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Biomedical subjects

J Takeda

Publications and source records attributed to J Takeda.

At least 235 records · Page 13Linked to original sources

Effects of nicardipine, nitroglycerin, and nitroprusside on left ventricular diastolic function during enflurane anesthesia.

The purpose of this study was to evaluate the effects of nicardipine (NCR), nitroglycerin (NTG), or nitroprusside (SNP) on left ventricular diastolic function during enflurane anesthesia in acutely instrumented dogs. Using echocardiography, time constants for the decline in isovolumic left ventricular pressure (T), stiffness constant (K), diastolic time intervals, and left ventricular filling rates were measured in 21 mongrel dogs during the following conditions: (1) 0% enflurane (control), (2) 3.3% enflurane, (3) intravenous infusion of NCR, 1 microgram/kg/min, NTG, 2 micrograms/kg/min, or SNP, 2 micrograms/kg/min, during 3.3% enflurane, and (4) intravenous infusion of NCR, 2 micrograms/kg/min, NTG, 4 micrograms/kg/min, or SNP, 4 micrograms/kg/min, during 3.3% enflurane. During 3.3% enflurane anesthesia, T and K increased significantly, and left ventricular filling rates decreased. The administration of NCR, NTG, or SNP returned T and K to control levels. Left ventricular rapid filling rate returned toward the control level only with NCR (P < 0.05, NCR v NTG, SNP). It is concluded that the depression of diastolic function during enflurane anesthesia was improved by NCR or other vasodilators. The extent and mechanism of action of these vasodilators might differ, however.

Anesthesia, Inhalation↗

Mutations in the glucokinase gene are not a major cause of late-onset type 2 (non-insulin-dependent) diabetes mellitus in Japanese subjects.

The role of the glucokinase gene in the development of diabetes in a group of 349 Japanese subjects with late-onset Type 2 diabetes was examined. These diabetic subjects and 197 non-diabetic controls were typed at two simple tandem repeat DNA polymorphisms in the glucokinase gene termed GCK2 and GCK3. Six and five alleles were evident in Japanese subjects at GCK2 and GCK3, respectively. There were no significant differences in allele, genotype or haplotype frequencies between diabetic and normal groups. In addition, the glucokinase gene of 340 diabetic and 170 non-diabetic Japanese subjects was screened for mutations using single strand conformation polymorphism analysis. Four nucleotide substitutions were identified: a silent substitution in exon 4 in the codon for proline 145 (CCC-->CCG), and A-->T, C-->G, and C-->A substitutions in introns 1b, 3, and 5, respectively. There were no significant differences in the frequencies of these nucleotide substitutions between diabetic and non-diabetic groups. These results suggest that glucokinase gene defects are not a major cause of late-onset Type 2 diabetes in Japanese subjects.

Amino Acid Sequence↗

Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations.

Pancreatic beta-cell function was studied in six subjects with mutations in the enzyme glucokinase (GCK) who were found to have elevated fasting and postprandial glucose levels in comparison to six normoglycemic controls. Insulin secretion rates (ISRs) were estimated by deconvolution of peripheral C-peptide values using a two-compartment model and individual C-peptide kinetics obtained after bolus intravenous injections of biosynthetic human C-peptide. First-phase insulin secretory responses to intravenous glucose and insulin secretion rates over a 24-h period on a weight maintenance diet were not different in subjects with GCK mutations and controls. However, the dose-response curve relating glucose and ISR obtained during graded intravenous glucose infusions was shifted to the right in the subjects with GCK mutations and average ISRs over a glucose range between 5 and 9 mM were 61% lower than those in controls. In the controls, the beta cell was most sensitive to an increase in glucose at concentrations between 5.5 and 6.0 mM, whereas in the patients with GCK mutations the point of maximal responsiveness was increased to between 6.5 and 7.5 mM. Even mutations that resulted in mild impairment of in vitro enzyme activity were associated with a > 50% reduction in ISR. The responsiveness of the beta cell to glucose was increased by 45% in the subjects with mutations after a 42-h intravenous glucose infusion at a rate of 4-6 mg/kg per min. During oscillatory glucose infusion with a period of 144 min, profiles from the subjects with mutations revealed reduced spectral power at 144 min for glucose and ISR compared with controls, indicating decreased ability to entrain the beta cell with exogenous glucose. In conclusion, subjects with mutations in GCK demonstrate decreased responsiveness of the beta cell to glucose manifest by a shift in the glucose ISR dose-response curve to the right and reduced ability to entrain the ultradian oscillations of insulin secretion with exogenous glucose. These results support a key role for the enzyme GCK in determining the in vivo glucose/ISR dose-response relationships and define the alterations in beta-cell responsiveness that occur in subjects with GCK mutations.

