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Biomedical subjects

F Walker

Publications and source records attributed to F Walker.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Esophageal anomalies developed from tracheobronchial remnants. Reports of two cases with delayed diagnosis in adults].

Congenital esophageal stenosis and bronchogenic cyst are secondary to the same dysembryoplastic disorder in spite of different clinical signs. These lesions are revealed during infancy, unusually during adult age. Dysphagia is the most common symptom. Our two cases highlight these topics. Imaging methods displayed, in case 1, a distal stenosis, associated with a proximal dilatation, in case 2, a benign independent mass, without connection with the respiratory tract. A chirurgical excision was carried out in the two cases and the post operative course was uncomplicated. Histologically the two resection specimens showed a respiratory mucosa trapping cartilaginous pieces.

Adult↗
PubMed1992

Glucose and citrate reduce the permeability changes caused by indomethacin in humans.

Nonsteroidal anti-inflammatory drug (NSAID)-induced increased intestinal permeability appears to be a prerequisite for NSAID enteropathy. It has been suggested that early metabolic events leading to the permeability changes may involve inhibition of glycolysis and the tricarboxylic acid cycle, in which case the coadministration of glucose and citrate (the substrates for these metabolic pathways) with indomethacin may afford some protection. The present study, using a combined intestinal absorption-permeability test including 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and [51Cr]ethylene-diaminetetraacetic acid (EDTA) as test probes and the differential urine excretion ratio of [51Cr]-EDTA/L-rhamnose, showed that indomethacin (50 + 75 mg) increased intestinal permeability. A formulation of indomethacin containing 15 mg glucose and 15 mg citrate to each milligram of indomethacin did not increase intestinal permeability significantly above baseline values. When given alone with indomethacin, neither glucose nor citrate (45 mg to each milligram of indomethacin) had any protective effects. Pharmokinetic studies showed that the effects of glucose and citrate cannot be explained on the basis of altered drug absorption. These results suggest a new approach to reducing the small intestinal side effects of NSAIDs.

Adult↗
PubMed1991

Reconstitution of the high affinity epidermal growth factor receptor on cell-free membranes after transmodulation by platelet-derived growth factor.

We have prepared plasma membranes from Balb/c 3T3 fibroblasts to study the transmodulation of the high affinity epidermal growth factor (EGF) receptor. Although phorbol esters do not transmodulate the high affinity EGF receptors on these membranes, the addition of platelet-derived growth factor (PDGF) or EGF to the membranes leads to the loss of high affinity EGF binding and to the phosphorylation of several membrane proteins, including the EGF receptor. The EGF receptor is phosphorylated at tyrosine residues although we have not yet established if this represents direct phosphorylation by the PDGF receptor kinase or is mediated by activation of other cell membrane-associated tyrosine kinases. Upon treatment of the membranes with PDGF, four major phosphoproteins (of apparent molecular masses of 69, 56, 38, and 28 kDa) are released from the membrane and can be retrieved from the supernatant fluid using a reversed-phase cartridge. As assessed by immunoprecipitation with an anti-phosphotyrosine antibody, all four proteins appear to be phosphorylated on tyrosine. The time course of dissociation of these proteins from the membranes closely parallels the loss of high affinity EGF receptors. The high affinity EGF receptor can be reconstituted on PDGF-transmodulated membranes by treating the supernatant fluid with alkaline phosphatase and adding the mixture to the membranes. It appears that dephosphorylation of the released proteins is sufficient to allow reassociation with the membranes and formation of the high affinity EGF receptor complex.

Animals↗
PubMed1991

Epstein-Barr virus--a possible missing link in the initiation of cervical carcinogenesis?

Salient epidemiological and molecular biological features of Epstein-Barr virus (EBV) infection correlate well with the natural history of carcinoma of the cervix. It is therefore hypothesised that the incorporation of EBV into the genome of cervical epithelial cells at an early age (teens) could be an important early event in cervical carcinogenesis.

Female↗
PubMed1991

A population survey of cardiovascular disease in elderly people: design, methods and prevalence results.

