[Liver cancer and hepatitis B].
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Biomedical subjects
Publications and source records attributed to M Kako.
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Interferon in the blood was rapidly cleared from the circulation after intravenous injection. Intramuscular injection of alpha-interferon caused low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon was never detected consistently in the blood after intramuscular or subcutaneous administration. Intraarterial administration of beta-interferon also caused low but stable interferon levels in the blood. Our studies suggest that beta-interferon should be given intravenously to see clinical beneficial. No difference in pharmacokinetics was seen between natural interferon and recombinant interferon. No difference was also noted between partially purified interferon and highly purified interferon.
An amino acid solution enriched in branched chain amino acids (BCAA) was administered to cirrhotic patients with encephalopathy and serial determinations of serum glucose, IRI and IRG were performed. Slight decrease of serum glucose was observed when only BCAA was given. On the other hand, when BCAA was infused with glucose, the serum glucose level decreased significantly after infusion (-77.5 +/- 26.2 mg/dl, p less than 0.01) and two cases of hypoglycemic shock were observed. Although both serum insulin and glucagon increased in these cases, the IRI/IRG molar ratio which was 8.9 at the start of infusion increased to 20.6 at the end of infusion. It was suggested that administration of BCAA with glucose caused hypoglycemia in cirrhotics with encephalopathy, possibly by synergistic action of BCAA and glucose on serum insulin level.
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MCNU is a new derivative of nitrosourea and experimental studies have shown equal or superior activity to known nitrosourea compounds. Twenty one cases were entered into our clinical studies with a phase II study. Nineteen cases have had a several courses of prior chemotherapy. Four out of 21 cases achieved a partial response (each one of lymphoepithelioma, parotid gland cancer, recurrent uterine cancer and recurrent breast cancer). The major toxicity encountered during treatment was myelosuppression. Full recovery of myelosuppression was delayed and was seen six to eight weeks after each injections. These initial results justify further clinical investigations with MCNU.
Recently, there has been an increasing interest in the diagnostic and prognostic usefulness of tumor-associated antigen of embryonic and fetal origin. Many approaches have been attempted to make an early diagnosis of the pancreatic cancer, where a specific screening blood test for the pancreatic cancer is required. By using antiserum to fetal pancreas, Banwo et al, discovered an oncofetal antigen that was present in human fetal pancreas, pancreatic tumor tissue, and sera from patients with the pancreatic cancer. Pancreatic oncofetal antigen (POA) was considered to be an oncofetal antigen for human pancreas, and its measurement seemed to be useful in the diagnosis of pancreatic cancer. But elevated levels of POA were also observed in the serum of some patients with cancer of the stomach, lung, colon, or liver as well as in the serum of some pregnant women and others with certain benign conditions. In summary, combined assay with various tumor markers was considered to be useful for the diagnosis of pancreatic cancer.
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Bile duct ligation in rats increased alkaline phosphatase activity in serum and liver. In the serum, the activity reached a peak 24 h after bile duct ligation, earlier than in the liver. This finding indicates that the elevation of serum alkaline phosphatase activity is not due to simple overspill of this enzyme from the liver into the circulation. An electrophoretic study, employing polyacrylamide gel with Triton X-100, and a gel filtration study disclosed that 24 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphatase in addition to the hepatic and intestinal isoenzymes. The high molecular weight form was also found in bile, indicating that regurgitation of bile contributed to the increase in alkaline phosphatase activity in the serum. The absence of the high molecular weight alkaline phosphatase in the sera of rats with intrahepatic cholestasis induced by alpha-naphthylisothiocyanate suggests that, in this type of cholestasis, regurgitation of bile alkaline phosphatase does not play an important role in the elevation of serum alkaline phosphatase activity. These findings indicate that the high molecular weight alkaline phosphatase in serum is a useful diagnostic marker of biliary obstruction.
The alterations of the alkaline phosphatase (ALP) activity in the rat liver following bile duct ligation were investigated by electron microscopical techniques. Serum ALP activity reached the maximum at 24 hours after ligation and two isozymes of ALP, high molecular and low molecular one, appeared in the serum. Bile canaliculi became dilated at 48 hours after ligation and the microvilli were destructed and diminished in number. ALP activity was observed almost only on the bile canalicular membrane of the liver cells in the control. On the other hand, in the bile duct-ligated rat, the ALP activity on the canalicular membrane was markedly increased initially, then it appeared on the lateral membrane, and finally on the sinusoidal membrane also. It was not stainable on the canalicular membranes which lacked microvilli. The proposed pathway through which hepatic ALP enters the blood stream in bile duct-ligated rats is as follows: ALP, being synthesized in the microsomes of hepatocytes, is initially transferred to the bile canalicular membrane and diffused to lateral membrane through tight junction, reaches to sinusoidal membrane then released into the blood stream.
A 32-yr-old female who suffered from typical Weber-Christian disease developed hepatosplenomegaly and hepatic dysfunction. A liver biopsy specimen displayed many fat droplets and alcoholic hyalins (Mallory bodies). Electron microscopic hepatic injury was indicated by many fat droplets, alcoholic hyalins, marked deformities of the rough endoplasmic reticulum, and by some deformed nuclei and nuclear bodies. There has been no other report describing alcoholic hyalins in the hepatic changes of Weber-Christian disease. Additionally, based on electron microscopic observation, we assume that fatty changes were due to a relative reduction in lipoprotein synthesis in the deformed rough endoplasmic reticulum.
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Three Japanese patients with lecithin: cholesterol acyltransferase (LCAT) deficiency, the offspring of a consanguineous marriage, are described. In addition to the characteristic clinical and laboratory findings of the disease, our patients had hitherto unreported manifestations, namely unconjugated hyperbilirubinemia, peripheral neuropathy and marked hypocholesterolemia. Although the mechanism of the unconjugated hyperbilirubinemia is not clear, the role of impaired hepatic bilirubin uridine-diphosphate-glucuronyl transferase activity combined with another unknown factor(s) was postulated. Non-random assortment was observed between LCAT deficiency and haptoglobin types, as previously reported. The discovery of Japanese patients with LCAT deficiency indicates that the distribution of this hereditary metabolic disorder is not confined to the Western hemisphere.
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From 1476 hospital admissions with head injury, 37 patients were selected on the basis of distinctive clinical features which appeared to share a single and benign aetiology. In head injuries of this type, transient neurological disorders resulted from trivial or rather mild head injuries. These disorders, which included headache, nausea and vomiting, pallor, somnolence, irritability and restlessness, stupor, hemiparesis and aphasia, appeared after a lucid interval which was usually less than two hours; then the patient either recovered, or went on to develop convulsive attacks. Recovery without convulsions was usual in children and adolescents; convulsions occurred both in infants and younger children. The symptoms were not attributable to cerebral compression but were probably due to a self-limiting cortical phenomenon. It appears that convulsive attacks occurring within a few hours of this type of head injury may not be significant as precursors of post-traumatic epilepsy. It is suggested that there is a close relation between the convulsive attacks and the non-convulsive symptoms seen in this type of injury and that both are based on a common process which has the characteristics of the spreading depression of Leão. This type of head injury should be classified as a distinct clinical entity, in which no surgical treatment is required and the prognosis is good.
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