Search PubMed⌕ Search

Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 145 records · Page 8Linked to original sources

[Influence of PEEP on left ventricular diastolic function].

We investigated the influence of PEEP on left ventricular diastolic function using the pressure-volume loops by employing a micromanometer catheter and a conductance catheter placed in the left ventricle of the eight mongrel dogs. Time constant of diastolic interval was shortened under the condition of 15 cmH2O of PEEP compared with the control value (PEEP 0 cmH2O) and the diastolic stiffness constant was prolonged under 15 cmH2O of PEEP. It was considered that the shortened time constant of diastolic interval was due to the decrease of preload. The prolongation of diastolic stiffness constant was possibly due to compression of the heart by increased intrapleural pressure. We conclude that decreased compliance of left ventricle caused by PEEP might impair the left ventricular function.

Animals↗

Isolation and characterization of a novel TP53-inducible gene, TP53TG3.

We applied the differential mRNA display method to isolate genes regulated by wild-type TP53 in cells of a colon-cancer line (SW480) in which we had established an inducible TP53 expression system under the control of the lactose operon. Here we report isolation and characterization of a novel TP53-inducible gene, termed TP53TG3 (TP53 target gene 3). Its DNA sequence was identical to sequences present in two BAC clones that had been mapped to chromosome band 16p13. The gene expressed several transcripts by alternative splicing; the two major transcripts, TP53TG3a and TP53TG3b, encoded 124- and 132-amino-acid peptides that were expressed predominantly in testis. Immunohistochemical analysis using cancer cells (HeLa or H1299) that had been transfected with plasmid DNA designed to express the MYC-fused TP53TG3 proteins indicated that these products were present mainly in the cytoplasm 20 hr after transfection. However, 40 hr after transfection, the recombinant proteins had accumulated in the nuclei of some cells. Because no known nuclear localization domain was present in the amino acid sequence, we suspect that this protein plays an important role in the TP53-mediated signaling pathway, when it forms complexes with other protein(s) and is transferred by them into the nucleus. Genes Chromosomes Cancer 26:329-335, 1999.

Amino Acid Sequence↗

[Ulcerative colitis and pregnancy].

Ulcerative colitis(UC) commonly affects young adults, many of whom wish to have children themselves. Women with ulcerative colitis who are pregnant have many concerns, such as the effect of the gestational period on UC, the effect of UC on the pregnancy, and the safety of drugs used to control the disease. We suggested that there was no significant difference in fertility between the patient with UC and the general population. The pregnancy rates in the UC patients were similar to those in the general population. As compared with the patients with an inactive bowel disease, those with an active disease at the beginning of pregnancy had a little higher risk of spontaneous abortion and premature delivery. The clinical course of UC during pregnancy was correlated with the disease activity at the time of conception. Women with UC should be advised preferably to conceive at the time when their bowel disease is in an inactive stage. Medical treatment with sulphasalazine, 5-Aminosalicylic Acid and corticosteroids appeared to have no obvious deleterious effects on the fetus and new-born child.

Adult↗

Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system.

We applied a differential display method to screen mRNAs isolated from a newly established cell line that carried a wild-type p53 transgene under control of the lactose operon. To investigate the p53 signaling pathway, we looked for genes whose expression was significantly induced or suppressed by induction of wild-type p53 protein, and identified seven. DNA sequence analyses revealed that the two genes that were upregulated encoded isozyme 6 of aldehyde dehydrogenase (ALDH6) and subunit I of cytochrome c oxidase (COI). The five genes that were downregulated encoded protein-tyrosine kinase (Syk), high mobility group chromosomal protein 17 (HMG-17), transferrin receptor, human alpha-tubulin, and sds22-like protein. The results indicated that genes related to cell cycle regulation, cell respiration, and cytoskeletal structure are involved in the process of growth arrest induced by wild-type p53.

Cell Cycle↗

Electron microscopic peritubular capillary lesions: a new criterion for chronic rejection.

Typical chronic rejection showing prominent glomerular and/or arterial lesions is less common in renal allograft patients treated with cyclosporin A (CsA). We investigated the value of peritubular capillary lesions as a criterion for chronic rejection in the CsA era. A total of 129 renal graft biopsies, taken from recipients showing graft dysfunction after more than 2 months post-operatively, were examined by electron microscopy, and peritubular capillary lesions were studied, especially multi-layered basement membrane lesions (MLPTC). Eighty-two biopsy specimens taken from non-transplantation patients were also studied as a control. Five biopsies (6%) showed mild and atypical MLPTC in the control group. Of the 129 allograft biopsies, MLPTC was seen in 55 (42.6%). The prevalence showed no significant relationship to the interval from operation to biopsy. MLPTC was either typical (n = 10) or incomplete (n = 45). Concomitant membrane disruption, edema and lymphocyte infiltration of the subendothelial space, reflecting acute cellular rejection, were occasionally noted in both groups. Incomplete MLPTC often developed within 1 yr after surgery, in association with acute rejection. It was found in 26-50% of biopsies at any time up to 5 yr post-operatively. The incidence of typical MLPTC was 5.7-12.8% over 1 yr post-operatively. These findings suggest that the development of chronic rejection is closely related to relapsing acute tubulo-interstitial allograft rejection which is often clinically silent. We concluded that MLPTC is useful as a specific criterion for chronic rejection.

Basement Membrane↗

A case of IgA nephropathy after ABO-incompatible living kidney transplantation.

