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Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 811 records · Page 45Linked to original sources
PubMed1991

The pattern of vasopressin-induced reduction in biliary output of cholephilic probes in the rat can be mimicked by dialysis.

During a recent study using isolated perfused rat liver, we concluded that the effects of vasopressin on biliary excretion of several anionic and cationic cholephilic probes could best be explained by passive diffusion of these probes through a paracellular pathway with permeability increased by vasopressin. Replication of the results of that study in an in vitro dialysis system would support the passive nature of the selective efflux of these cholephilic probes from the rat biliary tree and render metabolic events an unlikely explanation for the biliary excretory patterns of the probes. We studied biliary excretion of two bile acids-taurodehydrocholate and taurocholate-and two cholephilic cations-propidium and tributyl-methylammonium-perfused single-pass through the isolated rat liver. We collected bile and measured probe output before and during infusion of 10(-8) mol/L vasopressin. We also studied rates of diffusion of these probes in artificial solution and in whole rat bile through a 3,500 mol wt cut-off cellulose dialysis membrane. The relative order of probe efflux rates from the biliary tree with vasopressin administration paralleled their diffusion rates through the dialysis membrane. The only exception was that the biliary tree manifested charge selectivity. The data are compatible with the passive efflux of probe from the biliary tree, and metabolic events need not be invoked to explain their pattern of biliary excretion with vasopressin administration.

Animals↗
PubMed1991

Transport of free fatty acid and triglyceride in anhepatic rats.

Without a liver the fractional plasma removal of free fatty acid is one third and chylomicron triglyceride one half of that in the intact rat. The intestine of the anhepatic rat converted enteral fatty acid to plasma triglyceride but was unable to do the same for plasma free fatty acid. This decrease in plasma free fatty acid removal and the inability to recycle the acid as triglyceride were, in part, responsible for the conversion of large fractions of plasma triglyceride flux to the plasma free acid in hepatectomized rats. Increased intravascular triglyceride lipolysis resulting from high circulating lipoprotein lipase concentrations and reduced plasma triglyceride removal were other factors shifting the partition of anhepatic plasma fatty-acid transport from the ester to the free. After the anhepatic plasma clearance of either free fatty acid or triglyceride, relatively more of both compounds was recovered in the lipid of actively metabolizing (heart and muscle) as opposed to storage (adipose) tissue when compared with controls. Sequential evaluations of the recovery of plasma free fatty acid and triglyceride in tissues of anhepatic rats demonstrated accumulation or storage solely in adipose tissue and only when the plasma fatty acid was in triglyceride. This observation and the large conversion of anhepatic circulating triglyceride to the free acid may, in part, explain the lack of an increase in adipose lipid with reduced hepatic mass. The data help explain the preferential use of a lipid fuel in liver disease and the difficulties in obtaining carbon storage in this condition.

Animals↗
PubMed1991

Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment.

A new principle of sensorimotor control of legged locomotion in an unpredictable environment is proposed on the basis of neurophysiological knowledge and a theory of nonlinear dynamics. Stable and flexible locomotion is realized as a global limit cycle generated by a global entrainment between the rhythmic activities of a nervous system composed of coupled neural oscillators and the rhythmic movements of a musculo-skeletal system including interaction with its environment. Coordinated movements are generated not by slaving to an explicit representation of the precise trajectories of the movement of each part but by dynamic interactions among the nervous system, the musculo-skeletal system and the environment. The performance of a bipedal model based on the above principle was investigated by computer simulation. Walking movements stable to mechanical perturbations and to environmental changes were obtained. Moreover, the model generated not only the walking movement but also the running movement by changing a single parameter nonspecific to the movement. The transitions between the gait patterns occurred with hysteresis.

Animals↗
PubMed1991

Production of islet cell antibodies from Epstein-Barr virus-transformed peripheral blood lymphocytes in type 1 (insulin-dependent) diabetic patients.

