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Biomedical subjects

H McBride

Publications and source records attributed to H McBride.

At least 19 recordsLinked to original sources
PubMed2001

Rab proteins as membrane organizers.

Cellular organelles in the exocytic and endocytic pathways have a distinctive spatial distribution and communicate through an elaborate system of vesiculo-tubular transport. Rab proteins and their effectors coordinate consecutive stages of transport, such as vesicle formation, vesicle and organelle motility, and tethering of vesicles to their target compartment. These molecules are highly compartmentalized in organelle membranes, making them excellent candidates for determining transport specificity and organelle identity.

Endocytosis↗
PubMed2000

Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast.

Pho85 is a cyclin-dependent protein kinase (Cdk) in budding yeast with roles in cell metabolism and cell cycle progression. Activation of Pho85 occurs through association with Pho85 cyclins (Pcls), of which 10 are known. When complexed with the G1 cyclins, Pcl1 and Pcl2, Pho85 is required for cell cycle progression in the absence of the Cdc28-dependent cyclins, Cln1 and Cln2. To identify potential targets of Pcl2-Pho85, we performed a two-hybrid screen using the Pcl2 cyclin as bait and recovered the transcription factor Swi5 as a Pcl2-interacting protein. We performed both biochemical and genetic tests to discover the biological significance of the interaction between Pcl2 and Swi5 seen in the two-hybrid assay. We found that Swi5 interacts in vitro with Pho85 cyclins and is phosphorylated in vitro by the Pho80-Pho85 kinase. We discovered that a subset of genes that are controlled by Swi5 and a homologous transcription factor, Ace2, was misregulated in a pho85 deletion strain; expression of the ASH1 and CTS1 genes was reduced in an ace2 deletion strain, whereas expression of both genes was increased in an ace2Delta pho85Delta double mutant. We also found that overexpression of SWI5 caused cell lethality in a pho85 deletion strain. Our results are consistent with misregulation of Swi5 activity in vivo in the absence of Pho85 and implicate Swi5 as a potential substrate of Pho85 cyclin-dependent kinase complexes.

Cell Cycle Proteins↗
PubMed2000

The central matrix loop drives import of uncoupling protein 1 into mitochondria.

The uncoupling protein (UCP1) is a carrier protein of the inner mitochondrial membrane spanning the bilayer six times. It does not contain a typical amino-terminal targeting signal and the mechanism of targeting and insertion is unknown. Here we focus on the biogenesis of UCP1 by analysing the import signals contained within the three repeated units of the protein. The amino-terminal third of the protein can mediate insertion into the outer membrane and therefore acts as artificial targeting signal when fused to DHFR. However, in the context of full-length UCP, the targeting information contained within the first repeated unit is not sufficient to trigger insertion into the outer membrane. Deletion of either the first or third repeated unit from UCP1 did not reduce import into the inner membrane and bound to the outer membrane receptor protein hTom20 with the characteristics of full-length UCP1. Deletion of the second repeat of UCP1 completely abolished all import into the mitochondria. Consistent with this, the central repeat alone was efficiently imported to the inner membrane and bound hTom20 with the characteristics of UCP1. We conclude that the site for binding hTom20 is within the central repeat and that this domain contains the complete targeting signal for directing UCP1 to the inner membrane.

Animals↗
PubMed1998

Localization of the cellular expression of inhibin in trophoblastic tissue.

