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Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 217 records · Page 12Linked to original sources

[Use of hemostatic clips for endoscopic hemostasis and closure of an esophageal laceration caused by a fish bone].

An 82-year-old woman was admitted to our hospital because of hematemesis. She had had a feeling of a foreign substance in her throat for one week after having eaten fish. On admission she had a fever of 38 degrees C, Hb of 5.8 g/dl, CRP level of 8.8 mg/dl, and bilateral pleural effusions. Endoscopy revealed a deep longitudinal laceration with active bleeding in the esophagus that also caused mediastinitis. Endoscopic hemostasis and closure of the laceration was done with hemostatic clips. The esophageal injury seemed to have been caused by a fish bone. After the treatments described here were carried out, the patient's condition rapidly improved.

Aged↗

[An elderly case of post-bulbar Dieulafoy's ulcer].

The case is a 79-year-old man who came to our hospital with melena as chief complaint. Emergency endoscopy showed spurting bleeding from a small ulcer. We diagnosed as Post-Bulbar Dieulafoy's ulcer and performed hemostatic procedure with hemostatic clips. The forth endoscopy (7 days after admission) showed fresh clot and oozing bleeding after the third hemostatic clipping. Although we performed hemostatic procedure with the injection therapy of hypertonic saline epinephrine solution (HSE). The effective hemostatic procedure is discussed with reference to some related literature.

Aged↗

Attenuation of disrupted hepatic active oxygen metabolism with the recovery of acute liver injury in rats intoxicated with carbon tetrachloride.

In this study, we examined how disrupted hepatic active oxygen metabolism at a progressed stage of carbon tetrachloride (CCl4)-induced acute liver injury is attenuated with the recovery of the injury in fed rats. When the progression and recovery of liver injury were assessed by measuring the activities of serum transaminases, indexes of liver cell damage, at 2, 24, 48, and 72 h after a single intraperitoneal injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury was found at 2 h, the most progressed liver injury occurred at 24 h, and the progressed liver injury fairly recovered at 72 h. Hepatic superoxide dismutase and catalase activities decreased with the progression of liver injury but both decreases were maintained during the recovery of the injury. Hepatic glutathione peroxidase activity did not change with the progression and recovery of liver injury. Hepatic glutathione reductase activity decreased with the progression of liver injury and the decreased activity was returned up to the original level with the recovery of the injury. Hepatic glucose-6-phosphate dehydrogenase activity increased with the progression and recovery of liver injury but this increased activity was reduced at a late stage of the recovery. Hepatic reduced glutathione and ascorbic acid contents decreased with the progression of liver injury but both decreased contents were returned up to the original levels with the recovery of the injury. Hepatic vitamin E content decreased at an early stage of liver injury but this decreased vitamin E content increased over the original level with the progression of the injury and this increased vitamin E content was maintained during the recovery of the injury. Hepatic lipid peroxide content increased with the progression of liver injury and this increased content was returned near the original level with the recovery of the injury. These results indicate that in rats intoxicated once with CCl4, disrupted hepatic active oxygen metabolism at a progressed stage of liver injury is attenuated with the recovery of the injury mainly through the improvement of hepatic active oxygen metabolism mediated by the glutathione redox cycle and ascorbic acid.

Alanine Transaminase↗

[Development of beta-lactamase inhibitors].

The proportion of beta-lactamase producing bacteria in each species of clinical isolates is high (over 90%) in these years. According to the survey of bacterial resistance in 1995, higher proportion of resistant bacterial species against ampicillin, piperacillin (PIPC), cefazolin, cefotiam was observed. To overcome the bacterial resistance against these beta-lactam antibiotics, we have made a development of beta-lactamase inhibitor and its combination antibiotic. New beta-lactamase inhibitor, tazobactam (TAZ) showed strong inhibitory activity against various kinds of beta-lactamases including cephalosporinases. The combination antibiotic, TAZ/PIPC(TAZ combined with PIPC by 1 to 4) showed stronger antibacterial activity than PIPC against beta-lactamase producing stains. And also the activity of TAZ/PIPC was superior to PIPC in the mixed bacterial infection model in mouse. The in vitro and in vivo frequency of emergence of resistant bacteria from Enterobacteriacae treated with TAZ/PIPC was lower than that of PIPC or ceftazidime (CAZ). By these data, combined antibiotics with beta-lactamase inhibitor was effective to resolve the problems of bacterial resistances caused by beta-lactamases.

