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Biomedical subjects

H Fox

Publications and source records attributed to H Fox.

At least 19 recordsLinked to original sources
PubMed1995

Role of hepatic carbonic anhydrase in de novo lipogenesis.

The role of carbonic anhydrase in de novo lipid synthesis was examined by measuring [1-14C]acetate incorporation into total lipids, fatty acids and non-saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased incorporation of 14C into total lipids. Both fatty acid and non-saponifiable lipid components of the total lipid were inhibited to approximately the same extent by 100 microM TFMS (29 +/- 0.3% and 35 +/- 0.3% of control respectively in replicate studies). However, neither drug significantly affected ATP concentrations or the transport activity of Na+/K(+)-ATPase, two measures of cell viability. To establish the site of this inhibition, water-soluble 14C-labelled metabolites from perchloric acid extracts of the radiolabelled cells were separated by ion-exchange chromatography. TFMS inhibited 14C incorporation into citrate, malate, alpha-oxoglutarate and fumarate, but had no effect on incorporation of 14C into acetoacetate. Since ATP citrate-lyase, the cytosolic enzyme that catalyses the conversion of citrate into acetyl-CoA, catalyses an early rate-limiting step in fatty acid synthesis, levels of cytosolic citrate may be rate controlling for de novo fatty acid and sterol synthesis. Indeed citrate concentrations were significantly reduced to 37 +/- 6% of control in hepatocytes incubated with 100 microM TFMS for 30 min. TFMS also inhibited the incorporation of 14C from [1-14C]pyruvate into malate, citrate and glutamate, but not into lactate. This supports the hypothesis that TFMS inhibits pyruvate carboxylation, i.e. since all of the 14C from [1-14C]pyruvate converted into citric acid cycle intermediates must come via pyruvate carboxylase (i.e. rather than pyruvate dehydrogenase). Our findings indicate a role for carbonic anhydrase in hepatic de novo lipogenesis at the level of pyruvate carboxylation.

Adenosine Triphosphate↗
PubMed1995

Patterns of deterioration in senile dementia of the Alzheimer type.

OBJECTIVE: To determine rates of decline in Alzheimer's disease. DESIGN: A longitudinal review of patients diagnosed as having dementia during life, tested serially with the Extended Scale for Dementia, and confirmed by autopsy as having Alzheimer's disease. SUBJECTS AND SETTING: Twenty-nine dead patients with Alzheimer's disease from the participants in the University of Western Ontario Dementia Study Project, confirmed at autopsy as having Alzheimer's disease. METHODS: Analysis of the Extended Scale for Dementia data according to a trilinear model. FINDINGS: In the middle phase of the trilinear model, there was a mean annual change of 13% (range, 2.5% to 51.7%). CONCLUSIONS: It is likely that the common method of averaging a group of different individual scores from the initial and middle phases of observation of Alzheimer's disease collapses together individuals at different stages of the disorder, some of whom are in the initial plateau phase and whose conditions are not declining rapidly. The trilinear model of decline avoids this difficulty and the present study provides postmortem confirmed figures on rate of change.

Aged↗
PubMed1995

The Euro-Team Early Pregnancy (ETEP) protocol for recurrent miscarriage.

The underlying causes and rationale for treatment of recurrent abortion are not entirely clear. The Euro-Team early pregnancy protocol was developed as a diagnostic work-up based on the evaluation of risk factors. Possibilities for therapy can be based only on the expectancy that elimination of some risk factors may improve the prognosis.

Abortion, Habitual↗
PubMed1995

Brenner tumour of the vagina.

Polyps of the vagina are rare and are either of inflammatory/reactive or neoplastic origin. A case of extraovarian Brenner tumour of the vagina in a postmenopausal woman, who presented with a vaginal polyp, is described. The polyp was excised and on histological examination, had the triphasic pattern (transitional, glandular and stromal) characteristic of Brenner tumour. The histogenesis of Brenner tumour is discussed in the context of this unusual location and the controversy of its origin.

Aged↗
PubMed1995

Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-beta 1.