AIMS: Inhibin is a peptide hormone which is normally produced by ovarian granulosa cells and which inhibits the release of follicle stimulating hormone from the pituitary gland, thus acting as a modulator of folliculogenesis. Serum inhibin levels are higher during pregnancy than during the normal menstrual cycle and the placenta is thought to be a source of circulating inhibin. Previous studies have yielded conflicting results as to the cellular localization of inhibin in the placenta and the aim of the present study was to investigate the immunohistochemical localization of the hormone in placental tissue. We also wished to investigate whether inhibin could be demonstrated in choriocarcinoma and in non-gestational trophoblastic tissue. MATERIALS AND RESULTS: Immunohistochemical staining was performed using a monoclonal antibody against the alpha subunit of human inhibin. Specimens included in the study were intrauterine products of conception (n = 36), extrauterine products of conception (n = 4), decidualized endometrium (n = 15), extrauterine decidualized tissue (n = 3), hydatidiform mole (n = 5), uterine choriocarinoma (n = 2) and testicular embryonal carcinoma with syncytiotrophoblast giant cells (n = 6). In cases of products of conception, including hydatidiform mole, there was consistent strong positive staining of syncytiotrophoblast but no staining of cytotrophoblast with anti-inhibin. Staining with anti-inhibin highlighted trophoblastic cells within the placental bed. In a small number of cases there was focal weak positive staining of decidua. There was positive staining of the two cases of uterine choriocarcinoma and of syncytiotrophoblast giant cells in the six cases of testicular embryonal carcinoma. CONCLUSIONS: The study shows that immunohistochemically detectable inhibin alpha subunit in placental tissue is mainly localized within syncytiotrophoblast although in some cases there is also positive staining of decidua. Production of inhibin by these cells may account for raised serum levels during pregnancy. Inhibin can also be demonstrated in choriocarcinoma and in nongestational trophoblastic tissue. Inhibin is a sensitive marker of syncytiotrophoblast and staining with this antibody may prove useful in the diagnosis of choriocarcinoma and in the demonstration of trophoblastic cells in germ cell tumours.

Carcinoma, Embryonal↗
PubMed1997

Immunohistochemical detection of p53 and bcl-2 proteins in neoplastic and non-neoplastic endocervical glandular lesions.

The study examines p53 and bcl-2 protein expression in a variety of neoplastic and non-neoplastic endocervical glandular lesions. Immunohistochemical staining, using monoclonal antibodies against p53 (DO-7) and bcl-2, was performed on archival paraffin-embedded tissue following microwave antigen retrieval. With DO-7 there was positive nuclear staining in 23/33 cases of adenocarcinoma, 2/10 adenocarcinoma in situ, 2/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 1/17 normal endocervix. With adenocarcinoma in situ and non-neoplastic lesions, positive staining was confined to scattered cells. Nine of 23 positive cases of adenocarcinoma showed widespread staining. With anti-bcl-2 antibody, there was positive cytoplasmic staining in 9/33 cases of adenocarcinoma, 0/10 adenocarcinoma in situ, 7/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 0/17 normal endocervix. Five of nine positive adenocarcinomas showed widespread staining. There was widespread positive staining for bcl-2 in six of seven positive cases of tubo-endometrial metaplasia. The results indicate that p53 protein expression is frequent in endocervical adenocarcinoma and suggest that mutation of the p53 gene may be important in the evolution of some cases of endocervical adenocarcinoma. Scattered p53-positive cells may be seen in endocervical adenocarcinoma in situ and in non-neoplastic endocervical glandular lesions, the significance of which is uncertain. Bcl-2 protein expression is seen in a proportion of endocervical adenocarcinomas and may play a role in the evolution of these tumors through inhibition of apoptosis. Widespread positivity for bcl-2 protein is seen in most cases of tubo-endometrial metaplasia, suggesting that this type of metaplastic epithelium may represent an unusually stable population of cells.

Adenocarcinoma↗
PubMed1996

Suicide in old age: a tragedy of neglect.

OBJECTIVE: To investigate the incidence and treatment of depression in geriatric suicide. METHOD: All coroners' records, autopsy and police reports for suicide victims aged 65+ in Ontario (n = 543) over 3 years were examined. RESULTS: Over 80% of the elderly who committed suicide received no psychiatric referral. Of the sample, 87% were untreated while only 13% received antidepressants. Tricyclics, which are lethal in overdose, were the drugs of choice. None of the sample was treated with the safer specific serotonin reuptake inhibitors (SSRIs). Females were 3 times as likely to be treated as were males, and those seeing psychiatrists were 4 times more likely to be treated with antidepressants than those seeing general practitioners (GPs). The physically ill were rarely treated. CONCLUSIONS: These findings suggest that early geropsychiatric assessment and vigorous treatment could prevent many suicides in old age.

Aged↗
PubMed1995

Immunohistochemical staining of plastic embedded bone marrow trephine biopsy specimens after microwave heating.

