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Biomedical subjects

T Okabe

Publications and source records attributed to T Okabe.

At least 451 records · Page 25Linked to original sources

Long-term survival and aldosterone secretion pattern of aldosteronoma in culture.

In an attempt to obtain an in vitro experimental model for aldosteronoma, primary culture was initiated with adenomas from 3 patients with primary aldosteronism. The cells grown in culture retained the morphology and functional properties characteristic of aldosteronoma cells well for periods of up to 200 days. The cells formed monolayer cell colonies and showed an epithelioid morphology with small nuclei containing prominent nucleoli. The cells possessed a clear, eosinophilic cytoplasm resembling that of aldosteronoma cells in vivo. The cultured cells continued to secrete large amounts of aldosterone throughout the culture period. The cells responded to angiotensin II and III by increased release of aldosterone into the culture medium. They also responded to Db-cAMP and ACTH by increased secretion of the hormone.

Adenoma↗

Xenon-enhanced CT CBF measurements in cerebral AVM's before and after excision. Contribution to pathogenesis and treatment.

Unlike neurological deficits resulting from intracranial hemorrhage in patients with cerebral arteriovenous malformation (AVM), which have well defined etiology, the pathogenesis and treatment of progressive and/or fluctuating non-hemorrhagic neurological and psychological deficits require clarification. Values for local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were measured by the method using stable xenon (Xe)-computerized tomography (CT-CBF) scanning, and were compared to 133Xe inhalation values using external probes in 16 patients with cerebral AVM's. Values were measured by both methods before and after total excision of AVM's in five cases. Neurological and mental status assessments were compared with LCBF results. Clinical improvement was most evident after total excision of AVM's. Other procedures, such as clipping of vessels, partial excision, and ventriculoperitoneal shunting for hydrocephalus, were associated with frequent complications. Embolization carried risks of cerebral infarction and was not efficacious unless combined with excision. Medical treatment resulted in poor or unsuccessful seizure control, with neurological deterioration despite anticonvulsant therapy. Compared with age-matched normal individuals, LCBF values in patients with AVM's were significantly reduced, particularly adjacent to the AVM's. Mean L lambda values for gray and white matter were normal. After excision, LCBF values in gray and white matter increased significantly up to normal. Due to overestimation of CBF by shunt flow with the 133Xe method of measurement, no correlation was found with results of the CT-CBF method before AVM excision, but significant correlation of the two methods resulted after excision. If accurate LCBF values are obtained by high resolution, direct measurement of tracer clearance from brain tissue, progressive and/or fluctuating neuropsychological deficits correlate with the degree of cerebral steal.

Adolescent↗

Chronic effect of TSH on human thyroid tissue in organ culture.

The chronic effect of TSH on thyroidal cAMP concentrations and release of thyroid hormones was investigated using human thyroid tissue in organ culture. Normal human thyroid slices were placed in HAM's F-10 synthetic culture medium in Falcon organ tissue culture dishes, and incubated at 37 degrees in a humidified atmosphere of 5% CO2 in air. Medium was changed everyday and daily T3 or T4 release was determined using concentration of T3 or T4 in the medium. After incubation, slices were transferred to the medium containing 10 mM theophylline and incubated without TSH for an additional 30 min to determine thyroidal cAMP concentrations. Thyroidal cAMP concentrations in slices incubated with 10 mU/ml of TSH increased significantly at 2, 6, and 24 hr and even on the 6th day of incubation. Daily T3 release was significantly increased above control from the 3rd day and daily T4 release from the 4th day to the 11th day of incubation with 10 mU/ml of TSH. Histologically, almost all follicles were structurally maintained even on the 11th day of incubation. These results suggest that both thyroidal cAMP concentrations and release of thyroid hormones are stimulated chronically by TSH. This organ culture system is useful for investigating chronic effects of various materials on human thyroid tissue.

Cyclic AMP↗

[Laboratory and clinical studies on T-1982 (cefbuperazone) in the field of pediatrics].

T-1982 (cefbuperazone), a new 7 alpha-methoxycephem antibiotic, was fundamentally and clinically studied, and the following results were obtained. The antibacterial activities of T-1982 against clinical isolates of S. aureus, E. coli, K. pneumoniae, S. marcescens, P. mirabilis and P. aeruginosa were determined in comparison with those of CER, CEZ, CMZ and CTT. Against S. aureus, CER and CEZ exhibited excellent activity, whereas T-1982 was less active with the peak MIC of 12.5 micrograms/ml even with the inoculum size of 10(6) cells/ml. The activity of T-1982 was equal to that of CTT and by far superior to that of CER, CEZ and CMZ against E. coli, K. pneumoniae and P. mirabilis, the peak MICs with the inoculum size of 10(6) cells/ml being less than or equal to 0.1-0.2 microgram/ml, less than or equal to 0.1-0.2 microgram/ml and 0.2-0.39 microgram/ml, respectively. Against S. marcescens, T-1982 was superior to CMZ and CTT and 48% of the strains were inhibited by 3.13 micrograms/ml or less, whereas all the strains were resistant to CER and CEZ. The MIC of T-1982 against most strains of P. aeruginosa was more than 100 micrograms/ml. 10 mg/kg or 20 mg/kg of T-1982 was administered by one shot intravenous injection or 1 hour drip infusion to 23 pediatric patients to measure serum levels and urinary recovery. At 30 minutes after one shot injection of 10 mg/kg and 20 mg/kg, the highest serum levels of 22.0-38.8 micrograms/ml and 52.4-80 micrograms/ml were observed, the half-lives being 1.32 hours and 1.76 hours. When given by 1 hour drip infusion, the serum levels attained the peaks of 29.2-42.6 micrograms/ml and 49.0-75.6 micrograms/ml at the end of infusion, the half-lives being 1.24 hours and 1.19 hours. The urinary recovery rates within 6 hours were 74.2-92.5% and 50.2-66.5% by one shot injection and 63.4-84.2% and 53.9-79.0% by drip infusion. T-1982 was administered at a dose of 50 mg/kg by 30 minutes drip infusion to a child with purulent meningitis. The levels of T-1982 in the cerebrospinal fluid at 1 hour after administration were 4.8-6.7 micrograms/ml with the CSF/serum ratios of 4.4-8.4%. A total of 36 pediatric patients (21 cases of respiratory tract infection, 9 cases of urinary tract infection and each 1 case of purulent cervical lymphadenitis, scarlet fever, purulent meningitis, acute colitis, peritonitis and sinusitis) was treated with 40-80 mg/kg/day of T-1982 (252.6 mg/kg/day in purulent meningitis). The response was excellent in 27 patients and good in 7 patients, the efficacy rate being 94.4%. Diarrhea or eruption were observed in each 1 case. No abnormal laboratory findings were noted in any cases.

