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Biomedical subjects

I Komiya

Publications and source records attributed to I Komiya.

At least 91 records · Page 5Linked to original sources

Generation of hydrogen peroxide in cultured porcine thyroid cells: synergistic regulation by cytoplasmic free calcium and protein kinase C.

This study set out to elucidate the mechanism by which H2O2 generation is regulated in cultured porcine thyroid cells. We monitored continuously the effects of the calcium ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on H2O2 generation, using homovanillic acid and horseradish peroxidase. A23187 and TPA stimulated H2O2 generation. A23187 increased cytoplasmic free calcium and TPA activated protein kinase C. Generation of H2O2 is therefore regulated by cytoplasmic free calcium and protein kinase C. Exposure to A23187 or TPA augmented further the stimulation of H2O2 generation by TPA or A23187 respectively. Thus A23187 and TPA, by increasing cytoplasmic free calcium and activating protein kinase C respectively, synergistically activate H2O2 generation.

Animals↗

[Extensive bone marrow necrosis associated with carcinomatosis 7 years after operation for gastric cancer].

A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.

Adenocarcinoma, Mucinous↗

Cytoplasmic pH in the action of epidermal growth factor (EGF) in cultured porcine thyroid cells.

We demonstrate measurement of cytoplasmic pH (pHi), using 2',7'-bis(2-carboxyethyl)-5 (and 6-) carboxyfluorescein (BCECF), and internalized fluorescent pHi indicator, in thyroid cells. Using cultured porcine thyroid cells, we studied the effects of epidermal growth factor (EGF) on pHi and [3H] thymidine incorporation; 10 nM EGF alkalinizes thyroid cells and stimulates thymidine incorporation. The results indicate that Na+/H+ exchange or cell alkalinization may function as a transmembrane signal transducer in the action of EGF in the thyroid cells.

Animals↗

Absence of glucopenic inhibition of the insulin response to arginine at the onset of diabetes in BB/W rats.

To determine if the inhibiting effect of glucopenia on arginine-stimulated insulin secretion is impaired at the onset of autoimmune diabetes, the insulin response to arginine was studied at 5.6 and 2.8 mmol/l glucose in perfused pancreata isolated from BB/W rats on the first day of diabetes and from age-matched diabetes-prone BB/W rats without diabetes. During glucopenia the baseline insulin secretion was reduced by more than 80% in both groups. However, the arginine-stimulated insulin response in the diabetic group was only 16.5% lower during glucopenia compared to 79.1% lower in the nondiabetic controls. Also, enhancement of the arginine-stimulated glucagon response by glucopenia was modest compared to controls. The results indicated that at the onset of this form of autoimmune diabetes the surviving B cells are, for unknown reasons, hyperresponsive to arginine and that, in contrast to the controls, this response is not inhibited by glucopenia.

Animals↗

Urine flow-dependence and interspecies variation of the renal reabsorption of sulfanilamide.

A physiologically based model for drug reabsorption in renal tubules was applied to sulfanilamide reabsorption kinetics in rats, rabbits and dogs. The reabsorption percent of sulfanilamide decreased with an increase of urine flow rate in the three animal species examined. Furthermore, the reabsorption percent increased with the decrease of the glomerular filtration rate (GFR), even though the urine flow rate normalized by GFR was the same. The power law formula was obtained between AR (l) X Pe and the animal body weight. The power was 0.721, which was less than unity. In contrast, sigma was not dependent on animal body weight. The reabsorption percent of sulfanilamide in man was calculated using AR (l) X Pe and sigma obtained from animal data. The value thus calculated was 50-60%, which was comparable to the reported value (52%) in healthy human subjects. Therefore, the reabsorption percent of sulfanilamide in man was successfully predicted by the extrapolation of animal data.

Absorption↗

Seroconversion from HBs-Ag to anti-HBs in a case of liver cirrhosis associated with hepatocellular carcinoma.