AIMS: To investigate (1) whether adequate immunohistochemical staining can be achieved on sections cut from plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer; and (2) whether this immunohistochemical staining is comparable with that achieved on routine sections cut from paraffin wax embedded trephine biopsy specimens after decalcification procedures. METHODS: Sixty five consecutive bone marrow trephine biopsy specimens of more than 1 cm in length were divided transversely into two equal parts. One part was processed in paraffin wax followed by decalcification. The other part was embedded in the epoxyresin Polarbed 812 followed by the cutting of 1 micron sections. Both parts underwent immunohistochemical staining by an identical panel of antibodies. With Polarbed 812 plastic embedded sections, microwave heating in citrate buffer was undertaken before the application of antisera. RESULTS: On sections cut from plastic embedded material, immunohistochemical staining was generally satisfactory, easy to interpret and comparable with that achieved with paraffin wax embedded material. Exceptions were antibodies to neutrophil elastase and CD61 where immunostaining was consistently negative on plastic embedded sections. Immunohistochemical staining for CD20 was consistently more reliable on plastic embedded sections. CONCLUSIONS: The results provide evidence that, with few exceptions, satisfactory immunohistochemical staining is possible on plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer. This, combined with the advantage of superior cellular morphology with semi-thin (1 micron) sections of plastic embedded material, make such embedding procedures the preferred method for the processing of bone marrow trephine biopsy specimens.

Antibodies, Monoclonal↗
PubMed1991

Idiotypic vaccination against B-cell lymphoma leads to dormant tumour.

Idiotypic immunoglobulin, which can be considered to bear tumour-associated antigens in the context of B-cell lymphoma, has been obtained from the splenic A31 tumour, purified, and used to immunise syngeneic mice. On subsequent exposure to a lethal challenge of lymphoma cells, the mice showed no overt tumour development over an observation period of 6 months, whereas mice immunised with an unrelated idiotypic immunoglobulin succumbed to lymphoma after about 20 days. Anti-idiotypic immunity persisted in protected mice, since a second exposure to a lethal tumour dose 4 months after the first challenge also failed to induce lymphoma. Anti-idiotypic antibody appeared to have a major role in protection when analysed by passive transfer experiments, with no contribution from transferred cells. Protected mice were investigated for the presence of lymphoma cells 4-8 months following exposure to tumour, but the spleens, which were of normal weight and appearance, contained few or no tumour cells by phenotypic analysis. However, passage of cells dispersed from these spleens led, in 60% of cases, to tumour development in unimmunised recipients. The emergent tumours were indistinguishable from the original A31 lymphoma, with no evidence for variants, indicating that the cells were unable to grow in the immune mice, but that this dormant state could be disrupted by transfer.

Animals↗
PubMed1990

Possible relationship between chromosome alterations and in vitro cellular radiosensitivity of human malignant melanoma.

In the present study, in vitro radiation survival analysis was performed on 8 human malignant melanoma cell lines with defined karyotypes. Exponentially growing cells were irradiated to doses of 0 to 8 Gy and examined for soft agar clonogenicity. Two groups emerged from this analysis: 4 cell lines with a small shoulder (extrapolation number, n less than 2) and 4 cell lines with a large shoulder (n greater than 2). Of possible significance, 4/4 cell lines with extrapolation numbers greater than 2 demonstrated clonal structural abnormalities of chromosome 7. In contrast, 3/4 cell lines with extrapolation numbers less than 2 had no structural abnormalities of chromosome 7. These very preliminary results suggest that structural alterations of chromosome 7 may be associated with melanoma tumors with high extrapolation numbers.

Cell Line↗
PubMed1987

Adrenal hemorrhage: a complication of anticoagulant therapy--a case history.

A seventy-five year-old woman developed adrenal hemorrhage and acute adrenal insufficiency while receiving anticoagulant therapy. Abdominal CT scan was consistent with bilateral adrenal hemorrhage and was an important contribution to diagnosis and therapy. Acute adrenal hemorrhage should be suspected in patients, especially the elderly, who have recently begun anticoagulant therapy and develop upper abdominal pain followed by decreased sensorium, high fever, hypotension, and hyponatremia. Any consideration of the diagnosis of sepsis with shock in a recently anticoagulated elderly hospital patient should suggest the possibility of acute adrenal hemorrhage. Abdominal CT scan and a cosyntropin stimulation test should be performed to confirm the diagnosis. Failure of diagnosis has generally been associated with death in most patients, whereas prognosis in patients treated with corticosteroids is excellent.