Transgenic mice expressing transforming growth factor-beta 1 (TGF-beta 1) in the pancreatic beta-islet cells directed by human insulin promoter were produced to study in vivo effects of TGF-beta 1. Fibroblast proliferation and abnormal deposition of extracellular matrix were observed from birth onward, finally replacing almost all the exocrine pancreas. Cellular infiltrates comprising macrophages and neutrophils were also observed. Plasminogen activator inhibitor was induced in the transgenic pancreas as well as fibronectin and laminin, partly explaining accumulation of extracellular matrix. TGF-beta 1 inhibited proliferation of acinar cells in vivo as evidenced by decreased bromodeoxyuridine incorporation. Development of pancreatic islets was dysregulated, resulting in small islet cell clusters without formation of normal adult islets; however, the overall islet cell mass was not significantly diminished. Additional transgenic lines with less pronounced phenotypes had less expression of TGF-beta 1 transgene. These findings suggest that TGF-beta 1 might be a mediator of diseases associated with extracellular matrix deposition such as chronic pancreatitis, and this mouse model will be useful for further analysis of the in vivo effects of TGF-beta 1, including its potential for immunosuppression.

Animals↗
PubMed1993

Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium.

Immunohistochemical staining was carried out on a spectrum of normal, hyperplastic and malignant endometrial curettings, for proliferating cell nuclear antigen--PCNA (using the monoclonal antibody PC10) and for abnormally stabilized p53 (using the polyclonal antibody CM-1). The mean proportion of glandular epithelial cells showing PCNA immunoreactivity was significantly lower in atypical hyperplasia/intra-endometrial adenocarcinoma than in invasive adenocarcinoma, but the degree of overlap between the cases was such that this was not considered to be of diagnostic value. p53 immunoreactivity was detected in 47% of invasive adenocarcinomas and in a much smaller proportion of endometria showing simple hyperplasia and atypical hyperplasia, but staining was only focal in the last two conditions. The majority of p53-positive invasive adenocarcinomas had a large proportion of glandular epithelial cells expressing PCNA, but a significant number of p53-negative cases also had a high PC10 index. This suggests that, in endometrial neoplasia, there is not a simple relationship between abnormally stabilized p53 and PCNA expression.

Adenocarcinoma↗
PubMed1992

Figures of Eberth in the amphibian larval epidermis.

Figures of Eberth are prominent extensive filamentous structures in the basal epidermal cells of larval amphibians. They are compared and contrasted qualitatively and quantitatively in a number of species of the three groups of living amphibians. Fully developed Figures consist of massive skeins of tonofilaments oriented in three dimensions and hinged on hemidesmosomes within the cell. The overall appearance of the Figures is similar in anurans, urodeles and Ichthyophis among the apodans. However, in terms of size and number per unit length of the proximal cell margin, the hemidesmosomes and the thickness or their emergent skeins in anurans and Ichthyophis differ significantly from those parameters in urodeles, a feature that is presumably independent of cell size. Figures are poorly developed or missing in embryos of Typhlonectes, which has no larval stage in its life history. These ubiquitous skeletogenous structures in the aquatic larval amphibians, among other things, could be protective of underlying delicate tissues and act as a stabilizer in bodily movement during swimming. They could also serve as a reserve of cytokeratin for use during later cellular division and sloughing.

Animals↗
PubMed1992

Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.

AIMS: To study the pattern of expression and prognostic importance of c-erbB-2 protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical carcinoma, representing the three main tumour types, were investigated immunohistochemically for the presence of c-erbB-2 protein expression, using a monoclonal antibody (CB11) to its internal domain. Follow up of at least five years' duration was available in all cases. RESULTS: Definite membrane staining was seen in 38.7% of cases. There was a strong correlation with poor survival (p less than 0.0001) particularly. For those with adenocarcinomas, this was the case when nodal metastases were present. In contrast, for squamous carcinomas and adenosquamous carcinomas, the association with a poor prognosis was most apparent in those patients without lymph node metastases. CONCLUSIONS: These findings raise the possibility that immunostaining for c-erbB-2 protein could be used as a prognostic marker and may help identify those patients for whom early adjuvant treatment might be beneficial.

Adenocarcinoma↗
PubMed1991

Improved recognition of leukoaraiosis and cognitive impairment in Alzheimer's disease.

We identified 85 patients in a longitudinal study of dementia who had uncomplicated Alzheimer's disease and in whom computed tomography of the head and psychometric testing were conducted within a 6-month period following their entry into the study. Thirty-four patients (40%) had leukoaraiosis, which was disproportionately common in female patients (62% vs 15% in male patients). Analysis of covariance demonstrated a relative reduction of scores on the Extended Scale for Dementia in those patients who had leukoaraiosis, after adjusting for the confounding effects of age, sex, educational level, and duration of illness. Leukoaraiosis was also much more common in women, even after adjusting for the possible confounding effects of age, duration of illness, Extended Scale for Dementia score, and hypertension. Multiple regression analysis showed that leukoaraiosis accounted for 11.6% of the variance of the Extended Scale for Dementia scores. Leukoaraiosis, together with duration of illness, accounted for 18.2% of the variance. Leukoaraiosis is associated with a greater degree of cognitive impairment in patients with Alzheimer's disease.