This paper reports a case of liver cirrhosis associated with hepatocellular carcinoma (HCC) of a woman who was converted from hepatitis B surface antigen (HBs-Ag) positive to antibody against HBs-Ag (anti-HBs) positive in the serum through an immunoregulatory steroid rebound phenomenon. The histology of the biopsy specimen taken before the seroconversion showed an early stage of liver cirrhosis with moderate infiltration of mononuclear cells. At autopsy about 3 years after the seroconversion, the liver tissue free of the tumor was in an early stage of liver cirrhosis. Fibrosis did not advance as compared with the biopsy specimen. In addition, mononuclear cell infiltration decreased remarkably and piecemeal necrosis disappeared after the seroconversion. The immunohistologic examination of hepatocytes demonstrated that positive stainings for HBs-Ag and for hepatitis B core antigen (HBc-Ag) in the biopsy specimen turned to be negative in the autopsy specimen. These facts indicate that the steroid rebound phenomenon eliminated free hepatitis B virus (HBV) in the hepatocytes in the absence of massive necrosis of hepatocytes. HBV-DNA integration was proved in the genome of HCC by molecular hybridization method.

Carcinoma, Hepatocellular↗

[Absorption, distribution, and excretion of arbekacin after intravenous and intramuscular administration in rats].

Absorption, distribution, and excretion of arbekacin (HBK) were studied in rats after intravenous or intramuscular administration of HBK at a dose of 10 mg/kg or 20 mg/kg. Elimination half-lives of HBK were 0.69 hour for bolus intravenous administration, 0.55 hour for constant rate intravenous infusion, and 0.57 hour for intramuscular administration. Cumulative urinary excretions within 24 hours after administration were 74.7% of the dose for bolus intravenous administration, and 79.1% of the dose for intramuscular administration. No significant difference was observed in the cumulative urinary excretions between the 2 administration routes. Cumulative biliary excretions within 24 hours after administration were around 0.1% of doses regardless administration routes, bolus intravenous or intramuscular administration. The tissue or organ distribution of HBK after bolus intravenous administration was similar to that after intramuscular administration. The drug was distributed most abundantly into the kidney followed by plasma and the lung. The distribution of the drug into the liver was the least among the 6 tissues or organs examined in this study. The protein binding of HBK was studied by an equilibrium dialysis method at three different concentrations of HBK, 5, 10, and 20 micrograms/ml. Binding ratios of HBK to human serum, human serum albumin, and rat serum were less than 15%.

Absorption↗

Loss of insulin response to glucose but not arginine during the development of autoimmune diabetes in BB/W rats: relationships to islet volume and glucose transport rate.

The insulin and glucagon responses to 10 mM glucose and 10 mM arginine were studied in pancreata isolated from nondiabetic diabetes-prone and diabetes-resistant BB/W rats at 60, 80, and 140 days of age and in diabetic BB/W rats on the 1st and 14th days of their diabetes. In the former group the insulin response to glucose declined progressively with age (r = -0.575; P less than 0.01) and at 140 days was significantly below age-matched diabetes-resistant controls (P less than 0.05). The insulin response to arginine did not decline with age in either group. For diabetic rats, on the first day of the diabetes, the insulin response to glucose was absent but the response to arginine did not differ from nondiabetic controls. On day 14 responses to glucose and arginine were both absent. The glucagon response to arginine showed no trend despite a decline in baseline glucagon secretion. Endocrine tissue in nondiabetic diabetes-prone rats made up 0.8 +/- 0.2% of the pancreas at 60 days of age and 0.52 +/- 0.22% at 140 days of age; the latter was significantly less than in 140-day-old diabetes-resistant controls (P less than 0.05). In diabetic rats on the 1st and 14th days of diabetes endocrine tissue was 0.2 +/- 0.1% and 0.07 +/- 0.02%, respectively. The glucose transport rate in islets isolated on the first day of diabetes was profoundly reduced compared to age-matched nondiabetic diabetes-prone controls. Thus, a population of arginine-responsive, glucose-unresponsive islets with low glucose transport rates is present at the onset of overt diabetes in BB/W rats.

Age Factors↗

A rapid enzyme immunoassay for measurement of HBK in blood.