Animals↗

Rapid detection of lymphoma-specific translocations in interphase nuclei of non-Hodgkin's lymphoma by fluorescence in situ hybridization.

We have recently developed a method to detect tumor-specific rearrangement of the IgH gene in interphase nuclei by fluorescence in situ hybridization. Tumor-specific IgH gene rearrangement is equivalent to 14q32.33 translocation. Using this approach, we detected 14q32.33 translocation in 29 of 70 patients with B-cell non-Hodgkin's lymphoma (NHL). Chromosome t(3;14) was found in 10 of these 29 patients, and were demonstrated as a fusion signal of BCL6 and VH gene probes in interphase nuclei. Furthermore, in another series of 11 patients and a NHL cell line, we demonstrated t(14;18) and t(11;14) in interphase and metaphase cells with a combination of BCL2 (or PRAD1) with IgH gene probes. Interphase FISH with lymphoma-associated gene probes is a rapid procedure for cytogenetic diagnosis of B-cell NHL.

Cell Nucleus↗

An expression profile of genes in human retina and isolation of a complementary DNA for a novel rod photoreceptor protein.

PURPOSE: To characterize expression patterns of active genes in human retina, and to isolate novel genes that are uniquely expressed in this tissue. METHODS: A 3'-directed complementary DNA (cDNA) library that faithfully represents the composition of messenger RNA (mRNA) was constructed with an mRNA preparation from a cadaveric human retina. A total of 925 3' terminal sequences were collected by sequencing randomly selected clones, of which 789 were regarded as representing chromosomally coded genes (gene signatures [GS]). GS were compared with each other and searched against GenBank. The resulting expression profile, listing gene species and their frequency, represents the composition of mRNA in the retina. By comparing this expression profile with those obtained from 10 other source cells or tissues, genes uniquely active in the retina were discovered, including some not previously described. A full-sized cDNA corresponding to one of these was isolated and sequenced. Its expression was analyzed by multitissue Northern hybridization and in situ hybridization to the retina specimen. It was then mapped on human chromosomes. RESULTS: In the expression profile, 108 genes were detected recurrently, suggesting that they are very active. Fifty-five of them were identified in GenBank, including the most abundant opsin gene and several other genes for phototransduction. Among the remaining novel and active genes, 19 were considered unique to retina on the basis of their representation status in other expression profiles and in dbEST. One of these was identified as a gene that encodes a novel secretory protein expressed in a rod photoreceptor that maps to chromosome 18p11.3. CONCLUSIONS: The expression profile of active genes in the retina represents the composition of mRNA, which reflects the relative activities of genes in this tissue. A comparison of this expression profile with those obtained with other tissues resulted in isolation of a novel cDNA specifically expressed in the rod photoreceptor. It is anticipated that additional novel genes that are uniquely active in the neural retina may be obtained with the same strategy, leading to further clarification of the biologic or physiological characteristics of this tissue.

Amino Acid Sequence↗

Closed-loop subcutaneous insulin infusion algorithm with a short-acting insulin analog for long-term clinical application of a wearable artificial endocrine pancreas.

Considering the management and safety of the insulin delivery route when a wearable artificial endocrine pancreas is applied to ambulatory diabetic patients on a long-term basis, we developed a s.c. insulin infusion algorithm by analyzing the dynamics of a s.c. injected short-acting insulin analog (Insulin Lispro) by a three-compartment model. Principally the insulin infusion algorithm was developed as a transfer function with the first-order delay in both proportional and derivative actions to blood glucose concentrations. The parameters for this algorithm were calculated to simulate a physiological plasma insulin profile as closely as possible. By applying this algorithm with regular insulin, diabetic patients showed a 2 h postprandial hyperglycemia and a delayed hyperinsulinemia, followed by hypoglycemic episodes 4-5 h after oral glucose load, just as observed in the computer simulation study. However, using Insulin Lispro, a near-physiological glycemic control (postprandial blood glucose of 153.1 +/- 8.3 mg/100 ml at 60 min and 90.3 +/- 7.1 mg/100 ml at 180 min, respectively) could be achieved without showing any delayed hyperinsulinemia or hypoglycemia. Daily glycemic excursions were also controlled near-physiologically and although the daily insulin requirement (731.7 +/- 160.5 mU/kg/day) was slightly higher, it was not significantly different from that with i.v. insulin infusion (622.3 +/- 142.6 mU/kg/day). These results indicate that the application of s.c. insulin infusion algorithm with Insulin Lispro is feasible for long-term glycemic control with a wearable artificial endocrine pancreas in ambulatory diabetic patients.

