Biomedical subjects

S Onishi

Publications and source records attributed to S Onishi.

At least 163 records · Page 9Linked to original sources

PubMed1994

The arterial blood ketone body ratio as a possible marker of multi-organ failure in patients with alcoholic hepatitis.

The arterial blood ketone body ratio (AKBR: acetoacetate/3-hydroxybutyrate) within 48 h of admission is reported to be an excellent prognostic indicator for acute hepatic failure. In this study, we assessed the AKBR in 63 patients receiving supportive medical therapy for alcoholic hepatitis, in order to investigate its efficacy for predicting complications and the prognosis. Twelve patients (19%) died and 51 patients (81%) survived. Hepatic encephalopathy, severe coagulopathy, and renal failure were the critical complications (P < 0.01), and the AKBR at 72 h of hospitalization was closely correlated with these complications (P < 0.01), although they could not be predicted in any other way during the early admission period. The AKBR of normal individuals ranged from 1.0 to 2.1 (1.54 +/- 0.26, mean +/- SD), so an AKBR > 1.0 (mean-2SD) was defined as normal. The AKBR value at 48 and 72 h of hospitalization showed a significant difference between survivors and non-survivors (P < 0.01). All survivors showed an increase of the AKBR to above 0.7 at 72 h, with subsequent maintenance of the ratio over 1.0, while eight of the 12 non-survivors had sustained suppression of the AKBR below 0.7 at 72 h. Seven of these eight patients subsequently developed multiple organ failure. These findings suggest that the AKBR could be a possible marker of potentially fatal complications and a poor prognosis in patients with alcoholic hepatitis.

Acetoacetates↗

PubMed1994

Immunological functions of mouse liver resident high density lymphocytes.

Liver-derived high density lymphocytes (Matsunaga cells) have been detected as members of resident T cells in the mouse liver. In this study, we assessed the immunological functions of liver-derived high density lymphocytes of BALB/c mice in comparison with those derived from spleen and peripheral blood. Liver-derived high density lymphocytes proliferated in response to the syngeneic and allogeneic mixed lymphocyte reaction, as well as those derived from spleen and peripheral blood. The allo-activated cytotoxic T lymphocyte activity of liver-derived high density lymphocytes against PHA-blasts of C57BL/6 mice was lower than that of spleen- and peripheral blood-derived lymphocytes. The suppressor activity of syngeneic- or allo-activated high density lymphocytes of the liver, spleen, and the peripheral blood was assessed by measuring their suppressive effect on the proliferation or on the generation of allo-specific cytotoxic activity in allogeneic mixed lymphocyte reaction. The suppression was concentration-dependent and strongest in liver-derived lymphocytes.

Animals↗

PubMed1994

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters.

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

Angiotensin II↗

PubMed1994

A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I.

Crigler-Najjar syndrome (CN) type I, which is characterized by the complete absence of bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT) activity, is inherited as an autosomal recessive trait associated with unconjugated hyperbilirubinemia. Phenobarbital has no effect on the bilirubin concentration in the serum of patients with CN type I. Recently, cDNA for two human liver bilirubin UGT (UGT1A and UGT1D) were isolated, and their genetic organization was determined. The UGT1A (UGT1*1) and UGT1D (UGT1*4) genes each have a unique exon 1, whereas exons 2-5 are common to both genes. It has been predicted that some defect in the exons common to both genes is responsible for the absence of UGT1A and UGT1D activities in CN type I, and five cases with such a mutation have been reported. We describe here a new type of defect in the gene for bilirubin UGT in a patient with CN type I, namely, an abnormality in the exon 1 that is characteristic of the UGT1A gene. This mutation is a single nucleotide substitution, that is, C is changed to A at base position 840 in UGT1A cDNA, and this change results in a stop codon. Our patient is homozygous for the defect, and his nonconsanguineous parents and elder brother, who are clinically normal, are heterozygous for the defective allele. No mutation was detected in any exons of the UGT1D gene. Our results suggest that a homozygous nonsense or deletion mutation is detected not only in the exons common to UGT1A and UGT1D genes but also in unique exon 1 of UGT1A in CN type I.

Amino Acid Sequence↗

PubMed1994

Successive cardiac death of brothers in association with stress.

A 38-year-old man (Case 1) suddenly collapsed while resting. His 54-year-old brother (Case 2) came soon thereafter began to perform cardiac massage and mouth-to-mouth resuscitation. However, the elder brother suddenly died after resuscitating his younger brother for about 30 minutes. Necropsy revealed an occlusive thrombus of the left anterior descending coronary artery and coagulation necrosis of the myocardium in Case 1. Case 2 was diagnosed as sudden cardiac death on the basis of the moderate coronary sclerosis and myocardial lesions including contraction band, fragmentation, waviness, bleeding, and mild subendocardial fibrosis. Pulmonary edema in the both cases revealed the presence of left ventricular heart failure. Case 2 is a good example of the contribution of psychological and physical stress to sudden cardiac death.

Adult↗

PubMed1994

Class II-restricted presentation of an immunoglobulin heavy-chain-gene product by a gene-transfected B-cell line.

