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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1999

Role of PI3-kinase in Bcl-X induction and apoptosis inhibition mediated by IL-3 or IGF-1 in Baf-3 cells.

In Baf-3 cells, IL-3 and IGF-1 both inhibit cell death. These growth factors act at least on two different pathways involved in the inhibition of apoptosis. They both upregulate Bcl-X at the mRNA and protein levels and also activate a pathway which inhibits apoptosis in the absence of protein synthesis. Recently, these two growth factors have been shown to activate the PI3-kinase-AKT pathway which leads to the phosphorylation of the pro-apoptotic Bcl-XL regulator Bad. In this study, we have investigated the role of PI3-kinase in the regulation of Bcl-X expression and in the survival of Baf-3 cells. We show that PI3-kinase activation is involved in the upregulation of Bcl-X mRNA induced by both IL-3 and IGF-1. Moreover, PI3-kinase activity is also necessary for inhibition of apoptosis and caspase regulation by IGF-1 but not IL-3.

Animals↗
PubMed1999

Accuracy of intraoperative frozen-section analysis of axillary nodes. Edinburgh Breast Unit team.

BACKGROUND: Intraoperative assessment of axillary lymph node involvement would allow selection of patients who would benefit from axillary lymph node dissection. METHODS: Eighty-eight patients undergoing mastectomy or wide excision had four nodes sampled and sent for frozen-section examination. RESULTS: Frozen-section analysis of the nodes was correct in 81 of the 88 patients but missed seven of the 26 patients who had involved nodes on paraffin section (sensitivity 73 per cent). CONCLUSION: Frozen-section analysis of axillary lymph nodes as currently practised cannot be recommended for routine use although it may have a role in specific groups of patients.

Adolescent↗
PubMed1999

Pulmonary inflammation without bronchial hyperresponsiveness in vivo or in vitro after sephadex instillation in pigs.

1. In rodent models, Sephadex produces pulmonary inflammation that may be associated with bronchial hyperresponsiveness. In the present study we examined whether Sephadex-induced inflammation altered airway narrowing in pigs. 2. Twenty millilitres of 10 mg/mL Sephadex suspension was instilled twice intratracheally into anaesthetized pigs (days 1 and 7 of a 9 day study). In vivo bronchial responsiveness was assessed from the effect of acetylcholine (ACh) aerosol on airways resistance and dynamic compliance before Sephadex instillation and on days 3, 5 and 9. Lung histology and in vitro bronchial responsiveness was assessed on day 9. In vitro responsiveness was assessed by measuring the reduction in flow through perfused 2 mm i.d. bronchial segments in response to ACh applied luminally and adventitially. 3. Sephadex produced a focal peribronchial granulomatous reaction characterized by the presence of macrophages, eosinophils, neutrophils and giant cells. Changes in airway resistance and lung compliance in response to ACh did not change over the study period. The response of perfused bronchial segments to luminally or adventitially applied ACh was also unaltered. 4. Sephadex-induced pulmonary inflammation does not alter airway narrowing in vitro nor bronchial hyperresponsiveness in vivo in the pig.

Animals↗
PubMed1999

Composite renal cell carcinoma and angiomyolipoma: a study of the histogenetic relationship of the two lesions.

The purpose of the present study was to investigate the possible histogenetic relationship of renal cell carcinoma (RCC) and angiomyolipoma (AMYL) occurring in the same renal nodule by examining two cases of composite RCC and AMYL in patients without stigmata of tuberous sclerosis and by reviewing the medical literature of similar cases. Case 1 represents an epithelioid variant of AMYL with multiple additional nodules of typical AMYL in a surgically removed kidney. The patient subsequently developed a lesion consisting of a mixture of epithelioid variant of AMYL and RCC 24 months later in the retroperitoneum and, an additional 4 months later, in the liver. The RCC cells resembled mononucleated epithelioid cells of the epithelioid AMYL except that they were focally reactive with epithelial membrane antigen (EMA) in the retroperitoneum and focally reactive with both EMA and cytokeratin (CK) in the liver. Case 2 consisted of a typical AMYL admixed with a chromophil cell RCC. A review of the medical literature revealed seven additional cases with histopathological findings similar to this case. All cases had multiple foci of typical AMYL. Immunostaining results are available in five tumors. Chromophil RCC showed variable reactivity with CK and EMA. In addition, RCC in the two cases in the present study also displayed a positive reaction with mucin staining and a positive reactivity with carcinoembryonic antigen. There appears to be a spectrum of histopathological and immunohistochemical changes from the epithelioid variant of AMYL through a mixed epithelioid AMYL/RCC to chromophil RCC in three successive specimens in case 1. Moreover, the intimate admixture of AMYL and RCC and the similar expression of epithelial markers of RCC in the two cases in the present study, as well as other cases in the literature, suggest that some RCC develop from the same precursor cell as AMYL or from a component of AMYL.

