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Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 361 records · Page 20Linked to original sources

Destruction of implanted gastric tumors in rats by acridine orange photoactivation with an argon laser.

The phototoxicity of acridine orange and argon laser irradiation on Walker carcinosarcoma 256 stomach tumors was studied. Wistar strain rats bearing stomach tumors 4-6 mm in diameter 5-10 days after their implantation were injected intraperitoneally with 40 mg/kg of acridine orange 2 hr before irradiation. Then the forestomach was opened and the tumors were exposed to the argon laser at 488 nm at an intensity of 15 mW/cm2 for 20 min. Tumors in rats treated with acridine orange were brightly fluorescent during irradiation. No marked temperature rise was detected during irradiation. Argon irradiation significantly prolonged the survival of rats treated with acridine orange. Histologically, complete or partial tumor necrosis was observed, with sparing of surrounding mucosa, in rats treated by the combination therapy. Phase-contrast and electron microscopy showed that cytotoxicity was mediated by changes in the cell, nuclear and lysosomal membranes. Neither the dye nor laser alone had any effect.

Acridine Orange↗

A case of glycogen storage disease type I associated with an incomplete type of Fanconi syndrome; the protective role of lysosomal alpha 1,4-glucosidase and insulin deficiency against hypoglycemia.

A 59-year-old Japanese farmer with asymptomatic fasting hypoglycemia and with exaggerated hypoglycemic episodes induced by insulin and oral hypoglycemic agent administered for his postprandial hyperglycemia was diagnosed as glycogen storage disease type I. This diagnosis was suggested by unresponsiveness of blood glucose level to glucagon and confirmed by 13% normal level of glucose 6-phosphatase activity in liver biopsy specimen and by the presence of PAS positive amylase digestable glycogen in liver specimen. This case was associated with an incomplete type of Fanconi syndrome characterized by hyperphosphaturic hypophosphatemia, partial aminoaciduria, mild proteinuria and hyperuricosuric normouricemia in spite of the lactic acidemia due to glycogen storage disease type I. The etiology for the absence of hypoglycemia and other typical manifestations of glycogen storage disease type I was studied. The glucose production from glycogen by lysosomal alpha 1,4-glucosidase especially at prolonged fasting and the presence of postprandial hyperglycemia by insulin deficiency are regarded as responsible for keeping this patient free from typical manifestations of glycogen storage disease type I.

Biopsy↗

Effect of free Mg2+ on liver phosphorylase kinase activity.

When pig liver phosphorylase kinase was assayed at various concentrations of Mg2+, about 2-fold stimulation was observed around 2-3 mM Mg2+ (Mg2+/ATP ratio, 20-30) compared with the activity at 0.3 mM Mg2+ (Mg2+/ATP ratio, 3). This stimulation was specific for Mg2+ among the divalent cations tested and the process was reversible. Km values for ATP and phosphorylase b were decreased 3.6- and 9.5-fold, respectively, at 3 mM Mg2+ compared with those obtained at 0.3 mM Mg2+. These results indicate that the activity of liver phosphorylase kinase is influenced by free Mg2+.

Animals↗

Values of serum carcinoembryonic antigen and elastase 1 in diagnosis of pancreatic carcinoma.

Carcinoembryonic antigen (CEA) and elastase 1 in the serum were determined by enzyme immunoassay and radioimmunoassay, respectively, in 224 healthy subjects, 49 patients with pancreatitis, 53 patients with pancreatic carcinoma and 129 patients with cancer in other organs. The CEA concentrations in the serum were significantly higher in patients with pancreatic carcinoma than in those with pancreatitis, but this concentration was not a satisfactory indicator of pancreatic carcinoma localised to allow irradication by resection as it was raised in only 47% of the patients. High CEA concentrations were also slightly, but not significantly, more frequent in patients with cancer of the pancreatic body or tail, and unresectable cancer or cancer of more than 6.0 cm in longest diameter than in those with cancer of the pancreatic head, resectable cancer or cancer of less than 6.0 cm diameter. Serum elastase 1 was raised in only 42% of the patients with pancreatic carcinoma and could not be used to distinguish patients with pancreatic carcinoma from those with pancreatitis. In contrast with CEA, however, its concentration was abnormally high significantly more frequently in patients with cancer of less than 6.0 cm in longest diameter than in those with larger tumours. It was also raised slightly, but not significantly, more frequently in those with cancer of the pancreatic head and in patients with resectable cancer than in those with unresectable cancer. A combination of these two tests raised the diagnostic rate of pancreatic carcinoma to 77% without a remarkable decrease in the specificity for pancreatic carcinoma. In particular, it raised the diagnostic rates of cases of cancer of the pancreatic head, resectable cancer and cancers of less than 3.0 cm and 3.0-6.0 cm in longest diameter. Therefore, a combination of measurements of CEA and elastase 1 in the serum is very useful for early detection of pancreatic carcinoma.