Aged↗
PubMed1991

Ultrastructure of the normal human placenta.

In this review, the ultrastructure of the normal human chorionic villus is examined and illustrated. The outer covering of trophoblast, comprising the generative cytotrophoblast and the multinucleated syncytiotrophoblast which is derived from it, is described, including such features as the microvillous surface, vesicles and vacuoles, endoplasmic reticulum and secretory droplets. The structure, composition, development and inclusions of the trophoblastic basement membrane are discussed, and the ultrastructure of the various components of the stroma, including reticulum cells, fibroblasts, Hofbauer cells, capillaries and the non-cellular matrix are illustrated and described, with special reference to their inter-relationships and function.

Basement Membrane↗
PubMed1991

A contemporary view of the human placenta.

Our current knowledge of the human placenta is briefly reviewed. Particular stress is placed upon the considerable functional reserve capacity of the placenta, the unimportance of most visible abnormalities of the placenta, the lack of any evidence that the placenta ages during gestation and the lack of significance of placental weight. The effects on the placenta of infection and of maternal cigarette smoking are considered and the concept of placental insufficiency critically discussed. It is concluded that most cases of 'placental insufficiency' are, in reality, examples of maternal vascular insufficiency resulting from inadequate placentation during the early stages of pregnancy.

Female↗
PubMed1991

A comparison of the growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian tumours.

The growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian malignancy, benign ovarian tumours and non-tumour related gynaecological conditions have been investigated using an ovarian carcinoma cell line (OAW 42), mesothelial cells (58MC) and rat kidney cells (NRK-49F). Colony stimulating activity (CSA) for tumour cells and transforming activity (TA) for mesothelial cells were weakly correlated, but whereas elevated TA was tumour-associated, CSA was not. However, TA was not cancer-associated and, although the difference between the mean TA values of benign and malignant cyst fluids was of borderline significance, some benign cyst fluids from cystadenomas showed high TA values. Higher levels of TA in the cystadenomas showed a significant correlation with the menopausal status of the patient and higher levels of TA in the malignant cyst fluid/peritoneal fluid groups were associated with more advanced disease. Results indicated that some fluids contained TGF-beta-like activity, but there was no direct evidence for the presence of TGF-alpha/EGF-like activity in the fluids. Heparin inhibited clonogenic growth of tumour cells but not mesothelial cells. The reduced CSA which was observed after treatment of fluids with both heparin and thrombin implicated coagulation factors in the manifestation of CSA. It was concluded that CSA in the fluids was due, at least partly, to fibrin coagulation, and TA was due to unknown growth factor(s) which may include TGF-beta-like activity. The results are discussed in the context of the aetiology of ovarian carcinoma, and the possible clinical significance of TA.

Animals↗
PubMed1991

Rosai-Dorfman disease of the uterine cervix.

A case of Rosai-Dorfman disease of the uterine cervix is described. The disease is characterized by a mixed chronic inflammatory cell infiltrate in which histiocytic cells predominate. A characteristic feature is the presence within many of the histiocytic cells of engulfed, but undamaged, lymphocytes. Rosai-Dorfman disease is of unknown etiology and pursues a benign course. The disease can occur at a wide variety of extranodal sites, but this appears to be the first reported instance of female genital tract involvement.

Adult↗
PubMed1991

Pathology of the uterine body.

During the past year, evidence has compiled to suggest that uterine carcinosarcomas are, in fact, metaplastic carcinomas and that mitotic counts are of no value in distinguishing between high- and low-grade endometrial stromal sarcomas in stage I cases. The pathologic and biologic behaviour of uterine müllerian adenosarcomas has been comprehensively reviewed. Prognostic factors have been identified in a large series of surgically staged endometrioid adenocarcinomas of the endometrium, while the sinister nature of the serous papillary and clear cell carcinomas of the endometrium have been confirmed. It has been claimed that a papillary pattern of growth is an independent prognostic factor in endometrial neoplasia and shown that the accuracy of macroscopic estimation of depth of myometrial invasion decreases with increasing tumor grade. The value of peritoneal cytologic examination in early stage endometrial adenocarcinoma has been questioned, as has the value of DNA flow cytometry in endometrial neoplasia. The prognostic significance of steroid receptor status has been confirmed and studies of oncogene amplification are beginning to yield prognostically useful information. Evidence is also beginning to emerge concerning chromosomal abnormalities in many women with endometrial adenocarcinoma.

Adenocarcinoma↗