[A simple identification system for clinically important mycobacteria].
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Biomedical subjects
Publications and source records attributed to S Mizuno.
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In human cancers, the contribution of genetic determinants is often difficult to distinguish from environmental influences. However, some cancers are inherited in Mendelian pattern, and some have closely associated with the diseases with hereditary factors. This paper reviewed characteristics of hereditary cancers, the diseases with high incidence of cancers and familial aggregation of cancers, and discussed the role of host factors in the etiology of cancer clinico-epidemiologically.
For the purpose of studying the relation of diversities of basic lesion as well as clinical manifestation to hormonal abnormality in Cushing's syndrome, 12 kinds of steroid hormones was simultaneously measured in plasma by using 2 types of Sephadex LH-20 column chromatography in a total of 30 patients comprosing 28 cases of Cushing's syndrome and 2 cases of adrenocortical carcinoma which had abnormal plasma steroid hormone levels without sign or symptom of Cushing's syndrome. In the group of Cushing's syndrome were included cases of pituitary ACTH-dependent hyperplasia (Hp.), adrenocortical adenoma(Ad.), bilateral nodular hyperplasia, ectopic ACTH syndrome as well as recurrent Cushing's syndrome following subtotal adrenalectomy. Twelve steroids measured in plasma were pregnenolone(Preg)., 17-OH pregnenolone(17Preg.), progesterone(Prog.), 17-OH progesterone(17Prog.), 11-deoxycorticosterone (DOC), corticosterone(B), aldosterone(Ald.), 11-deoxycortisol(S), cortisol(F), dehydroepiandrosterone(DHA), androstendione(A-dione) and testosterone(T), including precursors (Prec.: Preg., 17-preg., Prog., 17-prog.) as well as hormones belonging to the 3 systems in the biosynthetic pathways of steroid; i.e., glucocorticoids(Glu.C.'s: S,F), mineralocorticoids(Min.C.'s: DOC, B, Ald.) and sex steroids(And.'s: DHA, A-dione, T). In addition, steroidogenesis in isolated adrenal cells obtained surgically from patients with Cushing's syndrome due to Hp. and Ad, was observed. The results were as follows: (1) In cases due to Hp., plasma levels of Glu.C's and And.'s were slightly elevated, while levels of Min.C.'s were within the normal range. On the whole, however, the 3 systems were well balanced. (2) In cases due to Ad., elevated secretion of Glu.C.'s and Min.C.'s was observed, while secretion of And.'s was depressed. Among the 3 fractions of And.'s, depression of DHA and A-dione was characteristic of Ad.. (3) Elevation of And.'s in Hp. and Min.C.'s in Ad. in addition to elevation of Glu.C.'s was in fair correlation with moderate virilism in Hp. and with hypertension and hypokalemia in Ad. respectively. (4) In vitro experiments revealed that Ad. produces not only F but all 12 steroids hormones and that increased DOC and depressed DHA secretion reflected in their plasma levels were the characteristics of Ad. in steroidogenesis. Furthermore, isolated adenoma cells were found to produce Ald. at a higher rate than normal or hyperplasia adrenal cells. This finding may suggest that an intermediate type between Cushing's syndrome and primary hyperaldosteronism can exist in cases of adenoma. (5) In ectopic ACTH syndrome, plasma levels of Glu.C.'s, Min.C.'s and And.'s were equally but more markedly elevated as compared with Hp.. The increase of B was characteristic of this disorder and, coupled with a marked increase of F, seems to be the main cause of hypokalemic alkalosis frequently associated with this syndrome. (6) Nodular hyperplasia was accompanied by elevated Min.C...
Out of 97 strains of M. tuberculosis isolated from the sputum of the same number of patients, 11 were shown to consist of a mixed population of M. tuberculosis and a strain of the M. avium-M. intracellulare (MAI) complex. The most effective method for isolating strains of the MAI complex was to incubate the culture first at 42 degrees C for 3 weeks and then at 45 degrees C for 3 weeks. By this method, the growth of M. tuberculosis was suppressed, while the contaminant mycobacteria formed colonies.
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Thin-layer chromatography (TLC) of ethyl ether-ethanol extracts of mycobacteria obtained after incubation with [35S]methionine is useful for differentiation among mycobacterial species, as the distribution of radioactive spots in TLC shows a characteristic pattern except for a few species, including M. intracellulare and M. gordonae. Some supplementary studies have been carried out in the present investigation and the following results have been obtained. 1. Pretreatment of bacterial cells with trichloroacetic acid (TCA) is required to remove radioactive sulfur-containing amino acids. 2. The radioactive spots that appear in TLC of the ethyl ether-ethanol extract are divided into the following groups: (1) Petroleum ether-soluble fraction (the spot at Rf value 0.95); (2) acetone-soluble (petroleum ether-insoluble) fraction (the spots at Rf values 0.50, 0.30, and 0.13--0.20); (3) ethanol-soluble (petroleum ether- and acetone-insoluble) fraction (the spot at Rf value 0.10); (4) petroleum ether-, acetone-, and ethanol-insoluble fraction (the spot at Rf value 0.00). The spot which appears in the region of Rf values 0.13--0.20 (it may appear as two spots) in the TLC of ethyl ether-ethanol extracts is composed of two compounds, one soluble in acetone and the other insoluble in acetone but soluble in ethanol. 3. Strains of the M. avium-M. intracellulare complex have been divided into three subgroups by the pattern of radioactive spots B, C, and D, which show Rf values of 0.13--0.20, 0.30, and 0.50, respectively, in the TLC of the ethyl ether-ethanol extracts. The first group shows none of these spots, and strains of the serotypes 1, 2, and 8 belong in this group. The second group shows spot B, and strains of the serotypes 4, 18, and 20 belong in this group. The third group shows spots B, C, and D, and strains of the serotype 16 belong in it.
