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Biomedical subjects

F Walker

Publications and source records attributed to F Walker.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Age-related deposition of amyloid P component in normal human testis.

The distribution of amyloid P component in normal human testes from fetal life to old age was studied by a direct immunofluorescent technique on frozen sections. Amyloid P is readily and invariably detected in association with elastic fibres around seminiferous tubules and in blood vessels from the age of 30 years upwards. The same is true for most cases during the twenties, but in no case below the age of 18 was its presence demonstrable.

Adolescent↗
PubMed1989

A case of IgA nephropathy associated with vitiligo, primary hypothyroidism and primary adrenocortical insufficiency.

A 14 year old boy presented with recurrent attacks of macroscopic haematuria preceded by tonsillitis. Clinical examination revealed generalised vitiligo. Renal function was normal with microscopic haematuria. Percutaneous renal biopsy showed mesangial proliferation on light microscopy with deposition of IgA and IgM in a granular pattern in the mesangium and glomerular basement membrane compatible with a diagnosis of IgA nephropathy. Biochemical investigations revealed primary hypothyroidism and primary adrenocortical insufficiency with negative organ specific autoimmune screen. Renal function has not deteriorated after three years follow-up. This particular association has not been previously described to our knowledge.

Adolescent↗
PubMed1989

Multiple levels of regulation of megakaryocytopoiesis.

A working hypothesis for the regulation of megakaryocytopoiesis is described on the basis of current data. The hypothesis proposes that in vivo megakaryocytes are generated by 1) the expansion of clonable progenitor cells into immature megakaryocytes by locally produced (and regulated) interleukin-3 (IL-3) and 2) the development and maturation of immature megakaryocytes by a dual system; by a lineage specific mechanism involving thrombopoietic stimuli in the steady state and thrombocytopenic conditions, and by a lineage nonspecific mechanism via IL-3 in damaged or reconstituting marrow. The hypothesis predicts that if IL-3 is a significant in vivo regulator of megakaryocyte formation and development, receptor for IL-3 should be present on megakaryocytes and may be vestigially on platelets. Small but significant levels of 125I IL-3 were found to bind to platelets from normal mice. The level of binding on platelets was found to be enhanced sevenfold from mice that had received high levels of irradiation followed by bone marrow transplantation. This contrasted with a twofold increase in the level of binding to platelets from mice made acutely thrombocytopenic with antiplatelet serum. The data suggest that IL-3 may be involved in the in vivo regulation of murine megakaryocytopoiesis and may be a significant factor in rebound thrombopoiesis following bone marrow damage.

Animals↗
PubMed1988

Transmodulation of the epidermal-growth-factor receptor in permeabilized 3T3 cells.

Binding of murine epidermal growth factor (EGF) to its high-affinity receptor can be modulated by a variety of structurally unrelated mitogens. The transmodulation, however, is temperature-dependent and has not been observed in isolated membranes. We report here the transmodulation of high-affinity EGF receptors by platelet-derived growth factors (PDGF) and tumour-promoting phorbol esters in 3T3 cells even when they are rendered incapable of fluid-phase endocytosis by treatment with phenylarsine oxide or by permeabilization with lysophosphatidylcholine. The relative affinity of the EGF receptors in the absence of modulating agents is not significantly altered by phenylarsine oxide treatment. Thus the difference in affinity between the two classes of EGF receptors seems to be unrelated to dynamic membrane changes or to differential rates of internalization. In permeabilized cells, non-hydrolysable GTP analogues transmodulate the high-affinity EGF receptor; however, the effects of these analogues are blocked by the protein kinase C inhibitor chlorpromazine. In contrast, transmodulation by PDGF is not blocked by chloropromazine. Thus the high-affinity EGF receptor can be transmodulated by both protein kinase C-dependent or -independent pathways, and the transmodulation processes do not require fluid-phase endocytosis.

Animals↗
PubMed1988

Murine epidermal growth factor: structure and function.

Murine epidermal growth factor (EGF), a 53 amino acid protein, has been modified by enzymic digestion, site-specific chemical reactions, and recombinant DNA technology. After trypsin digestion the EGF derivatives EGF1-48 (called EGF-T) and EGF1-45 (called EGF-T2) were separated from the residual EGF and the C-terminal pentapeptide by reversed-phase high-performance liquid chromatography. EGF-T competes for binding to EGF receptors with the same efficiency as EGF. The EGF-T2 derivative had no detectable receptor binding activity even at 100 nM. The in vitro mitogenic potencies of EGF and EGF-T for Balb/c 3T3 cells were indistinguishable. Treatment of EGF-T with carboxypeptidase Y yielded two derivatives, EGF-T-(des-Arg48) and EGF-T-des(Leu47-Arg48). There was only a 3-7-fold diminution in the binding efficiency and mitogenic potency for EGF-T-(des-Arg48). However, there was more than a 100-fold decrease in the binding efficiency and mitogenic activity of EGF-T-des (Leu47-Arg48). These results indicated that Leu47 is intimately involved in the formation of the ligand-receptor complex. Studies with a number of proteases indicated that the C-terminus of EGF was susceptible to enzymic digestion; however, the N-terminus appears to be folded into a conformation which prevents access to proteolytic digestion. Consequently, the N-terminus was modified by preparing an analogue with recombinant DNA technology. Oligonucleotides corresponding to EGF(3-48). Met3 Lys21 residues were ligated in frame to a beta-galactosidase expression vector. The beta-Gal-EGF fusion protein was cleaved with cyanogen bromide and EGF(4-48).Lys21 purified.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Internalisation and recycling of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on a murine myelomonocytic leukemia.

