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Biomedical subjects

P Shepherd

Publications and source records attributed to P Shepherd.

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

Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance.

A decline in insulin sensitivity is associated with aging, inactivity, and obesity. The effects of exercise training on glucose homeostasis independent of weight loss in older glucose-intolerant individuals are not well established. We examined the effects of exercise training on oral glucose tolerance, insulin action, and concentration of the GLUT-4 glucose transporters in skeletal muscle. Exercise training at 50 and 75% of heart rate reserve was performed for 12 wk in 18 individuals (age = 64 +/- 2, body fat = 37.0 +/- 1.5%). Peripheral insulin action was determined 96 h after the last exercise bout using a two-step hyperinsulinemic-euglycemic glucose clamp (insulin = 192 and 708 pmol/l). Percent body fat and fat-free mass (FFM) were unchanged with training. Diet composition, assessed by diet record, did not change over the 12 wk. Improved oral glucose tolerance was observed, as exhibited by lower plasma glucose concentrations after training (P < 0.05), whereas plasma insulin response remained unchanged. The rate of glucose disposal was unchanged during the low insulin concentration but increased 11.0% at the high insulin concentration (P < 0.05) after training (54.4 +/- 4.4 vs. 60.4 +/- 5.5 mumol.kg FFM-1.min-1). Skeletal muscle glycogen and GLUT-4 concentration increased 24 and 60%, respectively, with training. There was no direct relationship between the change in GLUT-4 protein and the change in glucose disposal rate. These findings demonstrate that chronic exercise training without changes in body composition improves peripheral insulin action in subjects with impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

The detection of human papillomaviruses in cervical biopsies by immunohistochemistry and in situ hybridization.

The presence of human papillomavirus (HPV) types 6, 16 and 18 in cervical biopsies can be detected by an immunoperoxidase technique using type-restricted monoclonal antibodies raised against fusion proteins representing the L1 major capsid proteins of these three HPV types. In a retrospective study (n = 54) we have used these antibodies and biotinylated DNA probes of HPV 6, 16 and 18 to detect and type HPV in formalin-fixed material from the cervix. The biopsies were classified histologically into normals, wart infections without dysplasia, cervical intraepithelial neoplasia (CIN) and squamous cell carcinomas. Antibody staining showed that 22% of all CIN was positive for HPV 16 and 40% of cervical warts were positive for HPV 6, 16 and 18. There was no HPV capsid protein detected in the normals and squamous cell carcinomas using these antibodies, whereas 25% of the tumours were positive for HPV 16 by in situ hybridization. Sections of cervical warts and CIN positive for HPV types by in situ hybridization were also positive by antibody staining which suggests that both techniques are detecting replicating virus. We feel these two techniques complement each other in detection and typing of HPV in cervical biopsies from patients with active disease.

Biopsy↗
PubMed1992

Granulocytic sarcomas of small intestine and brain are associated with acute myelomonocytic leukaemia with abnormal eosinophils and inversion of chromosome 16.

We report two cases of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in which the presenting feature was small bowel obstruction. We suggest there is a unique clinicopathological association between small intestine involvement with leukaemia and the M4Eo subtype. Central nervous system involvement by myeloblastoma occurred in one of the two cases which is a recognised feature of M4Eo and should necessitate prophylaxis with intrathecal therapy. Inversion of chromosome 16 which is a cytogenetic marker for M4Eo was demonstrable in one of the two cases.

Biomarkers, Tumor↗
PubMed1990

Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil.

Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas.

Adult↗
PubMed1990

Idiopathic portal hypertension associated with cytotoxic drugs.

Four patients developed clinically important portal hypertension with histological features of idiopathic portal hypertension while they were receiving cytotoxic drugs for chronic myeloid leukaemia and Hodgkin's disease. Mild sclerosis of some small portal triads was the only abnormality seen at light microscopical examination in three of the four cases. In the remaining case light microscopical findings seemed to be normal. Two cases examined by electron microscopy showed perisinusoidal fibrosis; in one case this was the only abnormality detected. There is an association between idiopathic portal hypertension and the use of chemotherapeutic agents, particularly thioguanine. Adequate histological examination of liver tissue, including electron microscopic studies, is recommended for patients who develop hepatic problems while receiving cytotoxic treatment to elucidate this problem.

Adult↗
PubMed1988

Urolithiasis in children: innovations in management.

Management of urolithiasis in children remains a challenge despite newer technological innovations. During the last 3 years we have treated 19 children with a combination of extracorporeal shock wave lithotripsy, percutaneous stone extraction and ureteroscopy, as well as with traditional methods. The newer technological methods perfected in adults are equally applicable to children in experienced hands.

Adolescent↗
PubMed1988

A prospective study of acute idiopathic neuropathy. III. Immunological studies.

