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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 829 records · Page 46Linked to original sources

Selective induction by N-nitrosoethylurea of oligodendrogliomas in fetal forebrain transplants.

Induction of neuroepithelial neoplasms by a single transplacental exposure to N-nitrosoethylurea (NEU) has been widely used as an experimental model for human brain tumors. NEU-induced gliomas are variably composed of neoplastic oligodendrocytes, astrocytes, and ependymal cells. It has remained controversial whether these neoplasms originate from differentiated glia or from pluripotent precursor cells of the subependymal matrix layer. We have taken a novel approach to define the histogenesis of these gliomas based on neural grafting techniques and the extraordinary difference in susceptibility between the fetal and adult brain to neoplastic transformation by alkylnitrosoureas. Pregnant rats received a single i.v. dose of NEU (50 mg/kg) on the 14th day of gestation. One day later, suspensions were prepared from the fetal forebrain and stereotactically injected into the caudoputamen of adult rats. These host animals received additional i.v. injections of NEU (50 mg/kg each) 8 days and 9 weeks posttransplantation. After a mean survival time of 316 days, all animals developed brain tumors within the neural graft. Histopathologically, these neoplasms were classified as oligodendrogliomas, ranging from early neoplastic foci to large, infiltrating malignant tumors. The selective induction of oligodendrogliomas indicates that neoplastic transformation in the nervous system can occur in a differentiated glial cell or in a precursor cell committed to oligodendrocytic differentiation, and that transformation of a pluripotential stem cell is not necessary. Omission of the first (prenatal) dose of NEU led to a much lower tumor incidence, whereas this dose in itself, i.e., without additional postgrafting exposure, did not produce brain tumors in any of the experimental animals. This differential effect of pre- and postgrafting exposure to NEU constitutes the first in vivo evidence of a multistep development of brain tumors.

Animals↗

Sensitive serum markers for detecting pancreatic cancer.

Serum amylase, immunoreactive elastase (IRE), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA 19-9) were measured in 40 patients with pancreatic cancer. IRE and CA 19-9 were further assayed in nonpancreatic malignancies (n = 98) and chronic nonmalignant disease (n = 194). In pancreatic cancer, elevated values were observed for amylase in 30% of the patients, for IRE in 70%, for CEA in 28%, and for CA 19-9 in 68%. Elevation of IRE and/or CA 19-9 was found in 95% of the 40 patients. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA 19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE tends to occur at earlier stages of pancreatic cancer. No one test is adequate for the accurate diagnosis of pancreatic cancer. However, the two assays complement each other, and their combined use would provide a sensitive clue for tentative diagnosis of pancreatic cancer.

Adenocarcinoma↗

Subunit structure of a yeast site-specific endodeoxyribonuclease, endo SceI. A study using monoclonal antibodies.

Endo SceI is a eucaryotic site-specific endoDNase of 120 kDa that causes double-stranded scission at well-defined sites, but is distinguishable from procaryotic restriction endonucleases by its mode of sequence recognition and lack of related specific DNA modification. In purified preparations of endoSceI, only two polypeptide species of 75 kDa (75-kDa peptide) and 50 kDa (50-kDa peptide) are detected in apparently equal amounts. We prepared mouse monoclonal IgGs that bound specifically to the 75-kDa peptide (but not the 50-kDa peptide) without inhibiting the endoSceI activity. Immunoprecipitation experiments with these IgGs revealed that the 75-kDa peptide and the 50-kDa peptide are physically associated with each other and with the endonucleolytic activity. Full endoSceI activity was recovered by mixing the purified 75-kDa peptide and the partially purified 50-kDa peptide, each of which exhibited little or no endonuclease activity alone. These observations indicate that endoSceI consists of two non-identical subunits of 75 kDa and 50 kDa, and that both subunits are required for full enzyme activity.

Antibodies, Monoclonal↗

Ki-67 immunoperoxidase stain as marker for the histological grading of nervous system tumours.

