differences in numbers or mean-cross sectional diameter of immunoreactive terminals in striatum ipsilateral versus contralateral to vehicle injections. Ipsilateral to the 6-OHDA injections, the density (numbers/area) of striatal TH-immunoreactive terminals was reduced by 50-90% in the majority of animals. In the most extensively lesioned rats, the cross-sectional areas of the remaining immunoreactive axons were significantly larger than in the contralateral striatum of the same animal or either hemisphere of vehicle injected controls. These results confirm and extend earlier findings on the plasticity of residual dopaminergic terminals in adult animals after neurotoxic damage. They also establish a quantitative method for ultrastructural analysis of the density of immunoreactivity in thick sections of tissue labeled prior to plastic embedding. The method has broad applicability to quantitative studies of neurotoxicity and plasticity in brain.

Animals↗
PubMed1995

Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.

Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.

Amino Acid Oxidoreductases↗
PubMed1995

Investigating the influence of treatment philosophy on outcome of methadone maintenance.

This study is based on a 'natural experiment' in which a cohort of heroin users was assessed at one unit, then referred on geographic grounds for treatment to one of two clinics--one orientated to long-term maintenance (Clinic 2, with 61 subjects), the other to time-limited treatment aimed at achieving abstinence from all drugs including methadone (Clinic 1, 141 subjects). The outcome measure was heroin use as measured by urine testing performed regularly at both clinics. Overall, 25% of urine tests from Clinic 1 were positive for heroin compared to 18% in Clinic 2. This difference reflected in part a high rate of heroin use during the period of mandatory withdrawal from treatment in clinic 1. Statistical models were developed to identify factors associated with heroin use. There was a strong association between methadone dose and heroin use; relative to a daily dose of 40 mg, a dose of 80 mg/day of methadone was less likely to be associated with a heroin-positive urine (OR 0.55, 95% CI [0.45, 0.68]). Average doses prescribed in Clinic 1 were lower, reflecting the clinic's orientation to abstinence. Adjusting for dose, and for the fact that certain individuals tend to use heroin heavily while others do not, there was no difference between the clinics in risk of heroin use during maintenance treatment. The higher rates of heroin use in the abstinence-orientated clinic were attributable to time-limited treatment and the use of lower doses of methadone. This finding confirms that in investigating the effects of treatment factors, the powerful influence of methadone dose needs to be taken into account.

Adult↗
PubMed1995

Intensive consolidation chemotherapy for newly diagnosed acute myeloid leukemia using a regime containing moderate dose cytosine arabinoside and mitoxantrone.

Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy.

Adolescent↗
PubMed1995

Arterial conduits in emergency coronary artery surgery.

The internal thoracic artery (ITA) is considered to be the conduit of choice for coronary bypass (CABG), but there has been some reluctance to utilize the ITA for revascularization in emergency situations. In a 9-year retrospective analysis from 1986 through 1993, 484 patients had emergency CABG, 237 were not associated with failed PTCA (noninstrumented) and 247 were within 24 hours of PTCA (instrumented). About 62% of noninstrumented and 49.3% of instrumented patients received one or more ITA grafts, the others receiving only saphenous vein grafts (SVGs). Those who received an ITA graft tended toward male sex, better ejection fraction, and a generally lower clinical risk score. Instrumented patients tended toward a lower incidence of diabetes and left main coronary disease, higher ejection fraction, and lower clinical risk score than noninstrumented patients. The postoperative results were not significantly different between ITA and SVG groups with respect to new Q waves, need for reexploration, sternal wound infection, respiratory complications, or stroke. However, ITA patients more often had an event-free postoperative course, received fewer blood transfusions, and experienced fewer cardiac deaths (2.7% vs 9.4%, p < 0.01). There were few obvious differences in postoperative results between instrumented and noninstrumented patients. These results indicate that the ITA can be used for emergency CABG in selected patients with good results.

Aged↗
PubMed1995

Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis.