Adult↗
PubMed1999

Basolateral store-operated Ca(2+)-entry in polarized human bronchial and colonic epithelial cells.

Bronchial epithelial cells respond to extracellular nucleotides from the luminal and basolateral side activating Cl- secretion via [Ca2+]i increase. In this study we investigated the differences of apically (ap) and basolaterally (bl) stimulated [Ca2+]i signals in polarized human bronchial epithelial cells (16HBE14o-). Specifically we investigated the localization of 'capacitative Ca2+ entry' (CCE). 16HBE14o- cells grown on permeable filters were mounted into an Ussing chamber built for the simultaneous measurement of Fura-2 fluorescence and electrical properties. Application of ATP from both sides induced a rapid [Ca2+]i increase and subsequent sustained [Ca2+]i plateau due to transmembraneous Ca(2+)-influx. The use of different nucleotides revealed the following rank order or potency which was very similar for addition from the apical or basolateral side: UTP (EC50 ap: 4 microM, bl: 5 microM) > ATP (EC50 ap: 4 microM, bl: 10 microM) > ADP (n = 4-7 from both sides). 2-MeS-ATP, AMP, adenosine and beta gamma-methylene ATP were ineffective (n = 3 from both sides). The ATP- (ap and bl) induced Ca2+ influx was only abolished by removal of basolateral Ca2+. This was also true for receptor-independent activation of Ca(2+)-influx by intracellular Ca(2+)-store depletion with 2,5 Di-(tert-butyl)-1,4-benzohydroquinone (BHQ) (10 microM). Also in polarized T84 cells the basolateral carbachol and BHQ activated Ca2+ plateau was exclusively sensitive to removal of basolateral Ca2+. We propose that in all polarized epithelial cells the CCE entry pathway is located in the basolateral membrane. We furthermore suggest that Ca2+[i elevating agonists acting from the apical side of the epithelium lead to the opening of a basolateral CCE pathway.

Adenosine Triphosphate↗
PubMed1999

Ethnic minorities and their vulnerability to AIDS in a border state of India.

To successfully stall the spread of HIV/AIDS among the ethnic minorities in India, it is imperative that we not only understand the complexity of issues in India with regard to HIV spread among ethnic groups but also comprehend that straightforward measures that might have worked in the context of other countries may not work in the Indian context. The authors present field work data and the results of interviews with 635 opinion leaders from eight 'tribal groups' from the north eastern border state of Manipur in India where a high rate of HIV infection is reported among the IDUs (intravenous drug users). The study found community support for AIDS, sex and drug education, along with an increasing perception of social vulnerability. Even though respondents perceive the threat of infection, few feel that they are personally susceptible. As HIV/AIDS prevention programmes compete with other socioeconomic conditions, the prevention blue print must be tailored to meet diverse demands in the study area and of the ethnic minorities in India.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Death by neglect as a deletional mechanism of peripheral tolerance.