The monoclonal antibody Ki-67 recognizes a nuclear antigen which is expressed during the G1, S, G2 and M phases of the cell cycle. Immunostaining of frozen biopsy material thus presents a convenient and rapid method for the estimation of the growth fraction in human neoplasia. This report summarizes the results obtained in 178 neurosurgical biopsies. The highest incidence of Ki-67 positive nuclei was observed in 8 metastatic carcinomas (mean: 20%) and in 53 cases of glioblastoma multiforme (10%). Glioblastomas showed considerable variation, the fraction of stained nuclei ranging from 1 to 28%. For astrocytomas and oligodendrogliomas we found a close correlation between the Ki-67 index and the histological grade in agreement with known biological behaviour. In anaplastic gliomas (WHO grade III) the upper limit was 11%, in grade II gliomas, 6%. Juvenile pilocytic astrocytomas and pituitary adenomas showed mean staining indices of approximately 1%. In 13 meningiomas the mean Ki-67 index was 1% but rose to 5% in recurrent and anaplastic meningiomas. Assessment of the growth fraction in human brain tumours by immunostaining with Ki-67 could become an important tool in the prediction of the biological behaviour of nervous system neoplasms and the planning of adjuvant therapy.

Adult↗

Dynamic positron emission tomography with 13N-ammonia in liver tumors.

Dynamic positron emission tomography (PET) of the liver tumor was performed with a whole body multi slice PET device and 13N-ammonia. Sixteen patients with hepatocellular carcinoma (HCC) and seven patients with metastatic liver tumor were studied. In 12 of 16 patients with HCC, in which cases rich tumor vessels and dense tumor stain were proven by hepatic angiography, the tumors showed remarkable uptake of 13N-ammonia from the first scan, whereas the radionuclide accumulation was more gradual in the other part of the liver, and high tumor to liver ratio (T/L ratio) (2.62 +/- 1.09) was observed in the 1st scan, so that the tumor was clearly visualized by high contrast. However, HCC with poor blood supply from the hepatic artery or central necrosis of the tumor were demonstrated as low T/L ratio. In seven cases with metastatic liver tumor, the accumulation of 13N-ammonia was also lower than the normal liver throughout the scan. The results suggested that hepatic arterial blood flow of the liver tumors can be assessed with dynamic PET, which may provide valuable information for the characterization of tumors as well as for the evaluation of the treatment.

Ammonia↗

Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs.

To confirm the role of cholecystokinin (CCK) and secretin in digestion, exocrine pancreatic secretion, plasma CCK, and secretin were measured simultaneously in six dogs prepared with gastric and pancreatic fistulas after feeding a solid meal. Plasma CCK concentration determined by radioimmunoassay increased significantly from the basal level, reached a peak 35 min after meal ingestion, and after a dip it further increased toward the end of the 3-h observation. Pancreatic protein output increased significantly, peaked at the fifth 10-min period, and then declined progressively. Plasma CCK concentration and pancreatic protein output correlated significantly during the first postprandial hour. Plasma secretion demonstrated significant elevation at 15 min and a peak at 25 min after a meal. Plasma secretin correlated significantly with both bicarbonate output and flow rate during the 3 h. Simultaneous measurements of plasma CCK and secretin and of pancreatic secretion suggested that postprandial pancreatic secretion is primarily mediated by releases of CCK and secretin, but these hormones do not seem to be the only factors responsible for the secretion.

Animals↗

Ventricular septal perforation following acute myocardial infarction in a patient with hypothyroidism--a case report.

A 61-year-old woman with profound hypothyroidism underwent surgery for a ventricular septal perforation 15 days following an acute myocardial infarction, with no preoperative thyroid replacement. Her immediate postoperative course was complicated by a low cardiac output, respiratory suppression and high output renal failure, requiring prolonged hemodynamic and respiratory support. Thyroid replacement (50 micrograms of thyronine and 100 micrograms of thyroxine daily) was given in two installments on the 2nd day after the operation. The effect of the inotropic agents increased gradually and the patient was weaned off intra-aortic balloon pumping. A large quantity of diuretics, hydration and hyperalimentation also successfully reduced her elevated BUN and serum creatinine. After full thyroid replacement, she was discharged in good health on the 40th postoperative day.

Female↗

Serum levels of pancreatic enzymes in lean and obese subjects.

Serum amylase and trypsin, but not lipase, were significantly lower in obese subjects than in lean subjects. Serum amylase and trypsin, but not lipase, had significant inverse correlation with body weight. Low serum amylase was associated with low protein, fat and carbohydrate intakes per kg body weight, whereas low serum trypsin was associated with low carbohydrate intake per kg body weight. Low serum pancreatic enzymes readily increased with diet therapy. It is assumed that lowered serum pancreatic enzymes in obese subjects are somehow related to their diet intake. The mechanism through which pancreatic enzymes in the blood reflect the composition of food is unclear.

