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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 577 records · Page 32Linked to original sources

Asymptomatic constant isolated proteinuria in children.

The clinical features, renal biopsy findings, and subsequent course in 53 children with asymptomatic constant isolated proteinuria were studied retrospectively (1) to determine the prevalence of renal pathologic abnormalities among these children, (2) to identify those clinical characteristics that may enable recognition of children with an increased likelihood of having renal pathologic abnormalities, and (3) to assess the clinical course. All biopsy specimens were examined by light, immunofluorescence, and electron microscopy. Twenty-five patients (47%) had significant glomerular changes (15 had focal segmental glomerulosclerosis, 4 IgA nephropathy, 3 diffuse mesangial proliferative glomerulonephritis without IgA deposition, and 3 membranous glomerulonephritis), and 28 had minimal glomerular changes. There were no differences between the patients with significant glomerular changes and those with minimal glomerular changes with regard to clinical and laboratory findings except for a predominance of boys in the former group. At the latest follow-up, seven patients with significant glomerular changes, but none with minimal glomerular changes, had chronic renal impairment. Because of the high incidence of significant glomerular changes and the high rate of progression to chronic renal impairment, we believe that a renal biopsy is indicated for a child with asymptomatic constant isolated proteinuria.

Adolescent↗

Urinary excretion of endothelin-1 in normal subjects and patients with renal disease.

To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity (L1) in 17 patients with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-L1 excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was significantly (P less than 0.005) greater than that of normal subjects (77 +/- 5 ng). In patients with renal disease. ET-1-L1 clearance (CET) exceeded creatinine clearance (CCR); CET/CCR (305 +/- 81%) was significantly (P less than 0.005) greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion of ET-1-L1 in patients with renal disease showed significant correlation with that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P less than 0.05), beta 2-microglobulin (r = 0.614, P less than 0.01) and albumin (r = 0.484, P less than 0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not affect urinary ET-1 excretion rate. These data suggest that urinary excretion of ET-1 derives mainly from renal tubular secretion at least in patients with renal disease, and that degradation and/or reabsorption of ET-1 at the tubular site may also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET-1 should serve as a potential marker for renal injury.

Acetylglucosaminidase↗

Locus coeruleus stimulation exerts different influences on the dynamic changes of cerebral pial and intraparenchymal vessels.

The present experimental study was undertaken to investigate the effects of locus coeruleus stimulation on the dynamic changes of intraparenchymal vessels and pial vessels. Twelve cats were anaesthetized with alpha-chloralose and urethane. For stimulation of the locus coeruleus, a concentric stainless-steel needle electrode was inserted stereotaxically. During the stimulation, volumetric changes of the intraparenchymal vessels were monitored by a photoelectric method for estimating the cerebral blood volume (CBV) (6 cats), and the diameters of pial arteries were measured continuously using a video camera system (6 cats). The CBV followed a decreasing course during the stimulation of the locus coeruleus. The decrease in CBV from the control value (6.3 vol%) was 0.14 +/- 0.04 vol% at 80 s (p less than 0.05), 0.15 +/- 0.05 vol% at 100 s (p less than 0.05), and 0.15 +/- 0.03 vol% at 120 s (p less than 0.01). After cessation of the stimulation, CBV showed a gradual recovery. On the other hand, the diameters of the pial arteries did not change during or after the stimulation of the locus coeruleus. The above results suggest that the locus coeruleus has a vasoconstrictive effect on the intraparenchymal vessels, although it exerts no apparent influence on the pial arteries.

Animals↗

Isolation and characterization of major urinary oligosaccharides excreted by a patient with type 3 GM1 gangliosidosis.

Two major oligosaccharides were isolated from the urine of a patient with type 3 GM1 gangliosidosis. From structural studies including compositional sugar analysis, fast-atom bombardment mass spectrometry, direct-inlet chemical ionization mass spectrometry, methylation analysis, chromium trioxide oxidation, and proton magnetic resonance spectroscopy, their structures were deduced to be as follows: [formula: see text] Both oligosaccharides have beta-linked galactose at the non-reducing ends. Oligosaccharide 1 is one of the most common urinary oligosaccharides found in type 1 and type 2 GM1 gangliosidosis. Oligosaccharide 2, lacto-N-difucohexaose II, has not been described in the urine of GM1 gangliosidosis patients. Excretion of oligosaccharide 1 in the type 3 patient was much less than that of a type 2 patient. Thin-layer chromatographic analysis revealed that the excretion of oligosaccharides with higher molecular weight than that of oligosaccharide 1 (octasaccharide) in the type 3 patient was much less than that of a type 2 patient, raising the possibility that the mutant beta-galactosidase of type 3 GM1 gangliosidosis can still act to some extent on higher molecular weight oligosaccharides containing beta-linked galactose at the non-reducing end.