In contrast to most organs, the anatomy of the liver may allow naive CD8(+) T cells to make direct contact with liver parenchymal cells. We have previously shown, using a combination of TCR transgenic T cells specific for H-2 K(b) and hepatocytes expressing a transgenic H-2 K(b) molecule, that hepatocytes can induce antigen-specific activation and proliferation of naive CD8(+) T cells independently of CD28 co-stimulation. However, T cell activation by hepatocytes leads to premature T cell death and tolerance, both in vivo and in vitro. In this study, we investigated the mechanisms of T cell death induced by hepatocytes in vitro using primary hepatocytes to activate purified CD8(+) T cells. Neither Fas nor tumor necrosis factor receptor were involved, indicating that hepatocyte- induced death was distinct from activation-induced cell death. Before they started to divide, T cells activated by hepatocytes expressed lower levels of the bcl-x(L) survival gene and 30 times less IL-2 mRNA than CD8(+) cells activated by splenic antigen-presenting cells. Since CD28 co-stimulation increases both IL-2 and bcl-x(L) expression, this suggests that hepatocyte-activated T cells die by neglect because they fail to receive effective co-stimulatory signals. In agreement with this model, premature death promoted by hepatocytes could be prevented by cross-linking CD28. Survival after CD28 cross-linking correlated with increased IL-2 and bcl-x(L) expression, and sustained T cell proliferation, while cytotoxic T lymphocyte activity was prolonged as compared with cells stimulated without CD28 co-stimulation. This study confirms that high- affinity TCR transgenic antigen-specific CD8(+) T cells can be activated to proliferate and differentiate into cytotoxic effector cells. However, prolonged T cell survival and cytotoxicity required CD28 co-stimulation as well. To our knowledge, this is the first report suggesting that tolerance in the context of lack of CD28 co-stimulation can result from Fas-independent peripheral deletion rather than from anergy.

Animals↗
PubMed1999

How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia.

This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications. A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry. Patients in the original study were randomly assigned to haloperidol or clozapine and followed for 12 months, at maximum tolerable doses. Patients who completed a full year of treatment with clozapine (n = 122), or with either haloperidol or another conventional antipsychotic medication (n = 123) and who also completed the 9- or 12-month assessment were included. Response to treatment was defined as 20 percent improvement on standard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews. More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup. Among patients who did not improve at 6 weeks, 3 months, or 6 months, there were no significant differences between clozapine and comparison patients in outcomes at 1 year. Among patients who did improve, maintenance of that improvement also did not differ between the groups at 1 year on symptom measures. Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months (p < 0.04). Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment.

Adult↗
PubMed1999

Traditional coronary risk factors in African Americans.

The importance of traditional coronary artery disease risk factors in the development of coronary heart disease is well known. African Americans have a higher prevalence of such risk factors as hypertension, diabetes mellitus, obesity, cigarette smoking, and left ventricular hypertrophy, which might account for the disproportionate rate of coronary heart disease mortality in African Americans. Compelling data from randomized lipid-lowering trials show conclusively that lowering cholesterol levels, specifically low-density lipoprotein cholesterol, lowers coronary heart disease morbidity and mortality. Recent data has also demonstrated the beneficial effects of lowering blood pressure on cardiovascular mortality. Left ventricular hypertrophy, which results from elevated blood pressure, seems to raise coronary heart disease risks independently. Diabetes mellitus, cigarette use, physical inactivity, stress, and obesity play critical roles collectively and individually in increasing coronary heart disease, morbidity, and mortality. Clustering of coronary heart disease risk factors in African Americans must be strongly considered to play a critical role in the excess mortality from coronary heart disease seen in African Americans. New innovative approaches are required if the course of coronary heart disease is to be altered.

Black or African American↗
PubMed1999

Effect of topical rh-TGF-beta 1 on second intention wound healing in horses.