The presentation of an antigen endogenously processed by B lymphocytes was investigated. The expression plasmid vectors, harboring genomic rearranged V genes from two monoclonal B cells and genomic mu-constant region gene, were constructed. Two B-cell lines, the MOPC104E myeloma mu-heavy chain expressing AMB line and the control hybridoma mu-heavy chain expressing AHB line, were established by gene transfection into A20.2J B lymphoma cell line. The cloned transfectant cell lines expressed surface and cytoplasmic IgM. Radioimmunoprecipitation analysis of surface IgM revealed that both cell lines used transfected mu-heavy chain and host-derived kappa-light chain. The T-cell line, MRT-2, specific for the MOPC104E protein, proliferated on AME B cell lines but not on control AHB-cell lines. MRT-2 proliferation was inhibited by anti-I-Ed,k,p,r but not by anti-I-Ad monoclonal antibody. Although the AME-transfectant lines secrete IgM into the culture medium, double chamber-type culture-experiments revealed that MRT-2 proliferation is not mediated by the uptake of secreted IgM. The results suggest that B cells process and present their own immunoglobulin heavy-chain V-region peptides to T cells in the context of MHC class-II molecules.

Amino Acid Sequence↗

PubMed1994

Serum alpha-L-fucosidase activity and tumor size in hepatocellular carcinoma.

The serum level of alpha-L-fucosidase activity has been suggested as a useful marker in the diagnosis of hepatocellular carcinoma, although the precise mechanism behind the elevation of this parameter has not been determined. We found that the serum alpha-L-fucosidase activity level was significantly higher in 67 patients with hepatocellular carcinoma (695.1 +/- 245.5 nmol/ml/hr) than in 47 patients with cirrhosis (389.1 +/- 188.2 nmol/ml/hr; p < 0.001) and in 54 controls (202.0 +/- 104.6 nmol/ml/hr; p < 0.001). However, alpha-L-fucosidase activity was not correlated with tumor size (r = 0.134), whereas the alpha-fetoprotein level was correlated with tumor size (r = 0.580, p < 0.001). When 515.8 nmol/ml/hr was taken as the cutoff value (mean value in the controls plus 3 standard deviations), alpha-L-fucosidase activity was above the cutoff value in 12 of the 17 patients with a hepatocellular carcinoma less than 2 cm in diameter, in 28 of the 37 patients with a hepatocellular carcinoma less than 3 cm in diameter and in 52 of the 67 patients with hepatocellular carcinoma. In contrast, only 10 of the 47 patients with cirrhosis had levels above the cutoff value. These findings suggest that an increase in serum alpha-L-fucosidase activity in patients with cirrhosis may be a marker for detecting a hepatocellular carcinoma, especially a small tumor, because alpha-fetoprotein and des-gamma-carboxy-prothrombin are less promising as tumor markers.

Biomarkers↗

PubMed1994

Appearance of sinusoidal inclusion-containing endothelial cells in liver disease.

Sinusoidal "inclusion-containing endothelial cells" were studied histopathologically and immunohistochemically in various liver diseases, and their clinical importance was investigated. A total of 498 needle liver biopsies were examined. Endothelial inclusions inside the cells were recognized as eosinophilic granules in hematoxylin-eosin-stained sections. Electron microscopy showed that these inclusions corresponded to round cytoplasmic dense bodies with a single limiting membrane. The contents of these bodies were generally homogeneous, but sometimes heterogeneous. The inclusions appeared to contain protein, but were resistant to trypsin digestion, and immunohistochemistry failed to identify any immunoglobulins or hepatocyte-derived proteins. These endothelial cells also contained an increased number of micropinocytotic vesicles when compared with ordinary cells. The inclusion-containing endothelial cells appeared frequently in chronic hepatitis, but were relatively rare in other liver diseases. The incidence was higher in chronic aggressive hepatitis than in chronic persistent hepatitis or inactive cirrhosis. Although the density of these cells varied considerably even among patients with the same histological diagnosis and the phenotypical changes of these endothelial cells, assessed by monoclonal antibodies, were not apparent, the serum gamma globulin level tended to increase in relation to the density of inclusion-containing endothelial cells and the correlation was significant in hepatitis C.

Chronic Disease↗

PubMed1994

Acute hepatic failure with swollen mitochondria and microvesicular fatty degeneration of hepatocytes triggered by free radical initiator.

BACKGROUND: Reye syndrome and acute fatty liver of pregnancy are characterized by acute hepatic failure associated with characteristic pathologic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these conditions have been proposed, although none has demonstrated sufficiently similar laboratory and pathologic features. EXPERIMENTAL DESIGN: A single dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free radical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure. RESULTS: The hepatocytes displayed microvesicular fatty degeneration with severely swollen mitochondria. CONCLUSIONS: This is the first model of acute hepatic failure with microvesicular fatty degeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.

Adenine Nucleotides↗

PubMed1993

Orientation of erythrocytes in a strong static magnetic field.