The immune responses of 100 patients who presented with an acute idiopathic neuropathy were compared with those of age and sex matched controls. Blood lymphocytes and their subsets were counted with a fluorescent activated cell sorter. CD8+ (putative suppressor) lymphocytes were significantly reduced in the first week of the disease but total lymphocytes, total T and CD4+ (putative helper) cells were not altered. This reduction depended on the nature of the preceding infection. Serum complement C3 and C4 concentrations remained normal and immune complexes were rarely detected with a C1q binding assay. Complement-fixing antibodies to human peripheral nerve antigens were discovered in the serum of 7% of patients but only 1% of controls. Complement-fixing antibodies to galactocerebroside were not discovered in any sera. Enzyme-linked immunoassays detected increased antibody responses to galactocerebroside but none at all to human P2 myelin protein in the patient sera. Forty microliter of serum from five patients injected into the sciatic nerves of rats did not induce significantly more demyelination than the serum from control patients. It is concluded that auto-immune responses can only be detected by these techniques in a small minority of patients with acute idiopathic neuropathy.

Adolescent↗
PubMed1987

Increasing the rate of identification of battered women in an emergency department: use of a nursing protocol.

In recognition of the increasing problem of family violence, the authors developed and tested an interview protocol focused on female victims of family violence. The purpose of the protocol was to increase nurses' identification of battered women receiving care in the emergency department. Using a time-series design, data were collected from patient records during four months prior to introduction of the protocol. These data were compared to comparable post-protocol data. There was a significant increase in nursing staff identification of female domestic violence victims following introduction of the protocol.

Clinical Protocols↗
PubMed1987

Human autoantibodies to thyroglobulin are directed towards a restricted number of human specific epitopes.

Significant binding of thyroglobulin (Tg) autoantibodies was restricted to primate Tg, although some sera showed weak cross-reactivities with other species at high concentrations. In contrast rabbit anti-human Tg bound to all other animals' Tg in addition to human and this was not due to crossreactions with the thyroxyl residues. Mouse antihuman Tg monoclonal antibodies (MoAb) showed at least three different patterns of cross-reactivities. Group 1 MoAb, like Tg autoantibodies, were primate specific; two out of six MoAb bound only human Tg. Group 2 MoAb also bound a few other animals' Tg in addition to human. Of the three MoAb in group 3, two reacted with most or all of eight animal Tg tested while the other bound to all eight. However the binding of thirteen out of the fourteen MoAb against human Tg including all of the primate Tg specific group 1 MoAb was not inhibited by any of the nine Tg autoantibodies. Reactions of MoAb with heat-treated human Tg varied. Examples of decreased, increased or no change in reactivity could be demonstrated. On this basis at least five or possibly six separate human-specific epitopes could be defined by group 1 MoAb. Monoclonal antibody 1D6 (group 2) was inhibited by six out of nine Tg autoantibodies at high concentrations. This MoAb, similarly to the eight Tg autosera tested, had reduced reactivity with heat treated Tg. These studies demonstrated that human Tg has immunogenic structures conserved in the Tg of many species. The protein also has, however, primate and human-specific antigenic sites but at least five or possibly six of these are not related to autoantibody binding.

Animals↗
PubMed1986

An efficient one-step method for isolating immune complexes from whole serum using a monoclonal anti-C3g affinity immunosorbent.

A simple and efficient method of extracting complement-fixing immune complexes (IC) from whole serum and recovering them has been developed. 125I-labelled, in vitro prepared IC in whole serum were incubated with Sepharose 4B covalently linked to monoclonal anti-C3g or anti-C1q and the binding and recovery of IC was monitored by radioactivity. The anti-C3g immunosorbent bound 45% and 76% of HAGG and BSA-anti-BSA IC respectively, all of which were recovered by elution with 4M MgCl2. The anti-C1q immunosorbent only bound 14% and 12% of the same IC and only 64% were recovered by eluting with 4M MgCl2. The IC extracted by the anti-C3g immunosorbent included those capable of extraction by the anti-C1q. The anti-C3g monoclonal recognizes not only the iC3b fragment of C3 and will therefore bind IC with affinity for bovine conglutinin but also subsequent degradation products containing the C3g antigen. Its wide range of reactivity for IC plus its excellent recovery properties make it the immunosorbent of choice for isolating complement-fixing IC.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibody HMFG-2 retains activity in vivo and binds to high molecular weight components expressed by metastatic breast cancers.

The monoclonal antibody HMFG-2 was raised against components of the human milk fat globule and human milk epithelial cells. It recognizes an epitope on glycoproteins of varying molecular weight; it is tumour-associated and expressed heterogeneously by most breast cancers. An intravenous injection of 131I-labelled HMFG-2 has been given to patients with recurrent cutaneous metastasis from breast carcinomas. Clearance of radioactivity from the plasma was measured and the label was shown to be carried on intact circulating antibody that had the ability to bind in vitro to the specific determinant as expressed by both the patients own tumour and by cultured breast cancer cells. Antibody was found to be associated with biopsy material taken from skin metastases 24 hours after administration of labelled antibody. However, the amount of radioactivity was insufficient for the production of a positive isotopic scan.