We have recently demonstrated that the macrophage L-arginine-dependent cytotoxic pathway effectively kills the virulent Erdman strain of Mycobacterium tuberculosis in vitro via the generation of toxic reactive nitrogen intermediates by the enzyme nitric oxide synthase. This report demonstrates that two distinct inhibitors of nitric oxide synthase (aminoguanidine and NG-monomethyl-L-arginine) render similar deleterious effects on tuberculous infection in mice, as assessed by mortality, bacterial burden, and pathological tissue damage, thus confirming the importance of reactive nitrogen intermediates in resistance against M. tuberculosis.

Amino Acid Oxidoreductases↗
PubMed1995

Insulin receptor-related receptor messenger ribonucleic acid: quantitative distribution and localization to subpopulations of epithelial cells in stomach and kidney.

A novel member of the insulin receptor family, the insulin receptor-related receptor (IRR), was initially identified by cloning genomic DNA homologous to the insulin receptor. We have now used Northern blot and polymerase chain reaction analyses of a variety of human tissues to demonstrate that the kidney is a major site of IRR gene expression. IRR transcripts (approximately 6 and approximately 2 kilobases) were detected only in human kidney by Northern blot analyses. Quantitative competitive polymerase chain reaction analysis revealed that IRR messenger RNA levels were distributed more widely. IRR transcripts in human kidney were approximately 3- to 10-fold greater than those in thymus, brain, heart, and stomach and approximately 150-fold higher than those in placenta, skeletal muscle, and liver. In situ hybridization histochemical analysis revealed that IRR transcripts were present in a subpopulation of cells within distal tubules of human kidney, beyond the most proximal segment of the distal convoluted tubule. In rat stomach, IRR messenger RNA was localized to a subset of neuroendocrine cells in gastric glands of the fundic mucosa. This selective distribution of IRR transcripts in human and rat tissues suggests that IRR may mediate the responses of a neuroendocrine factor involved in regulating select aspects of cell function in a highly tissue-specific manner.

Base Sequence↗
PubMed1995

The impact of cancer pain education on family caregivers of elderly patients.

PURPOSE/OBJECTIVES: To examine the impact of pain education on family members providing home care to elderly patients with cancer. DESIGN: Quasiexperimental. SETTING: Homes of selected patients from two California medical centers. SAMPLE: Fifty family caregivers of patients experiencing cancer-related pain. METHODS: The pain education program included three components: pain assessment, pharmacologic interventions, and nonpharmacologic interventions. Patients and their family caregivers were evaluated prior to initiation of the program and at one and three weeks following the interventions. MAIN RESEARCH VARIABLES: Quality of life (QOL); knowledge and attitudes about pain; and caregiver burden. FINDINGS: Findings based on measures of QOL and caregiver burden demonstrated the physical and psychological impact of family caregiving and pain management. Comparison between elderly patients with cancer and family caregivers revealed the pain experience's significant impact on family members caring for a loved one in pain. CONCLUSIONS: The pain education program was effective in improving knowledge and attitudes regarding pain management. IMPLICATIONS FOR NURSING PRACTICE: Pain management is a priority for nurses, and use of interventions such as structured pain education improves QOL outcomes for elderly patients and their family caregivers.

Adaptation, Psychological↗
PubMed1995

Integrated and collaborative computing in a medical workgroup environment.

The demand for integrated and collaborative computing in the practice and research of pediatric medicine today is particularly strong within the Division of Haematology/Oncology at the Hospital for Sick Children, Toronto, Canada. As the lead institution in pediatric oncology, the hospital and the division are championing the use of information technology and automation methodology to stage an environment with viable system solutions in which distinct working groups and units coexist and cooperate to promote total quality patient care and front-line medical research. A medical information management paradigm, utilizing the concept of computer-oriented workgroup collaboration, is implemented to enable data, knowledge, and work flow integration in a functionally separate workgroup setting.

Hospital Information Systems↗
PubMed1994

Ultrastructure of Met5-enkephalin terminals in the caudate-putamen nuclei of adult rats receiving neonatal intranigral 6-hydroxydopamine.

