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Biomedical subjects

K Okamura

Publications and source records attributed to K Okamura.

At least 523 records · Page 29Linked to original sources

Strain differences among rats in response to Remington iodine-deficient diets.

Male rats of five different strains (Simonsen albino, Wistar, Long-Evans, Holtzman Sprague-Dawley, and Charles River Sprague-Dawley) were tested for their response to the U.S. Biochemical Corp. Remington low iodine diet containing 15-18 microgram I/kg. Measurements made after the diet had been fed for 28-30 days indicated that Simonsen albino and Wistar strains consistently showed the greatest response, based on degree of thyroid enlargement, depletion of thyroidal iodine, reduction in serum T4, and elevation of serum TSH. Long-Evans and Holtzman Sprague-Dawley rats responded relatively poorly to the low iodine diet. One experiment included female rats, and the limited data suggested that within a given strain there was no significant sex difference. With more prolonged feeding (84 days), the difference between a rapidly responding strain (Simonsen albino) and a more slowly responding strain (Holtzman Sprague-Dawley) was not so marked. Our results indicate that given sufficient time and a diet sufficiently low in iodine, even a more slowly responding strain will ultimately develop signs of extreme iodine deficiency. However, it is inconvenient and expensive to maintain rats on a Remington low iodine diet for 3 months, and studies on the effect of severe iodine deficiency are much more rapidly performed using a rapidly responding strain such as the Simonsen albino. Our observation that rats of different strains differ markedly in their responses to an iodine-deficient diet suggests that hereditary factors play an important role in this response.

Animals↗

Hypothyroidism in severely iodine-deficient rats.

The thyroid status of severely iodine-deficient rats was assessed by measurement of the resting metabolic rate (RMR) and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). Rats maintained on the iodine-deficient diet for 2 or 3 months showed significantly reduced RMR and alpha-GPD, compared to rats on the same diet supplemented with KI in the drinking water. They also displayed markedly reduced serum T4 levels, slightly reduced serum T3 levels, and highly elevated serum TSH levels. A significant decrease in liver alpha-GPD was observed 29 days after the rats were placed in iodine-deficient diet. However, the decrease in RMR in the same animals was not statistically significant. These results suggest that measurement of liver alpha-GPD may be a more sensitive index of impending hypothyroidism than measurement of O2 consumption. The present study demonstrates that a hypothyroid state can be induced in rats exposed to a severely iodine-deficient diet. In severe iodine deficiency, the compensatory mechanisms of increased TSH stimulation and preferential T3 secretion from the thyroid are insufficient to prevent a fall in serum T3. The hypothyroid state results from the inability to maintain a normal serum T3 level and possibly also from the very low levels of serum T4.

Animals↗

Elevated serum levels of T3 without metabolic effect in nutritionally deficient rats, attributable to reduced cellular uptake of T3.

Rats receiving a nutritionally deficient diet displayed markedly elevated serum free T3 levels but showed no increase in oxygen consumption. This was associated with greatly reduced ratios of hepatic cellular and nuclear 125I-T3 to serum 125I-T3. Kinetic data supported the conclusion that cellular uptake of T3 was decreased in the nutritionally deficient rats. The lack of metabolic effect, despite the elevated serum T3 levels, is attributable to reduced availability of serum T3 to tissue nuclear receptor sites.

Animals↗

Effect of cycloheximide on iodothyronine formation in vitro.

The unique inhibitory effect of cycloheximide (CH) on the coupling of iodotyrosines was examined in vitro. Rat thyroid lobes were incubated for 8 h under our improved condition. In the presence of 10(-4) - 10(-3) M CH, the per cent uptake of 131I decreased, proportionate synthesis of [131I]MIT increased slightly, and that of [131I]T4 or [131I]T3 decreased markedly. The incorporation of medium 127I into T4 or T3 during the 8 h incubation period decreased markedly, but was fairly constant into MIT and only slightly decreased into DIT. Thus the inhibitory effect of CH seemed more prominent on iodothyronine formation than on iodotyrosine formation in this in vitro system. Inhibition of formation of newly labelled iodothyronines seemed to occur almost in parallel with the inhibition of [3H]amino acid incorporation into the thyroidal soluble protein. However, the coupling of iodotyrosines prelabelled in the absence of CH did not seem to be affected by CH. The presence of 10(-4) M CH induced the Wolff-Chaikoff effect at a lower iodide concentration than that which occurred in the absence of CH, suggesting that CH sensitized the Wolff-Chaikoff effect. However, the organification of 127I and T4 synthesis were markedly reduced in the presence of CH even before the apparent Wolff-Chaikoff effect was initiated. These results give further support to out contention that prethyroglobulin is more important for organification of iodide than pre-existing thyroglobulin. We conclude that CH reduces coupling efficiency indirectly, probably by inhibiting the formation of prethyroglobulin with a favourable structure for coupling.

Amino Acids↗

Unilateral germinomas involving the basal ganglia and thalamus.

Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy.

Adolescent↗

[Primary hypothyroidism as a possible cause of hypertension from long-term follow-up studies of patients with Graves' disease (author's transl)].

