Biomedical subjects

H Ishiguro

Publications and source records attributed to H Ishiguro.

At least 145 records · Page 8Linked to original sources

PubMed1996

Increase in hepatic tissue blood flow by teprenone.

The major objective of the present study was to evaluate mechanisms by which teprenone, a gastric mucosal protecting agent, increases hepatic mucosal blood flow using male Sprague-Dawley rats. Hepatic and gastric blood flow was measured using a laser blood flow meter after administration of teprenone, dissolved in Tween 80, into the inferior vena cava. Teprenone itself increased hepatic and gastric blood flow. It also increased hepatic and gastric blood flow in rats with acute hepatic disorders due to carbon tetrachloride (CCL4) and improved histological changes, such as inflammatory cell infiltration and fatty changes in the liver. The fact that blood endothelin (ET) concentrations increased after administration of teprenone suggest that teprenone has great affinity for ET beta receptors and shows ET beta-receptor antagonist-like effects. Hepatic blood flow decreased after administration of N-nitro-L-arginine methyl ester, a nitric oxide (NO) synthetase inhibitor, suggesting that teprenone increase NO activity. Teprenone was thought to increase hepatic and gastric blood flow by different mechanisms, because it increased gastric mucosal prostaglandin E2 concentrations.

Animals↗

PubMed1996

[A clinical evaluation of chest wall reconstruction].

From April 1987 to June 1995, we performed the chest wall reconstruction in 13 cases of 25 ones who had chest wall resection. The clinical records of these 13 patients were reviewed as follows. The histological diagnosis of these cases were direct invasion by primary lung cancer in 13 cases, malignant tumor of the chest wall in 5 cases, benign tumor or inflammation of the chest wall in 4 cases, local recurrence of the breast cancer and post operative radiation ulcer in each 1 case respectively, and mediastinal peripheral nerve sheath tumor in 1 case. Full diagnosis of the mediastinal malignant tumors were Ewing' sarcoma, chondrosarcoma, malignant lymphoma, malignant fibrous histiocytoma and eosinophilic granuloma in each 1 case respectively. The total number of resected ribs was 10 (bilateral 5 ribs with sternal body) in 1 case, 4 in 1 case, 3 in 6 cases, 2 in 2 cases and 1 in 4 cases. The following statement shows our methods of chest wall reconstructions. We treated one case with wide anterior chest wall resection, we treated by the Marlex-resin sandwich, 4 cases with 4 or 3 ribs of anterior or lateral chest wall, by sheets of Marlex mesh in layers, 3 cases with 3 ribs of posterior site, 1 case with 2 ribs and 4 cases with one rib, these 7 cases treated by cross sutures. And, we treated another 2 cases by pedicle omental flap and major pectoral muscle in each case respectively. The Marlex-resin sandwich has easy fixation and excellent stability, but it has also foreign body reaction. Therefore our case needed to remove of sandwich 10 months later for cellulitis and infection after the operation. Recently we use mostly sheets of Marlex mesh in layers, for the reconstruction of the chest wall with 3 or more rib's defect, but if it is more small defect, we use the cross suture method. The cross suture is very easy and effective method to maintain the stability of small chest wall defect.

Adolescent↗

PubMed1996

[Abnormal branching of left pulmonary artery to the lateral and posterior basal segments].

A 70-year-old male, underwent left lower lobectomy due to lung cancer, had an extremely rare form of left pulmonary artery branching. His pulmonary artery supplying to lateral and posterior basal segments (A9 + 10) was arisen anteriorly from the root of the left pulmonary artery in the mediastinum and ran below in the anterior portion of the upper lobe stem bronchus. Embriologically, this abnormality might be due to a derangement of anastomosis between the pulmonary arch system and splanic plexus in primitive lung, and was interpreted as one of the pulmonary sequestration. Clinically, particularly at thoracotomy, the presence of a large vessel in an unexpected location is very hazardous, so that preoperative pulmonary angiography is useful to detect the abnormal branching.

