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Biomedical subjects

H Nagashima

Publications and source records attributed to H Nagashima.

At least 271 records · Page 15Linked to original sources

Effect of various central nervous system-acting drugs on ethanol and acetaldehyde metabolism in rats.

Blood ethanol levels following intravenous ethanol administration were much higher during anesthesia with diethyl ether (ether), phenobarbital and pentobarbital than in unanesthetized control rats. Blood acetaldehyde levels were significantly lower during anesthesia with ether. Ether inhibited alcohol dehydrogenase (ADH) activities in vitro in an uncompetitive fashion; Ki, ether concentration which produced 50% inhibition of NADH formation, was 9.7 mM. Pentobarbital produced slight elevations of ADH activities in vitro and phenobarbital had no effects. Acetaldehyde levels during anesthesia with phenobarbital and pentobarbital were slightly higher than in unanesthetized animals. Phenobarbital and pentobarbital inhibited aldehyde dehydrogenase (ALDH) activities in vitro in a noncompetitive fashion; Ki were 29 and 37 mM, respectively. Ether did not influence ALDH activities in vitro. Thus, pentobarbital was suggested as the most appropriate anesthetic agent in such animal experiments.

Acetaldehyde↗

Treatment of HBeAg-positive chronic hepatitis with a streptococcal preparation (OK-432).

Forty-two patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis were treated by intramuscular injections with OK-432, an immunopotentiator possessing interferon-inducing activity. They were monitored with serial measurements of virological parameters to evaluate therapeutic effectiveness, and compared with a group of seventy-five untreated patients (natural course group). In the group receiving OK-432 therapy, twenty-seven patients (64.3% of the forty-two patients) became negative for HBeAg in an average observation period of 20.1 months. Of these, fourteen patients (33.3% of the forty-two patients) underwent seroconversion from HBeAg to anti-HBe antibody (anti-HBe). In the natural course group, twenty-three patients (30.7% of the seventy-five patients) lost HBeAg reactivity in a mean follow-up period of 32.3 months, and thirteen patients (17.3% of the seventy-five patients) became seroconverted. Thus, the drug group showed significantly higher percentages of patients with disappearance of HBeAg and seroconversion, notwithstanding the shorter duration of the follow-up. Young males and females, females generally, or patients with high serum GPT levels were more likely to respond to the therapy. The serum GPT level tended to stabilize more in patients receiving OK-432.

Adult↗

Scanning electron microscopy and the study of Fc and C3b receptors of cultured fat-storing cells from rat liver.

Non-parenchymal fat-storing cells (FSCs) were isolated from rat liver by Metrizamide density centrifugation after liver perfusion with media containing pronase and/or collagenase. These cells were cultured in Williams' E medium with 20% fetal calf serum under the usual conditions. FSCs, identified by vitamin A-specific fluorescence (VAF), were viewed under conventional light microscopy 24, 48 and 72 h after seeding. At 24 h, some FSCs remained hemispheric; at 48 h all FSCs were well spread out, and at 72 h the number of FSCs had increased and the VAF intensity had become weaker. Scanning electron microscopy revealed that the features of the FSCs clearly differed from those of the other non-parenchymal cells. The in vitro FSC features closely resembled the in vivo features. FSCs cultured for 48 h had flattened, triangular or oval shapes with fairly smooth surfaces that showed scattered microvilli 0.1 micron long. Two types of processes, long slender (130 microns maximum length) and short broad ones, protruded from the cell body. These processes had smaller projections 0.2 micron wide that looked like fern leaves. Many lipid droplets could be seen under the cell surface. IgG-coated sheep erythrocytes (EAs) and IgM-C3-coated ox erythrocytes (EACs) were used to investigate whether there are Fc and C3b receptors on the FSCs. No rosette-formation characteristic of EAs or EACs was present on the FSCs; proof that FSCs have neither receptor.

Animals↗

Electron microscopy of fat-storing cells in liver diseases with special reference to cilia and cytoplasmic cholesterol crystals.

