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Biomedical subjects

J McBride

Publications and source records attributed to J McBride.

At least 55 records · Page 3Linked to original sources
PubMed1995

A 8-year follow-up of the Edwards-Duromedics bileaflet prosthesis.

Following reports of leaflet escapes, distribution of the Edwards-Duromedics prosthesis (ED), introduced in 1982, was suspended from 1988 to 1990. From our experience of 257 patients operated on between March, 1983, and April, 1988, it appeared to us that, among the five key factors identified by extensive studies, surgical mishandling, specially in mitral position, could have been the main contributing factor. These 257 patients, mean age 57 years (range 2 to 75 years), underwent 138 aortic (AVR), 86 mitral (MVR), and 33 double valve (DVR) replacements. Hospital mortality was 2.3% (6 patients): 1.4% for AVR, 3.5% for MVR, and 3% for DVR, none of them being directly valve-related. But there were 3 early replacements of a mitral ED for intra or postoperative impingement of one leaflet. Follow-up has been 93%, with a total of 1.155 patient-years. Among the 20 late deaths (8%), 4 (20%) were considered as valve-related; there was one MV thrombosis and 7 non-fatal systemic emboli, the total incidence of thromboembolism being 0.7% patient-year. No structural failure or leaflet escape was observed in this series. At 8 years, actuarial survival, hospital mortality excluded, was 85.5% for AVR, 95% for MVR, and 89% for DVR. The ED prosthesis is, from a hydrodynamic point of view, an advance in terms of both mechanical and bileaflet valve: the valve design accounts for its low thrombogenicity. But its persistent drawback remains the prohibitive vertical exposure of leaflets in mitral position, that can be responsible for immediate or delayed leaflet entrapment, or for incautious handling for rotating the mechanism, leading to extensive fissuration of pyrolitic carbon and delayed rupture. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis.

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster.

Transforming growth factor-alpha (TGF-alpha) and TGF-beta 1 have been proposed as important regulators of processes critical to successful wound healing. Although various cells present in wounds represent potential sources of either TGF-alpha and/or TGF-beta, including macrophages, neutrophils, keratinocytes, fibroblasts, and endothelial cells, we recently identified eosinophils as an additional potential source of these cytokines. We therefore used in situ hybridization and immunohistochemistry to determine whether eosinophils represent significant sources of TGF-alpha and/or TGF-beta 1 in skin wounds in the hamster. We found that these wounds developed a prominent infiltration of eosinophils, and that eosinophils were a cellular source of both TGF-alpha and TGF-beta 1 mRNAs. TGF-alpha and TGF-beta 1 proteins were detectable both within eosinophils and extracellularly. Moreover, there was a sequential pattern of TGF-alpha and TGF-beta 1 expression by infiltrating eosinophils, with the onset of eosinophil-associated TGF-alpha expression preceding that of TGF-beta 1. This sequential pattern of TGF expression suggests that eosinophils may help to regulate critical biological processes during wound healing.

Amino Acid Sequence↗
PubMed1992

Use of postauricular skin grafts for vestibular reconstruction.

The use of full-thickness postauricular skin grafts for vestibular reconstruction is described. The procedure offers the advantages of a concealed donor scar, minimal patient discomfort and morbidity, ease of procurement, and confinement of the operations to a single region. Its use in 17 patients (31 grafts) resulted in complete take in 90.3% of the grafts. Maintenance of vestibular depth in most patients was maintained at 1-year follow-up. The disadvantages of the procedure are the limited amount of skin available and the need to suture the graft to the recipient site.

Ear, External↗
PubMed1991

Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1.

The infiltration of eosinophils into tissues during pathologic responses is often associated with extracellular matrix alterations such as fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) is a well-characterized multifunctional cytokine known to exert potent effects on the extracellular matrix. In this report, we showed the production of TGF-beta 1 by human eosinophils from patients with blood eosinophilia. Northern blot analysis using RNA isolated from eosinophils purified from a patient with the idiopathic hypereosinophilic syndrome (HES) detected the 2.5-kb TGF-beta 1 transcript. In situ hybridization and immunohistochemistry of leukocytes from two patients with HES and two patients with blood eosinophilia localized TGF-beta 1 messenger RNA (mRNA) and protein to eosinophils. No other cell type contained TGF-beta 1 mRNA by in situ hybridization, whereas other leukocytes contained detectable TGF-beta 1 protein by immunohistochemistry. Eosinophils from four normal donors contained little or no detectable TGF-beta 1 protein by immunohistochemistry, whereas eosinophils from two of these four normal donors labeled weakly for TGF-beta 1 mRNA by in situ hybridization. These results show that eosinophils in the peripheral blood of patients with blood eosinophilia can express TGF-beta 1, but that eosinophils in the blood of normal donors contained little or no TGF-beta 1.

Adult↗
PubMed1991

Molecular cloning of the complementary DNA encoding for the hamster TGF-alpha mature peptide.

