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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 109 records · Page 6Linked to original sources

Statistical test of the shortening of latent periods in experimental radiation carcinogenesis under competing risks.

The mean life span of animals killed by a specific type of tumor is influenced by competing risks. The parametric inference method of Noda et al. was applied to a set of mouse experimental data in order to correct for the appearance of observed life span distribution under competing risks and to test statistical significances of difference between corrected mean life spans. Data were from an experiment on tumors induced in mice by X-rays: whole body irradiated with 600 R; head with 800 R; trunk or lower body with 800 R. The statistically significant changes were found: Whole body irradiation shortened the mean latent period of malignant lymphomas whereas the head irradiation shortened the latent periods of none of tumors. Trunk irradiation shortened mean latent periods of lung tumors. Lower body irradiation showed a tendency to shorten the mean latent periods of mammary tumors. Results that differed from the above were obtained when there was no correction for competing risks.

Animals

Seroepidemiological survey of chlamydial infections in light horses in Japan.

To investigate the overall prevalence of chlamydial infections in light (i.e. non-draught) horses in Japan, 599 sera obtained from 12 localities in 1991 were tested for complement fixation antibodies. The mean antibody positive rates of the all sera were 15.2% (91/599) and the regional positive rates were higher in Honshu (19.1%, 48/251) and Kyushu (20.0%, 20/100) than in Hokkaido (9.3%, 23/248). In Honshu, the highest rate (56.0%, 28/50) was observed in Utsunomiya. Analysis of the positive rate in different age groups showed that the 2-5 years age-group had the highest prevalence of chlamydial infections. This indicates that chlamydial infection is prevalent in light horses in Japan.

Animals

Evaluation of diagnostic assays for neonatal and infantile chlamydial infections.

Several diagnostic assays for neonatal and infantile chlamydial infections, isolation with tissue culture, antigen detection by enzyme immunoassay (EIA) (IDEIA Chlamydia test), a nonisotopic DNA probe (Gen-Probe PACE 2 assay), serum IgM antibody detection by EIA (SeroELISA Chlamydia TRUE IgM), and polymerase chain reaction (PCR), were evaluated. Of 210 clinical specimens (170 nasopharyngeal and 40 conjunctival swabs) from 53 neonates and 102 infants with respiratory insufficiency and respiratory tract infections which were suspected to be associated chlamydial infection, chlamydial antigens were detected in 30 by IDEIA Chlamydia. Of these 30 samples, C. trachomatis was isolated from 27 specimens. Samples from 15 neonates and 6 infants were culture-positive and IDEIA Chlamydia-positive. Of 30 samples, 27 were tested with PCR and 8 with DNA probe. Twenty-three of 27 specimens were positive with PCR, while only one specimen was positive with DNA probe. EIA can be used for the diagnosis and screening of neonatal and infantile chlamydial infections.

Antibodies, Bacterial

An immunohistochemical study on the gastrointestinal endocrine cells of three honeyeaters: singing honeyeater (Meliphaga virescens), spiny-cheeked honeyeater (Acanthogenys rufogularis) and brown honeyeater (Lichmera indistincta).

The gastrointestinal endocrine cells of the singing honeyeater (Meliphaga virescens), spiny-cheeked honeyeater (Acanthogenys rufogularis) and brown honeyeater (Lichmera indistincta) were studied immunohistochemically with special reference to their degree of dependency upon nectar. The nine types of immunoreactive endocrine cells were detected in their gastrointestinal mucosa. Coexistence of motilin and serotonin in the same cells was confirmed in the pyloric region. In the duodenum and jejunum, a few peptide tyrosin tyrosin (PYY)-immunoreactive cells were detected. The clear difference in the distribution and frequency of the gastrointestinal endocrine cells among three types of honeyeaters, which differ in the degree of dependency upon the nectar, could not be confirmed. However, some differences were found that serotonin-, somatostatin- and gastrin-releasing peptide (GRP)-immunoreactive cells in the gizzard, gastrin-immunoreactive cells in the duodenum and jejunum, enteroglucagon-immunoreactive cells in the caeca and in the colon, and pancreatic glucagon-immunoreactive cells in the ileum of brown honeyeaters were more numerous (p < 0.05) than other two species.

Animals

[Epidural buprenorphine under nitrous oxide-oxygen-enflurane anesthesia in elderly patients].

