Studies on vocal fold injection and changes in pitch associated with alcohol intake.

The current study was carried out with particular emphasis on the association between phonetic function tests and alterations in the appearance of the hypopharyngeal and laryngeal mucosa, such as capillary dilatation, edema, and vocal fold injection after alcohol intake. The results demonstrated the occurrence of previously unrecognized pathophysiological changes associated with synchronous phonetic functions in the vocal pathway after alcohol intake. Serum ethanol and aldehyde concentration levels were evaluated hourly for 2.5 h after ingestion of alcohol. When an electronystagmogram showed the typical pattern of alcohol intake, the study was initiated. Occasionally, rhinography was performed on subjects complaining of a stuffy nose after alcohol intake.

Alterations in hepatic delta-aminolevulinic acid synthetase and heme oxygenase activities after chronic ethanol consumption in rats.

In the present study, the effect of chronic ethanol consumption in rats on the hepatic heme metabolism was investigated. Male Wistar rats were fed a nutritionally adequate liquid diet containing ethanol as 36% of the total calories for 5 weeks. After an overnight fast, the livers were excised and centrifuged to obtain mitochondrial and microsomal fractions. Chronic ethanol feeding of rats resulted in about 19% hepatomegaly as represented by the increased liver/body weight ratio. There was no difference in the mitochondrial protein content between the ethanol-treated and control rats, but the microsomal protein content was significantly increased in the ethanol-treated rats. Hepatic microsomal content of cytochrome P-450 (P-450) was markedly enhanced by chronic ethanol ingestion. Microsomal contents of cytochrome b5 (b5) and total heme were also increased to a lesser extent. After chronic ethanol abuse, the hepatic activity of delta-aminolevulinic acid (ALA) synthetase, which is a rate-limiting enzyme for heme production, was significantly increased and that of the heme oxygenase was slightly increased. These data indicate that ALA synthetase activity is induced by the negative feedback mechanism in order to compensate the depletion of heme caused by the utilization of heme for P-450. It is also speculated that, in response to excessive production of heme as described above, heme oxygenase activity is secondarily induced to regulate the amount of heme.

[Rupture of hepatocellular carcinoma with multiple pulmonary metastasis successfully treated by transcatheter arterial embolization (TAE) of tumor: a case report].

A 66-year-old woman was hospitalized in a state of shock with rupture of hepatocellular carcinoma and multiple pulmonary metastasis. Her bleeding was successfully controlled by emergency transcatheter arterial embolization with Lipiodol (Lp-TAE). Treatments with UFT, OK-432 and two additional Lp-TAE caused the disappearance of pulmonary metastasis with AFP levels decreased and natural killer cell activity increased. The patient died one and a half years after the emergency Lp-TAE. The disappearance of pulmonary metastatic lesions seemed to be caused by improvement of the patient's immunity, which related to the regression of primary tumor after Lp-TAE. It was suggested that Lp-TAE is worth undertaking even in rupture of hepatocellular carcinoma with remote metastatic lesions.

Effect of hyperbaric oxygenation on macrophage function in mice.

Hyperbaric oxygenation (HBO) has an immunosuppressive effect. The possible mechanisms of this immunosuppressive effect were assessed by determining the production of interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as phagocytosis by splenic macrophages from HBO-treated mice. Although HBO treatment did not have any significant effect on IL-6 production and phagocytotic activity, a marked decrease in IL-1 production and a significant decrease in PGE2 production were observed. These results suggest that the reduction of IL-1 production may play an important role in the immunosuppressive effect of HBO.

Effect of interleukin 1 (IL-1) on the levels of cytochrome P-450 involving IL-1 receptor on the isolated hepatocytes of rat.

In the present study, the expression of IL-1 receptor (IL-1 R) on the primary cultured hepatocytes was determined and the effect of IL-1 on the intracellular amount of cytochrome P-450 was investigated. The kinetics of IL-1R on the hepatocytes was studied by [125I]-IL-1 alpha and revealed that 5,000 molecules of IL-1 bound to a hepatocyte with a Kd of 4.0 x 10(-9) M. Incubation of the hepatocytes with IL-1 for 18 hrs decreased the contents of cytochrome P-450 in a dose-dependent manner. These findings suggest that IL-1 potentially depresses the drug metabolism involving IL-1R which is expressed on hepatocytes.

