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Biomedical subjects

Y Fukumoto

Publications and source records attributed to Y Fukumoto.

At least 91 records · Page 5Linked to original sources

Secretin prevents taurocholate-induced intrahepatic cholestasis in the rat.

Secretin is known to stimulate the flow of bicarbonate-rich bile from the bile-duct epithelium, but has no effect on hepatocytes. To investigate the effects of secretin on bile production during intrahepatic cholestasis, we infused secretin into rats with taurocholate-induced cholestasis. Secretin was given at 0.25 and 0.50 units.min-1.kg-1 to Wistar rats that simultaneously received a continuous infusion of taurocholic acid at above its maximum hepatic transport capacity to produce cholestasis. When taurocholic acid was infused at doses of 1.4 and 1.6 mumol.min-1.100 g b.w.-1, bile volume decreased in control rats. In contrast, the simultaneous infusion of secretin significantly increased bile flow and the biliary excretion of bile acids and bicarbonate. The serum taurocholic acid level at the end of the experiment was significantly lower in the secretin-treated groups than in the control group. These findings indicate that secretin prevents taurocholate-induced cholestasis and may enhance the biliary excretion of bile acids.

Animals↗

Abducent nerve paralysis during interferon alpha-2a therapy in a case of chronic active hepatitis C.

A 59-year-old woman with chronic active hepatitis C was treated with recombinant human interferon alpha-2a. After three days of administration, the patient complained of diplopia with dizziness and head heaviness. Ophthalmic examinations revealed a disturbance of the movement of left eye ball to the outer side without any other neurological signs. The diplopia, which was diagnosed as abducent nerve paralysis, improved rapidly and reversed at about 6 weeks after discontinuation of interferon and during infusion of hydrocortisone. To our knowledge, this is the first report of abducent nerve paralysis associated with alpha-2a interferon.

Abducens Nerve↗

[123I-OIH renoscintigraphy in children with chronic disorder of glomerulus].

To evaluate the usefulness of 123I-orthoiodohippurate (OIH) renography, 31 patients with chronic disorder of glomerulus, from 5 years to 15 years old, were studied. In chronic glomerulonephritis and nephrotic syndrome with resistance to steroid therapy, Tmax and T 1/2 of the time-activity curve were statistically prolonged. Most of the renograms (time-activity curves) of the patients showed the hypofunction pattern. In most of the patients, other laboratory data, including BUN, PSP test and creatine clearance, didn't show abnormal values. 123I-OIH scan was considered to be a sensitive and useful method to evaluate the renal function in pediatric patients with chronic glomerulonephritis.

Adolescent↗

Functional roles of valine 37 and glycine 38 in the mobile loop of porcine cytosolic aspartate aminotransferase.

The functional roles of Val37 and Gly38 in porcine cytosolic aspartate aminotransferase have been studied in the site-directed mutants V37A, G38A, and G38S where the size and hydrophobic character of these residues has been altered. Previous x-ray studies have shown that Val37 and Gly38, which are part of a flexible loop, interact directly with bound substrate. From x-ray and solution experiments we find that the V37A, G38A, and G38S mutations do not cause significant perturbations to the unliganded enzyme. Replacing Val37 with a less bulky alanine residue does not affect the maximal catalytic rate (kcat), but it does increase significantly the Michaelis constants for substrates in the overall transamination reaction between aspartate and 2-oxoglutarate. On the other hand, replacing Gly38 with alanine or serine results in striking decreases in kcat to 5 and 0.6%, respectively, of the value observed for the wild-type enzyme, as well as in considerable increases in Km values. Consequently, the catalytic competence, kcat/Km, decreases by 3 orders of magnitude for G38A and by 4 orders of magnitude for G38S. Single turnover reactions of G38A and G38S with four individual substrates (aspartate, glutamate, oxalacetate, and 2-oxoglutarate) are characterized by kinetic parameters that are largely consistent with those of the overall reaction. In addition, the mutations at position 38 impair more seriously the catalytic competence of the enzyme toward C5-substrates than toward C4-substrates. We conclude that Gly38 is probably required for proper function of the enzyme because it permits a high level of flexibility for the 36-39 peptide, which in turn allows the essential substrate-induced movement of the small domain.

Amines↗

The reversal effect of insulin on diabetes-induced alterations in beta adrenergic and muscarinic receptors in rat prostate.