Islet cell antibodies are usually detected in the sera of almost all Type 1 (insulin-dependent) diabetic patients within several months after onset of the disease. The antibodies then disappeared quite early during the course of the disease. The present study was undertaken to detect islet cell antibody-producing clones in peripheral blood lymphocytes of Type 1 diabetic patients whose islet cell antibodies could not be detected in sera. Epstein-Barr virus-transformed lymphocytes were employed to enhance the production of antibodies and to detect the clones from peripheral blood lymphocytes. Peripheral blood lymphocytes were obtained from 40 islet cell antibody-negative Type 1 diabetic patients, 10 antibody-positive Type 1 diabetic patients, 30 Type 2 (non-insulin-dependent) diabetic patients and 40 normal control subjects. Epstein-Barr virus-transformed lymphocytes were cultured for 4 weeks and the culture supernatants were used for assay of islet cell antibodies. Islet cell antibody assays were performed by immunohistochemical methods using peroxidase-labelled protein A for IgG antibodies, peroxidase-labelled anti-human IgM antibodies for IgM antibodies and fresh frozen human pancreatic tissue. IgG-islet cell antibodies were detected in 26 islet cell antibody-negative patients (65%), eight antibody-positive patients (80%) and one Type 2 diabetic patient (3%) in the culture supernatants. Islet cell antibodies in the supernatants could not be detected in any of the control subjects. IgM-islet cell antibodies could not be detected in any of the patients or control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1991

A Japanese family pedigree of patients with severe combined immunodeficiency disease with X-linked inheritance.

We described three patients with severe combined immunodeficiency disease (SCID) with B lymphocytes from a single family. Adenosine deaminase and purine nucleoside phosphorylase activities were normal. Two of them received bone marrow transplantation from an HLA haplotype-mismatched mother and an HLA-identical sibling, respectively, with successful immunological reconstitution. Another patient died of severe pneumonia. X-linked inheritance was suggested through the analysis of the pedigree extending four generations. This is probably the largest SCID kindred reported in Japan.

Asian People↗
PubMed1991

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients.

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.

Administration, Oral↗
PubMed1991

Hyperprolactinemia in multiple sclerosis.

In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.

Adult↗
PubMed1991

Focal segmental glomerulosclerosis associated with infantile spasms in five mentally retarded children: a morphological analysis on mesangiolysis.

We report five cases of nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) in mentally retarded children with severe infantile spasms. Four of the five children diagnosed as West syndrome, Lennox syndrome, or petit mal epilepsy also had cerebral palsy and microcephaly. The other patient had petit mal epilepsy without cerebral palsy and microcephaly. All patients first developed infantile spasms, with the time of onset ranging from 1 week to 2 years of age, and subsequently developed proteinuria, followed by the nephrotic syndrome at 3 to 14 years of age. Four of the five developed terminal renal failure between 7 and 11 years of age. Three subsequently died, but the other underwent kidney transplantation and is still living without further complications. The light, electron microscopic, and immunohistochemical studies performed on the renal biopsies from all the patients and on the autopsy specimens from two cases exhibited FSGS-like lesions. Besides segmental hyalinosis, differing degrees of mesangiolysis were seen, which sometimes developed into dissecting microaneurysms of the glomerular capillary loops. The clinical picture described can be differentiated from congenital nephrotic syndrome (CNS) or infantile nephrotic syndrome (INS) with respect to the age of onset, outcome, and morphological appearance. We reviewed the previous literature and extended earlier observations about an unusual association between the nephrotic syndrome due to FSGS-like lesion, mental retardation, infantile spasms, and/or microcephaly in children.

Adolescent↗
PubMed1991

Purification, some properties, and tissue distribution of a major lysosome-associated membrane glycoprotein (r-lamp-2) of rat liver.

We previously purified and characterized a major lysosomal membrane glycoprotein (r-lamp-1) from rat liver [Akasaki et al. (1990) Chem. Pharm. Bull. 38, 2766-2770]. The present study describes the purification of another major lysosomal membrane glycoprotein (r-lamp-2) from rat liver and compares the tissue distribution of r-lamp-1 and r-lamp-2 in rats. R-lamp-2 was purified to apparent electrophoretic homogeneity from rat liver by a simple method with a protein yield of approximately 4.0 micrograms/g wet weight of liver. The purification procedure includes: preparation of tritosomal membranes, extraction of tritosomal membranes with Lubrol PX, wheat germ agglutinin (WGA)-Sepharose affinity chromatography, and monoclonal antibody-Sepharose affinity chromatography. R-lamp-2 exhibited an Mr of 96,000 on SDS-PAGE and had an acidic pI of less than 3.5. R-lamp-2 contained 52.3% carbohydrates. Its carbohydrate moieties were composed of numerous sialyl complex type N-linked oligosaccharides and small amounts of O-linked oligosaccharides. Both r-lamp-1 and r-lamp-2 were detected in all rat tissues examined by immunoblot analyses, while their apparent molecular weights differed among the tissues. Immunological quantitative analysis showed that the protein concentrations of r-lamp-2 were consistently lower than those of r-lamp-1 in all the tissues tested. There was a significant correlation with a regression coefficient of 0.86 in the tissue distribution between r-lamp-1 and r-lamp-2. A good correlation was also observed in the tissue distribution between acid phosphatase and r-lamp-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Human monoclonal antibody detects a cell surface antigen expressed on hematopoietic malignant cells of lymphoid lineage.