The expression of transforming growth factor alpha (TGF-alpha) is consistently associated with the malignant transformation of oral mucosal tissues in both hamster and human. The cheek pouch of the Syrian hamster represents an ideal model to elucidate the role of TGF-alpha in epithelial cancer development. A prerequisite for such investigations at the molecular level is to obtain hamster-specific TGF-alpha molecular probes. Here we report the successful cloning of the hamster TGF-alpha cDNA from a hamster oral cancer cell line (HCPC-1) by the polymerase chain reaction technique using synthetic oligonucleotide primers based on human TGF-alpha cDNA sequence. Analysis of the nucleotide sequence of the newly isolated hamster cDNA encoding the portion of the mature TGF-alpha peptide revealed that it is 92.6% (139/150) homologous to that of the rat and 93.3% (140/150) homologous to that of the human sequences. The predicted hamster TGF-alpha amino acid sequence is 96% (48/50) similar to that of human, while 94% (47/50) similar to that of rat. Using this hamster TGF-alpha cDNA as a probe, molecular hybridization experiments revealed that it detects hamster TGF-alpha mRNA with approximately 40 times and approximately 5 times greater sensitivity than similar probes from human and rat origin respectively. This hamster TGF-alpha cDNA should be of great value as a probe to evaluate the role of TGF-alpha in the normal and pathological processes using the hamster as an experimental model.

Amino Acid Sequence↗
PubMed1991

Human antibody response to the major merozoite surface antigen of Plasmodium falciparum is strain specific and short-lived.

The precursor of the major merozoite antigen of Plasmodium falciparum, gp190, is considered a candidate for inclusion in a malaria vaccine. This protein, which consists of conserved, dimorphic, and polymorphic sequences, is very immunogenic in humans. In a longitudinal study carried out with 94 inhabitants of a rural community in Mali, West Africa, we show that in this endemic area naturally acquired gp190-specific antibodies are predominantly directed against the dimorphic parts of one of the main alleles of gp190. The presence of antibodies against these dimorphic regions correlates with the prevalence of the corresponding antigen in the infecting parasite population. Moreover, qualitative as well as quantitative differences were found in the time course of the humoral immune response to the dimorphic regions in adults and children, who differ in their susceptibility to malaria infection.

Adolescent↗
PubMed1991

A survey of pharmacy-coordinated investigational drug services.

Over the past few years, pharmacy involvement in investigational drug studies has grown. In 1986, Kingston General Hospital conducted a nation-wide survey assessing the extent of pharmacy involvement in clinical drug trials. The aims of the present survey were to show how Investigational Drug Services (IDS) have changed in recent years, to determine areas that need improvement, and to characterize methods of reimbursement for IDS. A total of 148 Canadian hospitals (300 or more beds) were mailed a detailed IDS questionnaire. A response rate of 68% was achieved. Survey results were grouped in the following categories: increase in clinical trials involvement, IDS staffing levels, sponsorship of trials, major areas of clinical drug research, areas of IDS needing improvement, and reimbursement issues. The results of this survey indicate that since 1986 pharmacy departments are becoming more involved in the coordination of clinical drug trials. Perceived areas for improvement in IDS were strikingly uniform between institutions, despite a large variation in the extent of existing services. Reimbursement procedures are not consistent and several methods are used to obtain pharmacy funding. Recommendations are offered for assistance in the development or expansion of pharmacy-coordinated IDS in Canadian hospitals.

Canada↗
PubMed1991

Localization of transforming growth factor-alpha in adult Syrian hamster tissues.

Using the cheek pouch of the Syrian hamster as an experimental model for oral carcinogenesis, it has been shown that the expression of transforming growth factor-alpha (TGF-alpha) is consistently associated with the malignant transformation process. We have recently shown that production of TGF-alpha has been localized to normal hamster oral epithelium and bone marrow eosinophils. In this study we investigated the production of this cytokine in other normal hamster adult tissues. By using an EGF-radioreceptor assay, immunohistochemistry, Northern blot analysis, and in situ hybridization we have now further detected the presence of TGF-alpha mRNA and/or protein in the kidney, stomach, and pancreas of normal adult hamster. Together with the previously reported detection of TGF-alpha in oral mucosa and bone marrow eosinophils, these adult normal tissue/cellular sources can serve as sites of TGF-alpha production. The availability of hamster specific reagents (cDNA and monoclonal antibodies) and the delineation of the various adult tissues that could produce TGF-alpha make the Syrian hamster a suitable model for the study of how this multifunctional cytokine can influence normal and pathological processes.

Animals↗
PubMed1990

Human eosinophils express transforming growth factor alpha.