Adult↗

Selective elimination of chromosomally unbalanced zygotes at the two-cell stage in the Chinese hamster.

The gametic and zygotic selection of genome imbalance was investigated in the Chinese hamster by direct chromosome analyses of spermatocytes and preimplantation embryos from crosses between chromosomally normal females and males heterozygous for a reciprocal translocation, T(2;10)3Idr, abbreviated here as T3. The karyotypes and the frequencies of embryos observed at the first cleavage in the cross +/+female X T3/+male were consistent with those expected from MII scoring in male T3 heterozygotes. Therefore, it was concluded that there was neither gametic selection against genome imbalance nor zygotic selection from fertilization until the first cleavage metaphase. However, 9.1-10.8% of embryos were arrested at the two-cell stage, and karyotypes of these embryos were confirmed as 22(2,10,10,10(2)), 21(2,10,10), and 21(2,10,10(2)). The common abnormality of these embryos was partial monosomy of chromosome 2. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of other segments of chromosomes 2 and 10, had fewer blastomeres than chromosomally balanced embryos. This finding suggests that cleavage of these embryos had been retarded by day 4 of gestation.

Animals↗

Carcinoembryonic antigens in the pericardial fluid of patients with malignant pericarditis.

The diagnostic accuracy of measurement of carcinoembryonic antigen (CEA) and of analysis of the cytological characteristics of pericardial fluid was assessed in 10 patients with benign pericarditis and 7 patients with malignant pericarditis. The mean CEA levels of pericardial fluid specimens from patients with malignant pericarditis were significantly higher than those from patients with benign pericarditis. However, a high CEA level was not seen in a specimen of pericardial fluid which contained nonepithelial tumor cells. Positive cytological findings were obtained in specimens of pericardial fluid from 85.7% of the patients with malignant pericarditis. Correct diagnosis of malignancy was made by CEA assay alone or by cytological examination alone in 85.7% of the patients examined, while a combination of these methods raised the diagnostic rate to 100%.

Carcinoembryonic Antigen↗

Photodynamic effects of exposure to hematoporphyrin derivatives and dye-laser radiation on human gastric adenocarcinoma cells.

The phototoxicity of hematoporphyrin derivatives (HPD) and dye-laser radiation on adenocarcinoma cells of the human stomach was examined by light and electron microscopy. Adenocarcinoma cells were obtained from human stomach tissue by endoscopic biopsy. The cells were incubated for 5 minutes in the patient's own serum that contained 0.6 mg HPD/ml and then were exposed to dye-laser radiation at 630 nm at an irradiance of 15 mW/cm2. Electron microscopy showed that cytotoxicity was mediated by mitochondrial damage, dilatation of the rough endoplasmic reticulum, and alterations of the nuclear membrane. The degenerative changes were greater and more frequent in poorly differentiated adenocarcinoma cells than in well-differentiated ones. No marked temperature rise was detected during irradiation. Neither the dye alone nor light alone had any effect. A singlet oxygen-trapping agent, 1,3-diphenylisobenzofuran, prevented adenocarcinoma cell degeneration that otherwise would result from exposure to HPD and dye-laser radiation. Thus singlet oxygen may be the cytotoxic agent in this system.

Adenocarcinoma↗

Significance of carcinoembryonic antigen levels and cytology of pure pancreatic juice in diagnosis of pancreatic cancer.

The diagnostic accuracies of measurement of carcinoembryonic antigen (CEA) and analysis of the cytologic characters of pure pancreatic juice were assessed in 16 control subjects, 20 patients with pancreatitis and 22 patients with pancreatic cancer. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a duodenofiberscope after intravenous administration of secretin. The pancreatic fluid was centrifuged and the supernatant was used for CEA assay, while the cell pellet was examined cytologically. Abnormally high CEA levels in the pure pancreatic juice were significantly more frequent in patients with pancreatic cancer; an increased CEA concentration in the pancreatic juice was found in 68.2% of the patients. The location of the cancer had no influence on the CEA level of the pancreatic juice, but the level tended to be high when the tumor had distant metastases. Positive cytologic findings were obtained in specimens of pure pancreatic juice of 68.2% of the patients with pancreatic cancer. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail, and those with localized tumors had the lowest yield of positive cytologic results. For sensitive tests, it was necessary to collect pure pancreatic juice containing no contrast medium. High CEA levels and positive cytological results were significantly more frequent in pancreatic juice obtained 10 to 20 minutes after secretin stimulation than in those collected immediately after stimulation. Correct diagnosis of malignancy was made by CEA assay alone or by cytological examination alone in 68.2% of the patients examined, while a combination of these methods raised the diagnostic rate to 86.4%.

Adenocarcinoma↗

Cytologic examination and CEA measurement in aspirated pancreatic material collected by percutaneous fine-needle aspiration biopsy under ultrasonic guidance for the diagnosis of pancreatic carcinoma.