Adult↗

Nicardipine and MK-801 attenuate platelet-activating factor increases following cerebral ischemia-reperfusion in gerbils.

The effects of pretreatment with nicardipine (dihydropyridine Ca2+ channel antagonist), Bay K8644 (dihydropyridine Ca2+ channel agonist), and MK-801 (N-methyl-D-aspartate-receptor antagonist) on changes of platelet-activating factor (PAF) concentrations in transient ischemic brain are reported. The tissue concentration of PAF increases significantly in hippocampus, cortex and thalamus by 210%, 169% and 168% of controls without ischemia-reperfusion, respectively after 1 h of reperfusion. Nicardipine (5 mg/kg) reduces the accumulation of PAF, the remaining increases in hippocampus, cortex and thalamus being 151%, 138% and 145% of the controls, respectively. In contrast, Bay K8644 (2.5 mg/kg) enhances the accumulation of PAF, its concentrations in hippocampus, cortex and thalamus being 376%, 233% and 204% of the controls, respectively. The Bay K8644 enhancement in hippocampus is completely inhibited by pretreatment of nicardipine (5 mg/kg). MK-801 (10 mg/kg) reduces the accumulation of PAF, the remaining increases in hippocampus, cortex and thalamus being 152%, 147% and 144% of the controls, respectively. Moreover, brain tissue from animals subjected to the combined pretreatment with nicardipine (5 mg/kg) and MK-301 (10 mg/kg) indicates there is greater inhibition of ischemia-induced PAF increases than with either drug alone. These results indicate that PAF production in the ischemic brain may be regulated by Ca2+ influx through voltage-sensitive Ca2+ channels which are antagonized and agonized by nicardipine and Bay K8644, respectively and receptor-operated Ca2+ channels which are antagonized by MK-801. Because it is known that increases of intracellular Ca2+ in the brain accompany ischemia and early periods of reperfusion and that PAF exhibits neurotoxicity, the present findings support the role of PAF as a mediator in ischemia-induced brain damage at early stages of reperfusion.

Analysis of Variance↗

Cloning and characterization of the 5'-upstream regulatory region of the Ca(2+)-release channel gene of cardiac sarcoplasmic reticulum.

To elucidate the transcriptional regulation mechanism for the Ca(2+)-release channel gene of the cardiac sarcoplasmic reticulum (RYR2), we isolated and analyzed the 5'-upstream flanking region of the gene. Sequence analysis indicated that the core promoter region lacks canonical TATA and CAAT boxes, but contains three overlapping GC boxes. A gel shift assay indicated that Sp1 binds to the region containing the GC boxes. Different 5'-deletion constructs in the 5'-flanking region of the RYR2 gene were fused to the luciferase gene, and their promoter activity in rat neonatal cardiac myocytes was subsequently determined. The results revealed the presence of a region containing positive regulatory elements in the 5'-flanking region. Analyses of substitutional mutations introduced into the GC boxes and the regulatory region indicated that in addition to the GC box located at -56 to -51, two regulatory elements (RYR2P1 and RYR2P2) are essential for the promoter activity. These results indicated that Sp1 and transcription factors that bind to RYR2P1 and RYR2P2 cooperatively enhance the expression of the RYR2 gene. In a transient transfection experiment involving promoter-luciferase gene constructs in skeletal muscle cells, we identified a negative regulatory region between positions -209 and -90 that represses the expression of the RYR2 gene in skeletal muscle cells.

Animals↗

Conversion of gamma-glutamylcysteinylethyl ester to glutathione in rat hepatocytes.