Transforming growth factor alpha (TGF-alpha) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-alpha (hTGF-alpha). No other identifiable leukocytes in these lesions contained detectable hTGF-alpha mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-alpha mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-alpha peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-alpha was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-alpha mRNA and none of these eosinophils contained immunohistochemically detectable TGF-alpha product. Taken together, these findings establish that human eosinophils can express TGF-alpha, but suggest that the expression of TGF-alpha by eosinophils may be under microenvironmental regulation. Demonstration of TGF-alpha production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.

Adenocarcinoma↗
PubMed1990

Production of transforming growth factor alpha by hamster eosinophils.

Previously it was demonstrated that malignant transformation of the Syrian hamster cheek pouch mucosa is associated with the expression of TGF-alpha. Therefore in situ hybridization and immunohistochemistry was used to investigate the cellular sources of TGF-alpha production in this model system. Surprisingly one cell type in the inflammatory infiltrate present in the connective tissue adjacent to the transformed epithelium represented a major source of TGF-alpha mRNA. Detailed analysis of these cells revealed that they were eosinophils. In addition to TGF-alpha mRNA, about 40% of the eosinophils associated with the oral tumors exhibited TGF-alpha product reactive with a monoclonal antibody against the C terminus of the mature TGF-alpha peptide. Normal hamster bone marrow eosinophils also exhibited TGF-alpha mRNA and product by in situ hybridization and immunohistochemistry. These results suggest that the eosinophil represents a biologically significant source of TGF-alpha.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

A rapid method to determine proliferation patterns of normal and malignant tissues by H3 mRNA in situ hybridization.

A general method applicable for the determination of any mammalian tissue's proliferative pattern is described. This method determines the cellular mRNA level of a proliferation-dependent gene, histone H3, by in situ hybridization. The cell-cycle S-phase-specific expression of this highly conserved ubiquitous cellular gene, and the lack of it in resting cells, permits the unambiguous identification of cycling cells in any tissues, normal or diseased. This method can be conveniently coupled with routine biopsy and could be streamlined for a central laboratory with results obtainable in 2 days. Furthermore, this procedure works successfully on formalin-fixed paraffin-embedded sections, thus allowing retrospective studies of biopsies or autopsy materials.

Cell Cycle↗
PubMed1989

Detection of transforming growth factor-alpha messenger RNA in normal and chemically transformed hamster oral epithelium by in situ hybridization.

We have recently demonstrated the consistent detection of transforming growth factor alpha (TGF-alpha) in chemically transformed hamster oral tumors. By Northern blot analysis, no TGF-alpha mRNA can be detected in normal cheek pouch mucosa. The consistent expression of TGF-alpha associated with the malignant transformation in the well-defined hamster oral cancer model prompted us to hypothesize that the aberrant expression of this important cellular gene could be related to a specific stage of epithelial alteration. In situ hybridization was used to test this hypothesis. We now report that by in situ hybridization we can detect TGF-alpha mRNA in normal hamster oral epithelium and also at all stages of transformation. In all epithelium, labeling of TGF-alpha mRNA in the basal layer is more pronounced than that observed in the spinous and squamous layers. There is a significant increase of TGF-alpha mRNA labeling early in 7,12-dimethylbenz(a)anathracene-induced oral carcinogenesis. This increase is associated with morphological changes of epithelial hyperplasia or dysplasia. Although lesions exhibiting full-thickness epithelial dysplasia (carcinoma in situ) showed more labeling of TGF-alpha mRNA than do areas of lesser dysplasia, the transition to full-fledged papillary or invasive squamous cell carcinoma is not associated with further elevations of TGF-alpha expression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Detection of Ki-ras messenger RNA in normal and chemically transformed hamster oral keratinocytes.

The cheek pouch of the Syrian hamster is an excellent model for the experimental study of oral carcinogenesis. The carcinogenic chemical 7,12-dimethylbenz[a]anthracene consistently produces epidermoid carcinomas in the cheek pouch of the Syrian hamster, giving rise to characteristic histopathological lesions in a time-dependent manner. We now present experimental evidence that c-Ki-ras mRNA can be detected in all 7,12-dimethylbenz[a]anthracene-induced tumors examined (in vivo and in vitro) in this experimental oral cancer model while no detectable c-Ki-ras mRNA can be found in the normal hamster cheek pouch epithelium. Cellular synchronization experiments using a cell line (hamster cheek pouch carcinoma cell line 1) derived from one of these 7,12-dimethylbenz[a]anthracene-induced hamster oral tumors revealed that the c-Ki-ras protooncogene is expressed during the G1 phase of the cell cycle (proliferation dependent). Serum starvation and RNA synthesis inhibition experiments using hamster cheek pouch carcinoma cell line 1 cells suggest that the c-Ki-ras protooncogene is indeed quiescent in the normal hamster cheek pouch epithelium and that failure to detect its mRNA is not related to the slower proliferation of the normal epithelial cells. These results suggest that the transcription of the c-Ki-ras protooncogene is associated with malignant transformation in the cheek pouch of the Syrian hamster.

9,10-Dimethyl-1,2-benzanthracene↗