Aged↗

PubMed1995

Identification of a negative regulatory element in the 5'-flanking region of the human dopamine beta-hydroxylase gene.

Transient transfection experiments indicate that a 5'-flanking upstream domain, residing between -437 and -262 bp of the human dopamine beta-hydroxylase (DBH) gene, has a cell type-specific silencer function. This domain contains a putative silencer motif (which we designate DBH negative regulatory element, DNRE), showing sequence homology with the neural-restrictive silencer element (NRSE or RE-1) recently characterized in type II sodium channel, SCG10 and synapsin I genes. When the DNRE was placed at the proximal 262 bp of the homologous (DBH) promoter, it exhibited strong silencer activity both in DBH-expressing SK-N-BE(2)C as well as in DBH-nonexpressing HeLa cells. In addition, the DNRE also exhibited modest silencer activity upon a heterologous tk (herpes simplex virus thymidine kinase) promoter in both cell lines. Electrophoretic mobility shift assay demonstrated that nuclear extracts from both SK-N-BE(2)C and HeLa cells contain protein(s) that specifically bind to the DNRE. Formation of this DNRE/protein complex was specifically inhibited by an excess of unlabeled DNRE or NRSE. Finally, a similar sequence motif residing in the corresponding upstream area of the rat DBH gene also had a negative regulatory function, indicating that the silencer function of the DNRE is conserved in human and rat DBH genes.

Base Sequence↗

PubMed1995

Changes of growth inhibitory factor after stab wounds in rat brain.

The growth inhibitory factor (GIF) is a new metallothionein (MT)-like protein that is downregulated in Alzheimer's disease (AD) brain. The biological function of GIF has not been fully clarified yet. We have raised an antibody to the synthetic polypeptide that is specific for rat GIF. The purified antibody reacted to recombinant GIF and native rat GIF but not to MT or maltose-binding protein. Using the antibody and GIF cDNA probe, we investigated changes of GIF and GIF mRNA by Western and Northern blotting techniques in rat brains after stab wounds. The levels of GIF and GIF mRNA began to increase 4 days postoperation, reached a maximum at 14-21 days and sustained the increased level at least through 28 days. While both glial fibrillary acidic protein (GFAP) and GIF were recognized in astrocytes, the increases of these 2 proteins after stab wounds showed different patterns. The results indicated that GIF could play an important role in the repair after brain damage and also produce new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP.

Alzheimer Disease↗

PubMed1995

High-performance liquid chromatographic assay for farnesyl-protein transferase activity with dabsylated peptide.

An HPLC assay for farnesyl-protein transferase activity using a dabsylated peptide is described. The substrates used were a synthetic dabsylated nonapeptide, N-dabsyl-L-serinyl-L-methioninyl-L-glycinyl-L-++ +leucinyl-L-prolinyl-L-cysteinyl- L-valinyl-L-valinyl-L-methionine, corresponding to the C-terminal peptide sequence of human N-Ras p21 without the N-terminal serine, and farnesyl diphosphate. The product was separated from the substrates on a reversed-phase C18 column, using gradient elution with acetonitrile (0.05% trifluoroacetic acid)-water (0.1% trifluoroacetic acid) and was detected at 436 nm. The addition of the farnesyl group to the peptide was confirmed by MS and NMR. Enzymatic reaction was ascertained from the dependences on time, on the protein of the enzyme source and on the substrates. The reaction was specifically inhibited by L-cysteinyl-L-valinyl-L-valinyl-L-methionine, the tetrapeptide corresponding to the "CAAX" motif. The limit of detection was 2 pmol per 100-microliters reaction mixture. The farnesyl-protein transferase activity can quantitatively be measured up to 200 micrograms cytosolic protein in human liver. This method provides a convenient and quantitative assay for crude materials, such as tissue homogenate from clinical samples, without the use of radioactive probes and large amounts of Ras protein.

Alkyl and Aryl Transferases↗

PubMed1995

Cerulein-induced acute pancreatitis diminished vitamin E concentration in plasma and increased in the pancreas.