Adolescent↗

Reduced levels of messenger ribonucleic acid for calcium channel, glucose transporter-2, and glucokinase are associated with alterations in insulin secretion in fasted rats.

Expression of the genes for voltage-dependent calcium channels (VDCCs), glucose transporter-2 (GLUT2), and glucokinase was studied in pancreatic islets obtained from normal rats after periods of fasting and refeeding using a competitive polymerase chain reaction procedure. A 72-h fast induced about a 3-fold decrease in the beta-cell/neuroendocrine type VDCC alpha 1-subunit and GLUT2 messenger RNA (mRNA) levels and about a 2-fold decrease in insulin and glucokinase mRNA levels compared to those in fed and refed rats. No significant differences were found in beta-actin and the cardiac-type VDCC alpha 1-subunit mRNA levels among fed, fasted, anf refed rats. We also studied insulin secretion from the isolated perfused pancreata obtained from these animals. We found an elevated threshold and decreased insulin release in response to a stepwise increase in glucose concentrations in the isolated perfused pancreata obtained from fasted rats. Fasting also resulted in a dramatic decrease in insulin secretory responses during the application of an L-type VDCC agonist, Bay K8644 (1 microM). Furthermore, fasting resulted in a significant decrease in both 45Ca2+ uptake by the isolated islets and insulin release from the islets. A strong positive correlation was observed between glucose-induced 45Ca2+ uptake and insulin output among the animals studied. On the other hand, after a 24-h refeeding, significant increases in the insulin secretory response to glucose and Bay K8644 were found, with a normalization in mRNA levels for these components. It, thus, appears that the alterations in beta-cell sensitivity to glucose that occur with fasting and refeeding are the result of complex metabolic alterations in the islet associated with reductions in expression of at least in part the beta-cell/neuroendocrine type VDCC in addition to two components of the glucose-sensing apparatus, including glucokinase and GLUT2, and the reduction in mRNA for insulin.

Animals↗

Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT2.

The acute insulin response (AIR), a measure of pancreatic beta-cell function, aggregates in families and is a predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to determine if linkage exists between these marker loci and measurements of AIR and NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin response (P = 0.04), but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single-strand conformation polymorphism analysis. A single base change was identified in exon 3 in approximately 5% of the study population, and it constitutes the first reported mutation in the human GLUT2 gene. This base change resulted in an amino acid substitution (Thr110-->Ile110) in the second membrane-spanning region of the GLUT2 protein. No significant association was noted between AIR and the presence or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians.

Amino Acid Sequence↗

Total gastrectomy for gastric cancer: 12-year data and review of the effect of performing lymphadenectomy.

A total of 1,272 patients with gastric cancer were admitted to our institute for surgery during 12 years (1975-1986). Of these, 1,059 (83.4%) underwent gastrectomy. Among these, 252 (23.8%) were total gastrectomy (TG), involving 160 (63.5%) cases of cancer mainly located in the upper third of the stomach, 81 (32.1%) in the middle third and 11 (4.4%) in the lower third. Radical TG was performed in 65.9% and palliative TG in 34.1%. Roux-en-Y reconstruction was selected in 80%, jejunal interposition in 17.6% and double tract in 2.4%. The survival rate was improved by introducing extended lymph node dissection, especially in the cases of stage III & IV cancer in which a combined pancreatico-splenectomy could lead to cure when associated with lymphadenectomy. In cases of a positive serosal exposure, the 5-year survival rate was increased by extended lymphadenectomy from 21% to 46% (p < 0.02). Anastomotic leakage occurred in 4.2%. The postoperative mortality rate was 1.6%, occurring in only 4 patients.

Adenocarcinoma↗

Surgical management of gastric cancer patients with liver cirrhosis.