The effects of epidural buprenorphine (Bn) under nitrous oxide-oxygen-enflurane (E) anesthesia in elderly patients were examined. The subjects were older than 65 years (n = 82) and scheduled for abdominal surgery. They were divided randomly into two groups according to epidural drugs used. The first group received epidural Bn 0.1-0.2 mg (group B, n = 41). The second group received epidural Bn 0.1-0.2mg + 1% lidocaine (group BL, n = 41). The enflurane concentration was 1.13% in group B, and it was significantly higher than 0.78% of group BL (P < 0.01). There was no intra-group difference in the highest systolic blood pressure during operation. The lowest systolic blood pressure during operation was 92.0 +/- 2.1 mmHg in group BL and it was significantly lower than 100.2 +/- 2.9 mmHg of group B (P < 0.05). The percentage of patients who needed vasoconstrictor drugs was 12% in group B, and it was significantly smaller than 42% of group BL (P < 0.01). On the other hand the percentage of patients who needed vasodilator drugs was 39% in group B, and it was significantly larger than 17% of group BL (P < 0.05). There was no intra-group difference in arousing time from anesthesia. Concerning the postoperative respiratory state, there was no intra-group difference in the respiratory rate, tidal volume and PaO2. But the PaCO2 value was 44.7 +/- 0.8 (mean +/- SE) mmHg in group BL, and it was significantly higher than 40.7 +/- 0.7 mmHg of group B (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

[Effects of high doses of beclomethasone dipropionate in bronchial asthma].

To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.

Adult

Scintigraphic evaluation of gastroesophageal reflux following gastrectomy.

We used scintigraphy to detect and quantify gastro-esophageal reflux, and determined the sensitivity of this method for identifying patients with clinical symptoms and/or endoscopic evidence of reflux. Thirty gastrectomy patients with heartburn and regurgitation, and 8 healthy controls were studied. The gastro-esophageal reflux index, calculated from imaging data, correlated significantly with the symptom score of the subjects, and the index was significantly larger in the symptomatic patients group (7.07 +/- 1.21) than in the healthy control group (1.54 +/- 0.22) (p < 0.001). Our study suggests that scintiscanning is capable of detecting gastro-esophageal reflux accurately, rapidly, noninvasively, and with a high degree of sensitivity. In addition, scintiscanning can be employed to quantify reflux in gastrectomy patients.

Adult

Malabsorption after small-bowel transplantation.

Following small intestinal transplantation for the short-bowel syndrome the absorptive capacity of the grafted bowel is markedly reduced in the early postoperative period. This impairment is thought to be due primarily to perioperative ischemic damage and complete denervation. To determine which of these was the more important factor, we compared three groups of mongrel dogs. A sham-operated group (n = 5), a denervation group (n = 4), and an autotransplantation group (n = 5). D-xylose absorption and graft tissue levels of substance P and ATP were measured at 4 and 5 weeks postoperatively. A significant reduction in the intestinal absorption of D-xylose was observed in the denervation and autotransplantation groups (P < 0.01, P < 0.05). In contrast, the denervation and autotransplantation groups had significantly higher substance P levels in small-bowel biopsy tissues than the control group (P < 0.01). However, the tissue ATP levels were similar in all three groups, suggesting that perioperative ischemic damage was reversible. These findings indicate that the impaired absorption following small-bowel autotransplantation was largely due to intestinal denervation.

Animals

Analysis of hepatic encephalopathy after distal splenorenal shunt--PTP image and pancreatic hormone kinetics.

The Warren-Zeppa selective distal spleno-renal shunt is aimed at decompressing esophageal varices while at the same time ligating left gastric, gastroepiploic and umbilical veins. But in the long term follow-up loss of shunt selectivity was observed in a number of cases (7/76), with hepatic encephalopathy resulting in 9.3%. In this study, we carried out percutaneous transhepatic portography and investigated pancreatic hormone kinetics in portal blood after arginine load, mainly in cases of hepatic encephalopathy after distal splenorenal shunt compared with non-encephalopathy cases of LC + Varix. These data suggested that as a cause of encephalopathy after distal splenorenal shunt, (1) a marked decrease in portal blood flow due to portal systemic shunt via the pancreatic vein was considered from PTP image, (2) a marked decrease in I/G ratio was considered from pancreatic hormone kinetics in portal blood.

Blood Glucose

[The circulatory and respiratory effects of methylprednisolone associated with catecholamine administration of a few hours].