A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

HIV induces modulation of functionally important cellular antigens.

Infection of T lymphoblastoid CEM cells with the IIIB isolate of HIV-1 results in modulation of the expression of several cellular antigens in addition to the CD4 molecule. The intercellular adhesion receptor LFA-1 (CD11a/CD18) and HLA-DR are markedly induced in the cytoplasm and at the cell surface, and the CD7 antigen is down-regulated, being virtually undetectable by sensitive immunocytochemical techniques in the infected cell population. These modulatory effects are to some degree dependent on the virus isolate examined, as the CBL-1 British isolate did not induce comparable phenotypic changes in the CEM cell line. Furthermore, these effects are not reproduced by recombinant gp120 (IIIB isolate) or p24 added exogenously to uninfected CEM cells. The CD7 molecule appears to play a regulatory role in T cell proliferation, and the LFA-1 integrin molecule is involved in a wide range of immunologically important cell-cell interactions, as well as HIV-induced syncytium formation. The possible contributions of such effects to the pathogenesis of HIV infection are considered.

Antibodies, Monoclonal↗
PubMed1991

Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development.

Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.

Cell Differentiation↗
PubMed1990

Resistance to receptor-mediated degradation of a murine epidermal growth factor analogue (EGF-Val-47) potentiates its mitogenic activity.

In most cell types two classes of epidermal growth factor (EGF) receptors can be found: a major class that binds EGF with relatively low affinity and a minor class that binds with very high affinity. Structure-function studies have shown that mutations at amino acid 47 in the EGF molecule severely reduce its affinity for the EGF receptor but do not cause preferential binding to one or the other subclass of receptors. Using three EGF derivatives with a mutation at amino acid 47 (Ser-47, Leu-37-Tyr-47, and Val-47), we have investigated the relative contribution of the two receptor subclasses to the EGF-dependent mitogenic response. We show that mitogenicity correlates exclusively with occupancy of the high-affinity receptor and that full occupancy of this subclass is required for maximal stimulation. In addition we demonstrate that for the EGF-Val-47 analogue this requirement can be abrogated and half-maximal biological activity reached with a high-affinity receptor occupancy of only 8%. While the rate of internalization did not significantly differ between EGF-Val-47 and native mEGF, the analogue was much more resistant to degradation by cellular proteases and, after binding and receptor-mediated internalization, was released into the medium predominantly in an intact form. We propose that the increased mitogenicity of EGF-Val-47 is due to its prolonged half-life, resulting in continued occupancy of the high-affinity EGF receptor.

Animals↗
PubMed1990

Natural killer cells in cutaneous malignant melanoma.

Using immunocytochemical techniques on fresh surgical samples, a series of 16 cases of cutaneous malignant melanoma (CMM) were examined to characterize further the host inflammatory response. Antibodies to the following cluster of differentiation (CD) antigens were used: CD-3, CD-4, CD-8 (T-cell markers), CD-11b, CD-14 (macrophage marker), CD-16 [an antigen expressed by natural killer (NK) cells and granulocytes], and CD-25. Also examined were a small number of other melanocytic lesions [two cases of lentigo maligna (Hutchinson's melanotic freckle) and five of intradermal naevi]. The results of the study document a population of cells with the morphological and immunophenotypic characteristics of NK cells in association with 10 of the 16 cases of CMM. These cells were consistently absent from the other melanocytic lesions studied. The presence of NK cells in association with some cases of CMM bears no clear relationship to the Breslow thickness, Clark level, tumour ulceration, or the presence of activated T cells as determined by expression of the CD-25 antigen. Whilst an explanation for the significant numbers of NK cells in some CMM lesions in unclear, their presence in intimate association with tumour cells does prompt speculation regarding a possible role in determining the biological behaviour of the tumour. Additionally, the study has confirmed and extended previous findings with respect to the broad characterization of mononuclear cells present in the host infiltrate associated with CMM.

Antibodies, Monoclonal↗
PubMed1990

Metabolic activity in the calcified zone of cartilage: observations on tetracycline labelled articular cartilage in human osteoarthritic hips.