From 1966 to 1992, a total of 3,118 gastric cancer (GC) patients were referred to the First Department of Surgery, Kurume University Hospital. Fifty-six (0.02%) of these patients also had liver cirrhosis (LC). Forty-nine (87.5%) of these patients with LC underwent GC resection. Postoperative complications occurred in 32.7%, but the operative mortality rate was zero using our preoperative assessment of liver function to decide the operation. The 5-year survival rate following curative resection was 69% in early cancer and 17% in advanced cancer. Deaths were mainly cirrhosis-related in the early cancer cases, while cancer recurrence and hepatic failure were the main causes of mortality in the advanced cancer cases.

Female↗

[Plasma N-methylhistamine levels following intravenous administration of pipecuronium in man].

The half life of released plasma histamine (HA) is short but N-methylhistamine (N-MHA) which is a metabolite of HA has a longer life. Measuring both HA and N-MHA, it is possible to know the release of HA in the plasma. The purpose of this study was to ascertain the release of HA by pipecuronium (PPB) by measuring both HA and N-MHA in the plasma. Ten patients received 0.04 mg.kg-1 and other 10 patients received 0.08 mg.kg-1 of intravenous PPB. Plasma levels of HA and N-MHA were measured 1 minute before and 1, 3, 5 and 10 minutes after the administration of PPB. Release of plasma HA and N-MHA was not observed following administration of PPB. We concluded that PPB does not cause the release of histamine because there is no increase of the metabolite, N-MHA, of HA, and PPB can be used safely for patients with allergy.

Adult↗

Gastric cancer surgery in patients aged at least 80 years old.

Fifty-six patients with gastric cancer who were at least 80 years of age (range 80-88) (Group 1) were retrospectively investigated and compared with younger patients. The resectability rate was 80% (45/56) in Group 1, 88% (331/373) in Group 2 (patients aged between 70 and 79) and 91% (992/1,087) in Group 3 (patients aged under 70 years). Of the cases resected, 73% had advanced cancer in Group 1, 61% in Group 2 and 55% in Group 3. Total gastrectomy was performed in only 11% of the resected cases in Group 1, in 25% of those in Group 2 and in 33% in Group 3. Of these, combined resections were employed in none of the patients in Group 1, in 38% of those in Group 2 and in 47% of those in Group 3. Pathologically, 78% of Group 1 cancers were of the differentiated type, 68% of Group 2 and 49% of Group 3 cancers (Group 1: Group 3, p < 0.001). R3 gastrectomy was performed for advanced cancer in none of the patients in Group 1, in 21% in Group 2, and in 39% of those in Group 3. In resected early cancers, the lymph node metastasis (n) rate was 0% for Group 1, 10% for Group 2, and 9% for Group 3. In the advanced cases, n(+) was 67% for Group 1, 65% for Group 2, and 73% for Group 3. Postoperative complications occurred in 25% of Group 1 and in 12% of Group 2 patients. Anastomotic leakage occurred in 4% of Group 1 and in 5% of Group 2 patients. The 5-year-survival rate was 47% for all resected cases in Group 1, and 68% for Groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Expression cloning of genes for GPI-anchor biosynthesis.

Cloning genes for glycosylphosphatidylinositol (GPI)-anchor biosynthesis is important to further understand its mechanisms and regulation. We have been using expression cloning methods in which a cDNA library was transfected into GPI-anchor-deficient mutant cells. The transfectants which restored surface expression of GPI-anchored proteins were isolated and the plasmids were rescued. In this way we previously cloned cDNAs of genes for complementation classes A and F, and named them PIG-A and PIG-F, respectively. In the present study we have cloned the gene for class B, termed PIG-B. In each case we used different methods. For cloning PIG-A cDNA we used a cDNA library made with an Epstein-Barr-virus-based vector and human class A mutant JY5 which expresses EBNA-1 protein. The EBNA-1 protein allows stable replication of oriP-containing plasmids in the episomal form. For cloning PIG-F cDNA we chose a transient expression method and cotransfected a human T-cell cDNA library made with a vector bearing an origin of replication of polyoma virus with a plasmid bearing polyoma virus large T into the class F murine thymoma mutant. This cotransfection strategy was unsuccessful for cloning PIG-B due to low transfection efficiency of the class B thymoma mutant SIA-b. Thus, we first established large T-expressing SIA-b cells and then transfected them with a cDNA library. PIG-B cDNA restored the surface expression of Thy-1 on SIA-b cells and also synthesis of mature type GPI-anchor precursors in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Surgical treatment of gastric cancer with hepatic cirrhosis].