OBJECTIVE: To investigate the effects on wound healing of transforming growth factor-beta 1 as a topical treatment to full-thickness, excisional wounds of the distal limb of horses. DESIGN: A randomised block study using four horses, each with wounds assigned to four treatment groups. ANIMALS: Four adult Standardbred geldings. PROCEDURE: Four, 4 cm2, full-thickness wounds were created on the dorsomedial and dorsolateral aspect of the metacarpus or metatarsus of each limb of four horses, giving a total of 64 wounds. For each limb, wounds were randomly assigned to four treatment groups: no treatment (control), carrier (Methyl Cellulose gel), 50 ng/wound rhTGF-beta 1 in carrier, and 500 ng/wound rhTGF-beta 1 in carrier. Wounds were treated on day 0 and day 8. Effects of treatment were evaluated on the basis of the presence of exuberant granulation tissue requiring excision, number of times excision was required, total wound area, area of epithelialisation, area of granulation, and histological evaluation of biopsy samples of wounds on day 8 and excised wounds on day 21. RESULTS: Topical application of TGF-beta 1 at the two concentrations studied had no significant effect on the total area of wounds (P = 0.7), the area of granulation tissue (P = 0.78), the area of epithelialisation (P = 0.92), histological assessment or subjective clinical assessment of wounds. CONCLUSION: TGF-beta 1 had no beneficial effects on wound healing. Additional trials are needed to test if it has value for wound treatment in horses.

Administration, Cutaneous↗
PubMed1999

Use of molecular assays in diagnosis and monitoring of cytomegalovirus disease following renal transplantation.

We compared two commercial molecular assays (the Murex Hybrid Capture CMV DNA assay [HCA], version 2, and the Roche Amplicor plasma PCR assay) with a standard shell vial assay in detecting and predicting cytomegalovirus (CMV) disease in a group of renal transplant patients and assessed the role of viral load measurements (using the HCA) in their management. The sensitivity of the HCA and Amplicor assay in terms of disease detection was 100%, compared to 71% for the shell vial assay. Both the HCA and the PCR assay detected all cases of disease, at medians of 11 and 12.5 days before the onset of symptoms, respectively. Significantly higher viral loads were detected in those patients with symptoms (7.9 x 10(5) copies/ml) than in patients without symptoms (7.9 x 10(4) copies/ml; P < 0.0001). There was also a trend towards higher viral loads in those patients with primary infections (7.8 x 10(5) copies/ml) than in those patients with reactivations of CMV disease or reinfections. Successful treatment with ganciclovir was associated with a >90% reduction in viral load. Both of these new assays are sensitive and easy to use. A comparison of accurate quantitation is also useful in monitoring responses to antiviral therapy.

Adult↗
PubMed1999

Impact of clozapine on negative symptoms and on the deficit syndrome in refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

OBJECTIVE: This study compared the effect of clozapine and haloperidol on positive and negative symptoms of schizophrenia and in patients with high levels of negative symptoms or the deficit syndrome. METHOD: Patients were participants in a 15-site double-blind, random-assignment Veterans Administration trial comparing clozapine (N=205) and haloperidol (N=217) in hospitalized patients with refractory schizophrenia. Analysis of covariance examining change at 6 weeks, 3 months, and 1 year evaluated 1) clozapine's effect on positive and negative syndromes; 2) clozapine's effect on each syndrome, statistically controlling for the other; and 3) the interaction of clozapine treatment and the presence or absence of high levels of negative symptoms at baseline and the deficit syndrome. RESULTS: Patients treated with clozapine showed significantly greater improvement than control subjects on positive symptoms at all time points and on negative symptoms at 3 months. Clozapine had no independent effect on negative symptoms at any time after control for positive symptoms, but its effects on positive symptoms persisted after control for negative symptoms at 6 weeks only. There were no significant differences in response to clozapine between patients with high and low levels of negative symptoms at baseline or between patients with and without the deficit syndrome. CONCLUSIONS: The greater effectiveness of clozapine as compared to conventional medications in refractory schizophrenia is not specific to either negative clinical symptoms or clinical subtypes defined by prominent negative symptoms or evidence of the deficit syndrome.

Analysis of Variance↗
PubMed1999

Cardiac neoplasms at the Canadian Reference Centre for Cancer Pathology.