Carbohydrate Conformation↗

Expression of CD45R0 (UCHL1) by CD4+ and CD8+ T cells as a sign of in vivo activation in infectious mononucleosis.

CD45R0 (UCHL1), a member of leucocyte common antigen family, is expressed largely on previously activated or memory T cells. We examined CD45R0 expression of T cell subpopulations in patients with Epstein-Barr virus (EBV) induced infectious mononucleosis (IMN) as a sign of in vivo activation. Consistent with the notion that activated CD8+ T cells expand in acute IMN; the majority of CD8+ T cells in patients with acute IMN expressed CD45R0 to the similar extent to HLA-DR expression. Most CD4+ T cells in these patients also demonstrated marked expression of CD45R0 as well as HLA-DR antigens, compared with age-matched controls. Expression of CD45R0 by CD4+ T cells in patients with acute IMN was more notable than their HLA-DR expression. While predominant CD8+ T cells resulted in decreased percentages of CD4+ T cells, CD4+ T cells expressing CD45R0 were shown to be significantly elevated in absolute number. The results suggest that both CD4+ and CD8+ T cells may be activated by stimulation with EBV infection. The appearance of two T cell subpopulations expressing CD45R0 in acute IMN implies their immunoregulatory roles in the control of EBV-infected cells.

Antigens, CD↗

Metabolic engineering of Klebsiella oxytoca M5A1 for ethanol production from xylose and glucose.

The efficient diversion of pyruvate from normal fermentative pathways to ethanol production in Klebsiella oxytoca M5A1 requires the expression of Zymomonas mobilis genes encoding both pyruvate decarboxylase and alcohol dehydrogenase. Final ethanol concentrations obtained with the best recombinant, strain M5A1 (pLOI555), were in excess of 40 g/liter with an efficiency of 0.48 g of ethanol (xylose) and 0.50 g of ethanol (glucose) per g of sugar, as compared with a theoretical maximum of 0.51 g of ethanol per g of sugar. The maximal volumetric productivity per hour for both sugars was 2.0 g/liter. This volumetric productivity with xylose is almost twice that previously obtained with ethanologenic Escherichia coli. Succinate was also produced as a minor product during fermentation.

Carboxylic Acids↗

Genetic improvement of Escherichia coli for ethanol production: chromosomal integration of Zymomonas mobilis genes encoding pyruvate decarboxylase and alcohol dehydrogenase II.

Zymomonas mobilis genes for pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adhB) were integrated into the Escherichia coli chromosome within or near the pyruvate formate-lyase gene (pfl). Integration improved the stability of the Z. mobilis genes in E. coli, but further selection was required to increase expression. Spontaneous mutants were selected for resistance to high level of chloramphenicol that also expressed high levels of the Z. mobilis genes. Analogous mutants were selected for increased expression of alcohol dehydrogenase on aldehyde indicator plates. These mutants were functionally equivalent to the previous plasmid-based strains for the fermentation of xylose and glucose to ethanol. Ethanol concentrations of 54.4 and 41.6 g/liter were obtained from 10% glucose and 8% xylose, respectively. The efficiency of conversion exceeded theoretical limits (0.51 g of ethanol/g of sugar) on the basis of added sugars because of the additional production of ethanol from the catabolism of complex nutrients. Further mutations were introduced to inactivate succinate production (frd) and to block homologous recombination (recA).

Acetyltransferases↗

Monoclonal antibody against Porphyromonas (Bacteroides) endodontalis lipopolysaccharide and application of the antibody for direct identification of the species.

The aim of the present study was to develop a monoclonal antibody that recognizes the shared antigen of Porphyromonas endodontalis so that we could use the antibody in direct identification and detection of P. endodontalis in infectious material from apical periodontal patients. We established a hybridoma cell line producing monoclonal antibody (BEB5) specific for P. endodontalis. BEB5 antibody reacted with all of the P. endodontalis strains tested, but not with any of the other black-pigmented Porphyromonas and Bacteroides spp. The antibody reacted specifically with the lipopolysaccharide (LPS) of three P. endodontalis strains of different serotypes (O1K1, O1K2, and O1K-). Western blotting (immunoblotting) analysis confirmed the specificity of the antibody to these LPSs, because the antibody recognized the typical "repetitive ladder" pattern characteristic of LPS on sodium dodecyl sulfate-polyacrylamide electrophoretic gels. These observations demonstrate that P. endodontalis LPS is the shared antigen of this species. The antibody can specifically identify P. endodontalis on nitrocellulose membrane blots of bacterial colonies grown on agar. The antibody is also capable of directly detecting the presence of P. endodontalis in infectious material by immunoslot blot assay. These results indicate that LPS is the shared antigen of P. endodontalis and that BEB5 antibody against LPS is a useful one for direct identification and detection of the organisms in samples from apical periodontal patients.

