Search PubMed⌕ Search

Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 811 records · Page 45Linked to original sources

[Dose calculations for local irradiation of endometrial carcinoma].

A program for a personal computer has been developed to calculate and optimize dose distributions around a high dose intracavitary afterloading applicator having a single source. The problems of the local irradiation of the endometrium-carcinoma are emphasized in connection with the optimization criteria for an adequate irradiation planing. Exemplarily, the anisotropic proportions of absorption around a special type of applicator are calculated. In addition, an algorithm for optimization of dwell times of three-dimensional arranged source positions according to a prescribed dose distribution is theoretically presented. Further, an easy way of finding isodosis by given source positions and dwell times is introduced by taking into consideration the need to superimpose the dose distribution with external radiation fields. All calculations are tested in a water phantom.

Brachytherapy↗

Amiodarone-induced enhancement of doxorubicin and 4'-deoxydoxorubicin cytotoxicity to rat colon cancer cells in vitro and in vivo.

The mechanisms of the resistance of intestinal cancer to anthracyclines were studied on an experimental model of rat colon cancer cells. The accumulation of anthracyclines in the nucleus of living cancer cells was observed by fluorescence microscopy. This accumulation depended on both the capacity of anthracyclines to penetrate into the cell and the activity of an efflux mechanism extruding the drug from the cell. We found that 4'-deoxydoxorubicin was superior to 4 other anthracyclines in its capacity to penetrate into confluent colon cancer cells. Amiodarone, an antiarrhythmic agent used in cardiology, inhibited the efflux mechanism efficiently and increased the toxicity of anthracyclines to the colon cancer cells. Association of amiodarone and 4'-deoxydoxorubicin was able to cure 5 of 13 rats that had been inoculated i.p. previously with syngeneic colon cancer cells. This association could be of interest in the treatment of human colon cancer.

Adenocarcinoma↗

Therapeutic monitoring of chlorpromazine. III: Minimal interconversion between chlorpromazine and metabolites in human blood.

Chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), and chlorpromazine N-oxide (CPZNO) were each incubated (37 degrees C), for various timed intervals up to 60 min, with pooled human whole blood. Plasma and red blood cells were then separated and analyzed by a high performance liquid chromatographic method that avoids the use of alkaline extraction procedures. It was found that CPZ, CPZSO, and CPZNO were remarkably stable in whole blood under physiological conditions. CPZ was converted into CPZSO to a small extent (1%). Reports of 15-50% conversion of CPZ into CPZSO are largely due to artifacts, which result when red blood cell materials come into contact with alkali. CPZNO was recovered (85%) unchanged from the plasma. A small portion (1%) of the CPZNO was reduced to CPZ in the red blood cells. Thus, on the basis of these in vitro data, blood does not appear to be an important tissue for the metabolism of CPZ, CPZSO, or CPZNO.

Biotransformation↗

Increased survival with high-dose multifield radiotherapy and intensive chemotherapy in limited small cell carcinoma of the lung.

From June 1979 through April 1982, we treated 35 patients with limited small cell carcinoma on an intensive chemo-radio-immunotherapy regimen, consisting of induction with cyclophosphamide, doxorubicin, and vincristine, alternately cycled with VP-16 and cisplatin. Patients were stratified by performance status and randomized to thymosin, fraction V, or no thymosin. Induction was followed by consolidation, consisting of prophylactic whole-brain radiotherapy and multifield radiotherapy to the primary and mediastinum with cyclophosphamide and vincristine. Patients who were complete responders (CRs) postconsolidation resumed maintenance immediately. Patients were followed from 1 to 3.8 years (median, 2.2 years) at the time of analysis. After induction, 35% (12/34) had become CRs; after consolidation radiotherapy, an additional 10/34 became CRs for a total CR rate of 65% (22/34). There were only 9/34 local failures (26%), of which all but one were impatients who had not become CRs. A prolonged median survival (21 months) has been obtained in patients with limited small cell carcinoma of lung treated with an intensive combined modality regimen. At 1 year, survival is 83%; at 2 years, 46%. There is a 33% long-term survival (greater than 3 years). There is no difference in survival or recurrence rate between patients treated with or without thymosin.