Adult↗

Elevation of serum pancreatic secretory trypsin inhibitor following serious injury.

Twenty-six of 31 seriously injured patients (84%) showed a marked elevation of serum pancreatic secretory trypsin inhibitor (PSTI) to more than twice the initial level within the first 2 weeks after admission. Serum PSTI rose from the second or third post-traumatic day and reached the maximum at day 5.8 on average. In uneventful cases, it returned to the level on admission within 2 weeks. The maximum serum PSTI in these patients was significantly correlated with the severity of the injury as judged at the time of admission, indicating that the elevation of serum PSTI in these patients was related to the extent of initial damage. In contrast, serum PSTI in patients with serious complications remained at high level even at 2 weeks after trauma, and it was not correlated with the initial severity of the injury.

Adult↗

A quantitative method of evaluating the diuretic response to furosemide in rats.

Furosemide effects are usually evaluated by measuring the urinary excretion rate of Na+ (UVNa) in humans. In the present study, however, UVNa showed a nonlinear relationship with urine flow rate after intravenous injection of furosemide in rats. In contrast, when the urinary excretion rate of (Na+ + K+) (UVNa + K) was plotted against the urine flow rate, a linear regression line was observed, with small interindividual variations in normal rats and in rats with uranyl nitrate-induced acute renal failure (ARF). Piretanide, a loop diuretic, also showed a similar relationship, while other types of diuretics revealed different slope values for the relationship. Although the urinary excretion rate of Cl- (UVCl) vs UVNa + K is expected to show a linear relationship in normal rats, the correlation coefficient of the linear regression line was smaller than that of the urine flow rate vs UVNa + K. Further, the slope of UVCl vs UVNa + K was slightly different in ARF rats. Therefore, UVNa + K provides a better quantitative measure of diuretic response to loop diuretics than UVNa or UVCl.

Acute Kidney Injury↗

Feedback regulation of basal pancreatic secretion in humans.

The effect of intrajejunal infusion of pancreatic juice on basal pancreatic secretion was studied in patients who had received pancreatoduodenectomy for pancreatic, biliary, or duodenal malignancy. Pure pancreatic juice was obtained through a drainage tube inserted into the main pancreatic duct. There was little fibrosis in the pancreatic remnant and daily pancreatic juice output was more than 200 ml. After intraluminal infusion of pancreatic juice, water, protein, bicarbonate, and enzyme outputs were decreased significantly by about 30%. Intraluminal trypsin also reduced pancreatic secretion. Trypsin inhibitor (aprotinin) suppressed the significant decrease caused by autopancreatic juice or trypsin solution. We conclude that basal pancreatic secretion in humans is under negative feedback control by intestinal pancreatic juice or tryptic activity.

Adult↗

Distal trisomy of chromosome 17q due to inverted tandem duplication.

A female infant with distal trisomy 17q is described. The anomaly resulted from a de novo inverted duplication of the 17q2405----q25.3 region as defined by high-resolution banding. The proband's overall clinical picture was in good agreement with those of previously reported cases of partial trisomy 17q. The phenotypic features relatively common to our and other reported cases, included mental and growth retardation, microcephaly, temporal retraction, blepharophimosis, saddle nose, thin upper lip, down-turned corner of the mouth, high-arched palate, low-set and deformed ears, webbed neck and lowered posterior hairline. A unique feature of the present case was systemic hirsutism.

Abnormalities, Multiple↗

Pancreatic and biliary excretion of camostat in dogs.

It has been reported that camostat (Foy-305), a synthetic proteinase inhibitor, is excreted into the biliary-pancreatic juice in rats. To confirm whether camostat is excreted into bile or pancreatic juice, camostat (5 mg/kg/h) was given intravenously to dogs with pancreatic or biliary fistulae. Camostat and its active metabolite (Foy-251) in bile and pancreatic juice were measured by high-performance liquid chromatography (HPLC) and by their trypsin-inhibitory activity. Camostat did not alter the exocrine pancreatic secretion of fluid, bicarbonate, protein or trypsin stimulated by secretin (1 Crick-Harper-Raper unit/kg/h) and cerulein (50 ng/kg/h). Camostat and its active metabolite were detected in bile by HPLC and trypsin-inhibitory activity (the mean excretion rate was 1.3% of the intravenous dose of camostat), but they were not detectable in pancreatic juice. In conclusion, camostat and its active metabolite were excreted into bile but not into pancreatic juice.

Animals↗