Two hundred and ten fat-storing cells in the liver of patients with liver diseases were examined electron microscopically, and 5 of them were found to project a single cilium from the perinuclear region to the space of Disse. Three cilia were in the space between a hepatocyte and their own cell body, and 2 were between a sinusoidal endothelial cell and their own cell body. In cross sections of the cilium, the axoneme consisted of 9 pairs of microtubules arranged in a cylinder and lacked a central pair of microtubules ("9 + 0" pattern). Arms and spokes were also absent in the axoneme. Therefore, the single cilium of fat-storing cells was considered to be immotile. Some fat-storing cells from a patients with alcoholic liver cirrhosis contained an angular electron lucid inclusion, which was identical to cholesterol ester crystals, suggesting the presence of disturbed cholesterol metabolism.

Cholesterol↗

Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC) were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC). They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%), large depressions (69%), and a markedly rounded edge of the liver (33%) more often than NALC patients (18, 43 and 3%, respectively). Nodularity differed between the right and left lobes in ALC (41%) more often than in NALC (16%). Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively) than in ALC (8 and 5%, respectively). Lymphatic vesicles were observed both in ALC (85%) and NALC (78%). In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.

Adult↗

Comparison of estimation methods of liver maximum removal rate of indocyanine green.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).

Humans↗

Metabolism of branched-chain amino acids in rats with acute hepatic failure: a tracer study using 15N-leucine.

Fulminant hepatic failure (FHF) was produced in rats with intraperitoneal injection of D-galactosamine. Control rats received only physiological saline. 15N-leucine (200 mg/kg of body weight) was injected into the rats via the tail vein. Arterial blood was drawn before and 5, 15, 30 and 60 min after the injection of 15N-leucine. 15N-amino acids were determined quantitatively by gas chromatography and mass spectrometry. The plasma 15N-leucine level decreased logarithmically in the same manner in both groups. This result suggests that leucine is mainly metabolized in extrahepatic tissues. The incorporation of 15N into plasma isoleucine and valine was not significantly different between the groups. Plasma alanine and glutamine concentrations increased in controls and decreased in FHF rates after the injection. The incorporation of 15N into plasma alanine in rats with FHF was significantly later than in controls. This result may suggest that undergoing hyperammonemia causes to form more glutamine from glutamate in extrahepatic sites as the same manner as for chronic hepatic failure. Additionally, insulin levels increased temporarily after the injection of leucine in both groups. This increase may play a role in the decrease in plasma isoleucine and valine concentrations after injection of leucine.

Alanine↗

Responses of plasma cyclic AMP, serum immunoreactive insulin, C-peptide immunoreactivity and blood sugar levels to glucagon in patients with liver diseases.

Levels of plasma cyclic AMP, serum immunoreactive insulin (IRI), serum c-peptide immunoreactivity (CPR) and blood sugar (BS) were determined 0, 15, 30, 45 and 60 min after a glucagon injection (0.01 mg per kg body weight) in normal controls, patients with acute hepatitis and liver cirrhosis. Plasma cyclic AMP responses to glucagon in liver disease patients varied widely in peak value, and only in patients with fulminant hepatitis and decompensated liver cirrhosis with poor prognosis was the response suppressed. The peak response of BS was found significantly later in liver cirrhosis patients than in normal controls. IRI and CPR responses to glucagon were lower in acute hepatitis patients than in normal controls and liver cirrhosis patients. IRI levels and their sum were also lower in acute hepatitis patients, although CPR levels were not significantly different. Thus, the ratio of the sum of CPR from 0 to 60 min to that of IRI was significantly higher in acute hepatitis, indicating impaired pancreatic secretion of insulin to glucagon stimulation as well as increased uptake of insulin by the liver in acute hepatitis.

Adult↗

Evaluation of Talbot's safety zone of infusion volume and osmolality in infusion therapy for decompensated liver cirrhosis.

Problems with infusion therapy for correcting fluid and sodium imbalance in decompensated liver cirrhosis (DLC) were investigated by establishing the safety zone of Talbot et al. for parenteral fluid therapy in 4 DLC patients infused with over 900 ml of fluid each day for at least 9 days. The safety zone was different in each case. The safe infusion volume decreased and the safe electrolyte concentration shifted to a lower osmolality when there was ascites with renal failure than ascites without renal failure. Infusion therapy was performed without deterioration of the water and sodium balance in those patients whose infusion volume and fluid osmolality were in the safety zone. In contrast, ascites retention increased and peripheral edema appeared in patients whose infusion volume and osmolality were out of the safety zone. Therefore, the safety zone should be determined repeatedly during infusion therapy.