Redistribution of vitamin E in the rat body was studied during acute pancreatitis induced by two intraperitoneal doses of cerulein 40 micrograms/kg of body weight at 1-hr intervals. Hyperamylasemia (2064 +/- 521 vs 6419 +/- 129 U/dL) and pancreatic edema (pancreatic water content, 71 +/- 1.2% vs 78 +/- 2%) were observed. In this model the increased level of lipid soluble fluorophore was also observed (274 +/- 18 vs 120 +/- 9.0 relative fluorescence per g dry wt). Parallel with these changes was a decrease in the level of vitamin E in the serum and an increase in the pancreas. The concentration of vitamin E in the pancreas after 6 h was 162 +/- 8.5 ng/mg dry mass vs 128.1 +/- 6.1 ng/mg dry mass in control animals. The effect of heparin on vitamin E redistribution induced by acute pancreatitis was also investigated. It was found that heparin at a dose of 100 U/kg body mass prevents the drop of the vitamin E level in the serum as well as the increases in the concentration in the pancreas tissue. It was concluded that acute pancreatitis induced redistribution of vitamin E in the rat body. Moreover, we studied the effects of heparin treatment on oxidative stress in the pancreas tissue. Acute pancreatitis caused an increase in lipofuscin accumulation, and a decrease in protein sulfhydryl groups in citrate synthetase (CS) and in malate dehydrogenase (MDH) activity. Heparin treatment that protected vitamin E accumulation in the pancreas tissue did not influence the changes in the level of lipofuscin and proteins sulfhydryl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Expression of growth inhibitory factor (GIF) in normal and injured rat brains.

Immunohistochemical study on growth inhibitory factor (GIF) in rat brain has revealed that a glial cell layer on the surface of cerebral cortex and the cells surrounding Purkinje cells has been reported. In addition, neurons in gray matter were weakly immunostained for GIF. In situ hybridization using digoxigenin-labeled single-strand RNA probes also demonstrated that most of the neurons and small round cells, which were presumably astrocytes, expressed GIF mRNA in the cerebral cortex of rat brain. These findings indicate that GIF is produced in neurons as well as in astrocytes. The most prominent findings in this study are, a very strong reaction of GIF and GIF mRNA in the reactive astrocytes around the site of injury induced by stab wound or kainic acid injection. These results raised the possibility that GIF may act as an acute-phase protein in reactive astrocytes and have a role in tissue repair.

Animals↗

PubMed1995

[Familial myopathy associated with tubular aggregates--report of two siblings].

We reported two siblings with slowly progressive muscle weakness in proximal and peroneal muscles without atrophy, myalgia, cramps, or episodic weakness. The serum creatine kinase level was moderately elevated. The prominent features of their muscle pathology were accumulation of tubular aggregates in type 2 fibers, predominantly in type 2B fibers, and marked type 1 fiber atrophy. Three to eleven % of muscle fibers contained tubular aggregates. Electron microscopic examination revealed accumulation of double-walled tubular structures. Familial myopathy with tubular aggregates as a hallmark of muscle pathology is considered to be a new clinical form of childhood-onset familial myopathies.

Child↗

PubMed1995

The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on amylase secretion from guinea pig pancreatic acini.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel hypothalamic peptide, structurally related to vasoactive intestinal peptide (VIP). Our previous study in conscious dogs revealed that PACAP stimulated exocrine pancreatic secretion in a manner different from VIP. The objectives of this study were to characterize the effects of PACAP on amylase secretion and intracellular cAMP production in guinea pig pancreatic acini and to compare them with those of VIP and secretin. PACAP38 and PACAP27 (10(-10)-10(-8)M) stimulated amylase secretion from pancreatic acini in a concentration-related manner. The order of potency for amylase secretion was PACAP27 = VIP > PACAP38. The maximally stimulated amylase secretion by PACAP27 was not enhanced by VIP or secretin, but was synergistically increased by cholecystokinin and A23187. PACAP38 and PACAP27 (10(-2)-10(-7)M) increased intracellular cAMP levels in a concentration-related manner. The potency for cAMP production was PACAP38 = PACAP27 = VIP. These results suggest that PACAP38 and PACAP27, like VIP, directly stimulate amylase secretion from guinea pig pancreatic acini through alterations in cellular cAMP levels.