A one-step enzyme immunoassay for human manganese superoxide dismutase with monoclonal antibodies.

A one-step enzyme immunoassay for the determination of manganese superoxide dismutase in serum has been developed with two kinds of monoclonal antibodies. Proposed method had high sensitivity (assay range, 0.4-200 ng/ml), good recovery (recovery percentage, 102.9-106.2%) and reproducibility (intraassay, C.V. = 1.87-3.66%; interassay, C.V. = 3.03-10.4%). From these results, it is possible to apply this method to routine clinical analysis and biochemical research with various purposes.

[Clinical experiences of LAK therapy in patients with hepatocellular carcinoma].

A patient with hepatocellular carcinoma (HCC) was treated with newly established adoptive immunotherapy using LAK cells (LAK therapy) together with transcatheter arterial embolization therapy (TAE). This patient responded well, and the therapeutic efficacy still continues 6 months after the therapy. Since the efficacy of LAK therapy does not last long, it is recommended that LAK therapy should be employed in combination with such therapeutic maneuvers as TAE or anticancer drugs in patients with HCC.

Endotoxin-induced hypercoagulability: a possible aggravating factor of alcoholic liver disease.

The present experiments were designed to study the effect of chronic ethanol consumption on endotoxin toxicity. The intravenous injection of endotoxin produced a more pronounced increase of serum AST and ALT activities in chronic ethanol-fed rats, when compared to controls. The activities of hepatic mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, were also distinctly decreased by endotoxin treatment in chronic ethanol-fed rats. Consistent with these biochemical alterations, light and electron microscopic examinations revealed severe liver injury after endotoxin injection in chronic ethanol-fed rats. Furthermore, the increase of blood BUN and creatinine levels accompanied by the degeneration of the renal tubulus and slight infiltration of neutrophils into the glomerule were produced by endotoxin treatment and were more conspicuous in chronic ethanol-fed rats than controls. Therefore, the biochemical and histological evidence indicates that endotoxin markedly potentiates organ injury after chronic ethanol consumption. In addition, a more pronounced decrease in blood antithrombin III activity accompanied by an increase in fibrin degradation product level in blood was recognized in chronic ethanol-fed rats receiving endotoxin, when compared to controls receiving endotoxin. This increase of blood fibrin degradation product level correlated well with the decrease of antithrombin III activity (r = -0.6116; p less than 0.005). These findings of blood antithrombin III activity and fibrin degradation product level indicate that the coagulation-fibrinolysis system is more activated by endotoxin treatment after chronic ethanol consumption. Furthermore, the activation of the coagulation-fibrinolysis system was well correlated with biochemical and histological alterations representing hepatorenal involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of singlet oxygen in pathogenesis of liver injury in rats treated with D-galactosamine].

A study was conducted to elucidate the possible role of singlet oxygen in pathogenesis of D-galactosamine-induced liver injury. Tissue and plasma levels of singlet oxygen were determined with chemiluminescence analysis. Following results were obtained: 1) Chemiluminescence as well as malondialdehyde, which is regarded as one of terminal products of lipid peroxidation, significantly increased in the liver and plasma of rats treated with D-galactosamine. 2) Elevation of plasma GPT and total bilirubin was also observed in rats with D-galactosamine-induced liver injury. Histological examination of the liver revealed submassive hepatic necrosis. 3) Administration of vitamin E, a radical scavenger of singlet oxygen, significantly inhibited the increases of chemiluminescence and MDA in the liver and plasma as well as the elevations of GPT and total bilirubin in the plasma. Histological changes of the liver were also found to improve significantly by vitamin E administration. In conclusion, singlet oxygen seems to be definitely involved, at least in part, in pathogenesis of liver damage induced by D-galactosamine. In addition, inhibition of the liver injury is possible, to some extent, by administration of vitamin E, one of the potent radical scavengers of singlet oxygen.

