Search PubMed⌕ Search

Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 19 recordsLinked to original sources
PubMed1992

A novel orally active inhibitor of IL-1 generation: synthesis and structure-activity relationships of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acid derivatives.

A new series of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acids was prepared and the inhibitory activities of its members on IL-1 generation were evaluated both by in vitro systems using human monocytes and/or rat exudated macrophages stimulated with LPS, and by an in vivo system using the rat CMC-LPS air-pouch model. Many compounds in this series were found to be potent inhibitors of IL-1 generation both in vitro and in vivo. Structure-activity relationships indicated that in the rat CMC-LPS air-pouch model by oral administration the (Z)-2-substituted propenoic acids with 3-alkoxy, 5-alkyl, and 4-hydroxy substituents on the naphthalene ring exhibit optimal inhibition. Among the compounds evaluated, (Z)-3-(5-ethyl-4-hydroxy-3-methoxy-1-naphthalenyl)-2-methyl-2-propeno ic acid (20a), which inhibited IL-1 generation from human monocytes with an IC50 value of 3.0 microM and had an IC50 value of 1.4 microM for rat exudated macrophages, showed the most potent inhibitory activity in the rat CMC-LPS model by oral administration. Compound 20a also showed antiinflammatory effects in animal models of inflammation.

Acrylates↗
PubMed1992

A silencer-like cis element for the testis-specific phosphoglycerate-kinase-2-encoding gene.

Phosphoglycerate kinase (PGK), a glycolytic enzyme, possesses two isozymes: somatic-type PGK-1 and testis-specific PGK-2, encoded by distinct genes. Tissue-specific expression of the two PGK-encoding genes (Pgk) seems to be transcriptionally controlled, since tissue distribution of the mRNAs coincides well with that of the proteins. In the present study, we determined the cis-acting DNA elements that regulate the transcription of mouse Pgk-2. A transient expression assay of DNAs having various portions of the Pgk-2 upstream region linked to the chloramphenicol acetyltransferase (CAT)-encoding gene (cat) was performed using mouse cell lines that exclusively express Pgk-1. A substantial increase in cat expression was observed when the region between nucleotides (nt) -1404 and -685, relative to the most distal transcription start point at nt +1, was lost. This cis-acting region appeared to function as a silencer, since it repressed cat expression independently of either orientation to or distance from the Pgk-2 promoter. Moreover, the cis element inhibited Pgk-2 transcription with no effect on Pgk-1 transcription in a cell-free system using nuclear extracts of rat liver. These results suggest that a silencer-like negative cis element is responsible, at least partly, for tissue-specific transcription of Pgk-2.

Animals↗
PubMed1992

Single crystal structure of a mixed-chain triacylglycerol: 1,2-dipalmitoyl-3-acetyl-sn-glycerol.

The mixed chain triacylglycerol 1,2-dipalmitoyl-3-acetyl-sn-glycerol was synthesized and its crystal structure was determined to a final reliability factor (R) of 0.11. Two molecules are present in the monoclinic unit cell: space group P2(1); a = 5.375(1), b = 8.286(2), c = 42.96(1) A; beta = 93.30(2) degrees, V = 1910 A3, rho = 1.065 g/cm3, and mu = 5.7 cm-1. The structure is a trilayer: a bilayer of palmitate chains packed in the beta mode (T parallel) and an interdigitated monolayer of acetates. The glycerol backbone and acetate extend roughly linearly from the sn-1 chain. The sn-2 chain bends around the C-2 carbon to lie next to the sn-1 chain. Analysis of the torsion angles indicate that the glycerol conformation of 1,2-dipalmitoyl-3-acetyl-sn-glycerol is markedly different from single acid triacylglycerols and from 1,2-diacyl-sn-glycerols but very similar to 1,2-dimyristoyl-sn-glycero-3-phosphocholine.

Crystallography↗
PubMed1992

Genetic linkage of Werner's syndrome to five markers on chromosome 8.

Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, and patients and their cells show many differences compared with normals. Despite extensive study of the clinical and biochemical features of this disorder, the primary genetic defect remains unknown. We have undertaken a genetic linkage study in an effort to identify the locus of the primary defect. Here we report close genetic linkage of the WS mutation to a group of markers on chromosome 8.

Chromosome Mapping↗
PubMed1992

Hepatic tissue oxygenation as a predictive indicator of ischemia-reperfusion liver injury.