We studied the circulatory and respiratory effects of methylprednisolone (MPS) associated with catecholamine administration of a few hours after cardiopulmonary bypass (CPB). Forty patients undergoing coronary artery bypass grafting were randomly divided into two groups. Twenty patients in group 1 [MPS (-) group] did not receive MPS and 20 patients in group 2 [MPS (+) group] received MPS 15 mg.kg-1 i.v. 60 minutes after CPB. The circulatory and respiratory parameters were measured 60 minutes after CPB, 30 minutes after MPS i.v. and 60 minutes after MPS i.v. The values in MPS (-) group were compared with those in MPS (+) group. CI and SVI decreased, and SVRI and PQR increased in MPS (-) group, but these values were unchanged in MPS (+) group. RAP, mPAP, PCWP and PVRI were unchanged in MPS (-) group. PCWP increased and the other values were unchanged in MPS (+) group. The blood gases and pulmonary alveolar function were not different between the two groups. The oxygen delivery decreased in MPS (-) group, but it was unchanged in MPS (+) group. The oxygen consumption was unchanged in the two groups. Blood cortisol increased and epinephrine and norepinephrine decreased in MPS (+) group. Methylprednisolone had an effect to improve the decreased CI and the increased SVRI, and no respiratory problems were observed in patients for coronary artery bypass grafting with catecholamine administration for a few hours after cardiopulmonary bypass.

Blood Circulation

Differential regulation of mRNAs encoding three protein-tyrosine phosphatases by insulin and activation of protein kinase C.

Protein-tyrosine phosphatases (PTPases) play an essential role in the control of signalling through phosphotyrosine pathways. Since little is known about the regulation of these enzymes, we examined the effect of insulin and phorbol 12-myristate 13-acetate (PMA) treatment of well-differentiated rat hepatoma (Fao) cells on the expression of mRNAs encoding three major PTPase homologs in liver: PTPase1B, an intracellular enzyme with a single conserved PTPase domain, and two tandem-domain, transmembrane PTPases, known as LAR and LRP. Treatment of serum-deprived cells with 100 nM insulin increased the abundance of the 4.3 kb and 1.6 kb mRNAs encoding PTPase1B on Northern analysis by 1.6 and 3.1-fold, respectively (p < or = 0.02). Similarly, exposure to 100 ng/ml PMA increased the 4.3 and 1.6 kb PTPase1B mRNAs by 4.5 and 5.7-fold, respectively (p < or = 0.035). In contrast, treatment with insulin or PMA had no significant effect of the abundance of mRNA encoding either LAR or LRP. PMA appeared to have a transcriptional effect on the PTPase1B gene by a protein kinase C-mediated mechanism. The increase in PTPase1B mRNA expression by insulin and PMA suggests that this PTPase may provide feed-back regulation of signalling through the insulin action pathway as well as a potential link between the action of protein kinase C and the regulation of specific phosphotyrosine residues in cells.

Animals

Insulin receptor protein-tyrosine phosphatases. Leukocyte common antigen-related phosphatase rapidly deactivates the insulin receptor kinase by preferential dephosphorylation of the receptor regulatory domain.

A number of protein-tyrosine phosphatase(s) (PTPases) have been shown to dephosphorylate the insulin receptor in vitro; however, it is not known whether any individual PTPase has specificity for certain phosphotyrosine residues of the receptor that regulate its intrinsic tyrosine kinase activity. We evaluated the deactivation of the insulin receptor kinase by three candidate enzymes that are expressed in insulin-sensitive rat tissues, including the receptor-like PTPases LAR and LRP, and the intracellular enzyme, PTPase1B. Purified insulin receptors were activated by insulin and receptor dephosphorylation, and kinase activity was quantitated after incubation with recombinant PTPases from an Escherichia coli expression system. When related to the level of overall receptor dephosphorylation, LAR deactivated the receptor kinase 3.1 and 2.1 times more rapidly than either PTPase1B or LRP, respectively (p less than 0.03). To assess whether these effects were associated with preferential dephosphorylation of the regulatory (Tyr-1150) domain of the receptor beta-subunit, we performed tryptic mapping of the insulin receptor beta-subunit after dephosphorylation by PTPases. Relative to the rate of initial loss of 32P from receptor C-terminal sites, LAR dephosphorylated the Tris-phosphorylated Tyr-1150 domain 3.5 and 3.7 times more rapidly than either PTPase1B or LRP, respectively (p less than 0.01). The accelerated deactivation of the insulin receptor kinase by LAR and its relative preference for regulatory phosphotyrosine residues further support a potential role for this transmembrane PTPase in the physiological regulation of insulin receptors in intact cells.

