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Blood ammonia levels in patients with various liver diseases were determined quantitatively by a simple and rapid method using the Amitest Meter System. The results were compared to those obtained by an enzymatic method and were well correlated. This simple Amitest is also useful in animal experiments, particularly when there is a need to determine blood ammonia levels serially. This paper test was evaluated as being accurate and reliable for clinical and experimental use.

Characteristics of gamma-aminobutyric acid (GABA) were investigated in the rat central nervous system by radioreceptor assay (RRA). Scatchard analysis revealed that the rat brain had two distinct GABA binding sites with an apparent dissociation constant (Kd) of 11.7 nM and 34.7 nM. The highest level of specific [3H]-GABA binding was found in the rat cerebellum. Imidazole acetic acid, a potent GABA agonist, was effective in displacing [3H]-GABA binding but beta-alanine was slightly effective in inhibiting [3H]-GABA binding. Muscimol, the most potent GABA agonist, has been used as a ligand to characterize the postsynaptic GABA receptors. However, the maximal binding capacity (Bmax) of muscimol-RRA was about 3 times larger than that of GABA-RRA, suggesting that muscimol might label not only GABA receptors but other unknown receptors as well. An endogenous inhibitor of GABA receptor binding was purified from the P2 fraction of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA on GABA binding sites. The inhibition by the endogenous inhibitor of GABA receptor binding was blocked by the allosteric effect of diazepam. In the presence of diazepam, [3H]-GABA binding with the endogenous inhibitor was larger than that with GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself. The molecular weight of the endogenous inhibitor was estimate by gel filtration to be less than 3,000 daltons.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.

We reported a 62-year-old man with malacoplakia of the prostate, and reviewed 49 cases of malacoplakia hitherto observed in Japan in which the lesions originated from the urogenital tract, except for one gastric case. E. Coli was emphasized as a possible causative agent for malacoplakia especially in the urogenital tract. The possible histiocytic origin of von Hansemann cells was stressed by demonstrating cytoplasmic processes and desmosomes in our prostatic case. An adjuvant use of cholinergic agents and ascorbic acid with chemotherapeutic agents was recommended for treating malacoplakia.

The complement-mediated solubilization of precipitable immune complexes (complex-release activity) in serum specimens was determined by a simplified method using peroxidase as an immune complex antigen. The results correlated well with the hemolytic activity via the classical complement pathway and that via the alternative complement pathway. This simplified method proved to be reliable and useful.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.

Glycoproteins play a significant role in neoplastic transformations. Both the levels of fucose and the activity of fucosyl transferase, which mediates the assembly of the oligosaccharide moieties of the glycoprotein chains, have been found to be elevated in neoplastic conditions. Since these elevations are common features of a variety of neoplastic cells, these two have been designated as non-specific markers of malignancy. In the present study, the fucose level and fucosyl transferase activity were determined in the sera of cancer patients and an attempt was made to establish a relationship between the two. It was found that both the fucose levels and fucosyl transferase activities showed considerable elevation in the five cancer groups studied, establishing them as useful diagnostic parameters. However, it was also observed that the rate of increased fucosyl transferase activity was not fully reflected in the resulting serum fucose levels in a few cases.

Levamisole (LMS) was given to stage III gastric cancer patients starting three days before gastrectomy, at a does of 150 mg/day for three consecutive days every other week. Survival rates of these patients were compared with those of stage III gastric cancer patients previously operated in our Department who had not received levamisole. The background factors of both groups were matched as closely as possible. Both groups were concomitantly treated with mitomycin C and FT-207. The survival rate of the LMS group was significantly higher than that of the control group when the tumor had a diameter of 4.0-8.0 cm, cancer cells infiltrated to the gastric serosa, there were metastases within the regional lymph nodes, cancer cells slightly invaded the venous capillaren and there was moderate infiltration of the stroma.

