Biomedical subjects
A Barrett
Publications and source records attributed to A Barrett.
5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose.
The presence of a previously unidentified enzyme, tentatively designated 5-methylthioribose kinase, has been demonstrated in cell-free extracts of Enterobacter aerogenes. The enzyme catalyzes the ATP-dependent phosphorylation of 5-methylthioribose. ADP is one of the products of the reaction and, based on functional group analyses, the other product is 5-methylthioribose 1-phosphate. A 40-fold purified enzyme preparation has been obtained from a cell-free extract of E. aerogenes. Activity of the partially purified enzyme is totally dependent on the presence of a divalent cation and a sulfhydryl reagent. The substrate specificity of the enzyme is quite narrow, and the Km values for ATP and 5-methylthioribose are 7.4 X 10(-5) M and 8.1 X 10(-6) M, respectively. These results suggest that 5-methylthioribose kinase may be a primary enzyme involved in the recycling of the methylthio group of 5-methylthioribose back into methionine.
Failure of methyl-C.C.N.U. and 5-fluorouracil in colorectal cancer.
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A retrospective study of 131 cases of carcinoma of the posterior pharyngeal wall.
Between 1958 and 1973, 131 patients with carcinoma of the posterior pharyngeal wall were treated at the Institute Gustave-Roussy (127 men, 4 women, mean age 61 years). Nine had a tumor of the oropharynx, 37 of the hypopharynx and 85 of the oro-hypopharynx. Nine had T1 tumors, 19 T2 and 103 T3 (TNM-UICC 1975). 122 patients were treated by irradiation: 83% were T3 lesions, 81% were more than 4 cm in diameter, 80% were ulcerated and 42% were staged N3. The survival rate of these patients was very poor (3% at five years). The nine patients who had been treated by surgical excision had a better survival rate and three are alive at 5 years, but the initial prognostic factors were better in this group. It seems that the indications for surgery should be widened to increase the survival rate in these poor prognosis cancers.
Prophylactic lung irradiation in the treatment of osteogenic sarcoma.
A minimum 52 month follow-up is recorded, in a series of 14 patients with classical osteogenic sarcoma treated by limb irradiation followed in the last 2 1/2 weeks of their therapy by prophylactic lung irradiation. Six of these 14 patients survived for more than 52 months.
Prolactin concentrations during anaesthesia.
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Kinetic properties and the effect of substrate analogues on 5'-methylthioadenosine nucleosidase from Escherichia coli.
5'-Methylthioadenosine nucleosidase (EC 3.2.2-) from Escherichia coli has been purified 220-fold. A molecular weight of 31 000 for the enzyme was estimated from gel filtration on Sephadex G-150. The Km for 5'-methylthioadenosine was 3.1-10(-7) M. In addition to 5'-methylthioadenosine, the nucleoside analogues 5'-ethylthioadenosine, 5'-n-propylthioadenosine, and S-adenosyl-homocysteine also served as substrates for the enzyme. These substrate analogues acted as competitive inhibitors of the reaction with 5'-methylthioadenosine. The Ki values for 5'-ethylthioadenosine, 5'-n-propylthioadenosine, and S-adenosylhomocysteine were determined to be 1.3-10(-7) M, 4.6-10(-8) M, and 1.92-10(-7) M respectively.
Letter: Bromocriptine and growth hormone.
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New primary cancers in patients originally presenting with carcinoma of the cervix.
A total of 4502 patients with carcinoma of the cervix was studied: in 113 patients 116 other primary neoplasms were found and tumours of lung, breast, colon and rectum occurred most frequently. Most of the patients in our series died with the other primary present. Treatment of the cancer of the cervix by radiotherapy seemed to play no role in the induction of anot;er primary cancer.
Bromocriptine in the treatment of advanced breast cancer.
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Anterior pituitary function following hypophysectomy for breast cancer.
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Letter: A breast carcinoma dependent on human placental lactogen.
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Loxapine in newly admitted chronic schizophrenic patients.
The standard drug Stelazine (STEL), at a dose of 50 mg/day, exhibited therapeutic activity significantly different from placebo (PL) activity on several variables, most notably BPRS, attesting to the sensitivity of the experiment. On the other hand, the investigational drug, loxapine (LOX), in doses of 100 mg/day for four weeks, could be differentiated from PL as treatment in the described population on only one variable (NGI-Imp.) and one item of the BPRS. On several variables, positive trends were noted, but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05. One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose.
Bronchial carcinoma with eosinophilia and cardiomegaly.