[An experimental study on the severe type of alcoholic liver disease--a pathogenetic role of potentiated activation of complement system by endotoxin after chronic ethanol consumption].

Endotoxemia frequently appears in severe type of alcoholic liver disease. However, we have little knowledge how endotoxin influences the progression of alcoholic liver injury. Thus, to study the causal mechanism for the progression to the severe type of alcoholic liver diseases, endotoxin (0.2 mg/100 g BW, E. Coli O26:B6) was intravenously injected in chronic ethanol-fed rats and controls, and then, rats were sacrificed after 16 hours of endotoxin treatment. The elevation of serum GOT and GPT activities induced by endotoxin was significantly higher in chronic ethanol-fed rats than controls, and these biochemical changes were well correlated with the grade of necrosis of liver histology. Furthermore, in chronic ethanol-fed rats, endotoxin treatment tremendously increased blood BUN and creatinine levels and produced the degeneration of renal tubuli with neutrophil infiltration into glomerulus. These experimental findings are very similar to the severe type of alcoholic liver disease. On the other hand, endotoxin significantly decreased serum values of CH50 in chronic ethanol-fed rats, but not in controls. Such alterations of CH50 induced by endotoxin were well correlated with the several parameters indicating the injury of liver and kidney. Therefore, the present study may indicate that chronic ethanol ingestion aggravates endotoxin-induced organ injury, and that the activation of complement system may associate with such progression of organ injury.

[Alteration of prostaglandin metabolism in alcoholic liver disease: its association with platelet dysfunction after chronic alcohol ingestion].

Recently, hepatic microcirculation has been focused on as an important pathogenic factor in progression of alcoholic liver disease (ALD). Therefore, blood levels of several prostaglandins, which are associated with organ microcirculation, were determined in various liver diseases, including ALD. Blood thromboxane B2 (TXB2) level was significantly increased in ALD, when compared to other types of liver diseases, whereas both 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and prostaglandin E were not changed. These consequences resulted in the imbalance of 6-keto PGF1 alpha to TXB2, which might promote platelet aggregation and blood vessel contraction. Indeed, the increase of beta-thromboglobulin and platelet factor 4 in blood was observed in ALD. Furthermore, in ALD, the rate of arachidonate-induced platelet aggregation was prominently enhanced, and malondialdehyde production in platelet, which was well correlated with blood TXB2 levels, significantly increased. Thus, the present study may indicate that, in ALD, hyper-aggregability of platelet is produced, because of the derangement of prostaglandin metabolism and platelet dysfunction.

Extrarenal Wilms' tumor in the adult patient. A case report and review of the world literature.

A case of an extrarenal Wilms' tumor arising in the retroperitoneal region of a 49-year-old male is reported. A review of the world literature indicates that the incidence of the tumor arising in the extrarenal region is extremely rare. A total of 14 cases have previously been reported, but the number of cases that occurred in adult patients is only 2. The clinical and pathologic features are briefly discussed.

Alcohol-induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics.

It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in mitochondrial GOT (m-GOT) activity after chronic alcohol consumption: clinical and experimental observations.

In order to clarify the origin and the mechanism of increased serum activity of glutamic oxalacetic transaminase (GOT) in chronic alcoholics, clinical and experimental investigations were carried out. Mitochondrial (m-GOT) and cytosolic GOT (c-GOT) isoenzymes were separated chromatographically by using a mini-column packed with Sephadex A50. Sixty percent of 63 alcoholics had elevated serum GOT. The m-GOT activity in alcoholics with total serum GOT activity of over 50 Karmen Units was 17.2 +/- 1.6 K.U. and the m-GOT/GOT ratio was the highest when compared to those in non-alcoholic liver diseases. In in vitro study, six hours of incubation of isolated hepatocytes from rats fed ethanol chronically resulted in an increased leakage of m-GOT into the incubation medium and also showed a tendency of a higher m-GOT/GOT ratio than that from control rats. The m-GOT activity thus released into the medium showed a highly significant inverse correlation with the viability of hepatocytes. These data suggest that m-GOT substantially contributes to an increased serum GOT often observed in chronic alcoholics.