Previous studies from our laboratory demonstrated that 8 weeks after the induction of diabetes by the administration of streptozotocin (STZ) there was a downregulation of beta adrenergic and muscarinic cholinergic receptors in rat prostate, and that early insulin treatment (started 3 days after the onset of diabetes) prevented these alterations from occurring. In the present study, the effects of later insulin treatment (started 8 weeks after the onset of diabetes) on the reversibility of diabetes-induced alterations in beta adrenergic and muscarinic receptors in rat prostate were investigated. Three groups of rats were maintained for 16 weeks: 1) diabetics, 2) insulin-treated diabetics (subcutaneously injected with 5 to 8 U per day starting 8 weeks after the onset of diabetes) and 3) age matched controls. Binding studies with [3H]dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB) showed a significantly lower density of beta adrenergic and muscarinic cholinergic receptors in the diabetic rat prostate than in prostate from either controls or insulin-treated diabetic animals. Inhibition of [3H]DHA binding by isoproterenol, a beta adrenergic agonist, and binding of [3H]QNB by carbachol, a muscarinic agonist, indicated the presence of low and high affinity agonist binding sites for each receptor. The relative proportion of high affinity to total binding sites as well as the low and high affinity constants were similar in all groups. These data indicate that insulin treatment, begun 8 weeks after the onset of diabetes, can reverse the diabetes-induced downregulation of both beta adrenergic and muscarinic cholinergic receptors in STZ-diabetic rat prostates.

Animals↗

Primary liposarcoma of the omentum.

This report is of a 54 year old female with omental liposarcoma. Diagnosis was made by ultrasonography, computed tomography, angiography and operation. The patient was treated by surgical excision. The histological examination revealed that the tumour was round cell liposarcoma. This is the first report to our knowledge of round cell liposarcoma of the omentum.

Angiography↗

Prognostic significance of atrial fibrillation in dilated cardiomyopathy.

We evaluated the relation of atrial rhythm to a clinical course of treatment in 147 patients diagnosed with dilated cardiomyopathy (DCM). Thirty-six of the patients (24%) had either transient (9 patients) or persistent (27 patients) atrial fibrillation (AF). Compared with DCM patients with sinus rhythm (SR), the AF patients did not differ in age, left ventricular (LV) dimension, fractional shortening, or hemodynamic parameters, but the AF patients had slightly larger left atria. After a mean follow-up of 3.8 +/- 2.9 years, the NYHA functional classifications in the AF patients improved in 20 of the 36 (56%), whereas those of the SR patients improved in only 30 (27%) (p < 0.01). The actuarial 5-year survival rate was significantly better for AF patients than for SR patients (93% versus 68%, p < 0.05). LV function remained unchanged in SR patients but improved significantly in AF patients, particularly in patients with transient AF and with "rate-controlled" AF (those with a mean heart rate of less than 90 beats/min). This study suggests that atrial fibrillation may result in significant LV dysfunction, which is reversible in some cases once the arrhythmia is controlled. Aggressive antiarrhythmic therapy should be considered for patients initially diagnosed with dilated cardiomyopathy and atrial fibrillation.

Actuarial Analysis↗

Single crystals of bovine heart cytochrome c oxidase at fully oxidized resting, fully reduced and CO-bound fully reduced states are isomorphous with each other.

Fully reduced and CO-bound fully reduced forms of cytochrome c oxidase from beef heart muscle were crystallized in the presence of sodium ascorbate under N2 or CO atmosphere. Hexagonal bipyramidal and tetragonal crystals were obtained for both forms depending on buffer species. The hexagonal bipyramidal crystals, as large as 0.6 mm in the largest dimension, diffracted X-rays at 7 A resolution, showing an identical space group and cell dimension, P6(2) or P6(4) and a = b = 209 A, c = 283 A, respectively. These parameters coincide with those for crystals of the fully oxidized resting enzyme. This result suggests that a large conformational change, like a subunit arrangement, is not induced by the redox change and/or binding of CO (and possibly O2) to heme a3.

Anaerobiosis↗

Effects of secretin on bile production in two kinds of cholestatic models by choledocho-caval fistula and bile duct ligation in rats.

Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24-hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance.

Animals↗

Analysis of lymphoid follicles in liver of patients with chronic hepatitis C.

Using immunohistological methods, we studied the lymphoid follicles in liver biopsy specimens obtained from patients with chronic hepatitis C(CH-C) to determine whether they represented an autoimmune manifestation. In 84 specimens obtained by liver biopsy from 76 patients positive for C-100 antibody, we assessed the presence or absence of lymphoid follicles within the portal areas, and then compared the clinical and immunohistological profiles of the two groups defined on this basis. There were no significant differences in the serological and clinical profiles of the two groups, but the T4:T8 cell ratio within the portal areas differed significantly. A T4:T8 cell ratio > 1.0 was more common in the specimens containing lymphoid follicles. This finding resembled the distribution of T cell subpopulations in the portal areas of patients with autoimmune hepatitis, and suggested that lymphoid follicles may be worth investigating to elucidate the relationship between chronic hepatitis C and autoimmune hepatitis.

Autoimmune Diseases↗

Partial anomalous pulmonary venous return showing anomalous venous return to the azygos vein.