Animals

Insulin receptor and epidermal growth factor receptor dephosphorylation by three major rat liver protein-tyrosine phosphatases expressed in a recombinant bacterial system.

Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of signal transduction mediated by reversible protein-tyrosine phosphorylation. In order to characterize individual rat hepatic PTPases that might have specificity for autophosphorylated receptor tyrosine kinases, we isolated cDNA segments encoding three PTPases (PTPase 1B, LAR and LRP) that are expressed in insulin-sensitive liver and skeletal muscle tissue, and evaluated their catalytic activity in vitro. The intrinsic PTPase activities of the full-length PTPase 1B protein and the cytoplasmic domains of LAR and LRP were studied by expression of recombinant cDNA constructs in the inducible bacterial vector pKK233-2 using extracts of a host strain of Escherichia coli that lacks endogenous PTPase activity. Each of the cloned cDNAs dephosphorylated a cognate phosphopeptide derived from the regulatory region of the insulin receptor. Despite having only 30-39% sequence identity in their catalytic domains, LAR and PTPase 1B had similar relative activities between the peptide substrate and intact insulin receptors, and also displayed similar initial rates of simultaneous dephosphorylation of insulin and epidermal growth factor (EGF) receptors. In contrast, LRP exhibited a higher rate of dephosphorylation of both intact receptors relative to the peptide substrate, and also dephosphorylated EGF receptors more rapidly than insulin receptors. These studies indicate that three PTPases with markedly divergent structures have the catalytic potential to dephosphorylate both insulin and EGF receptors in intact cells and that redundant PTPase activity may occur in vivo. For these PTPases to have specific physiological actions in intact cells, they must be influenced by steric effects of the additional protein segments of the native transmembrane enzymes, cellular compartmentalization and/or interactions with regulatory proteins.

Amino Acid Sequence

Approaches to the molecular cloning of protein-tyrosine phosphatases in insulin-sensitive tissues.

The intrinsic tyrosyl kinase activity of the insulin receptor is regulated by a balance between insulin-induced receptor autophosphorylation, which stimulates the receptor kinase, and enzymatic dephosphorylation of the receptor, which deactivates its kinase activity. The cellular protein-tyrosine phosphatase (PTPase) enzymes responsible for reversing the activated state of the insulin receptor have not been characterized. Our laboratory is interested in identifying and cloning the specific PTPase(s) that regulate the phosphorylation state of the insulin receptor. This chapter will summarize the design and results of our initial molecular cloning studies to identify specific PTPases in insulin-sensitive tissues that may have a potential physiological role in insulin action and clinical insulin resistance.

Amino Acid Sequence

Effect of nicardipine on haemodynamic response to stress in hypertension.

The effects of the calcium antagonist nicardipine on the pressor response to mental arithmetic, cold pressor and exercise tests have been studied in fifteen patients with established mild to moderate essential hypertension. Nicardipine 20 mg p.o. showed a hypotensive effect within 60 min, associated with a fall in total peripheral resistance and an increase in heart rate. As the pressor response to each stress was not affected by nicardipine, the peak blood pressure reached during each stress was lower. Nicardipine lowers blood pressure at rest as a result of arteriolar dilatation, associated with reflex tachycardia. The pressor responsiveness to various stresses was not affected by nicardipine.

Adult

Abnormal messenger ribonucleic acid (mRNA) transcribed from a mutant insulin receptor gene in a patient with type A insulin resistance.

In a previous report on a 16-year-old Japanese girl with type A insulin resistance, we found that one allele of the insulin receptor gene was inherited from her mother and contained a 1.2 kilobase pair deletion which removed the 14th exon in the beta subunit. We extended investigation of the proband and found the deletion between two Alu sequences. To determine the effect of the deletion on the level of transcription and the splicing pattern of messenger ribonucleic acid (mRNA), we synthesized the complimentary DNA and used the polymerase chain reaction to amplify the region which included the deleted area. The deletion shifted the reading frame, resulting in a termination codon after amino acid 867 (Glu), thereby producing a truncated insulin receptor without a transmembrane region and cytoplasmic domain. We also sequenced each of 22 exons of the insulin receptor gene but found no mutation in exons of the insulin receptor gene, except for deletion of exon 14 of the maternal allele. Thus, the proband is a heterozygote for a single mutant allele. Abnormal mRNA transcribed from the mutant allele resulted in a decrease in insulin binding.

Adolescent