A patient with a giant cell carcinoma of the bronchus presented with headache and flushing attacks and a blood eosinophilia. He developed a right bundle branch block and later congestive cardiac failure. At post mortem he was found to have the appearance of Loeffler's endocarditis. A tentative mechanism for these events is proposed.
Gorlin's syndrome.
The uncommon familial syndrome of multiple odontogenic keratocysts, basal cell naevi and skeletal anomalies is reviewed, and seven cases are described, including one patient who developed squamous cell carcinoma in a previous odontogenic keratocyst of the maxilla. We wish to thank Consultants from the Royal National Throat, Nose and Ear Hospital, The Middlesex Hospital and the Eastman Dental Hospital, who allowed us access to their patients; Mr. D. Garfield Davies, Dr. M. F. Spittle, Mr. D. Winstock, Mr. H. P. Cook, Professor H. C. Killey and Mr. L. W. Kay. We are grateful to Professor L. Michaels and Mr. D. J. Connolly for preparation of the illustrations and to Mrs. A. Matthews for the typescript.
Synthesis of stable RNA in stringent Escherichia coli cells in the absence of charged transfer RNA.
It has been possible to demonstrate the complete absence of either charged tRNA(Glu) or charged tRNA(Val) at 42 degrees by the use of two stringent strains of E. coli, one temperature-sensitive for glutamyl-tRNA synthetase and the other temperature-sensitive for valyl-tRNA synthetase. In both strains, stable RNA synthesis ceases, and guanosine tetraphosphate accumulates upon incubation at the nonpermissive temperature. Unique among a series of antibiotics tested, only tetracycline was able to stimulate stable RNA synthesis and to cause disappearance of the guanosine nucleotide. In this regard tetracycline and the "relaxed" gene product appear to be analogous.
Bulky mediastinal Hodgkin's disease management and prognosis.
Of a total of 235 Stage I and II Hodgkin's disease patients treated between 1970 and 1979, 103 (43.8 per cent) had mediastinal involvement in 45 of whom the disease was bulky and in 58 non-bulky. This report concentrates on bulky disease patients of whom 45 per cent did not relapse after therapy and 71 per cent are alive. Patients with mediastinal disease were treated with radiotherapy (63), sequential chemo-radiotherapy (37) or chemotherapy alone (3). In the radiotherapy group the relapse rate for bulky disease was significantly higher (65 per cent) than for non-bulky disease (44 per cent) (P less than 0.05) although there was no significant difference in survival. Neither relapse rate nor survival differed significantly in bulky disease patients treated with radiotherapy compared with combined chemo-radiotherapy although there was a 20 per cent difference in relapse-free survival rate in favour of the combined treatment group at five years. Treatments were not allocated randomly and the chemo-radiotherapy group contained a disproportionate number of patients with adverse features (greater than 3 node areas involved, limited lung extension) compared with the irradiated group; 11/25 and 2/17 respectively. The number of lymph node areas involved appeared to influence the relapse rate in the radiotherapy group. There was no correlation between mediastinal mass size and number of node areas involved suggesting that these two features may be independent prognostic factors.
Optimum combination of targeted 131I therapy and total-body irradiation for treatment of disseminated tumors of differing radiosensitivity.
131I is the radionuclide most commonly used in biologically targeted radiotherapy at the present time. Microdosimetric analysis has shown that microtumors whose diameters are less than the beta-particle maximum range absorb radiation energy inefficiently from targeted radionuclides. Micrometastases of diameters < 1 mm are likely to be spared if targeted 131I is used as a single modality. Because of this, combined modality therapy incorporating targeted 131I, external beam total-body irradiation (TBI), and bone marrow rescue has been proposed. In this study, the minimum necessary TBI component is shown to depend on the radiosensitivity of the tumor cells. The analysis shows that the TBI component, to achieve radiocurability, increases directly with tumor radioresistance. For the most radiosensitive tumors, a whole-body TBI treatment dose 2 x 2 Gy is calculated to be obligatory, whereas practical arguments exist in favor of higher doses. For more radioresistant tumors, the analysis implies that a TBI treatment delivery of 5 x 2 Gy is obligatory. In all situations, external beam TBI appears to be an essential factor in providing reasonable probability of cure of disseminated malignant disease. Reasonable prospects of tumor cure by combination strategies incorporating 131I exist for the more radiosensitive tumor types (e.g., neuroblastoma, lymphoma, leukemia, myeloma, seminoma), but more resistant tumors are unlikely to be curable at present. Superior targeting agents, and the possible use of panels of different radionuclides, may be necessary to achieve high cure probabilities for less radiosensitive tumor types.