Active enhancement was induced in inbred rats with cardiac allografts using semisoluble antigens. The optimal time of antigen pretreatment and optimal dose of semisoluble antigens were examined. The presence of serum blocking factors in the sera of rats having had allografts for a long time was examined with a macrophage migration inhibition test and lymphocyte microcytotoxicity assay. Since the blocking factors of macrophage migration inhibition were increasing on the 7th day, that day was determined to be the optimal time of antigen pretreatment. The mean survival time (MST) of cardiac allografts in untreated rats was 17.2 +/- 7.5 days. Semisoluble antigens were administered at 2 mg/kg body weight 7 days before the graft, 4 mg/kg 7 days before the graft and 2 mg/kg divided over three days, 15, 8 and 1 day before the graft, and the MSTs of cardiac allografts of rats receiving these treatments were 71.2 +/- 39.9, 62.6 +/- 42.2 and 79.3 +/- 31.0 days, respectively. The MST in each group of the treated rats was significantly longer than that of the control group (p less than 0.01). Rejection of the allograft, however, was accelerated in a group treated with 8 mg/kg 7 days before the graft (MST: 8.4 +/- 3.2 days). Serum blocking factors were detected in the sera of approximately half of the rats having cardiac allografts which survived a long time.

A blood recipient, aged 66, was found to have positive adult T-cell leukemia-associated antigens (ATLA), approximately half a year after a transfusion. The donor's ATLA-antibody titer was 1: 640. Routine screening of blood donors for ATLA antibody was proposed.

Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH) following an intragastric administration of carbon tetrachloride (CCl4) to rats. Oxidized glutathione (GSSG) also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2.), glutathione peroxidase (EC 1.11.1.9) and malic enzyme (EC 1.1.1.40) activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

Electron microscopy of four human T-cell lines revealed the production of type C virus particles in two T-cell lines: one derived from acute lymphoblastic leukemia and the other from a leukemic T-lymphoid malignancy. Virus particles isolated from these cells had reverse transcriptase activity and the major internal structural protein of 30,000 daltons (p30). The indirect immunofluorescence test of these virus-producing cells with sera of patients with adult T-cell leukemia (ATL) was negative. The data indicate that these retroviruses are different from adult T-cell leukemia virus (ATLV).

Using the ventriculo-cisternal perfusion method, the effects of droperidol and ketamine hydrochloride on cerebrospinal fluid (CSF) production were studied in dogs. Neither droperidol (0.25 mg/kg, IV) nor ketamine (3 mg/kg, IV) caused a statistically significant change in CSF production rate. Positive correlation between CSF production and corresponding cerebral perfusion pressure (CPP) was observed in the ketamine study, whose unfavorable effect on neurosurgical anaesthesia would be obvious. On the other hand droperidol (0.25 mg/kg, IV) tended to decrease CSF production. Droperidol alone or in combination with other analgesics such as fentanyl as currently used in neurosurgical anaesthesia appears to be an appropriate choice in patients with increased intracranial pressure.

Computed tomographic arteriography (CTA) was performed in 30 patients with hepatocellular carcinoma (HCC). Detection of HCC by CTA was compared with that of conventional celiac or hepatic arteriography. CT scanning was performed immediately, 30 seconds and 1 min after an injection of 5 to 10 ml of contrast medium into the common or proper hepatic artery. Repeated infusions allowed whole liver sections to be visualized. HCC was localized in 28 of the 30 patients by conventional arteriography, with CTA detecting the masses in 27 of the 28 patients. CTA imaging presented the tumor mass in 1 of the 2 patients missed by arteriography. Conventional arteriography delineated the boundaries of HCC in 15 (50%) of the 30 patients. CTA clearly delineated the masses in 26 (87%) of the 30 patients including 11 patients in which the tumor borders were obscure by conventional arteriography. HCC lesions smaller than 1 cm in diameter were detected only by CTA in 6 (20%) of the patients. It was concluded that CTA is both useful and necessary in the demarcation of small HCC masses.

