Search PubMed⌕ Search

Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1993

Production of stable rabbit-mouse heterohybridomas: characterization of a rabbit monoclonal antibody recognizing a 180 kDa human lymphocyte membrane antigen.

Polyclonal rabbit antihuman thymocyte globulin (RATG) remains a key component of immunosuppressive strategies in transplantation. The human thymus immunization regimen that produces highly immunosuppressive RATG induces unique antibody specificities in the rabbit. Rabbit monoclonal antibodies (RAb MAbs) to human T cell antigens would be of value in the effort to investigate and reproduce the multiple specificities of RATG. We have fused mouse Sp2/0 cells with splenocytes from rabbits immunized with human thymus and have identified 52 rabbit-mouse heterohybridomas which secrete RAb MAbs directed against human lymphocyte surface antigens. The technical aspects of hybridoma isolation, stabilization and characterization are presented. Analysis by flow cytometry, preabsorption and immunoprecipitation suggests that RAb MAb 1A8 IgG may recognize LFA-1, one of the principal lymphocyte surface antigens recognized by RATG. The 1A8 antigen is 180 kDa and is expressed by 80-90% human PBL and thymocytes. LFA-1 and the 1A8 antigen exhibit 100% co-expression in two-color FACS analysis using four different murine anti-LFA-1 MAbs. 1A8 markedly inhibits the mitogenic response of lymphocytes to PHA, as do murine anti-LFA-1 MAbs. A combination of rabbit antilymphocyte MAbs may potentially reproduce the multiple specificities found in polyclonal RATG and lead to the production of a superior immunosuppressive clinical agent.

Animals↗
PubMed1993

The determinants of hospital CEO compensation.

This study finds a significant difference in the compensation levels of public and private hospital CEOs. The difference, however, is not found to be associated with ownership structure. Rather, it is attributable to hospital characteristics such as size, location, and affiliation with a multihospital chain, and human characteristics such as gender, education, and experience.

Chief Executive Officers, Hospital↗
PubMed1993

A 25-year prospective study of modified radical mastectomy (Patey) in 193 patients.

The results of a prospective study over 20 years of 193 patients with breast carcinoma treated by Patey mastectomy are presented together with details of the operative technique employed. One hundred and twenty-eight cases (66%) were stage 1 (T1/T2 N0), 46 (24%) were stage 2 (T1/T2 N1), 18 (9%) were stage 3 (T3 N0/N1), and one was stage 4 (M1). The probability of survival together with 95% confidence intervals for stage 1 (T1/T2 N0) at 10 years was 79% (71-88); and at 15 years 74% (61-87). For stage 2 (T1/T2 N1), the probability of survival at 10 years was 64% (48-79), and at 15 years 60% (44-76). For stage 3 (T3 N0/N1), the probability of survival at 10 years was 70% (45-95) and nobody survived at 15 years. These differences between the clinical stages lacked significance [Log-rank test: chi 2 = 3.44 df = 2 P = 0.18]. There were nine patients (5%) who developed local recurrence without systemic metastases. There was no postoperative mortality, and morbidity was low. Axillary node metastases depressed survival with probability of survival at 10 years 43% (29-57) in contrast to those without it 90% (84-96) [log-rank test: chi 2 = 39.42 df = 1 P < 0.0001]. Patey mastectomy should be considered for patients with T1 or T2 tumours who choose mastectomy rather than breast conservation. It is an effective local treatment which is of particular relevance in countries where radiotherapy is not available.

Breast↗
PubMed1993

Buprenorphine prevents and reverses the expression of chronic etorphine-induced sensitization of adenylyl cyclase in SK-N-SH human neuroblastoma cells.

Buprenorphine is an opiate drug with a mixed agonist-antagonist profile and has therapeutic efficacy in attenuating drug craving and addiction. Because the adenylyl cyclase system has been implicated in the biochemical basis of opiate withdrawal phenomena, we have compared the acute and chronic effects of buprenorphine with the full opiate agonist etorphine on cyclic AMP (cAMP) synthesis in the human neuroblastoma cell SK-N-SH. Both drugs acutely inhibited prostaglandin (PG)E1-stimulated cAMP accumulation; the inhibition caused by either drug was prevented by pretreatment with the opiate antagonist naltrexone or with pertussis toxin. Chronic treatment of the cells with etorphine induced an increase in PGE1-stimulated cAMP synthesis which was observed after withdrawal of the inhibitory drug. Chronic treatment with buprenorphine appeared to have the opposite effect, resulting in an attenuated PGE1 stimulation; additionally, buprenorphine prevented the etorphine-induced enhancement in cAMP synthesis, whether administered before or after prolonged incubation of the cells with etorphine. The attenuating effect of buprenorphine occurred within 5 min and was prevented by a prior application of naltrexone, but could not be reversed by a subsequent treatment with antagonist. These findings suggest that buprenorphine was binding (pseudo)irreversibly to the opiate receptor, resulting in a persistent inhibition of cAMP synthesis which masks the etorphine-induced enhancement of adenylyl cyclase activity. This hypothesis was confirmed by experiments demonstrating that treatment of the cells with buprenorphine significantly reduced available opiate receptor binding sites despite extensive washing of the cells to remove unbound buprenorphine. These pharmacodynamic actions of buprenorphine may be relevant to its therapeutic efficacy in treating drug abuse and addiction.