An enzyme immunoassay has been developed for the measurement of HBK (4-amino-2-hydroxybutylyldibekacin) a new semisynthetic aminoglycoside antibiotic. Antisera were raised in rabbits by immunization with HBK conjugated to bovine serum albumin (BSA). 3'-Eno-HBK conjugated to alkaline phosphatase (ALP) was used as an enzyme labeled antigen. The antibody-bound drug was separated from free using goat anti-rabbit IgG serum. The assay can be completed within one hr by co-incubating the first and the second antibody. The present immunoassay allows detection of 10 ng HBK per ml of serum, and is applicable for monitoring HBK level in blood. HBK concentrations in human sera were determined by the immunoassay during and after infusion and the levels were compared with those determined by high performance liquid chromatography (HPLC) and antimicrobial assay.

Aminoglycosides↗

[Pharmacokinetics and disposition of a new antitumor antibiotic (2''R)-4'-O-tetrahydropyranyladriamycin in rats. Distribution and excretion after multiple administration].

The accumulation of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) was studied in rats received intravenous administration of 14C-THP at a dose of 0.5 mg/kg/day for 14 consecutive days by determining blood and tissue levels and the excretion of the radioactivity. The radioactivity levels in plasma and blood cells after the multiple administration were higher than those after single administration. The half-life of the radioactivity after the multiple administration was longer in the blood cells but not in the plasma than the half-life after a single administration. Tissue levels of the radioactivity after the multiple injection were 2 to 4 times as high as the levels after a single injection except for the brain and testes in which a large accumulation of the radioactivity was observed. However, little accumulation of unlabeled THP was found in most tissues when determined by HPLC. The accumulation of radioactivity in tissues, therefore, was due to metabolites of THP. The disposition of 14C-THP was also examined in rats which had previously received unlabeled THP (0.5 mg/kg/day) for 13 days. The pretreatment did not affect the disposition of 14C-THP seriously, although the pretreatment raised tissue levels slightly and a rebound of plasma level of 14C-THP, and lowered the fecal excretion ratio. No induction of hepatic drug metabolizing enzymes was observed in rats after repeated administrations of THP for consecutive 14 days.

Aminopyrine N-Demethylase↗

[Transfer of fosfomycin into human burn blister fluid and its pharmacokinetic analysis].

Fosfomycin (FOM) (50 mg/kg) was administered to burned patients by intravenous bolus injection. Burn blister fluid and serum were taken during 8 hours after injection, and concentrations of FOM in burn blister fluid and serum were determined by bioassay using Proteus sp. (MB-838) as the test organism. The serum concentrations of FOM were 257 +/- 34.6 micrograms/ml at 15 minutes, 222 +/- 34.8 micrograms/ml at 30 minutes, 166 +/- 34.6 micrograms/ml at 1 hour, 114 +/- 43.9 micrograms/ml at 2 hours, 79.5 +/- 34.9 micrograms/ml at 3 hours, 63 +/- 36.4 micrograms/ml at 4 hours, 44.3 +/- 27.6 micrograms/ml at 5 hours, 29.6 +/- 20.9 micrograms/ml at 6 hours and 17.9 +/- 12.8 micrograms/ml at 8 hours after the injection. FOM concentrations in burn blister fluid were 64.4 +/- 18.1 micrograms/ml at 30 minutes, 77 +/- 26.0 micrograms/ml at 1 hour, 71.6 +/- 24.7 micrograms/ml at 2 hours, 64.8 +/- 23.6 micrograms/ml at 3 hours, 43.2 +/- 8.8 micrograms/ml at 4 hours, 24.8 +/- 7.9 micrograms/ml at 6 hours and 17.9 +/- 10.5 micrograms/ml at 8 hours after the injection. The obtained data were analysed pharmacokinetically. The serum levels were analysed by a two-compartment model, and the transfer of FOM into burn blister was analysed by a modified deconvolution method. In results, Tmax and Cmax of FOM levels in burn blister fluid were calculated as 1.3 hours and 80.9 micrograms/ml, respectively. The transfer rate constant of FOM from serum to burn blister fluid (K1) and that from burn blister fluid to serum (K2) were calculated as 0.612 hr-1 and 1.10 hr-1, respectively.

Adult↗

Coexistence of aldosteronoma and pheochromocytoma in an adrenal gland.