42 cases of gastric cancer associated with hepatic cirrhosis were reviewed retrospectively. These patients represented 2.8% of 1496 patients with gastric cancer who were treated over the 13 years period from 1980 to 1992. The male to female ratio was 3.7:1. On the basis of a detailed classification of the preoperative hepatic function into three risk groups, we have established a preoperative means of assessing surgical indication. Among the 42 patients, four patients were inoperable, and thirty-eight patients underwent gastric resection. One patient was died due to postoperative complication. In the preoperative assessment of operative risk, K-ICG was the most important factor.

Aged↗

[Vaporizer malfunction--a cause of high concentration halothane vapor delivery].

Excessively high concentration of halothane vapor was delivered to the inspiratory gas mixture due to the vaporizer malfunction (Fluotec 4). After disassembling the vaporizer, corrosion was observed on the internal components. This was considered as the reason for the high halothane output. Proper regular check up, use of appropriate monitoring devices, and a preuse equipment checklist may help improve the quality of patient care and decrease the morbidity and mortality associated with anesthesia equipment. Anesthesia machines should receive regular check up at least once a year and anesthesia providers should routinely use an equipment checklist. It is also important to realize that anesthesiologist's senses of sight, hearing, touch, and smell are exceedingly reliable monitors for decreasing the incidence of anesthesia mishaps.

Anesthesia, Inhalation↗

Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA.

Recent studies have identified a new family of inwardly rectifying K+ channels, members of which are known by the acronyms ROMK1, IRK1, and GIRK1. We have isolated cDNAs encoding the human homologue of ROMK1 from an adult kidney cDNA library. The sequences of the human kidney ROMK1 cDNA clones indicated that they were derived from at least two types of mRNAs, human ROMK1A and human ROMK1B, differing in sequence at their 5' ends. The isolation of the human ROMK1 gene, localized to chromosome band 11q24 by fluorescence in situ hybridization, indicated that the different ROMK1 transcripts were generated by alternative splicing. Human ROMK1A mRNA was predicted to encode a protein of 389 amino acids, having 93% identity with the 391-residue rat ROMK1 protein, and expression studies in Xenopus oocytes indicated that it encoded a Ba(2+)-sensitive inwardly rectifying K+ channel with properties similar to those reported for cloned rat ROMK1. Human ROMK1B mRNA was predicted to encode a protein of 372 amino acids whose sequence was truncated at the amino terminus but otherwise identical to that of the human ROMK1A protein. Translation of human ROMK1B mRNA was predicted to initiate at a codon corresponding to Met-18 of human ROMK1A mRNA. Reverse transcriptase-polymerase chain reaction amplification of human kidney mRNA revealed human ROMK1A and -B transcripts as well as a third type of transcript, human ROMK1C mRNA, which was predicted to encode a protein identical to human ROMK1B. Human ROMK1A, -B, and -C transcripts were identified in kidney, whereas only human ROMK1A mRNA could be detected in pancreatic islets and other tissues in which human ROMK1 was expressed at low levels. Thus, tissue-specific alternative splicing of human ROMK1 mRNA may result in the expression of a family of ROMK1 proteins.

Adult↗

Sequence and functional characterization of feline interleukin 2.

Since the discovery of its involvement in the pathogenesis of feline immunodeficiency virus infection ("cat AIDS") and feline leukemia virus infection, the role of feline interleukin 2 (IL-2) has been a focus of particular interest. The purpose of this study was to clone feline IL-2 cDNA, as well as synthesize bioactive recombinant feline IL-2. The isolation of cDNA encoding feline IL-2 was carried out using a PCR-based strategy and screening of a feline leukocyte cDNA library. Feline IL-2 consists of 154 amino acids including a putative signal sequence and has 81%, 69%, 60% and 64% identity to human, bovine, murine and rat IL-2, respectively. Feline IL-2 cDNA was expressed in COS-7 cells. The secreted protein has CTLL-4 murine cytotoxic T cell proliferative activity characteristic of authentic IL-2. These data confirm the synthesis of bioactive recombinant feline IL-2.

Amino Acid Sequence↗