Animals↗

Cellular mechanism of endothelin-1 release by angiotensin and vasopressin.

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependently stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin II-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V1-receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Hypothalamic histiocytosis X with diabetes insipidus and Korsakoff's syndrome--case report.

A 54-year-old female presented with apparent isolated hypothalamic histiocytosis X associated with diabetes insipidus and Korsakoff's syndrome. Computed tomographic and magnetic resonance imaging demonstrated a single hypothalamic mass. A craniotomy for biopsy found granulation tissue of unknown cause. Further investigation discovered genital bleeding before admission. Biopsy of the cervix uteri revealed histiocytosis X. Further studies showed the disease was restricted to the hypothalamus and the endometrium of the cervix uteri. Low-dose irradiation led to partial regression of the hypothalamic mass and improvement of Korsakoff's syndrome. Even when a diagnosis of isolated hypothalamic histiocytosis X is confirmed, the possibility of another histiocytosis X lesion in an unexpected region must be considered.

Alcohol Amnestic Disorder↗

Monoclonal antibody against platelet thrombospondin decreases erythrocyte aggregation rate.

The effect of thrombospondin, a major glycoprotein in the platelet alpha-granule, on the erythrocyte aggregation rate was investigated. Venous blood was sampled from 8 healthy male volunteers and anticogulated with 1.1 mg/ml EDTA(K2). The erythrocyte aggregation rate of each blood sample was measured with a whole-blood erythrocyte aggregometer before and after incubation with murine monoclonal antibody against human platelet thrombospondin. After 15 min incubation, the erythrocyte aggregation rate exhibited a significant decrease to 0.055 +/- 0.022/s, representing 71.9 +/- 8.7% of the control value (0.075 +/- 0.028/s) (p less than 0.0005). The results obtained suggest that thrombospondin may participate in the control of erythrocyte aggregability in the circulating blood.

Antibodies, Monoclonal↗

Individual custom-designed modelling for the finite element method to be used in the forward calculation of a body surface isopotential map.

Body surface potential maps differ considerably in their pattern even among normals, depending upon torso configuration. Thus individualized modelling of the heart-torso model is certainly desirable for a forward problem if it can be achieved without much effort. In this paper such a heart-torso model which is flexible enough to adapt to different body shapes with ease will be reported. As its basic structure, the innermost sphere represents the electromotive force of the heart, the outermost ellipsoid surface representing the torso surface and nine similar ellipsoid surfaces intervening between the two with step-wise increasing diameters were considered. We made 98 radiating penetration points for the innermost sphere as well as the 10 intervening ellipsoid surfaces. By making use of neighboring points of penetration as corners, the heart-torso model was divided into 4992 tetrahedral elements for a finite element method calculation. Once this basic structure was established, it was found to be very easy to be modified in a computer in order to make it fit to individual torso configurations quite faithfully by deforming the outermost ellipsoid. Individualized torso-heart models were built and their maps were simulated using data obtained from several healthy subjects. This paper discusses the results of two individuals, one muscular and the other slender, who exhibited considerably different body surface potential maps.

Adult↗

Immunological detection of the dystrophin molecule with antibody directed against the synthetic peptide.

We synthesized a peptide designated R8 (amino acid residues 1157-1201) based on the primary structure presumed from the nucleotide sequence of the cDNA clone from the gene for Duchenne muscular dystrophy. Antibody to the synthetic R8 generated by immunization of rabbits was tested on human and mouse skeletal muscle by Western blotting analysis. The antibody reacted with a component of the 400K dystrophin of normal human and mouse skeletal muscles, but not with components of the muscles of Duchenne muscular dystrophy patients and mdx mice. Thus we established that this peptide sequence is in fact missing in the protein product 'dystrophin' encoded by the DMD gene. The antibody may prove useful for the diagnosis of the Duchenne types of muscular dystrophy.

Amino Acid Sequence↗

Eosinophilic peritonitis responding to treatment with glycyrrhizin.

A 63-year-old man with diabetes mellitus for 15 years was admitted to our hospital in 1990 because of end-stage renal failure. Five days after beginning continuous ambulatory peritoneal dialysis (CAPD) he developed an eosinophilic peritonitis (EP). With protein loss in the dialysate and a decreased serum albumin level, the patient developed ankle edema. The patient was treated with glycyrrhizin, and his EP resolved. It is suggested that an allergic background may play an important role in the development of EP in patients on CAPD.

Anti-Inflammatory Agents, Non-Steroidal↗

[Phase I study of CI-898. CI-898 Study Group].

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).

Adult↗