The frequency of exposure to strong magnetic fields has increased as the magnetic-resonance image-diagnostic technique (MRI) and passenger transport systems based on the principle of magnetic levitation have come into wider use. Accordingly, it has become necessary to more systematically assess their influence on the body and set strict guidelines on acceptable limits of magnetism exposure. Therefore, we have assessed the influence of an uniform static magnetic field (8 T in maximum) on normal erythrocytes. The erythrocytes were oriented with their disk plane parallel to the magnetic field direction. These erythrocytes were influenced even by 1 T and almost 100% of them were oriented when exposed to 4 T. Furthermore, the degree of orientation was not influenced by the state of hemoglobin (oxy: diamagnetic, deoxy and met: paramagnetic). The dependence of the measured degree of orientation on the intensity of the magnetic field was in good agreement with the theoretical equation for the magnetic orientation of diamagnetic substances. As a result of a numerical analysis based on the equation, the anisotropic diamagnetic susceptibility of erythrocytes was found to be delta chi = 8 x 10(-22) electromagnetic units/erythrocyte. It was almost in agreement with the calculated value delta chi = 6 x 10(-22) emu/erythrocyte estimated from the diamagnetism of the membrane constituents of erythrocyte.

Cell Polarity↗

PubMed1993

Depressed immune functions in the early phase of varicella-zoster virus reactivation.

Varicella-zoster virus (VZV) infections are among the most common viral diseases characterized by recurrent episodes alternating with asymptomatic periods. VZV reactivation is believed to be induced by the impairment of the host's cell-mediated immune system; however, the precise mechanisms involved in the latency period and reactivation of herpes viruses in the infected host are not yet fully elucidated. We assessed the immune functions in noncompromised patients with typical herpes zoster to investigate the immunological status during the process of reactivation of VZV. The results indicated depressed immune functions in the early stage of VZV reactivation with gradual improvement during the recovery phase. These findings are in accord with the clinical course of herpes zoster and suggest a possible therapeutic trial.

Adult↗

PubMed1993

Long-latency event-related potentials in acute hepatitis patients with severe coagulopathy.

In 19 acute hepatitis patients with severe coagulopathy who were fully alert and oriented without any changes of mood or behavior, the P300 latency and the arterial blood ketone body ratio (KBR) were assessed as predictors of fulminant hepatitis. All 5 patients developing fulminant hepatitis had a corrected P300 latency longer than 345 msec and 4 of them had a KBR below 0.6. There was a significant negative correlation between the KBR and the blood ammonia level and between the KBR and the corrected P300 latency, while there was a positive correlation between the blood ammonia level and the corrected P300 latency. These data suggest that hepatic encephalopathy develops when loss of hepatic detoxifying activity allows toxic substances to reach the brain and induce cerebral edema. Our findings also suggest the clinical value of using the P300 latency combined with the KBR as predictors of fulminant hepatitis.

Acoustic Stimulation↗

PubMed1993

Primary mucinous carcinoma of the renal pelvis.

A case of primary mucinous carcinoma originating in the renal pelvis associated with renal lithiasis is reported. The left kidney removed was mostly occupied by mucinous carcinoma with areas of signet ring cell carcinoma. The epithelium covering the pelvis consisted of a single layer of columnar epithelium with scattered goblet cells and mucous glands. A series of careful examinations of the abdominal viscera failed to disclose any other primary lesion. The patient died with multiple peritoneal tumor disseminations eight months after the operation despite additional chemotherapy.

Adenocarcinoma, Mucinous↗

PubMed1993

Cytotoxic activity of spleen-derived T lymphocytes against autologous biliary epithelial cells in autopsy patients with primary biliary cirrhosis.

Autoimmunity against biliary epithelial cells is considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). However, cytotoxic activity of T lymphocytes against biliary epithelial cells has not previously been examined. This study has demonstrated that spleen-derived T lymphocytes were cytotoxic for autologous biliary epithelial cells in all of five patients with PBC, even though it was only detectable at high effector to target ratios. Such cytotoxicity was not found in non-PBC patients. CD8-positive T lymphocytes were shown to be responsible for the cytotoxicity by negative selection, and its inhibition was dependent on the ratio of cold to hot target cells. These observations may support a current hypothesis that the pathogenesis of PBC is partly due to T cell autoimmunity directed against the bile duct epithelium.

Aged↗

PubMed1993

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

Angiotensin II↗

PubMed1993

Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas.

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.

Adult↗

PubMed1993

Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma.

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.

Adult↗

PubMed1993

[Endoscopic correction of vesicoureteral reflux by Teflon].

From March 1988, 19 vesicoureteral reflux (VUR) patients were treated by endoscopic injection of Teflon paste. Of these patients 17 cases 27 ureters were followed for more than one year. After injection of Teflon paste, reflux was eliminated in 63%, decreased in 30%, and unchanged in 7%. Then 7 ureters were injected twice and 1 ureter three times. Finally, reflux was eliminated in 93% of all cases, and decreased in 7%. Early complications were fever up in 4 cases, flank pain 3, acute cystitis 1. In the follow up period, acute cystitis occurred in 1 patient, ureter stone in 1, and renal failure in 1. However, the ureter stone and renal failure were probably not caused by this procedure.

Adult↗