Destruction of dopamine neurons of the nigrostriatal pathway in the early postnatal rat enhances the levels of Met5-enkephalin in the adult dorsal striatum (caudate-putamen nuclei) and may contribute to the abnormal self-injurious behavior seen in humans with Lesch-Nyhan disease. We examined whether there were ultrastructural changes in Met5-enkephalin immunoreactive terminals in the rat model that might reflect cellular sites for enhanced activity of these opioid neurons. At 3 days postnatal, 10-20 nl injections of a 1% solution of the dopamine neurotoxin, 6-hydroxydopamine (6-OHDA), or vehicle were placed unilaterally in the region of the substantia nigra of 25 litters of male rat pups. In adulthood (72-80 days postnatal), the brains of these animals were fixed by vascular perfusion with an aldehyde solution. Met5-enkephalin immunolabeling was examined in coronal sections at three rostrocaudal levels through the caudate-putamen nuclei of control (ipsilateral and contralateral to vehicle and contralateral to 6-OHDA) and experimental (ipsilateral to 6-OHDA) groups. In selectively lesioned animals, there was a significant increase in the relative optical density of immunoautoradiographic labeling for enkephalin throughout the rostrocaudal striatum ipsilateral to 6-OHDA as compared to control groups. Electron microscopy revealed immunoperoxidase labeling for enkephalin in axon terminals and more rarely in soma and dendrites irrespective of drug treatment. In both experimental and control striatal tissues, the enkephalin immunoreactive terminals formed primarily symmetric synapses with unlabeled dendrites or spines. However, ipsilateral to 6-OHDA injections there was a small (5.4%), but significant increase in the proportion of enkephalin immunoreactive terminals contacting dendritic spines, the known targets of dopamine terminals. Appositions were commonly detected between enkephalin immunoreactive terminals and other morphologically heterogeneous axons in the striatum ipsilateral to 6-OHDA and in control tissues. Met5-enkephalin immunoreactive terminals in adult striatum ipsilateral to 6-OHDA injections showed a 214% increase in volume as compared to vehicle-injected controls. Concurrently, there was a small (13%), but significant increase in the numerical density (number/volume) of enkephalin-labeled terminals both contralateral and ipsilateral to 6-OHDA injections. These results suggest that a change in bouton size is the major mechanism by which striatal enkephalin neurons alter their synaptic efficacy and target associations to compensate for damage to the nigrostriatal dopamine neurons.

Animals↗
PubMed1994

alpha-Bungarotoxin blocks the nicotinic receptor mediated increase in cell number in a neuroendocrine cell line.

Exposure of H69 small cell lung carcinoma cells to nicotinic agonists resulted in a significant increase (up to 100%) in cell number after 6 to 12 days. The effect of nicotine (10(-8) M to 10(-4) M) was both dose and time dependent as was that of another nicotinic agonist cytisine (10(-6) M to 10(-4) M). Interestingly, both the nicotine and cytisine induced increases in H69 cell number were blocked by alpha-bungarotoxin, as well as d-tubocurarine a nicotinic blocker which appears to interact with most nicotinic receptors. These results suggest that the nicotine induced increase in cell number is mediated through an interaction at the nicotinic alpha-bungarotoxin receptor. This idea is further supported by experiments which show (1) that H69 cells possess high affinity alpha-bungarotoxin sites (Kd = 25 nM, Bmax = 10.4 fmol/10(6) cells) with the characteristics of a nicotinic alpha-bungarotoxin receptor and (2) that the potencies of nicotinic receptor ligands in the alpha-bungarotoxin binding assay were similar to those observed in the functional studies. Northern analysis showed that mRNA for alpha 7, a putative nicotinic alpha-bungarotoxin binding subunit, and for alpha 5 were present in H69 cells. The present data provide further evidence that nicotine increases cell number in small cell lung carcinoma and are the first to show that this effect is mediated through an interaction at the nicotinic alpha-bungarotoxin receptor population. These results suggest that the alpha-bungarotoxin site may be involved in modulating proliferative responses in neuroendocrine derived SCLC cells.