The purpose of this study was to determine whether hepatic tissue oxygenation after ischemia-reperfusion procedures is an indicator for later liver injury. Partial ischemia in the liver was induced by ligating the left pedicles. Rats were divided into two groups according to duration of ischemia: group A (30-min ischemia) and group B (60-min ischemia). Indices of blood oxygenation and blood volume in regional hepatic tissue, serum ALT levels and histological appearance of livers were evaluated. Twenty-four hours after ischemia and reflow, all rats in group A were alive, whereas only 67% survived in group B. Blood-oxygenation index and blood-volume index in group A rats rebounded quickly after reperfusion. In group B, blood-oxygenation index and blood-volume index remained significantly lower than in group A after reperfusion. Serum ALT levels at 60 and 120 min after reperfusion in group B were significantly higher than those in group A. Blood-oxygenation index measured at 5 and 60 min of reperfusion showed significant correlation with serum ALT levels at 120 min of reperfusion. When the percentage recovery of blood-oxygenation index at 5 and 60 min after reperfusion was more than 75%, all rats survived. No obvious signs of hepatocellular degeneration were observed histologically 5 min after reperfusion; however, substantial hepatocellular degeneration had occurred at 120 min of reperfusion in groups A and B. These data indicate that a decline in hepatic tissue oxygenation during the early phase of reperfusion (even when no obvious hepatocellular degeneration has been observed) can be a predictor of subsequent liver injury and prognosis.

Alanine Transaminase↗
PubMed1992

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1992

Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver.

The role of microcirculation in the pathogenesis of alcoholic liver injury was investigated in isolated perfused livers from fed rats. Infusion of ethanol into the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately on initiation of ethanol load and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury, into the effluent perfusate began to increase after 20 to 30 min of ethanol infusion and continued to increase until the end of the experiment (60 min after the initiation of ethanol infusion). The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100 mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly the ethanol-induced increases in portal pressure and lactate dehydrogenase release by abolishing hepatic vasoconstriction. In histological examinations focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei, was detected predominantly in midzonal and pericentral areas of the liver lobule after 60 min of ethanol infusion. Change in portal pressure during 60 min of ethanol infusion correlated significantly with levels of lactate dehydrogenase after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Assessment of portosystemic shunting from superior mesenteric vein by duodenal administration of iodoamphetamine I123.

Portosystemic shunting (PSS) from the superior mesenteric vein (SMV) was evaluated with the duodenal administration of iodoamphetamine I123 (IMP) in patients with chronic hepatitis and liver cirrhosis. After duodenal intubation, IMP was administered through a tube, and then scintigraphy including the pulmonary and hepatic regions was performed. In all patients, images of the liver and/or lungs were observed within 10 min and became clear with time, due to a good absorption of IMP from the intestine. On the other hand, IMP appears not to be absorbed from the stomach. The portosystemic shunt index was calculated by dividing counts of lungs by counts of liver and lungs. The shunt index (mean +/- SE) was 1.5% +/- 0.8%, 12.6% +/- 3.7% and 28.3% +/- 4.5% in chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, respectively. This index was significantly higher in cirrhosis, especially in decompensated cirrhosis. Therefore, transintestinal portal scintigraphy with IMP could be a useful method for the non-invasive and quantitative evaluation of PSS from the SMV in portal hypertension.

Amphetamines↗
PubMed1992

Clinical evaluation of three anti-HCV ELISAs in patients with various liver diseases.

We measured antibodies to hepatitis C virus (HCV) in 380 patients with various liver diseases by three enzyme-linked immunosorbent assays (ELISAs): HCV antibody ELISA test (C100), KCL-163 (KCL) corresponding to the nonstructural protein of HCV, and JCC based on the translation product of the presumptive HCV core gene. Of 233 cases of non-A, non-B (NANB) liver disease, 63.9% were anti-C100 positive, 69.1% were anti-KCL positive, and 79.8% were anti-JCC positive. Detection of serum HCV-RNA in 213 cases of chronic NANB liver disease revealed that the concordance was 80.3% for C100, 86.4% for KCL, 94.8% for JCC, and 95.3% for all three ELISAs. Overall, 85.4% of chronic NANB cases were considered to have type C disease with HCV infection. The most reliable assays for diagnosing chronic NANB liver disease as type C appeared to be the KCL and JCC ELISAs.

Adolescent↗
PubMed1992

In vitro susceptibility of clinical isolates of Bacteroides fragilis and Bacteroides thetaiotaomicron in Japan.