The tidemark is a metabolically active zone in the calcified layer of the cartilage in which it is possible to show that there is calcifying activity even over a short period of time using a tetracycline labelling technique. The tidemark slowly advances in the direction of the non-calcified cartilage and analysis of double-tetracycline labelled cartilage shows that this is not an appositional phenomenon like that occurring in bone, but that, where present, several tidemarks can be labelled at the same time. Each tidemark may therefore be metabolically active and it is not just the tidemark adjacent to hyaline cartilage which incorporates calcium.

Bone Development↗
PubMed1990

Audit of cranial computerised tomography in a general medical unit.

Over a two year period 108 patients had cranial computerised tomographic (CCT) scans while under the care of a general medical team. Sixty eight scans showed 70 abnormalities. Completed stroke, transient ischaemic attacks (TIA), epilepsy and headache were the most common indications for CTT while infarct, atrophy, haemorrhage and tumour were the most common abnormalities. Eight tumours were identified comprising 12% of epileptics and 9% of stroke patients.

Adult↗
PubMed1990

Breast cancers with extremely high oestrogen receptor protein status.

Seventeen cases of primary and one case of metastatic breast cancer which expressed greater than 900 fmol oestrogen receptor sites per mg soluble protein were examined. All these patients were post-menopausal at the time of their presentation. These were a heterogeneous group of well-differentiated cellular breast carcinomas, comprising cases of invasive duct carcinoma with extensive tubular differentiation or with focal argyrophilia, tubulolobular carcinoma, lobular carcinoma of mixed type containing abundant intracytoplasmic lumina, papillary carcinoma and type B colloid carcinoma. There was very little tumour necrosis. Nodal metastasis, tumour size and host inflammatory response did not appear to show any relationship with oestrogen receptor status. The patients, apart from two who died from other causes, remain alive (Fisher's exact test, P less than 0.01). In contrast, 17 randomly selected cases of oestrogen receptor negative breast cancer in the same study period were focally necrotic, poorly-differentiated invasive duct carcinomas. Six patients died from metastatic disease, seven were alive and well, one was alive with metastatic disease, one was lost to follow-up and two died from diseases unrelated to breast cancer.

Age Factors↗
PubMed1989

Taking mental health services to the people: the effects of referral to traditional psychiatric facilities.

This study investigated the effects of establishing a locally integrated mental health team in a small New Zealand township (Mosgiel), by comparing it with a similar township (Port Chalmers) without such established services. The rate of referral for out-of-district public and private inpatient and outpatient care was taken as an inverse measure of the strength of community resources to cope with psychiatric problems at the local level. In terms of referrals for inpatient care it was found that increased locally available mental health services did not reduce the number of onward referrals. However, length of hospital stay was significantly less. The total number of referrals to Dunedin for outpatient care also showed no significant change over time. The effect in this instance seems to be qualitative in that the proportion of first time referrals decreased while referrals tended to increase. It was also found that the lack of community mental health teams resulted in more self referrals to private health care. The appropriateness of this development needs further investigation. The presence of such a team is associated with a refinement in general practitioner referring practices.

Community Mental Health Services↗
PubMed1989

Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis.

To test the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) accelerate the progression of osteoarthritis by reducing synthesis of vasodilator prostaglandins, thereby diminishing joint perfusion, 105 osteoarthritis patients awaiting hip arthroplasty were treated prospectively with a strong or weak prostaglandin synthesis inhibitor, indomethacin or azapropazone, respectively. Pain and radiological joint space were monitored during the period up to arthroplasty and the condition of the excised femoral head was determined. As judged by radiological and histopathological data, the two treatment groups were at a similar pathophysiological end-point when they came to arthroplasty. In the indomethacin group the affected hips lost joint space more rapidly than did the contralateral hips, a difference not seen in the azapropazone group. The patients receiving azapropazone, who had higher concentrations of synovial vasodilator prostaglandins, took longer than the indomethacin group to reach the arthroplasty end-point. Potent inhibitors of prostaglandin synthesis may be inappropriate in the management of osteoarthritis of the hip.

Aged↗