Radioiodinated granulocyte-macrophage colony-stimulating factor (125I-GM-CSF) binds to specific receptors (molecular weight approximately 50,000 daltons) on the murine myelomonocytic leukemia, WEHI-3BD+. At 4 degrees C 125I-GM-CSF remains on the surface of the cells and can be eluted by washing the cells with acidified isotonic buffer. When the cells are warmed to 37 degrees C, the 125I-GM-CSF is internalized rapidly (t 1/2: 7 min). The internalisation appears to be entirely receptor mediated and is independent of energy sources inhibited by sodium azide. This GM-CSF-mediated internalisation is not due to a general increase in the turnover of cell surface molecules as the specific binding of 125I-transferrin is not affected by incubation of WEHI-3BD+ cells with GM-CSF. The initial 125I released when the cells are warmed to 37 degrees C appears to be intact 125I-GM-CSF; however, after 2 h 80% of the 125I released was not precipitable with trichloroacetic acid and presumably represented degraded 125I-GM-CSF. Ammonium chloride or monensin reduced the release of 125I-GM-CSF from the cells, suggesting that the receptor-bound ligand was processed through the lysosomes. A considerable proportion of the internalised GM-CSF receptors were recycled to the surface and were available for ligand binding. Synthesis of new GM-CSF receptors contributed to the re-expression of GM-CSF receptors after down-regulation and it is possible that the GM-CSF enhances the synthesis of its own receptors.

Ammonium Chloride↗
PubMed1987

Macrophage cell lines transformed by the malignant histiocytosis sarcoma virus: increase of CSF receptors suggests a model for transformation.

The malignant histiocytosis sarcoma virus (MHSV) contains Ha-v-ras-related oncogenic sequences and rapidly transforms myeloid cells in vivo and in vitro. Myeloid cell lines can be derived which do not require growth factor for continued proliferation. We initiated this work to define the process of transformation leading to autonomy of cell growth in transformed myeloid cells. Five established cell lines were examined. All express macrophage-specific cell-surface antigens and exhibit several other properties typical for mature macrophages. Growth properties, growth factor release, and growth factor receptor presentation were examined: Release of growth factors is not a consistent feature. All cell lines show cell-density-independent colony formation and do not release self-stimulating factors, thus excluding autocrine stimulation as a model leading to transformation. All cell lines express unusually high levels of granulocyte-macrophage (GM)- and multi-CSF receptors and, except for one, M-CSF receptors. The high increase in GM-CSF and other growth factor receptors may be causally related to the transformed state of the cells. MHSV can be used as a tool to easily derive cell lines of the macrophage pathway as a model to study myeloid transformation, differentiation, and macrophage function.

Animals↗
PubMed1986

Major histocompatibility complex class II antigen (HLA-DR, DQ and DP) expression in human fetal skin.

Monoclonal antibodies were used to analyse skin samples from human fetuses (15-19 weeks gestational age) for the presence of class II major histocompatibility antigens (HLA-DR, DQ and DP). Cells expressing these antigens were clearly demonstrated within the epidermis from a proportion (4/7) of cases and were completely absent from the others. The negative samples were uniformly those with an epidermis of three cell layers or less. Such material may prove useful in studying the induction of class II antigen expression and the role of these antigens in allostimulation.

Antibodies, Monoclonal↗
PubMed1985

Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells.

The hemopoietic growth factor granulocyte-macrophage colony-stimulating factor, GM-CSF, specifically controls the production of granulocytes and macrophages. This report describes the binding of biologically-active 125I-labeled murine GM-CSF to a range of hemopoietic cells. Specific binding was restricted to murine cells and neither rat nor human bone marrow cells appeared to have surface receptors for 125I-labeled GM-CSF. 125I-Labeled GM-CSF only appeared to bind specifically to cells in the myelomonocytic lineage. The binding of 125I-labeled GM-CSF to both bone marrow cells and WEHI-3B(D+) was rapid (50% maximum binding was attained within 5 min at both 20 degrees C and 37 degrees C). Unlabeled GM-CSF was the only polypeptide hormone which completely inhibited the binding of 125I-labeled GM-CSF to bone marrow cells, however, multi-CSF (also called IL-3) and G-CSF partially reduced the binding of 125I-labeled GM-CSF to bone marrow cells. Interestingly, the binding of 125I-labeled GM-CSF to a myelomonocytic cell line, WEHI-3B(D+), was inhibited by unlabeled GM-CSF but not by multi-CSF or G-CSF. Scatchard analysis of the binding of 125I-labeled GM-CSF to WEHI-3B(D+) cells, bone marrow cells and peritoneal neutrophils indicated that there were two classes of binding sites: one of high affinity (Kd1 = 20 pM) and one of low affinity (Kd2 = 0.8-1.2 nM). Multi-CSF only inhibited the binding of 125I-labeled GM-CSF to the high affinity receptor on bone marrow cells: this inhibition appeared to be a result of down regulation or modification of the GM-CSF receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