Amylases↗

PubMed1994

Homeobox-containing genes in the most primitive metazoa, the sponges.

The porifera represent the most primitive phylum of the metazoa. We identified three homeobox-containing genes in the freshwater sponge (Ephydatia fluviatilis). Genomic DNA of the sponge was subjected to amplification by PCR with two primers that corresponded to the helix-1 and helix-3 regions of the homeodomain. Using the amplified products as probes, we isolated two homeobox genes, designated prox1 and prox2. The amino acid sequences of the homeodomains of prox1 and prox2 were 72% and 62% identical to those of the NK-3 and Om(1D) genes of Drosophila, respectively. Screening of a sponge genomic library with degenerate oligonucleotides that corresponded to helix 3 further revealed the presence of one more homeobox gene, prox3. The amino acid sequence of the homeodomain of the prox3 product was 77% identical to that of the msh gene product of human. These results indicate that, when the metazoa appeared during the course of evolution, the multiple and distinct classes of homeobox-containing genes that have been identified in higher organisms already existed.

Amino Acid Sequence↗

PubMed1994

Interleukin-6 in transcatheter arterial embolization for patients with hepatocellular carcinoma. Effects of serine protease inhibitor.

BACKGROUND: Modulation of serum levels of circulating cytokines and inflammatory responses with a serine protease inhibitor was studied in 34 patients with hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS: The 34 patients were randomly divided into two groups: 17 patients received 500 mg gabexate mesilate, a serine protease inhibitor, intravenously twice a day for 5 days after TAE, and the remaining 17 patients did not receive the drug. RESULTS: In the patients not given the drug, circulating interleukin-6 (IL-6) markedly increased 1 day after TAE, reached a peak (approximately 8 times the pretreatment value) after 4 days, and remained elevated 7 days after TAE. In comparison, in the patients given the drug, circulating IL-6 was at a significantly lower level at 4 and 7 days after TAE (P < 0.05, respectively). Both groups did not show significant change in circulating interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) during the week after TAE. The drug also showed a tendency to keep patient temperature below 38 degrees C, and the elevation of serum C-reactive protein (CRP) concentration to less than 1 mg/dl after TAE (P < 0.05, respectively). CONCLUSIONS: The serum level of circulating IL-6 can be modulated by serine protease inhibitor, and this may contribute to suppressing inflammatory responses, such as fever and acute-phase protein synthesis, in the liver after TAE.

Aged↗

PubMed1994

Mechanical interactions between ice crystals and red blood cells during directional solidification.

Experiments in which red blood cells were frozen on a directional solidification stage under a microscope show that there is a mechanical interaction between ice crystals and cells in which cells are pushed and deformed by the ice crystals. The mechanical interaction occurs during freezing of cells in physiological saline and is significantly inhibited by the addition of 20% v/v glycerol to the solution. The addition of osmotically insignificant quantities of antifreeze proteins from the winter flounder or ocean pout to the physiological saline with 20% v/v glycerol generates strong mechanical interactions between the ice and the cells. The cells were destroyed during freezing in physiological saline, survived freezing in physiological saline with glycerol, and were completely destroyed by the addition of antifreeze proteins to the solution with glycerol. The difference in cell survival through freezing and thawing appears to be related, in part, to the habit of ice crystal growing in the suspension of red blood cells and the nature of mechanical interaction between the ice crystal and the cells. This suggests that mechanical damage may be a factor during cryopreservation of cells.

Animals↗

PubMed1994

Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate synthetase deficiency.

Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency.

Adult↗

PubMed1994

Modulation of the mevalonate pathway and cell growth by pravastatin and d-limonene in a human hepatoma cell line (Hep G2).