Adrenal Gland Diseases↗
PubMed1987

Attention deficit disorder and pathological gambling.

To examine the possibility that pathological gambling is related to the deficits in impulse control associated with attention deficit disorder, 14 pathological gamblers and 16 controls were administered questionnaires concerning their childhood behaviors. These self-reports indicated a strong correlation between pathological gambling and childhood behaviors related to attention deficit disorder.

Adult↗
PubMed1986

Casualty and surgical services in Perthshire general practitioner hospitals 1954-84.

The results are reported of a study of casualty and surgical services in five general practitioner hospitals in Perthshire - Aberfeldy, Auchterarder, Blairgowrie, Crieff and Pitlochry. Details of the total workload, the nature of the conditions treated and the referral rate to major hospitals are given. Figures for the Royal Infirmary, Perth, the main referral hospital for the county, are also given for comparison. The surgical service at one of the rural hospitals is described.Experience has demonstrated the usefulness of these hospitals in providing casualty and surgical services to both the local population and to visitors, and their superiority in providing these services over health centres because staff and beds are available 24 hours a day.Rural general practitioner hospitals merit a continuing share of resources and bed allocation as they spare major hospitals surgical and medical work. The general practitioners serving the hospitals studied here undertook almost 40% of the total accident and emergency workload in the Perth and Kinross area of Scotland.

Adolescent↗
PubMed1985

The virulence of clinical and environmental isolates of Campylobacter jejuni.

The virulence of Campylobacter jejuni and C. coli isolated from various water sources was compared with that of clinical strains by in vitro assays of adhesion, invasion and cytotoxicity to HeLa cells. Variation in degree of attachment was observed, but this did not appear to be related to strain source, However, water strains were less invasive and less cytotoxic to HeLa cells than clinical strains as shown by immunofluorescence and electron microscopy. These differences were particularly evident between clinical and water isolates of the same serotype and biotype implicated in an outbreak of campylobacter enteritis in a school. The enhanced virulence of the clinical isolates, possibly induced by passage, was confirmed by colonization tests on infant mice.

Adhesiveness↗
PubMed1985

Investigations on the role of flagella in the colonization of infant mice with Campylobacter jejuni and attachment of Campylobacter jejuni to human epithelial cell lines.

The biochemical and biological properties of the flagella of Campylobacter jejuni have been investigated using two variants selected from a flagellate, motile clinical isolate (strain 81116): a flagellate, non-motile variant (SF-1) and an aflagellate variant (SF-2). Phenotypic and biochemical analysis of the strains and amino acid analysis of the isolated flagella suggest that the variants differed from the wild-type strain only in the absence of flagella and/or motility. The aflagellate variant poorly colonized the gastrointestinal tract of infant mice but the flagellate, non-motile variant colonized the mice as successfully as the wild-type strain. 35S-labelled organisms were used to investigate the attachment of the variants to human epithelial cell monolayers in vitro. The flagellate, non-motile strain attached more efficiently to the cells than the wild-type strain or the aflagellate strain. Differences in attachment suggest that an adhesin is intimately associated with flagella of C. jejuni and that active flagella mediate only a tenuous association with host cells. This adhesin attached most efficiently to cells of intestinal epithelial origin and was not specifically inhibited by various sugars.

Adhesiveness↗
PubMed1984

The identification of outer membrane proteins and flagella of Campylobacter jejuni.

The outer membrane proteins of five clinical isolates of Campylobacter jejuni were identified by 125I-surface labelling and SDS-PAGE of outer membrane preparations. All isolates expressed a major outer membrane protein of variable molecular weight (43 000-46 000: 43K-46K). Several constant surface proteins were also identified including a 27K protein which was surface-exposed and acid-extractable but was not present in the outer membrane preparations. Isolated flagella comprised a major 62K protein and a minor 87K protein. Both proteins were absent in an aflagellate variant. The 62K protein was immunoblotted and immunoprecipitated by rabbit anti-flagella antisera.

Autoradiography↗