An extremely rare case is reported in which aldosteronoma and pheochromocytoma coexisted in an adrenal gland. Although the patients presented with clinical features of primary aldosteronism, preoperative examination showed an elevation of both plasma aldosterone and urinary catecholamines. Histology of the removed adrenal gland revealed that, concurrently with a round mass of adrenocortical adenoma, the adrenal medulla was totally occupied by the typical structure of pheochromocytoma.

Adenoma↗

Polyclonal plasma cell proliferation with systemic capillary hemangiomatosis, endocrine disturbance, and peripheral neuropathy.

An autopsy case of so-called plasma cell dyscrasia (PCD) of a 37-year-old woman was reported. This case showed typical clinical symptoms of PCD, except for no abnormality in serum immunoglobulins. Besides the typical histological findings often observed with PCD, the autopsy revealed an additional finding of systemic angiomatous proliferation of small blood vessels throughout the body, especially in the skin, kidneys, brain, various lymph nodes, and soft tissue. A peculiar glomerular lesion in this case, similar to membranoproliferative glomerulonephritis, was likely to be a result of proliferation of glomerular capillaries. In addition, this case showed histological evidence of retroperitoneal fibrosis and osteosclerosis. These findings were also considered to be due to the vascular abnormality. Although the etiology of the vascular lesions is obscure, it is emphasized that the abnormality is probably an important cause of the clinical symptoms seen in PCD.

Adult↗

Black (or brown) adrenal cortical adenoma: its characteristic features on computed tomography and endocrine data.

Seventeen patients with adrenal adenoma causing Cushing's syndrome, eight patients with Cushing's disease due to hypersecretion of ACTH, and five patients with primary aldosteronism due to an aldosteronoma were studied for their computed tomographic (CT) patterns, hormonal profiles, and macroscopic and microscopic findings of the adrenal gland. Black (or brown) adrenal adenomas were found in 71% of the patients with Cushing's syndrome, but not in patients with aldosteronoma. The adrenal tissue of patients with Cushing's disease was predominantly yellow. The number of compact cells was larger in black or brown adenomas than in yellow tumors or hyperplastic adrenal tissue. In patients with Cushing's syndrome, urinary excretion of 17-ketosteroids (17-KS) and serum aldosterone concentrations were lower in those with black or brown adenomas than in those with yellow adenomas (P less than 0.05). Patients with Cushing's disease had even higher 17-KS and serum aldosterone levels. No difference was found in serum cortisol concentrations and dexamethasone suppressibility in two types of adenomas causing Cushing's syndrome. Visual estimation of radiological density of the adrenal tissue relative to the kidney on CT scan and quantitative measurement of it by CT number revealed a difference between the two types of adrenal tumors causing Cushing's syndrome. Adrenal tumors with decreased density on CT scan were yellow adenomas with predominantly clear cells, and those with equal or increased density were black or brown adenomas with predominantly compact cells. All aldosteronomas had decreased density and consisted of clear cells. It is suggested that black or brown adenomas of the adrenal gland have higher radiological density and accompanying lower serum aldosterone and urinary 17-KS levels than ordinary yellow tumors. The abundance of compact cells may have some significance for the development of this particular type of adrenal tumor.

17-Hydroxycorticosteroids↗

Effects of thyrotropin-releasing hormone on pancreatic exocrine secretion in the dog.

Effects of thyrotropin-releasing hormone (TRH) on pancreatic exocrine secretion were investigated in isolated and blood-perfused canine pancreas preparations. During constant intra-arterial infusion of secretin (0.03-0.05 units/min), concentrations of protein and bicarbonate in the pancreatic juice were measured before and after intra-arterial injection of TRH (0.1-10 ng). TRH did not produce any significant changes in the flow rate of pancreatic juice and in the rate of pancreatic blood flow. TRH caused a significant suppression of protein and bicarbonate output in a dose-dependent manner. At 10 ng of TRH, this suppression lasted about 20 min. From these data, it is suggested that TRH acts directly on both acinar and ductular cells of the pancreas and inhibits the secretions of digestive enzymes and bicarbonate.

Animals↗