Antibodies, Monoclonal↗
PubMed1985

Antigenic determinants of human thyroglobulin differentiated using antigen fragments.

Human thyroglobulin (Tg) was digested with V8 protease and the fragments separated by high performance liquid chromatography (HPLC). The antigenic relationship of the fragments was investigated using mouse monoclonal antibodies to human Tg. The binding of Hashimoto's disease autoantibodies to the fragments was measured by radioimmunoassay. This demonstrated that a minority of the patients recognize an epitope on Tg which others do not. The epitopes identified by the autoantibodies were substantially destroyed in the smaller fragments tested, but these smaller fragments were more efficient stimulators of Tg-specific T-cell lines than the larger fragments which carry the antibody binding determinants. This suggests that the parts of the Tg molecule which stimulate autoimmune B cells differ from those which stimulate T cells.

Animals↗
PubMed1983

The effects of intravenous pulse methylprednisolone on immunological and inflammatory processes in ankylosing spondylitis.

Acute phase reactants, serum immunoglobulins and immune complexes and T cell function were measured in eight patients with active ankylosing spondylitis (AS) before and up to 3 months after three pulses of 1 g methylprednisolone. There was a two stage effect. The first stage was an early anti-inflammatory event with a fall in clinical disease activity mirrored by changes in acute phase reactants particularly prealbumin. The second stage occurred later and was an immunological event with a fall in serum IgA and IgG and a rise in mitogenic response, mixed lymphocyte response and delayed cutaneous hypersensitivity. Most of these changes returned towards pre-treatment levels by 3 months. This study has shown that pulse methylprednisolone has an immediate anti-inflammatory and a prolonged immunological effect in AS.

C-Reactive Protein↗
PubMed1982

Pyoderma gangrenosum associated with primary thrombocythaemia.

Pyoderma gangrenosum is most commonly associated with inflammatory bowel disease and rheumatoid arthritis, but it has been associated with various haematological malignancies. A 54-year-old man with no history of bowel disease or arthritis presented with a leg ulcer, which healed after treatment. Results of bone marrow aspiration were compatible with primary thrombocythaemia. Seven weeks later there were pronounced recurrence of the ulceration and pyoderma gangrenosum was diagnosed. The appearance of pyoderma gangrenosum associated with blood disorders may differ from that associated with bowel and joint disease.

Humans↗
PubMed1982

Effect of sera from patients with rheumatoid arthritis on normal lymphocytes: a possible immunoregulatory role for immune complexes.

The ability of rheumatoid sera to support concanavalin-A transformation of normal lymphocytes was inversely related to serum C1q binding activity. When C1q binding activity of the sera was removed by absorption with staphylococcal protein A, subsequent lymphocyte response increased to the level found in immune-complex negative sera. Gel filtration of a small number of sera suggested that the suppressive material had a molecular weight in the range 1.8-4.9 x 10(5) daltons. Aggregated human gammaglobulin suppressed con-A transformation of normal lymphocytes in a dose-dependent fashion. These results suggest that immune complexes present in rheumatoid sera can suppress lymphocyte responsiveness. The relevance of this observation to be clinical features of rheumatoid arthritis is discussed.

Adult↗
PubMed1982

Lymphocyte studies in rheumatoid arthritis. V. Suppressor cell function in peripheral blood.

Peripheral blood lymphocytes from 30 patients with rheumatoid arthritis and 14 controls were examined for suppressor activity by two different assays. These were the Concanavalin-A-induced and the short-lived suppressor cell assays. There was no difference in suppressor activity between patients and controls, the suppressor activity of HLA-DR3 positive patients was no less than that of non-DR3 patients. However, patients with nodules showed reduced suppression in the short-lived suppressor cell assay when compared with patients without nodules.

Adult↗
PubMed1981

Circulating immune complexes, serum immunoglobulins, and acute phase proteins in psoriasis and psoriatic arthritis.

Raised levels of circulating immune complexes were found in the plasma of 47% of patients with psoriasis and in 58% of those with psoriatic arthritis. The mean levels were significantly raised when compared with normals, but there was no difference between the 2 patient groups. The levels of acute phase proteins (C-reactive protein, fibrinogen, alpha-1-antitrypsin, and the 9th component of complement) were normal in those patients with psoriasis but were significantly raised in patients with psoriatic arthritis. Serum immunoglobulin G and A levels were equally raised in both patient groups, immunoglobulin M being normal. C-reactive protein and fibrinogen gave the best correlation with the clinical index of disease activity.

Antigen-Antibody Complex↗