Adenylyl Cyclases↗
PubMed1993

Treatment of cutaneous metastases from malignant melanoma using the carbon-dioxide laser.

Between October 1988 and September 1991, 60 patients with cutaneous metastases from malignant melanoma have been treated palliatively using carbon-dioxide laser ablation. The number of lesions per patient varied between 3 and 450; accordingly treatment was performed under local or general anaesthesia. The post-operative complication rate was low and the majority of wounds healed within 6 weeks. Control of in-transit metastatic disease and palliation of disseminated cutaneous melanoma can be achieved by carbon-dioxide laser ablation which provides a simple and effective alternative to isolated limb perfusion. Eighteen of the 32 patients in this series with stage IIIa disease were controlled by three or fewer laser treatments in the first year. We advocate laser vaporization as the initial treatment for non-nodal regional recurrence in the knowledge that isolated limb perfusion can be offered at a later stage for patients who cannot be controlled by the laser.

Adult↗
PubMed1992

Metastasectomy.

The literature on metastasectomy abounds in anecdote and retrospective studies of non-randomized patients. In this paper, the published evidence concerning the efficacy of metastasectomy in the lung, liver, brain, gastrointestinal tract and omentum is reviewed to formulate practical recommendations for patient selection and treatment. At some sites metastasectomy can be recommended with little hesitation for more widespread application, but surgery for liver metastases should still be regarded with some reservation.

Adult↗
PubMed1992

Early T-cell defects in pre-type 1 diabetes.

Alterations of lymphocyte subsets have been recently reported in pre-type 1 diabetes but the relation with other immunological markers, in particular islet cell antibodies (ICA), is still unknown. In the present study, we have investigated prospectively changes of lymphocyte subsets in 86 first-degree relatives of patients affected by type 1 diabetes and correlated such modifications with ICA titres. Among individuals with persistent ICA, 8 had ICA titres of more than 20 JDF units, 14 had ICA titres between 5 and 20 JDF units and 64 had ICA titres between 0 and 5 JDF units. First-degree relatives with ICA titres of more than 20 JDF units had significantly decreased proportions of CD3 cells. This reduction was predominantly in the CD4 subset, giving rise to a decreased CD4/CD8 lymphocyte ratio. Those with ICA titres between 5 and 20 JDF units showed abnormalities in both CD3 and CD4 lymphocytes, but not in CD4/CD8 lymphocyte ratio. Further characterization of the CD4 cell subset was performed using three other monoclonal antibodies, CD45RO (UCHL1), CD45RA and CD29, phenotyping memory T-cells, the inducer cells of suppressor function and helper-inducer cells, respectively. The proportions of total CD45RO and CD45RA were not significantly different among first-degree relative with distinct ICA titres in a cross-sectional study, whereas a trend towards a reduced proportion of CD4/CD45RA cells was observed. The longitudinal study demonstrated that individuals potentially susceptible to the development of type 1 diabetes and who possess high titres of ICA have impairment of CD4/CD8 lymphocyte ratio, mainly due to a reduction in the CD4 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Prolonged activation of inhibitory somatostatin receptors increases adenylate cyclase activity in wild-type and Gs alpha-deficient (cyc-) S49 mouse lymphoma cells.

Many cells develop enhanced adenylate cyclase activity after prolonged exposure to drugs that acutely inhibit the enzyme and it has been suggested that this adaptation may be due to an increase in Gs alpha. We have treated wild-type and Gs alpha-deficient cyc- S49 mouse lymphoma cells with a stable analogue (SMS 201-995) of the inhibitory agonist somatostatin. After incubation with SMS for 24 h, the forskolin-stimulated cAMP synthetic rate in intact cyc- cells was increased by 76%, similar to the increase found in the wild-type cells. Forskolin-stimulated adenylate cyclase activity in the presence of Mn2+ was also increased in membranes prepared from SMS-treated cyc- cells; however, guanine nucleotide-mediated inhibition of adenylate cyclase activity was not changed despite a small decrease in inhibitory Gi alpha subunits detected by immunoblotting. Pretreatment of cyc- cells with pertussis toxin prevented SMS from inducing the enhancement of forskolin-stimulated cAMP accumulation in intact cells. After chronic incubation of cyc- cells with SMS, exposure to N-ethylmaleimide, which abolished receptor-mediated inhibition of cAMP accumulation, did not attenuate the enhanced rate of forskolin-stimulated cAMP synthesis compared to N-ethylmaleimide-treated controls. These results with cyc- cells demonstrate that an adaptive increase in adenylate cyclase activity induced by chronic treatment with an inhibitory drug can occur in the absence of expression of Gs alpha.

Adenylyl Cyclases↗