A 39-yr-old Japanese man underwent living related kidney transplantation. Because the graft was ABO-incompatible, he was treated with double filtration plasmapheresis before transplantation and his immunosuppressive therapy was stronger than usual. However, immunoglobulin A nephropathy, accompanied by cellular crescents and necrotizing lesions, developed after 18 months. To our knowledge, the association of IgA nephropathy with ABO-incompatible kidney transplantation has not been reported previously.

ABO Blood-Group System↗

Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin.

We isolated a novel gene, APCL, that showed significant homology to the adenomatous polyposis coli (APC) tumor suppressor gene. This novel gene, located on chromosome 19p13.3, encodes a protein of 2303 amino acids that is expressed specifically in the brain. The predicted protein of APCL contains five copies of a 20-amino-acid motif (FXVEXTPXCFSRXSSLSSLS). Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. A reporter-gene assay revealed that APCL could also regulate interaction of beta-catenin with T cell-specific transcription factor, although less actively than APC. These results suggest that the APCL protein may be involved in the Wnt/Wingless signal pathway, and the identification of a novel relative of APC may provide new insights into the function of APC.

Amino Acid Sequence↗

Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion.

The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). GLUT-2 expression in beta cells of Zucker diabetic fatty (ZDF) rats is profoundly reduced at the onset of beta-cell dysfunction of diabetes. Because ZDF rats are homozygous for a mutation in their leptin receptor (OB-R) gene and are therefore leptin-insensitive, we expressed the wild-type OB-R gene in diabetic islets by infusing a recombinant adenovirus (AdCMV-OB-Rb) to determine whether this reversed the abnormalities. Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. GK protein rose 7-fold without and 12-fold with leptin. Preproinsulin mRNA increased 64% without leptin and rose no further with leptin, but leptin was required to restore GSIS. Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low. Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb.

Animals↗

Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors.

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH.

Adenoviridae↗

45,X/46,X,idic(Yq) mosaicism: clinical, cytogenetic, and molecular studies in four individuals.

45,X/46,X,idic(Yq) mosaicism is associated with a variety of sex phenotypes, including Ullrich-Turner syndrome (UTS), intersexuality, and complete male. It remains unclear whether the phenotypic variability results from a dilutional effect by the 45,X cell line in the primordial gonad or an abnormality of the SRY gene (SRY). We conducted cytogenetic and molecular studies on four patients with such mosaicism, two of whom had a complete male phenotype and two who had UTS. Chromosome analyses showed that the frequency of cells carrying an idic(Yq) chromosome in peripheral blood lymphocytes and skin fibroblasts was not related to the given sex phenotype. The SRY, PABY, and ZFY genes were present in all four patients. A fluorescence in situ hybridization (FISH) study showed that both a patient with a complete male phenotype and another with UTS had duplicate copies of SRY in their idic(Yq) chromosomes, whereas a patient with UTS had a single copy of the gene. These findings suggested that the coexisting 45,X cell line is more influential on the determination of the sex phenotype in individuals with 45,X/ 46,X,idic(Yq) mosaicism.

Adolescent↗

Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae.

Wilson disease is a genetic disorder of copper metabolism characterized by the toxic accumulation of copper in the liver. The ATP7B gene, which encodes a copper transporting P-type ATPase, is defective in patients with Wilson disease. To investigate the function of ATP7B, wild type or mutated ATP7B cDNA was introduced into a yeast strain lacking the CCC2 gene (delta ccc2), the yeast homologue of ATP7B. Wild type and the H1069Q mutant could rescue delta ccc2, however, the N1270S mutant could not, reflecting phenotypic variability of Wilson disease. In addition, the mutant containing only the sixth copper binding domain could rescue delta ccc2, indicating its functional importance.

Adenosine Triphosphatases↗

OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype.

In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islets have an approximately 50-fold increase in fat (TG), overproduce nitric oxide (NO), and lack a normal proinsulin mRNA response to fatty acids. We overexpressed the wild-type full-length "b" isoform of the leptin receptor (OB-Rb) in ZDF islets by perfusing ZDF pancreata with recombinant adenovirus containing the cDNA encoding OB-Rb. In cultured islets isolated from these animals, leptin lowered islet TG by 87% and completely blocked TG formation from free fatty acids. Overproduction of NO was reduced, and the preproinsulin mRNA response to free fatty acids was restored. This establishes defective leptin action as the proximate cause of lipotoxic diabetes in ZDF rats.

Animals↗

Appendicostomy irrigation for facilitating colonic evacuation in colostomy patients. Preliminary report.

A method for bowel irrigation through an appendicostomy (antegrade colonic enema) for patients with a left colostomy is described. The appendicostomy is easily constructed without morbidity. Irrigation through the appendicostomy is performed with minimum equipment, uses a small volume of irrigation water, and takes a relatively short time. This may improve colonic evacuation in patients with left colostomy.

Appendix↗

Minimally invasive needlescopic cholecystectomy.

We utilized a mini-sized grasper and retractor measuring 2.5 mm in diameter and a new mini-sized laparoscope measuring 3 mm in diameter to perform a laparoscopic cholecystectomy. A 10/12-mm trocar was inserted as the first trocar for the laparoscope and specimen extraction. Under a direct laparoscopic view, the mini-sized grasper and retractor were inserted and the laparoscopic procedures were performed mainly through the 5-mm trocar placed on the left upper quadrant as the working port. These procedures were successfully performed on five patients with a comparable operation time to that of a conventional laparoscopic cholecystectomy, but appeared to be more minimally invasive.

Cholecystectomy, Laparoscopic↗