OBJECTIVE: To review the Canadian Reference Centre for Cancer Pathology's experience with cardiac neoplasms by reviewing all cases with tumours involving the heart referred to the Centre from 1949 to 1995. Referred patient records, panel and consensus statement submissions and glass slides were reviewed in all cases. In selected cases additional immunohistochemical stains were obtained from paraffin block tissues. SETTING: National referral centre for difficult or interesting cancer pathology-related cases. PATIENTS: All cases were derived from referral of autopsy material and/or surgically resected neoplasms. Material was referred from 35 patients during 1949 to 1995. The group consisted of 17 males, 17 females and one infant patient in whom the sex was not specified. The patient age ranged from infancy to 85 years. RESULTS: The neoplasms referred consisted of 12 myxomas, 10 sarcomas, five lymphomas, two carcinomas, two papillary fibroelastomas and one each of rhabdomyoma, mesothelioma of the atrioventricular node, lipomatous hypertrophy of the intra-atrial septum and fibroma. The sarcomas were difficult to classify even with the use of additional immunohistochemical stains. All the lymphomas were of non-Hodgkin's type and were not of primary cardiac origin. CONCLUSIONS: The series of neoplasms referred to the Canadian Reference Centre for Cancer Pathology reflects changes in cardiac surgery, cardiac imaging and cardiac pathology as disciplines. Even with modern pathological techniques some cases, especially sarcomas, are still difficult to diagnose. The clinical presentation often reflects the chamber of origin of the neoplasm rather than being indicative of a specific tumour type.

Adolescent↗
PubMed1999

A database designed for utilization management in diagnostic imaging.

The methods and tools of health services research have been applied to a diverse number of health care areas. Surprisingly, they have been adopted only recently in diagnostic imaging, by a small number of professionals, in response to the severe fiscal constraints and widespread structural changes in the health industry, as well as to a growing concern that the value of social and individual investment in high-cost imaging services could not be validated objectively. As a result of the need for accountability for the use of scarce resources, regulators and payers of health services increasingly demand that a reasoned and objective evaluative process be adopted. To undertake a statistically driven evaluative approach that stands up to objective assessment of methodological rigour, an organized data-collection system is needed. Without this fundamental cornerstone, evaluators are left with little more than anecdotal evidence and professional and personal opinion to guide decision-making. It then becomes difficult to learn from both the successes and failures that are routinely experienced during times of rapid and fundamental change. This article describes the efforts made to integrate health services research in radiology into the routine daily activities and supporting systems of a large academic health system, the Hamilton Health Sciences Corporation and McMaster University Department of Radiology, in an attempt to move in the direction of evidence-based decision-making. The authors hope this will allow others to learn and improve on this work. Radiologists may then move the vast data systems and infrastructure associated with all imaging services to an evidence-based model for managing and guiding the vast resources entrusted to our collective stewardship.

Academic Medical Centers↗
PubMed1999

Outcomes from adult implantation, the first 100 patients.

We present the outcome of implantation in the first 100 adult patients treated under the Midland Cochlear Implant Programme. All patients were post-lingually deaf with profound or total hearing loss. Performance was tested in lip-reading, implant only and combined lip-reading and implant modes using BKB sentences, connected discourse tracking (CDT) and environmental sound recognition. Assessments were made at nine and 18 months post-implant. The dominant aetiologies were idiopathic and meningitis. Meningitis was associated with the greatest numbers of ossified cochleas. Forty-three per cent of cases of partial ossification were identified only at surgery. Four per cent of patients became non-users of their devices, however the majority used their implants for more than 12 hours each day. The mean scores at nine months post-implant, in the implant only mode, were for environmental sound recognition 56.7 per cent, for BKB sentences 46.6 per cent (80 per cent of patients scored above 0 per cent) and for CDT 31.2 words per minute (w.p.m.) (62 per cent scored above zero per cent). In the combined lip reading and implant mode the mean scores, at nine months, were for BKB sentences 81.5 per cent and for CDT 65.8 w.p.m. All results were sustained at 18 months. Patients reported that implantation significantly reduced their hearing handicap. Pre-operative measures of depression were also significantly reduced at nine months post-implant. Results were sustained at 18 months. Post-operative audiological outcomes in the electrical stimulation only mode correlated significantly with length of profound deafness. Results suggest that performance outcome is also related to the number of active electrodes.

Aged↗