A nationwide survey of the susceptibility of 433 isolates of Bacteroides fragilis and 149 isolates of Bacteroides thetaiotaomicron was conducted from December 1986 through November 1989 in Japan. These strains were collected from 16 university hospitals and one metropolitan hospital. Metronidazole was the most active drug against both species, with no resistant isolates found. The activity of imipenem and sulbactam-cefoperazone was good, with very low resistance rates determined in Bacteroides fragilis (1.4% and 1.6%, respectively) and in Bacteroides thetaiotaomicron (3.4% for both drugs), and was comparable to that of metronidazole. Cefoxitin, cefmetazole, cefotetan, cefbuperazone, latamoxef and ceftizoxime were found to be more active against Bacteroides fragilis, for which resistance rates were 3.2 to 9.5%, than against Bacteroides thetaiotaomicron, for which resistance rates were 18.1 to 21.8%. Rates of piperacillin resistance in the two species were 12.9% and 26.8%, respectively. Clindamycin was very active at a low concentration (MIC50 of 0.39 to 1.56 mg/l), but 24% and 27.5% of Bacteroides fragilis and Bacteroides thetaiotaomicron isolates, respectively, were resistant to this agent.

Anti-Bacterial Agents↗
PubMed1992

Inhibition of acetaminophen hepatotoxicity by acetaldehyde in the rat.

Since we have observed that acetaldehyde, an oxidative metabolite of ethanol, inhibits acetaminophen activation in rat liver microsomes, the in vivo effect of acetaldehyde on acetaminophen hepatotoxicity was tested. In vivo experiments in 3-methylcholanthrene-pretreated male Sprague-Dawley rats showed that administration of cyanamide (20 mg/kg, i.p.) and acetaldehyde (600 mg/kg, s.c.) given 3 and 1 h, respectively, prior to acetaminophen (500 mg/kg, i.p.) but not cyanamide alone prevented acetaminophen hepatotoxicity as assessed by serum transaminases and histology. Acetaldehyde may partly be responsible for the inhibitory effect of ethanol on acetaminophen hepatotoxicity.

Acetaldehyde↗
PubMed1992

Early metabolic effects of sepsis in the preterm infant: lactic acidosis and increased glucose requirement.

The effects of sepsis on carbohydrate metabolism were studied in preterm newborn infants (weight > 1.2 kg, appropriate for gestational age) without maternal endocrine problems who were being examined for infection. Plasma glucose, lactate, and insulin concentrations were measured at initial evaluation and then every 8 hours for a total of 48 hours. Blood, urine, and spinal fluid were obtained for culture and counterimmunoelectrophoresis. Dextrose was administered to each patient to maintain glucose levels in the normal range. Dextrose infusion rates were calculated in milligrams per kilogram per minute. Of the 29 infants, 6 had sepsis (positive culture and counterimmunoelectrophoresis results). Infants with sepsis had significant elevations of plasma lactate concentration (p < 0.003) but normal pH. The dextrose infusion rate was also significantly elevated in the infected infants (p < 0.01). No hypoglycemia or hyperglycemia was observed in either group. No significant difference in plasma insulin concentration was observed. We conclude that significant elevations in plasma lactate concentrations and dextrose infusion rate may be early clinical markers of neonatal sepsis in the first 48 hours of life.

Acidosis, Lactic↗
PubMed1992

Chromaticity analysis of immunostained tumor specimens.

In order to evaluate the correlation between immunohistochemical and morphometric data on the same histological sections, we have developed a flexible color image analyzer (Microcomputer-Assisted Picture Processing System type II, MAPPS-II), and established an effective method to analyze the immunostained colorectal neoplasms based on the color recognition theory of human visual system. Colorectal adenomas and adenocarcinomas were stained with a monoclonal antibody C 12, which recognizes abnormal H antigen, using Avidin-Biotin method and diaminobenzidine (DAB, brown dye). Nuclei were stained with Hematoxylin (blue dye). Density and colorimetric analyses revealed two results: (A) Separation of immunostained brown area from blue nuclei was best performed by plotting the representative sample areas on a standard chromaticity diagram, which displays the hue and saturation of colors simulating color of human visual system. (B) After separation of immunostained areas, usual density analysis was useful for the assay of nuclear morphometric information. Using these programs, normal mucosa was negative for C 12, and showed low nuclear/cytoplasmic ratio (NCR). Adenoma was occasionally focally positive for C 12, and showed medium NCR. Carcinomas were C 12 positive, and showed high NCR. Our method permits nuclear counterstaining by hematoxylin instead of low contrast methyl green, which will widen the field of combined immunohistochemical and morphometric study.