The conversion of gamma-glutamylcysteinylethyl ester (gamma-GCE) to glutathione in a reduced form (GSH) was examined using isolated rat hepatocytes pretreated with diethylmaleate, a GSH-depletor. Incubation of hepatocytes with 0.1 and 5.0 mM gamma-GCE (gamma-GCE-hepatocytes) over a 30-min period resulted in time-dependent increases in intracellular GSH and nonprotein-SH (NP-SH) concentrations. Hepatocytes incubated with 5.0 mM but not 0.1 mM GSH over a period of 30 min showed a time-dependent increase in intracellular GSH concentration. In the gamma-GCE-hepatocytes pretreated with bis-(p-nitrophenyl)phosphate (BNPP), a non-specific esterase inhibitor, an enhancement of intracellular GSH concentration was markedly reduced. gamma-GCE concentration in the gamma-GCE-hepatocytes with BNPP pretreatment was significantly higher than that in the cells without BNPP pretreatment, although there was no difference in the total amount of intracellular NP-SH, i.e., gamma-GCE, GSH, gamma-glutamylcysteine, cysteine ethyl ester, and cysteine between both gamma-GCE-hepatocytes. The present results indicate that gamma-GCE is transported into liver cells more easily than GSH itself, resulting in its conversion to GSH via esterase and glutathione synthetase within the cells.

Animals↗

Oxamflatin: a novel compound which reverses malignant phenotype to normal one via induction of JunD.

In the course of screening for inhibitors of tumorigenic phenotype of K-ras-transformed NIH3T3 cells (DT cells), we found a novel compound, oxamflatin, an aromatic sulfonamide hydroxamate derivative, which induces flat phenotype in these cells and suppresses their anchorage-independent growth. In contrast to DT cells, in v-raf-transformed NIH3T3 cells, no change in their morphology and no specific inhibition of their anchorage-independent growth was observed. Interestingly, oxamflatin was effective to NIH3T3 cells transformed by constitutively activated mutant of MEK, indicating the possibility that oncogene-induced morphological change is not necessarily induced by common signaling pathway such as MAP kinase cascade. In oxamflatin-treated DT cells, the expression of transcription factor junD was highly augmented, resulting in trans-activation of fibronectin gene by junD via cyclic AMP responsive element in its promoter. This behavior of junD was confirmed to correlate well with partial blocking of malignant phenotype in DT cells. Thus, oxamflatin can be categorized as the first reagent which induces genes whose products can interfere with oncogene-dependent transformation.

3T3 Cells↗

Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation.

The mammalian Cdc42 protein regulates various kinds of cellular responses, including formation of filopodia, polarization of T cells, and cell cycle progression. A non-receptor tyrosine kinase ACK, which specifically binds to the GTP-bound form of Cdc42, was isolated as a putative target of Cdc42. Here we show the induction of tyrosine phosphorylation of ACK in response to temperature shift-down to 25 degrees C, and hypertonic shock, as well as stimulation with epidermal growth factor (EGF) in human embryonic kidney (HEK) 293 cells. The increased tyrosine phosphorylation level upon temperature shift-down was sustained for at least 60 min, whereas reversion of the temperature to 37 degrees C caused rapid tyrosine dephosphorylation to the initial level. The responses to EGF and the high osmolarity were transient. Furthermore, we observed association of ACK with an adaptor protein Grb2, which may suggest the involvement of Grb2 in EGF receptor-mediated tyrosine phosphorylation of ACK.

Adaptor Proteins, Signal Transducing↗

Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene promoter.

The bone morphogenic proteins (BMPs) constitute a novel subfamily of the transforming growth factor type beta (TGF-beta) supergene family and play a critical role in modulating mesenchymal differentiation and inducing the processes of cartilage and bone formation. In this study we isolated the 5'-flanking region of the human BMP-5 gene. Nucleotide sequencing, primer extension, DNase I foot printing and functional analysis by transient expression showed that the cloned 1.5 kb promoter region contains two transcription start sites, a canonical TATA box (-17 approximately -12) and a number of consensus recognition sequences including GATA-1 (-582 approximately -576) and engrailed (-549 approximately -541).

Base Sequence↗

Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain.

The effects of transient global ischemia using bilateral carotid artery occlusion on regional cytokine levels in gerbil brain were investigated using enzyme-linked immunoassay techniques. Brain concentrations of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were increased during the early recirculation period ( < 6 h) after 10 min of ischemia, with lesser degrees of elevation following only 5 min of ischemia. TNF-alpha levels in the hippocampus and striatum were significantly increased as early as 1 h after recirculation, declining sharply to control levels by 12 h, then transiently increasing at 24 h. Elevated levels of IL-1 beta and IL-6 were not seen until 3-6 h post-occlusion. No significant increases in cytokine concentrations were observed in the cerebellum or thalamus. These results suggest that regionally selective increases in cytokines may be involved in the pathophysiological changes in hippocampus and striatum following transient cerebral ischemia.

Analysis of Variance↗