Alkaloids↗
PubMed1994

Met5-enkephalin is localized within axon terminals in the subfornical organ: vascular contacts and interactions with neurons containing gamma-aminobutyric acid.

Met5-enkephalin inhibits sodium and water excretion and antagonizes the central actions of angiotensin II in subfornical organ of rat brain. We examined the ultrastructural basis for enkephalin modulation in this circumventricular region. Additionally, we examined the possibility that there might be cellular sites for functional interactions involving Met5-enkephalin and gamma-aminobutyric acid (GABA), a known inhibitory transmitter throughout the central nervous system. Met5-enkephalin and GABA were identified in single coronal sections through the subfornical organ using immunoperoxidase and silver-enhanced immunogold labeling methods, respectively. Enkephalin-like immunoreactivity was most prominently localized within axon terminals. These were distributed primarily in the central, highly vascular, regions of the subfornical organ. Enkephalin-labeled terminals were apposed to the basement membranes of fenestrated capillaries and also formed symmetric, inhibitory type synapses with neurons. In terminals associated with either blood vessels or neurons, the enkephalin immunoreactivity was enriched in large (80-150 nm) dense core vesicles. The immunoreactive vesicles were usually located within portions of the axon in close proximity to astrocytic processes. In contrast, smaller vesicles in the same terminals were more often aggregated near the basement membrane of the capillaries and the active zone of the synapse. The targets of enkephalin-immunoreactive terminals were either unlabeled or GABA-labeled dendrites of local neurons. Enkephalin was also co-localized with GABA in perikarya and in axon terminals. Terminals containing only GABA were far more abundant than those containing enkephalin or enkephalin and GABA. GABA-immunoreactive terminals formed symmetric synapses on unlabeled dendrites some of which also received convergent input from terminals containing enkephalin. Additionally, the enkephalin-immunoreactive terminals were closely apposed to GABA-labeled and unlabeled terminals. These results suggest sites for nonsynaptic release of Met5-enkephalin from dense core vesicles in contact with astrocytes near blood vessels and synaptic complexes in the rat subfornical organ. Moreover, the observed dual localization and pre- and postsynaptic associations between neurons containing Met5-enkephalin and GABA indicate that inhibitory effects of opioids in the subfornical organ may be mediated or potentiated by GABA.

Animals↗
PubMed1994

Potentiation of radioimmunotherapy by inhibition of topoisomerase I.

Cancer therapy with radiolabeled antibodies is limited by the low uptake of radioimmunoconjugates into tumor masses. In this study, camptothecin, a topoisomerase I poison, was examined in vitro and in vivo for potentiation of radioimmunoconjugate therapy. gamma-Ray irradiation of AS-30D rat hepatoma cells followed by a 2-h exposure to camptothecin was found to act additively at low radiation doses (< 200 rad) and synergistically at higher radiation doses as shown by isobologram analysis with 20% survival used as the end point. A monoclonal antibody, RH1, was developed against AS-30D cells and shown to localize in hepatoma ascites in SD rats. Therapy of established ascites tumors with four weekly rounds of either camptothecin administered i.m. in a slow release form or 131I-labeled monoclonal antibody RH1 administered by i.p. injections prolonged rat survival but was ineffective at curing animals of tumors. In contrast, four weekly rounds of combined therapy consisting of i.m. injections of 5 mg/kg camptothecin suspended in lipiodol followed 24 h later by i.p. injection of 200 microCi 131I-labeled monoclonal antibody RH1 cured 86% of animals. Treatment with camptothecin and a 131I-labeled control antibody was no more effective than treatment with drug alone. These results show that camptothecin can potentiate the effects of radiation both in vitro and in vivo and suggest that topoisomerase I inhibitors may be useful for increasing the efficacy of radioimmunoconjugates for the treatment of cancer.

Animals↗
PubMed1994

Experimental approaches to mechanisms of protection and pathogenesis in M. tuberculosis infection.