An antigen with a molecular weight of 150 kilodaltons expressed on certain leukemia and lymphoma cells was recognized by a human monoclonal antibody (3H12), which had been established by the fusion of lymphocytes from a small cell lung cancer patient with a mouse myeloma cell line (P3U1). Peripheral blood mononuclear cells from 3 out of 4 cases with lymphoid crisis of chronic myelogenous leukemia (CML) were positively stained by 3H12, while cells from 5 cases with myeloid crisis of CML did not react to this antibody. The antibody did not show any reactivity to cells from the chronic phase of CML, other types of leukemias or normal hematopoietic cells. We further examined 29 cell lines of hematopoietic origin and found that 2 undifferentiated cells (BV-173 and K-562) reacted to the 3H12 antibody. In addition, we found that 3 out of 6 Burkitt lymphoma cells (DAUDI, RAJI and HR1K) reacted to 3H12. Taken together, these results suggest that the antigen recognized by 3H12 is a differentiation-associated antigen expressed on immature lymphoid cells, and could potentially be a reliable cell lineage marker.

Antibodies, Monoclonal↗
PubMed1991

Function of rat hepatocyte tight junctions: studies with bile acid infusions.

To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Acecainide↗
PubMed1991

Vasopressin and A23187 stimulate phosphorylation of myosin light chain-1 in isolated rat hepatocytes.

Vasopressin (VP) and other hormones that elevate intracellular Ca2+ concentration also increase tight junctional permeability in the liver cell. Data derived from study of other tissues suggest that microfilaments are instrumental in regulating tight junctional permeability. By analogy to microfilament contraction in smooth muscles, it is likely that the transduction pathway for these hormones involves Ca(2+)-stimulated complex formation between calmodulin and myosin light chain (MLC) kinase with activation of this latter enzyme. MLC kinase then phosphorylates MLC, which, in the presence of actin, exerts adenosinetriphosphatase activity and produces microfilament contraction. This transduction pathway in the hepatocyte remains speculative. To demonstrate the likelihood of this pathway, we stimulated isolated hepatocytes with 10(-8) M VP and assayed MLC phosphorylation. We did this by immunoprecipitation of myosin from homogenates of liver cells prelabeled with [32P]-orthophosphate. We used a polyclonal antibody raised in rabbits against rat liver cell myosin. Our data demonstrate that VP is a potent stimulator of MLC phosphorylation. Maximal rises in intracellular Ca2+ and maximal MLC phosphorylation occur within 40 s of VP administration. The dose-response curve for MLC phosphorylation by VP is similar to that for tight junctional permeabilization in perfused liver with maximal effect at about 10(-8) M VP. The calcium ionophore A23187 also stimulated MLC phosphorylation. MLC phosphorylation, therefore, is at least coincident with, and probably responsible for, tight junctional permeabilization caused by elevation of intracellular Ca2+ in the liver cell.

Animals↗
PubMed1991

Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells.

We and others have previously demonstrated that the human insulin receptor messenger RNA (mRNA) is alternatively spliced such that the 36-nucleotide sequence encoded by exon 11 of the receptor gene is included (Ex11+) or excluded (Ex11-). Although both Ex11- and Ex11+ insulin receptors which differ in the presence or absence of 12 amino acids in the carboxy-terminal alpha-subunit have been demonstrated to function as insulin receptors when independently overexpressed and studied, the possibility that subtle functional differences between the two isoforms exist has received limited attention. Given that the relative abundance of the two mRNA transcripts is highly regulated in a tissue-specific manner, differences in the functional properties of the two receptor variants might contribute to tissue-specific differences in insulin receptor function and insulin action that are known to exist. To address this hypothesis, we transfected cDNAs encoding the two receptor isoforms into Chinese hamster ovary (CHO) cells and prepared several stable CHO cell lines expressing high numbers of Ex11- or Ex11+ receptors. Several functional properties of the expressed insulin receptors were compared in parallel with the following results: 1) steady state binding of insulin to cells expressing the Ex11- isoform exhibited higher (approximately 2-fold) affinity; 2) using two different methods, a significant difference in receptor-mediated insulin internalization was noted such that the Ex11- isoform displayed a higher (approximately 25% increase in the rate constant, Ke) rate of internalization; 3) partially purified Ex11- and Ex11+ receptors displayed similar maximal and insulin dose-response characteristics for receptor autophosphorylation and kinase activity toward an exogenous substrate (poly Glu-Tyr, 4:1); 4) the ability of expressed Ex11- and Ex11+ receptors to couple to a metabolic (glucose incorporation into glycogen) and mitogenic (thymidine incorporation into DNA) action of insulin was not discernibly different. Thus, when expressed in CHO cells, the two alternatively spliced isoforms of the insulin receptor have subtle differences in insulin binding affinity and the kinetics of ligand-stimulated internalization that would be expected to influence the pattern of insulin receptor expression and signaling in vivo in a tissue-specific manner.