Aged↗

A vegetable protein-rich diet for the treatment of liver cirrhosis.

Twelve patients were administered a vegetable protein-rich diet, which was low in methionine and high in the branched-chain amino acid (BCAA) to aromatic amino acid (AAA) molar ratio, and an animal protein-rich diet, high in methionine and low in the BCAA/AAA molar ratio. These diets were administered successively for one week each. Actually ingested amounts of tyrosine and methionine were significantly lower during the feeding of the vegetable protein-rich diet than the animal protein-rich diet. Serum methionine concentrations increased while on the animal protein-rich diet and decreased following the switch to the vegetable protein-rich diet. No other amino acid concentrations were affected. Significant differences were not observed in nitrogen balance or serum protein concentrations.

Adult↗

Comparative diagnosis of alcoholic liver diseases by multivariate and histological analysis.

Sixty-seven cases of alcoholic liver disease were histologically classified into 4 groups: alcoholic liver cirrhosis (ALC), alcoholic hepatitis (AH), alcoholic liver fibrosis (ALF) and alcoholic fatty liver (AFL). They were statistically reclassified by the likelihood method using age, total alcohol intake, hepatomegaly and 12 liver function tests. A score table for likely diagnosis was constructed from the incidences of each range. The cases were re-evaluated using the score table, with an overall correct diagnosis rate of 73%. The best combination of 5 parameters included the indocyanine green plasma disappearance rate, total alcohol intake, cholesterol, choline esterase and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio. A correct diagnosis rate of 75% was attained using these 5 parameters, and 94% of patients were correctly diagnosed by the first or the second likelihood diagnosis. Differential diagnosis of alcoholic liver diseases was easily and confidently obtained with the likelihood score table.

Adult↗

Cerebral edema associated with acute hepatic failure.

The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64%) of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more frequently in patients later found to have cerebral edema. Moreover, the length of time from deep coma to death was much shorter in the brain edema cases with cerebral herniation than without herniation.

Acute Disease↗

Plasma branched chain amino acid abnormalities in sake-treated rats.

Plasma amino acid abnormalities in rats treated with large doses of sake and whisky for 3 days were investigated under adequate nutritional conditions. A significant decrease in plasma branched-chain amino acid (BCAA) levels was observed in sake- but not whisky-treated rats. However, known factors affecting BCAA levels, such as serum insulin and plasma glucagon levels ahd BCAA-metabolizing enzyme (BCAA transaminase and branched chain alpha-ketoacid dehydrogenase) activities in the liver and skeletal muscle, were not significantly altered in the sake group. Furthermore, ethanol-metabolizing enzyme (alcohol and aldehyde dehydrogenases and the microsomal ethanol-oxidizing system) activities in the liver were not altered in the sake group. Other mechanisms need to be considered for explaining the diminished levels of plasma BCAA in sake-treated rats.

Alcoholic Beverages↗

Nutritional treatment of liver cirrhosis by branched-chain amino acid-enriched nutrient mixture.

The effects of branched-chain amino acid (BCAA)-enriched nutrient mixture (nutrient-mixture) on the nitrogen metabolism and nutritional state were clinically investigated in 10 patients with liver cirrhosis. Nutrient-mixture-supplemented diet was prepared by adding 150 g nutrient-mixture daily to low-protein diet, and comparisons were made with a regular diet (control diet). Each diet supplied 2,100 kcal energy and 80 g protein per day. Patients were given control diet for 2 weeks and thereafter treated successively with nutrient-mixture-supplemented and control diet each for 2 weeks. Nitrogen balance improvement and positive balance were observed during the feeding of nutrient-mixture-supplemented diet. The composition of nitrogen compounds in urine and the fecal nitrogen excretion did not alter during the test period. Plasma aromatic amino acid (AAA) concentrations decreased and BCAA/AAA molar ratios increased significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration. Plasma methionine concentration also decreased in the 1st week. Plasma pre-albumin levels rose significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration, and the number connection test improved significantly following the supplemented diet. These results suggest that the use of nutrient-mixture in the nutritional treatment of liver cirrhosis had no deleterious effects on nitrogen metabolism and is useful for the improvement of plasma amino acid imbalance and protein-energy malnutrition.

Adult↗