Adult↗

Expression of the human proenkephalin gene in mouse pituitary cells: accurate and efficient mRNA production and proteolytic processing.

A recombinant plasmid containing the human proenkephalin gene ligated to pBR322 was introduced into a mouse pituitary cell line (AtT-20D16v) that normally expresses pro-opiomelanocortin but not proenkephalin. The plasmid was introduced by co-transformation with the G418-selectable plasmid, pRSVneo. Stable transformants were isolated and analyzed for the presence of the human proenkephalin gene. AtT-20 transformants which had one or more copies of the human proenkephalin gene integrated stably into the mouse chromosomal DNA expressed a 1.45 kb mRNA identical in size to human proenkephalin mRNA. Primer extension analysis indicated that the human proenkephalin gene was accurately and efficiently transcribed from its own promoter. AtT-20 transformants that expressed the 1.45 kb human proenkephalin mRNA also expressed proenkephalin protein and cleaved the protein to form free Met-enkephalin. This is of particular interest because these cells do not cleave all of the available pairs of basic amino acids in the endogenous protein, pro-opiomelanocortin, the precursor to ACTH, beta-endorphin and melanocyte stimulating hormones. The release of both ACTH and Met-enkephalin from these cells is stimulated by corticotropin releasing factor, a natural secretagogue for ACTH, indicating that the two classes of peptide share a related secretory pathway.

Adrenocorticotropic Hormone↗

Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire.

In an analysis of the genomic variation of AIDS retroviral isolates from patients living in New York, Alabama, and Zaire, restriction maps were constructed by using seven enzymes, each known to cleave the proviral DNA more than once, in conjunction with Southern blot analysis. The maps of LAV, HTLV-III, and ARV-2 as deduced from their published nucleotide sequences were included in this analysis. The results demonstrated that (i) several "signature" restriction sites were common to all isolates; (ii) with the exception of LAV and HTLV-III, the North American and European isolates were all different from one another and showed no geographical specificity; (iii) the African isolates as a group were more diverse than those from North America and Europe; and (iv) the genomic variability was concentrated within the env gene.

Acquired Immunodeficiency Syndrome↗

[Malignant lymphoma of the testis].

The incidence of non-Hodgkin's lymphoma of the testis is in the order of 1.8% in adults. Ten cases of lymphomas histologically proven after orchidectomy are reported: 5 were diffuse large cell, 4 immunoblastic and 1 diffuse small cell lymphomas. Mean age was 56 years. Five patients had stage IE or IIE and 5 stage IV disease after staging. Seven patients had received chemotherapy followed by subdiaphragmatic irradiation and 2 with localized lymphoma were treated by radiotherapy alone after orchidectomy. Four patients in remission relapsed after 6 to 24 months. Central nervous system involvement during the course of the disease was observed in 5 cases. Five patients are still alive in remission after an 18 to 80 months follow-up.

Adult↗

[Results of treatment in 118 foot necroses in relation to ankle blood pressure and diabetes. A one-year retrospective study of 108 patients].

The healing-rate in 118 necrotic lesions of the forefoot was investigated in 108 patients. The global healing frequency after 9 months amounted to 28%. A linear increase in healing was observed during this period. Later, no further healing occurred despite continuation of local treatment of the necrosis. The healing-rate was directly related to the distal (ankle) systolic blood pressure. Blood pressures under 50 mm Hg made healing impossible, whereas pressures above led to a healing-rate up to 37%. Diabetes mellitus had no influence on the healing-rate. Three guiding principles can be brought forward for the treatment of necrotic lesions of the forefoot: 1. When no healing is attained after 9 months, continuation of the local therapy is no longer worthwhile. 2. There is no likelihood of healing when the distal systolic blood pressure (ankle) is below 50 mm Hg. 3. Before commencing treatment the distal systolic blood pressure should be known. When this is low, measures to open vessels should be considered (operative, catheter technique, lysis) in order to raise the blood pressure above 50 mm Hg and thereby improve the healing prospects.