It has, for many years, been widely assumed that the fundamental mechanism of protection in tuberculosis infection is a CD4 T cell response producing lymphokines that activate macrophages to kill or restrict the intracellular growth of M. tuberculosis. Just as certain cytokines, e.g. IFN-gamma, are currently perceived to be important for protection, others, particularly tumor necrosis factor (TNF), are thought to be responsible for much of the tissue destruction associated with the disease. Yet there are remarkably few critical experimental or clinical data that have defined the immunological requirements for protection and pathogenesis. One of the initial stimuli to the work we have undertaken has been careful reflection on the results of the many prospective trials of BCG against tuberculosis. Two aspects have impelled us to reconsider conventional wisdom. The first, of course, is the wide discrepancy in the degree of protection imparted, ranging from 0% in South India to 77% in the British MRC trial (1, 2). The second is that, in all trials that examined them, skin test conversions to tuberculin positivity were 85% or greater, indicating a disparity between the presence of delayed hypersensitivity to tuberculin and protection. We and others have argued (1, 2) that there are multiple possible explanations for this discrepancy, the principal one being protection caused by infection with environmental mycobacteria. But, the general point raised is whether cell mediated immunity as manifested by CD4+ cell production of lymphokines and macrophage activation is a sufficient mechanism for protection against M. tuberculosis infection.

Animals↗
PubMed1994

Relationship between human immunodeficiency virus infection and salmonellosis in 20- to 59-year-old residents of New York City.

Among 20- to 59-year-old residents of New York City who have septicemia, gastroenteritis, urinary tract infection, and multiple site infections due to Salmonella, those listed in the New York City AIDS Registry were highly overrepresented. Among the patients listed in the registry, males outnumbered females by 4:1 (septicemia), 9:1 (multiple site infections), 5.6:1 (gastroenteritis), and 2.5:1 (urinary tract infection); among patients not listed, males outnumbered females by 2.7:1 (septicemia), 3:1 (multiple site infections), 1.2:1 (gastroenteritis), and 1.6:1 (urinary tract infection). These results strongly suggest that most nonlisted males with septicemia and multiple site infections, and a minority with gastroenteritis and urinary tract infection, were human immunodeficiency virus (HIV)-positive. Among individuals who were HIV-positive, or likely to be so, Salmonella enteritidis was more competent in causing septicemia and less competent in causing gastroenteritis than was Salmonella typhimurium; among HIV-negative individuals, the reverse was true. The different capacities for infection with and invasiveness of S. enteritidis, S. typhimurium, and other Salmonella serotypes in HIV-positive and HIV-negative individuals and the use of HIV testing for Salmonella-infected individuals are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1994

Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity.

This article reviews the evidence that the nodular form of lymphocyte predominance Hodgkin's disease ("nodular paragranuloma") should be recognised as a distinct clinico-pathological entity. The disease is characterised histologically by very large primary lymphoid follicles, containing polytypic small B lymphocytes and extensive meshworks of follicular dendritic cells. The "L and H" or "popcorn" cells scattered within the nodules show clear differences from classical Reed-Sternberg cells, both in their cytological appearance and in their marker profile, being frequently negative for CD15 and for the EBV genome, but often positive for B cell antigens, CD45 (leucocyte common antigen), CDw75 (LN1), epithelial membrane antigen (EMA) and J chain. These findings suggest that L and H cells may be Ig-synthesising monoclonal B cells. Nodular lymphocyte predominance Hodgkin's disease pursues a much more indolent courses that classical Hodgkin's disease, and long term survival is common. It has other distinctive clinical features, e.g. a unimodal age distribution, a predilection to involve single lymph nodes, and a very low incidence of thymic involvement. There is a tendency for diffuse large cell non-Hodgkin's lymphoma, usually of B cell type, to develop during the course of the disease. This type of Hodgkin's disease thus has many features that distinguish it from the nodular sclerosis and mixed cellularity varieties, and it is hoped that future studies will gather more information on its clinical behavior and on the nature of the putative neoplastic cells, as well as exploring different protocols for its treatment.

Hodgkin Disease↗