Animals↗
PubMed1991

[Preventive effects of green tea extract on lipid abnormalities in serum, liver and aorta of mice fed a atherogenic diet].

This study examined the preventive effects of green tea extract on hyperlipidemia and lipid accumulation in the liver and aorta of mice fed an atherogenic diet enriched with 1.5% cholesterol, 0.5% cholic acid and 5% linoleic acid for a period of 14 weeks. The animals were given green tea extract in drinking water at doses of 50, 100 and 200 mg/kg/day. Treatment with green tea extract prevented the increase of serum cholesterol induced by the atherogenic diet 6 weeks after the start of the experiment. The increase of serum lipid peroxides was markedly prevented in a dose-related manner. The green tea extract also tended to prevent the increase of serum phospholipid and the decline of lecithin: cholesterol acyltransferase, but could not prevent decreases in serum triglycerides and high-density lipoprotein cholesterol. As for liver cholesterol, its content, particularly free cholesterol, in mice fed the atherogenic diet could be prevented from increasing by treatment with the extract at 50 and 100 mg/kg/day. In addition, the increase of aortic cholesterol, particularly esterified cholesterol, could be prevented in a dose-related manner. These results suggest that green tea has anti-atherosclerotic activity.

Animals↗
PubMed1991

Islet cell antibodies in patients with autoimmune thyroid disease.

Islet cell antibodies (ICAs) were assayed in 316 patients with autoimmune thyroid disease (AITD; 190 with Graves' disease, 126 with Hashimoto's thyroiditis), 53 patients with insulin-dependent diabetes mellitus (IDDM), and 144 healthy control subjects. ICAs were measured by an immunohistochemical method with peroxidase-labeled protein A and human pancreatic tissues. The prevalence of ICAs in patients with AITD was 7.6% (24 of 316), whereas the prevalence in control subjects was 0.7% (1 of 144). Among 24 ICA+ patients, 20 (83%) had IDDM. In these 20 patients, the duration of diabetes from clinical onset was 5.4 +/- 5.1 yr. ICAs in patients with IDDM alone were positive in 90.9% at 1 yr and 7.7% at 5 yr after the onset of diabetes. These data have shown that most ICA+ patients with AITD have IDDM and that the prevalence of ICAs in patients with AITD in Japanese is as high as that found among whites, whereas the incidence of IDDM in Japanese is approximately one-thirtieth or one-fiftieth of that in whites.

Adolescent↗
PubMed1991

Effects of cyclosporin A and low dosages of steroid on posttransplantation diabetes in kidney transplant recipients.

OBJECTIVE: To investigate the adverse effects of cyclosporin A (CsA) on pancreatic beta-cell function in kidney transplant recipients. RESEARCH DESIGN AND METHODS: The study consisted of 73 patients without a history of diabetes mellitus who had undergone kidney transplantation in our clinic. RESULTS: We experienced a higher incidence of posttransplantation diabetes mellitus (PTDM) in patients receiving CsA and low dosages of methylprednisolone (6/20, 30%, P less than 0.05) than in patients receiving conventional therapy of azathioprine methylprednisolone (4/53, 7.5%) since the introduction of CsA. In all 6 patients in the CsA-treated group, PTDM occurred within 3 mo after transplantation. The CsA level during the initial 3 mo posttransplant was significantly higher in diabetic than nondiabetic subjects, and the highest CsA level was observed shortly (1 mo) before the development of PTDM. After an average of 71 days of insulin therapy, there was complete remission of PTDM in 5 of 6 diabetic patients, with a corresponding decrease in CsA level. For the patients who were in remission for greater than 1 yr, a significant improvement of glucose intolerance was observed in association with a significantly higher insulin response to oral glucose load; however, their glycemic profile still showed a significantly higher plasma glucose concentration and a prolonged continuous elevation without initial peak of the insulin-response curve in contrast to the normal pattern found in nondiabetic subjects in the CsA-treated group. CONCLUSIONS: This study suggests that CsA in combination with low dosages of steroid may have adverse effects on glucose metabolism, which may lead to effects similar to those in non-insulin-dependent diabetes mellitus.

Azathioprine↗