Diagnostic accuracy of the cytologic examination or CEA measurement in pancreatic fluid obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance, was investigated in 26 patients with histologically proven carcinoma of the pancreas, and the incidence of positive results of cytology and CEA assay were compared in pancreatic fluid obtained by percutaneous fine-needle aspiration biopsy and by endoscopic cannulation of the ampulla of Vater in the same 19 patients. Positive cytologic findings were observed in the fluid obtained by percutaneous aspiration biopsy of 88.5% of the patients with pancreatic carcinoma. The location of the cancer had no influence on the cytology, but positive results were more frequent in patients with distant metastases than in those with localized tumor or locally invasive carcinoma. Positive cytologic results were obtained in the pancreatic fluid obtained by endoscopic cannulation from the ampulla of Vater of only 15.8% of the patients examined by both methods, but percutaneous fine-needle aspiration biopsy significantly increased the diagnostic rate. In the specimens obtained by aspiration biopsy, tumor cells were much more abundant and easily recognizable. When cytologic examination does not provide any evidence of malignancy, measurement of CEA levels in pancreatic fluid is probably useful. Combination of the cytology and CEA assay of the specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Adenocarcinoma↗

Calcium--calmodulin-dependent activation of porcine liver phosphorylase kinase.

Porcine liver phosphorylase kinase was activated about 1.5-fold by calmodulin in a calcium-dependent manner. Half-maximal stimulation was observed at about 80 nM calmodulin and the activation was almost pH-independent. The specific binding of porcine liver phosphorylase kinase to calmodulin--Sepharose affinity column exhibited an absolute dependence upon the presence of calcium. The physiological role of the calmodulin-dependent activation for liver phosphorylase kinase is discussed.

Animals↗

Calcium-stimulated, ATP-magnesium-dependent inactivation of pig liver glycogen synthase.

Ca2+-stimulated inactivation of liver glycogen synthase was observed when a partially purified liver phosphorylase kinase fraction containing glycogen synthase was incubated with ATP-Mg2+. The Ca2+-stimulated portion of this inactivation was partially counteracted by trifluoperazine and slightly stimulated by exogenously added calmodulin. These results suggest that Ca2+-calmodulin may be involved as one of the factors causing this glycogen synthase inactivation. Although the exact mechanism mediated by Ca2+ has not been clearly determined, the possibility of the participation of some Ca2+-dependent protein kinase is discussed.

Adenosine Triphosphate↗

A dose-response study with dihydroergotoxine mesylate in cerebrovascular disturbances.

Basic pharmacologic evidences have suggested the effects of dihydroergotoxine mesylate (DEM) on neurotransmitters. In its clinical use, however, various therapeutic effects and side effects are observed when the dose is changed, because of the complexity of this compound and the delicate mechanism of neurotransmitters in the brain, especially when modified by aging and vascular lesions. In order to investigate the optimal dose, a double-blind study in 550 patients with cerebrovascular disorders was carried out at 68 centers under observation by experienced specialists. Dihydroergotoxine mesylate in sublingual tablets, 3 mg daily, and in oral tablets, 6 mg daily, respectively, was given for 12 weeks, and therapeutic effects at those doses were compared by a double-blind method. In utility ratings for subjective and psychiatric symptoms, the effects in the oral tablet group at a daily dose of 6 mg were significantly superior to those in sublingual tablet group at a daily dose of 3 mg. There was no significant difference between those two groups in the comparison of side effects. These results show that the daily oral administration of 6 mg of DEM is more suitable for the improvement of subjective and psychiatric symptoms due to cerebrovascular disorders than is the daily sublingual administration of 3 mg. These results suggest that, despite much complexity in the neurohumoral transmitter mechanism in the brain, relatively simple dose-dependent efficacy of the drug in the range of the therapeutic doses was confirmed for many subjective and psychiatric symptoms of patients with cerebrovascular disorders.

Administration, Oral↗

Promotion by histamine of carcinogenesis in the forestomach and protection by histamine against carcinogenesis induced by N-nitroso-N-methylnitroguanidine in the glandular stomach in W rats.

The effect of histamine on induction of tumors in the forestomach and the glandular stomach after N-nitroso-N-methylnitroguanidine (MNNG) administration was studied in male inbred W rats. Animals were given 50 micrograms MNNG solution/ml orally for 25 weeks and then 4 mg histamine dihydrochloride sc per day in depot form. Administration of histamine in depot form after MNNG significantly increased the incidence of tumors in the forestomach, but it significantly decreased the incidence of adenocarcinomas in the glandular stomach. All of the tumors induced in the forestomach were of the squamous cell type, and 50% of them were squamous cell carcinomas. Histamine alone had no apparent carcinogenicity in rats.

Adenocarcinoma↗