The effects of surgical intervention by removal of the primary focus, and the effectiveness of an immunomodulator, Corynebacterium parvum (Cp), on the proliferation of metastatic tumor tissue were investigated by following the postoperative changes in the 3H-thymidine labelling rate of metastatic tissue in an experimental model of metastasis in mice. In addition, the delayed type hypersensitivity reaction (DTH) was studied to investigate the immune capacity of the host. The labelling rate of mice that had the primary focus removed remained high with little variation, while that of the mice not operated on decreased gradually. On the other hand, in mice undergoing a sham operation, the rate was the same as that of the mice with the primary focus removed for a short while, but then gradually decreased. When Cp was administered, especially before removal of the primary focus, the rate was lower than that of the tumor bearing control group and decreased steadily. The number of pulmonary metastatic nodules was increased by removal of the primary focus, but this increase was inhibited by the administration of Cp which prolonged life. The depression in the DTH was less in the group given Cp preoperativeLy than in either the group of mice having the primary focus removed or those not having it removed.

Antibody-dependent cellular cytotoxicity (ADCC) increased with the development of tumors in C3H/He mice bearing spontaneous breast cancer or the syngeneic hepatoma MH-134 and in C57BL/6 mice bearing the syngeneic Lewis lung carcinoma 3LL. This cytotoxicity decreased after treatment with guinea pig, monoclonal IgM anti-Thy 1.2 serum and complement to the non-cancer level thus indicating that the increased ADCC in mice with cancer seems mainly attributable to cells with the Thy 1 antigen. On the other hand, NK activity decreased greatly when mice had tumors. Treatment with monoclonal IgM anti-Thy 1.2 serum and complement showed no significant influence on the natural killer (NK) activity of spleen cells of mice bearing MH-134 cancer, but in the 3LL-bearing mice the activity decreased significantly.

Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

We investigated the restriction of the host range to infectivity of MSV by helper leukemia virus in vivo. When newborn SD-rats were inoculated intracerebrally, subcutaneously, intraperitoneally or intramuscularly with xenotropic pseudotype Kirsten MSV, Ki-MSV(BV2), either brain tumors or myogenic sarcomas were induced, depending upon the route of inoculation. However, no tumors developed in SW-Icr mice inoculated with Ki-MSV(BV2) either intracerebrally or intramuscularly at birth. Ecotropic Ki-MSV(Ki-MuLV) induced myogenic sarcomas in mice when inoculated intramuscularly and also induced brain tumors and myogenic sarcomas in rats when inoculated intracerebrally and intramuscularly, respectively. Thus, the host range of pseudotype MSV appeared to depend on a helper leukemia virus.

A new nutritional product (SF-1008C) containing a high proportion of branched chain amino acids (BCAA) and low proportion of aromatic amino acids (AAA) and methionine was tested to see its effect on the impaired protein metabolism and abnormal nutritional state frequently observed in patients with advanced liver cirrhosis. A sharp increase in plasma BCAA levels and fall of AAA and methionine levels were found following the administration of an SF-1008C-supplemented diet to healthy controls and cirrhotic patients, which the BCAA levels increased only slightly following an isocaloric control diet. Blood ammonia levels increased within the normal range transiently following the diets. The SF-1008C-supplemented diet was given for 2 weeks to cirrhotic patients with histories of hepatic encephalopathy, who were taking a low-protein diet because of hyperammonemia. Serum prealbumin levels, nitrogen balance, molar ratio of plasma BCAA/phenylalanine and tyrosine, the number connection test and electroencephalograms improved during the period of the experimental diet. The results, therefore, indicate that a BCAA-supplemented diet is well tolerated by patients with advanced cirrhosis and useful for treatment of impaired protein metabolism. Furthermore, this product is beneficial in preventing hepatic encephalopathy in cirrhotics.