In order to study the prognosis of Graves' disease, 236 patients, who had been diagnosed as having had Graves' disease more than 10 years before, were examined. Although one patient had died of leukemia and 2 patients had been operated on for breast cancer after 131I therapy, and another 6 patients had died between the ages of 20 and 50, the patients were doing quite well. Generally, the prognosis of Graves' disease is not considered to be serious if the thyroid function is controlled. Among the 72 patients who had been treated with 131I therapy, 15 patients (21%) showed low serum levels of both T3 and T4 and were considered to be suffering from late-onset hypothyroidism. About 67% of the 131I-treated patients were considered to be almost euthyroid, but serum TSH levels were high in half of them, suggesting latent hypothyroidism. The incidence of hypertension seemed to be significantly higher in the TSH-elevated euthyroid group compared with the TSH-nonelevated patients. An excessive reaction of the hypothalamus and/or pituitary gland might have an unfavorable effect not only on the apparent hypothyroidism, but also on the latent hypothyroidism after the therapy for Graves' disease.

Adolescent↗

Dentinal response against carious invasion: localization of antibodies in odontoblastic body and process.

The pulpal origin of dentinal immunoglobulins was demonstrated by means of immunohistological methods. Immunoglobulins were located both in the cytoplasm of odontoblasts in pulp and at odontoblastic processes in dentin. Positive reactivity of the immunoglobulins to antigens was confirmed using peroxidase-immunized rabbits. IgG, IgA, IgM, C3, and C4 were observed on some invasive bacteria in human carious dentin.

Animals↗

Immunosuppressive factors in pregnancy serum: a preliminary report.

A serum component with suppressive activity on human lymphocyte responses to phytohemagglutinin was examined in pregnancy serum. No correlation could be found between the elevated level of alpha-2AP glycoprotein and the immunosuppressive activity. The active constituent was isolated by ultracentrifugation, salt fractionation, ion exchange chromatography and gel filtration. The immunosuppressive activity was found to be associated with alpha-globulin which consisted of neither lipoprotein nor alpha-2-AP glycoprotein. In terms of its antigenicity, the active fraction was found to be a mixture of 5 components.

Alpha-Globulins↗

PS-6 and PS-7, new beta-lactam antibiotics. Isolation, physicochemical properties and structures.

Antibiotics PS-6 and PS-7 which are shown to be 5R,6R-3-(2-acetamido)ethylthio-6-isopropyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid and 5R,6R-3-(E)-(2-acetamido) vinylthio-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid respectively, are new beta-lactam compounds isolated from fermentation broths of Streptomyces cremeus subsp. auratilis A271, S. fulvoviridis A933, S. olivaceus ATCC 31126 and S. flavogriseus NRRL 8139. Fermentation, isolation, physicochemical properties and structures of antibiotics PS-6 and PS-7 are described.

Anti-Bacterial Agents↗

PS-6 and PS-7, new beta-lactam antibiotics. In vitro and in vivo evaluation.

Biological properties of two new beta-lactam antibiotics, PS-6 and PS-7, containing the carbapenem nucleus were studied. The in vitro activities of PS-6 and PS-7 were tested against clinical isolates of Gram-positive and Gram-negative bacteria in comparison with those of cefazolin, ampicillin and PS-5. In general, the antibacterial spectra of PS-6 and PS-7 were similar to that of PS-5. PS-7 was slightly less active than PS-5 and ABPC against Staphylococcus aureus. Clinical isolates of Gram-negative bacteria were found to be 2- to 8-fold more resistant to PS-6 than to PS-5, while PS-7 was 2-fold more active than PS-5 against Enterobacter, Klebsiella, Proteus, Serratia and Escherichia coli. The therapeutic effect of PS-6 seemed slightly less than that of PS-5 in an experimental infection with Staph. aureus Smith in mice.

Ampicillin↗

PS-5 inhibition of a beta-lactamase from Proteus vulgaris.

Inhibition of Proteus vulgaris beta-lactamase by a new beta-lactam antibiotic, PS-5 was studied kinetically. There were two stages of inhibition. In the early stage, PS-5 inhibited the beta-lactamase by formation of a Michaelis-complex, and showed a competitive inhibition pattern with Ki-value of 0.22 microM (substrate, cephaloridine). After the formation of a Michaelis-complex between PS-5 and the enzyme, PS-5 showed a characteristic progressive inhibition pattern with time. Maximum inactivation was obtained after several minutes of preincubation of the enzyme with PS-5; as hydrolysis of PS-5 progressed, the enzyme activity was gradually recovered. Reactivation by an excess of substrate (cephaloridine) was not substantially realized in the presence of PS-5. PS-5 was very slowly hydrolyzed by the enzyme, showing a triphasic pattern in its reaction curve.

Anti-Bacterial Agents↗

[Studies on immunotherapy of uterine cervical cancer by administration of schizophyllan (SPG) (author's transl)].

This study was designed to investigate effects of immunopotentiator on cervical cancer. We administered schizophyllan (SPG) as immunopotentiator to patients of cervical cancer therapy with irradiation, and examined successively immunological parameters such as blastformation of lymphocytes, skin reaction of PPD, lymphocyte counts, concentration of serum immunoglobulins, and other clinical inspections. Moreover we examined ability of interferon induction of SPG. We also calculated and compared 3 year relative survival rate of the cases administered SPG and historical controls therapy with only irradiation. In patients administered SPG the results revealed: 1) an enhancement of stimulation index of lymphocytes blastformation with PHA, 2) an enlargement of skin reaction to PPD, 3) no effects to number of lymphocytes, serum immunoglobulins, liver function and renal function, 4) an interferon activity on patients' sera of cervical cancer after administration of SPG, and 5) patients administrated SPG had significantly high relative survival rate in comparison with the historical control of cervical cancer cases treated solely by irradiation.

Aged↗