Adult↗

[Alternating chemotherapy and radiotherapy in the induction treatment of small cell bronchial carcinoma (forms limited to the thorax)].

Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months). Local control at two years was 61% in group A and 82% in group B, while relapse-free 2 year survival rates were 32% and 37% respectively. The acceptable toxicity and high response rate of this combined modality therapy lead us to further research in maintenance therapy.

Antineoplastic Agents↗

Extravascular hemolysis following the administration of cefamandole.

Hemolytic anemia occurred in a 70-year-old female after a five-day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole-coated red cells sensitized with the patient's anti-cefamandole indicated that the anti-cefamandole could induce significant phagocytosis. The anti-cefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross-reactivity, with the antigenic site primarily the 7-amino-cephalosporanic acid nucleus. Penicillins could inhibit the anti-cefamandole but only when using concentrations 3-10 X those of cephalosporins. Eleven examples of anti-penicillin tested failed to react with cefamandole-coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole-coated red cells; three of these sera were also reactive with penicillin-coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anti-cefamandole-induced hemolytic anemia.

Aged↗

Inhibition of lymphocyte activation by cyclosporin A: interference with the early activation of the membrane phospholipid metabolism in rabbit lymphocytes stimulated with concanavalin A, anti-rabbit immunoglobulin or the Ca2+ ionophore A 23187.

Rabbit lymphocytes from the mesenteric lymph nodes were stimulated with concanavalin A, goat anti-rabbit immunoglobulin, or the Ca2+ ionophore A 23187. The stimulated incorporation of labeled uridine into RNA as well as of labeled thymidine into DNA was suppressed within a dose range of 40-1000 ng/ml cyclosporin A in both Con A-stimulated T lymphocytes and in anti-immunoglobulin-stimulated B lymphocytes, without affecting the resting cells. A 23187-stimulated rabbit lymphocytes proved to be more sensitive to cyclosporin A. At 40 ng/ml the immunosuppressive drug was effective in inhibiting elevated incorporation of labeled nucleosides into macromolecules in ionophore-stimulated cells. Cyclosporin A, at the same concentrations that were effective in inhibiting stimulated RNA and DNA synthesis, suppressed one of the earliest events occurring in stimulated lymphocytes, i.e., enhanced incorporation of unsaturated fatty acids into membrane phospholipids. Whereas cyclosporin A significantly inhibited the incorporation of arachidonic acid into phosphatidylcholine and phosphatidylethanolamine in concanavalin A-, anti-immunoglobulin-, and A 23187-stimulated cells, it proved to be ineffective in inhibiting the incorporation of arachidonate into phosphatidylinositol. The data indicate that cyclosporin A inhibits both T- and B-cell stimulation by interfering with a common target, e.g., the early activation of membrane phospholipid metabolism of rabbit lymphocytes.

Animals↗

Deep dyslexia and the right-hemisphere hypothesis for semantic paralexia: a reply to Marshall and Patterson.

Studies of deep dyslexia have conferred prominence upon observations of semantic paralexia (e.g. reading "town" as "city"). Landis et al. (Neuropsychologia 21, 359-364, 1983) have reported evidence indicating that such errors arise in the right hemisphere. However, Marshall and Patterson (Neuropsychologia 21, 425-427, 1983) have advanced both empirical and theoretical arguments against this interpretation: the present paper examines these arguments and finds them seriously flawed. It therefore concludes in favour of the right-hemisphere hypothesis for semantic paralexia.

Dominance, Cerebral↗

Monoclonal antibodies to antitumor Vinca alkaloids: thermodynamics and kinetics.