Adenocarcinoma↗
PubMed1992

Immunohistological quantitative analysis of S100 protein-positive cells in T-cell malignant lymphomas, especially in adult T-cell leukemia/lymphomas.

S100 protein-positive cells (S100+ cells) in 36 cases of T-cell lymphoma (T-ML) in the lymph node and 15 cases of T-ML in the skin were analyzed immunohistologically in order to study their quantitative features in adult T-cell leukemia/lymphoma (ATLL). The T-MLs were categorized according to the updated Kiel classification, and the T-cell pleomorphic type (Pleo) was subcategorized into 3 subtypes: Pleo-ATLL, Pleo-clear and Pleo-others. The population of S100+ cells and the first to fifth minimal distances of every S100+ cell were measured on micrographs of paraffin sections that had reacted to anti-S100 protein antibody according to the ABC method. Lymphoblastic and chronic lymphocytic leukemia types showed low populations of S100+ cells and long values of the first minimal distance. T-zone lymphoma without follicles and angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML had high populations and low values of the first minimal distance. Among the three subtypes of Pleo in the lymph node, Pleo-ATLL gave the highest population and the shortest value of the first minimal distance of S100+ cells, but this trend was not found in the skin. Clusters of more than five S100+ cells were more common in the Pleo-ATLL subtype than in the other two subtypes. The increase and clustering of S100+ cells in Pleo-ATLL suggests that the lymphoma cells act on S100+ cells as a helper.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Computer-Assisted↗
PubMed1992

Atrial contractility affects phasic blood flow velocity of atrial small vessels in the dog.

OBJECTIVES: The aim was to evaluate the relative contribution of atrial muscle contraction and atrial pressure to the phasic patterns of left atrial arterial and venous flows. METHODS: Using a laser Doppler velocimeter, blood velocities were measured in the atrial small arteries and veins (outer diameter: 150-500 microns) in anaesthetised open chest dogs (n = 21). The velocity sensor was fixed on the vessel surface with a drop of cyanoacrylate glue when good quality Doppler signals were consistently observed. Left atrial pressure and the contractility of the left atrium were changed by premature ventricular contraction and by intracoronary injection of isoprenaline (0.5 microgram), respectively. RESULTS: Premature ventricular contraction increased left atrial pressure significantly during arterial velocity measurements from 8.1(SD 2.7) to 16.4(1.3) mm Hg and during venous measurements from 8.2(1.2) to 14.3(3.7) mm Hg. However, premature ventricular contraction did not change the blood velocity patterns, the maximum deceleration rate of the systolic velocity wave in arteries, or the maximum acceleration rate of the systolic velocity wave in veins. Although isoprenaline did not change the left atrial pressure, it decreased minimum arterial blood velocity during atrial systole, from 3.3(3.4) to -2.5(3.2) cm.s-1, and increased maximum venous blood velocity from 15.9(5.5) to 19.2(7.4) cm.s-1. Isoprenaline also increased both the maximum arterial systolic velocity deceleration rate, from 90(45) to 234(143) cm.s-2, and the maximum venous systolic velocity acceleration rate from 356(230) to 763(366) cm.s-2. CONCLUSIONS: (1) Left atrial pressure is not a major determinant of the blood flow patterns of the atrial arteries and veins, and therefore it may not closely reflect pressure around mural vessels. (2) Atrial contractility affects the blood flow patterns of the atrial arteries and veins.

Animals↗
PubMed1992

Portal vein aneurysm demonstrated by blood pool SPECT.

Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts.

Adult↗
PubMed1992

Prolonged survival of rat hepatic allografts after total-body irradiation of the donors.

The effect of total-body irradiation of the donor on hepatic allograft survival was studied in the rat, with ACI(RT1a) as the donor and LEW(RT1(1)) as the recipient. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of only 10.2 +/- 0.3 days. The doses of irradiation were 450, 750, and 1000 rads administered 24 hr prior to harvesting or subsequent transplantation. TBI with a dose of 750 rads significantly prolonged the survival of the hepatic allograft to 30.3 +/- 1.7 days, without concomitant immunosuppression. However, neither 450 rads nor 1000 rads of TBI resulted in successful suppression of graft rejection. TBI appeared to have a beneficial effect on hepatic allograft survival and to have no deleterious effect on isograft survival, suggesting a possible modulation of the immunogenicity of the donor organ. Although the cause of this beneficial effect is not clear, TBI with a dose of 750 rads 24 hr prior to organ harvest seems to be optimal to eliminate-antigen presenting cells in the donor organs.

Animals↗