Glutathione contents in rat livers after acute and chronic exposure to ethylene oxide.

Wistar rats were subjected to a 6 hr exposure to ethylene oxide once at the concentration of 500 ppm, 3 times a week for 12 weeks as a chronic experiment. Hepatic glutathione contents were determined after these treatments. The specific content of reduced form of glutathione (GSH) in the rat livers of chronic exposures was 28.9 nmoles/mg protein, which is not significantly different from that of control group. On the other hand, the hepatic content of GSH in rats subjected to a 4 hr exposure to ethylene oxide at a concentration of 2500 ppm decreased markedly to the levels of 5% of control value. The present results suggest the involvement of glutathione, at least in part, in the detoxication of ethylene oxide.

[A clinicopathological study of 108 consecutive primary hepatic malignancies in the University of Occupational and Environmental Health].

At our University, the rate of hepatic malignancies among the total number of those autopsied was shown to be higher than the mean rate of Japan. The 108 cases investigated included 92 hepatocellular carcinomas (HCCs), 10 cholangiocellular carcinomas (CCCs), 4 cases of combined HCC and CCC, one undifferentiated carcinoma, and one angiosarcoma. The positive rate of serum HBsAg among the HCCs in our series was almost equal to the mean rate of Japan. Twenty-eight HBsAg positive and 64 negative HCCs were clinicopathologically compared. The mean age at death was ten years younger for the positive cases than in the negative ones (p less than 0.05). However, there was no significant difference between both groups in any other biologic or pathologic feature, except for a few minor matters. We describe herein the summary of our cases with reference to a comparison study between HBsAg positive and negative HCC cases.

Protective effect of acute ethanol administration on endotoxin-induced liver injury.

The effect of acute administration of ethanol on endotoxin-induced liver injury was studied. Biochemical and histological results indicated that ethanol pretreatment protected endotoxin-induced liver injury through the improvement of hepatic blood circulation, which is probably associated with an inhibitory effect of ethanol on platelet functions and coagulation system.

Platelet dysfunction and alteration of prostaglandin metabolism after chronic alcohol consumption.

To study the effects of chronic alcohol consumption on platelet functions, the rate of arachidonate-induced platelet aggregation, the production of malondialdehyde in platelets, and plasma levels of prostaglandin endoperoxide metabolites were examined in 88 chronic alcoholics and 24 healthy controls. The rate of platelet aggregation and the production of malondialdehyde in platelets were greater in chronic alcoholics both on admission and 1 week after. However, these alterations returned to the level of healthy controls within 4 weeks of abstinence from alcohol and were independent of the number of circulating platelets. Furthermore, on admission, plasma levels of thromboxane B2 were significantly increased in chronic alcoholics when compared with those of healthy controls (400.8 +/- 36.5 versus 241.7 +/- 28.9 pg/ml plasma; p less than 0.025) and were also significantly correlated with malondialdehyde production in washed platelet debris (r = 0.6049; p less than 0.001). In contrast, plasma levels of 6-keto prostaglandin F1 alpha and prostaglandin E were not altered after chronic alcohol consumption. As a result, the ratio of 6-keto prostaglandin F1 alpha to thromboxane B2 was markedly decreased in chronic alcoholics (0.31 +/- 0.03 versus 0.62 +/- 0.13; p less than 0.001). These results strongly suggest that the imbalance in prostaglandin endoperoxide metabolites is produced by chronic alcohol ingestion. Moreover, a significant correlation was observed between platelet aggregation rate and malondialdehyde production during platelet aggregation (r = 0.559; p less than 0.005). Thus, we conclude that chronic alcohol consumption alters platelet thromboxane metabolism, which is likely associated with the increased ability of platelets to aggregate.