Spleen cells from a mouse and a rat immunized with vinblastine coupled to bovine serum albumin were fused in two independent experiments with P3 X 63-Ag8 (non-secreting variant) mouse myeloma cells. Three mouse X mouse (Vinca 1-3) and two rat X mouse (Vinca 4 and 5) hybrids were selected for production of Vinca alkaloid binding monoclonal antibodies. Each antibody had characteristic cross-reactivities with alkaloids structurally related to vinblastine: Vinca 1 reacted preferentially with deacetylated alkaloids (deacetyl vinblastine and vindesine) and Vinca 2 had a higher affinity for vinblastine and vincristine. Vinca 3-5 recognized equally vinblastine, vincristine and vindesine but differed with respect to their affinities for other analogues. No significant cross-reactivity of the monomeric alkaloids vindoline or catharanthine was observed with any antibody, and dimeric alkaloids modified in the catharanthine moiety had reduced immunoreactivity. Mouse monoclonal antibodies (Vinca 1 and 3) showed moderate affinity (2.2 X 10(-7) and 5.8 X 10(-9) M) for their respective best ligands and fast kinetics (dissociation rate constants greater than 3 X 10(-3) sec-1). Vinca 4 and 5, derived from the rat X mouse hybrids, had much higher affinities (1.5 X 10(-11) and 1.1 X 10(-11) M) and slower kinetics (dissociation rate constants: 2.4 X 10(-5) and 7.2 X 10(-6) sec-1). The major difference between these two antibodies was that Vinca 4 binds and releases the antigen more rapidly than Vinca 5 does. Somatic hybridization techniques thus generated monoclonal antibodies recognizing a given class of low mol. wt antigens with variable specificity, affinity and kinetic behavior, allowing the selection of reagents most appropriate for particular immunochemical applications.

Animals↗

Phytase activity in chicken erythrocytes and its control by organic phosphates (glycerate-2,3-P2 and inositol-P5) during avian development.

The activity and basic kinetic constants of phytase were studied in chicken erythrocytes during animal development. The regulatory inhibition of phytase by IHP and 2,3-BPG takes place at key stages of the development. As in mammals, there is a specific control of the levels of organic phosphate involved in the oxygenation process of haemoglobin, during animal development.

2,3-Diphosphoglycerate↗

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease.

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.

Antineoplastic Combined Chemotherapy Protocols↗

Enalaprilat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises.

The effect of enalaprilat (MK-422), a newly synthesized, intravenous, nonsulfhydryl, angiotensin-converting enzyme inhibitor, was studied in seven patients with either severe or malignant hypertension. All subjects initially received a 1 mg bolus injection of enalaprilat followed in 30 minutes by 10 mg. Five subjects received an additional 40 mg. Mean (+/- SE) pretreatment blood pressure for the group was 226 +/- 9/141 +/- 7 mm Hg. Five minutes after the 1 mg enalaprilat dose, blood pressure decreased to 211 +/- 10/131 +/- 9 mm Hg and further fell to 201 +/- 14/123 +/- 11 mm Hg at 30 minutes. The maximal reduction in blood pressure to 169 +/- 14/112 +/- 10 mm Hg occurred 30 minutes after the 10 mg dose. No further blood pressure reduction was observed in those subjects who received the additional 40 mg dose. Within the entire group, five subjects exhibited sustained blood pressure reduction. No adverse side effects or symptomatic hypotension occurred in any subject.

Adult↗

Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus.

We have developed a continuous human T-cell line (A3.01) for the study of acquired immunodeficiency syndrome (AIDS)-associated retrovirus that mimics normal peripheral blood lymphocytes in susceptibility to viral cytopathic effect without the need for cell activation or conditioned medium. Following infection, substantial quantities of virus are produced during a 3- to 5-day period; the associated killing of cells can be monitored in a microtiter assay as a function of virus input. Southern blot hybridization of infected cellular DNAs indicated that no gross alteration occurred in the restriction maps of the proviral DNA during the transfer of virus to and its passage in A3.01 cells. This cell system offers an alternative to other AIDS retrovirus cell systems because it permits the monitoring of viral cytopathic effects.

Acquired Immunodeficiency Syndrome↗