A basic study was conducted on the method for the determination of thiobarbituric acid-reactive substances (TBARS) produced by platelets. Some modifications were introduced which enabled a precise semimicrodetermination. The average values of platelet TBARS production in hypertensives and in patients with cerebral infarction were higher than that in healthy controls. Among patients with cerebral infarction, those with angiographically demonstrated obstruction of internal carotid or middle cerebral arteries showed an increased production as compared with non-obstructive cases, these results may suggest the important role of platelet arachidonate metabolism in obstructive cerebrovascular disorders.
27 patients with Cushing's disease were treated over a period of 18 years at the Departments of Medicine and Surgery, Nagoya University School of Medicine and the following results were obtained. 1) Adrenalectomy. 21 of 27 patients with Cushing's disease underwent adrenalectomy. 19 patients had total bilateral adrenalectomy and 2 patients unilateral adrenalectomy. 4 patients died, the cause of death not being related directly to adrenalectomy. 9 of 15 bilaterally adrenalectomized patients had hyperpigmentation even though they had been given substitution therapy with cortisol 20-30 mg daily. They had elevated plasma ACTH levels, which were not completely suppressed by 2 mg of dexamethasone or 2.5 mg of bromocriptine per day. 2) Adenomectomy, 5 patients had adenomectomy via the transsphenoidal approach. 3 patients were cured but one of them has required postoperative substitution therapy with cortisol for hypopituitarism for one year until today. 2 of 5 adenomectomized patients had a recurrence of Cushing's syndrome after remission for 6-8 months. One of these recurrent cases has been subsequently treated successfully with bromocriptine, a dopaminergic drug. 3) Medical treatment. 2.5 mg per day of bromocriptine has been effective in 2 patients without a pituitary adenoma and ineffective in the other 4 patients with a pituitary adenoma. 24 mg per day of cyproheptadine, an antiserotoninergic drug was not effective in any of the 4 patients with a pituitary adenoma.
The cytotoxic effect of bleomycin toward mouse mammary carcinoma FM3A cells in culture was markedly potentiated by exposure of the cells to ethanol either before or after treatment with bleomycin. Ethanol-induced cell sensitization to bleomycin cytotoxicity produced a decrease in cell survival which became dependent on dose and time of drug treatment. The sensitizing effect of ethanol after drug treatment was maximum when ethanol exposure immediately followed drug treatment, and it rapidly decreased as the time interval between the two treatments was increased. Ethanol did not sensitize cells to the cytotoxic effects of cis-diamminedichloroplatinum(II) and macromomycin. These results are discussed in terms of the ability of ethanol to inhibit cell recovery from potentially lethal damage after bleomycin treatment.
The effects of hyperthermia and ethanol on bleomycin cytotoxicity toward mouse mammary carcinoma FM3A cells in culture were followed in terms of clonal growth in a soft agar medium. Heating the cells at 43 degrees during or before bleomycin treatment sensitized them to bleomycin. Heat treatment after drug treatment was less effective. Bleomycin cytotoxicity was also greatly potentiated by exposing the cells to ethanol at a concentration of more than 4% (v/v) at 37 degrees before or after drug treatment. However, when the cells were exposed to ethanol during bleomycin treatment, the potentiation of cytotoxicity was reduced, and a higher concentration of ethanol was required for inducing equivalent sensitization. The cytoxicity of pepleomycin, a potent antitumor agent derived from bleomycin, was also greatly potentiated by hyperthermia and ethanol. The cellular uptake of 3H-pepleomycin was not increased by either treatment, and thus the increased cytotoxicity was not correlated with a change in membrane permeability to the drug. The sensitizing effect of hyperthermia or ethanol was maximum when the drug treatment was carried out immediately after the cells were exposed to heat or ethanol. Sensitization decreased linearly as the time interval between the two treatments was increased, and after a 6 hr interval the sensitizing effect of either agent disappeared. This recovery from the sensitized state was not inhibited by cycloheximide or by incubation in phosphate-buffered saline instead of complete growth medium, but it was reversibly inhibited at 0 degrees. It is suggested that the modes of action of hyperthermia and ethanol in inducing cell sensitization of bleomycin are similar.
Bleomycin cytotoxicity toward mouse mammary carcinoma FM3A cells and human carcinoma HeLa S3 cells in culture was greatly potentiated by exposing the cells to a combination of a low concentration of ethanol and moderate hyperthermia. For example, the exposure of FM3A cells to a combination of 4.3% ethanol and 39 degrees, 2.4% ethanol and 41 degrees or 1.5% ethanol and 42 degrees induced a marked sensitization which was almost equivalent to that induced by exposure to 6% ethanol at 37 degrees and was greater than that induced by exposure to 43 degrees hyperthermia alone. However, when the cells were exposed to 3% ethanol at 37 degrees and then treated with bleomycin at 41 degrees, sensitization was hardly induced, indicating a requirement for simultaneous exposure to ethanol and hyperthermia to produce a synergistic increase in bleomycin cytoxicity. A possible application of these findings to cancer treatment with bleomycin is discussed.
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