Partial anomalous pulmonary venous return (PAPVR) is a congenital heart disease with a reported incidence of autopsied case. The location of the anomalous pulmonary venous return is usually the right atrium, superior vena cava (SVC), and sometimes the brachiocephalic vein, inferior vena cava (IVC) or coronary venous sinus. Recently we experienced a rare case of PAPVR showing anomalous right total pulmonary venous return to the azygos vein. Furthermore, downward translocation of the right upper lobe bronchus was evident. This rare case is reported along with a review of the related literature.

Azygos Vein↗

[A case of isolated absence of the right pulmonary artery].

A 40-year-old woman was admitted to our hospital for investigation of an abnormal chest roentgenogram. She had been well with normal exercise tolerance and had no history of pneumonia. The chest roentgenogram showed decreased vascularity of the right lung, ipsilateral small hemithorax, and shift of the mediastinum toward the right. In the right lung field, hazy and confluent micronodular shadows were seen, and the left lung was emphysematous and hyperlucent. Herniation of the left lung into the contralateral thorax was seen. Although lung perfusion scintigrams showed no detectable blood flow to the right lung, a krypton ventilation study revealed diminished but homogeneous ventilation of the ipsilateral lung. A bronchogram showed normal structure of the bronchi. Cardiac catheterization revealed normal pulmonary arterial pressure. A pulmonary angiogram showed no right pulmonary artery, and absence of other cardiovascular anomalies. Therefore, the diagnosis of isolated absence of the right pulmonary artery was confirmed. An aortic angiogram demonstrated collateral vessels originating from one of the bronchial arteries, the infradiaphragmatic artery, and the right coronary artery. Chest CT disclosed cystic changes in the right lung field.

Adult↗

Structural and functional role of the amino-terminal region of porcine cytosolic aspartate aminotransferase. Catalytic and structural properties of enzyme derivatives truncated on the amino-terminal side.

In porcine cytosolic aspartate aminotransferase, a dimeric enzyme, the amino-terminal region anchoring onto the neighboring subunit is linked to the adjoining floppy peptide segment (residues 12-47), an integral part of the small domain whose facile movement upon substrate binding is a striking "induced fit" feature of this enzyme. To assess the contribution by the amino-terminal region to small domain movement and protein stability, a series of enzyme derivatives truncated on the amino-terminal side (residues 1-9) was prepared by using oligonucleotide-directed in vitro mutagenesis. Deletion of residues 1-3 showed no effect on catalytic activity and heat stability. Del 1-5 mutant enzyme with an extra methionine at position 5 showed only 43% of the kappa cat value (in the overall transamination) of the wild-type enzyme. Further deletion up to residue 9 resulted in a slight decrease in kappa cat values. Del 1-9 mutant enzyme still retained a kappa cat value of 33% that of wild-type enzyme. Km values for aspartate and 2-oxoglutarate increased sharply upon deletion of residues 1-9. Accordingly, Del 1-9 mutant enzyme showed a striking decrease in the kappa cat/Km value, to only 2% of that for the wild-type enzyme. Deletion of amino-terminal residues 1-9 resulted also in a large decrease in thermostability and in an enhanced susceptibility to limited proteolysis by protease 401, which is known to cleave at Leu20 of the wild-type enzyme. These findings indicate that an increase in the conformational freedom of the floppy segment (residues 12-47) would occur upon the loss of most of the anchorage region, thereby presenting an entropic barrier to conformational changes that facilitate substrate binding with high affinity.

Amino Acid Sequence↗

Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like small GTP-binding proteins) and characterization of stimulatory GDP/GTP exchange protein.

We have recently purified to near homogeneity the stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like GTP-binding proteins) from bovine brain cytosol. This regulatory protein, named GDP dissociation stimulator (GDS), stimulates the GDP/GTP exchange reaction of smg p21s by stimulating the dissociation of GDP from and the subsequent binding of GTP to them. In this study, we have isolated and sequenced the cDNA of smg p21 GDS from a bovine brain cDNA library by using an oligonucleotide probe designed from the partial amino acid sequence of the purified smg p21 GDS. The cDNA has an open reading frame encoding a protein of 558 amino acids with a calculated Mr value of 61,066, similar to the Mr of 53,000 estimated for the purified smg p21 GDS by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sucrose density gradient ultracentrifugation. The isolated cDNA is expressed in Escherichia coli, and the encoded protein exhibits smg p21 GDS activity. smg p21 GDS is overall hydrophilic, but there are several short hydrophobic regions. The smg p21 GDS mRNA is present in bovine brain and various rat tissues. smg p21 GDS has low amino acid sequence homology with the yeast CDC25 and SCD25 proteins, which may regulate the GDP/GTP exchange reaction of the yeast RAS2 protein, but not with ras p21 GTPase-activating protein, the inhibitory GDP/GTP exchange proteins (GDP dissociation inhibitor) for smg p25A and rho p21s, and the beta gamma subunits of heterotrimeric GTP-binding proteins such as Gs and Gi.

Amino Acid Sequence↗