Adolescent↗

Association of hypercalcemia with tumors producing colony-stimulating factor(s).

Two human malignant tumors, which we previously reported to produce colony-stimulating factors (CSFs), were found to be accompanied by remarkable hypercalcemia. A patient with a CSF-producing lower jaw cancer (squamous cell carcinoma) developed a marked granulocytosis (150,000/microliters) and hypercalcemia (more than 215 mg/dl). The tumor was successfully transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and hypercalcemia (20 mg/dl). White blood cell and serum calcium concentrations of these mice decreased promptly to normal levels when the tumor was excised. Treatment with prednisolone (1.5 mg/kg) or indomethacin (5 mg/kg) had no effect on the serum calcium level of these mice. Parathyroid hormone or prostaglandin E was not increased in the serum of the mice or in the tumor tissue. However, the mice bearing the tumor excreted extremely large amounts of calcium in their urine, and their bony tissues contained less calcium and phosphorus than controls. Moreover, histology of bony tissues of these nude mice clearly demonstrated the decrease in trabecular tissues and cortical thickness as well as remarkable activation of osteoclasts. Another patient with a CSF-producing bronchogenic squamous cell carcinoma showed mild granulocytosis and hypercalcemia. The biopsied tumor tissue was transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and also severe hypercalcemia (18 mg/dl). These results suggest the presence of a new syndrome of granulocytosis and hypercalcemia associated with CSF-producing tumors. The causal mechanism of the hypercalcemia was shown to be some humoral factor which activates osteoclasts other than parathyroid hormone. Neither prostaglandins nor osteoclast-activating factor seemed to be the cause of the hypercalcemia.

Adult↗

Establishment and characterization of a new human functional cell line from a choriocarcinoma.

A new human functional tumor cell line, designated as T3M-3, has been established from a xenotransplanted choriocarcinoma grown in nude mice. One of the biggest problems of the in vitro culture of these tumor cells using the xenotransplanted tumors had been the dense contamination of fibroblasts of host nude mouse origin. In the present study, these fibroblasts were completely removed by incubating the cells with antiserum raised against nude mouse spleen cells. The cell line established from the remaining tumor cells has been successfully propagated in vitro for as long as 4 years. These cells show the morphology of epithelioid cells containing a prominent nucleus with one or two large nucleoli. The cells grow in a monolayered sheet with the population-doubling time of 19 hr. The cells show perfect tumor takes when they are reinoculated into nude mice. Chromosomal analysis revealed that the cell is a human aneuploid one with a hypotriploid mode. These cultured cells maintained well the function of secreting large amounts of human chorionic gonadotropin, progesterone, and estrogen. The secretion of human chorionic gonadotropin and progesterone by these cells is enhanced by stimulation with tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate and teleocidin B, or with epidermal growth factor in a dose-and time-dependent manner. Interestingly, however, the tumor promoters did not exert a marked effect on the cellular binding of epidermal growth factor, indicating that the receptors for these reagents in T3M-3 cells are not shared by epidermal growth factor.

Animals↗

Establishment of different clonal strains from a human sarcoma of the stomach: tumorigenic heterogeneity in athymic nude mice.

Twenty five clonal strains have been isolated from a single human sarcoma of the stomach. Two different types of clones have been recognized by their morphology and behavior in vitro. Type I clones were characterized by criss-crossed arrays and multilayers with high terminal density. Type II clones grew in a well-organized monolayer with lower saturation density. Although both types of clones exhibited fibroblastic appearance, type I clones showed a more rounded, refractile shape. The cells of this type showed multiple regions of criss-crossed arrays and multilayers throughout the culture vessels. Saturation density of this type of clone was 2- to 3-fold (1.7 to 2.1 X 10(5) cells/sq cm) higher than that of type II clones. Chromosomal analysis revealed that type I clones were human aneuploid ones with modal chromosome numbers ranging from 51 to 61. With the exception of clones 11 and 19, type I clones were able to produce tumors in athymic nude mice when injected s.c. Type II clones exhibited a more flattened and elongated appearance. The cells grew in a well-organized monolayer resembling fingerprint whorls. They showed lower saturation density (0.7 to 0.9 X 10(5) cells/sq cm). Chromosomal examinations revealed the clones to be human aneuploid ones with modal numbers from 47 to 54. Tumor formation was not observed in nude mice given injections of this type of cell. Both types of clones did not bear antigens cross-reacting with the antiserum against mouse spleen cells but had surface antigens which were affected by the antibody against HL-60 cells and complement. These results suggested that this human sarcoma was heterologous and that cells with widely different tumorigenic potential preexisted in the parental cell population.

Adult↗