Modulation of cell growth by a combination of pravastatin [a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor] and d-limonene (an inhibitor of protein isoprenylation) was studied using Hep G2, a human hepatoma-derived cell line. Pravastatin, at 0.1 mM, produced 85% inhibition of cholesterol biosynthesis in Hep G2 cells. The combination of 0.1 mM pravastatin and 1.0 mM d-limonene had no further effect on the reduction seen with pravastatin alone. Addition of 0.1 mM pravastatin or 1.0 mM d-limonene did not significantly suppress DNA synthesis by the cells, whereas the combination suppressed it to 50% of the control level. Production of m-p21ras was markedly decreased to 35% of the control level by the combination of these two inhibitors. Both the reduction by pravastatin of farnesylpyrophosphate as substrate for protein:farnesyl transferase and inhibition of protein farnesylation by d-limonene seem to be responsible for the profound suppression of m-p21ras formation in the cells. However, dolichol synthesis was not suppressed by the combination of these inhibitors. In human fibroblasts, the combination suppressed m-p21ras production but not DNA synthesis. These findings suggest that the combination of pravastatin and d-limonene acts on cancer cell growth through inhibition of the post-translational processing of cellular proteins including p21ras, rather than through the suppression of cholesterol and dolichol biosynthesis. Thus, the combination of an HMG-CoA reductase inhibitor and an inhibitor of protein isoprenylation offers potential as a new approach for cancer therapy.

Antineoplastic Agents↗

PubMed1994

Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis.

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.

Acute Disease↗

PubMed1994

The cAMP-dependent protein kinase regulates transcription of the dopamine beta-hydroxylase gene.

Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine, and is expressed specifically in neurons and neuroendocrine cells that release norepinephrine and epinephrine. In the present study, we used DBH-expressing human neuroblastoma SK-N-BE(2)C and rat pheochromocytoma (PC12) cell lines to investigate the role of cAMP-dependent protein kinase (PKA) in transcriptional regulation of the DBH gene. Coexpression of the catalytic subunit of PKA (PKAc) robustly stimulated the transcriptional activity of the DBH gene in a dose-dependent manner. Conversely, coexpression of a specific inhibitor of PKA abrogated forskolin- and cAMP-mediated but not phorbol ester-mediated transcriptional induction of DBH. Deletion of the cAMP response element (CRE) dramatically reduced the stimulatory effect of PKA, indicating that the CRE mediates the induction of DBH by PKA. In DBH-nonexpressing HeLa and C6 glioma cell lines, coexpression of PKAc changed the transcriptional activity of the DBH promoter to a minimal degree, indicating that basal and PKA-mediated transcription of the DBH gene occur in a cell type-specific manner. Finally, both basal and cAMP-stimulated transcription of the DBH gene are diminished in three PKA-deficient PC12 cell lines, compared to wild-type cells. Based on these data, we conclude that PKA, via the CRE, plays an important role in basal and cAMP-inducible transcription, but is not required for phorbol ester-mediated induction, of the DBH gene in noradrenergic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[An immunoelectron microscopic study of distribution and density of nerve fibers innervating the rat iris].

We studied the sympathetic, parasympathetic and sensory nerve fibers in the rat iris using electron microscopic immunohistochemical techniques. Antibodies raised against tyrosine hydroxylase (TH), substance P (SP), and calcitonin gene-related peptide (CGRP) were used alone or combined together to characterize the nerve fibers. The ratios of the TH-positive, SP/CGRP-positive and TH/SP/CGRP-negative fibers were 18%, 37%, and 45% in the anterior half of the dilator stroma, 11%, 3%, and 86% in the posterior half of the dilator stroma, 45%, 26%, and 29% in the sphincter stroma, and 23%, 1%, and 76% in the sphincter muscle layer. These results confirm that the sympathetic and parasympathetic fibers doubly innervate both rat iris sphincter and iris dilator muscles, whereas sensory nerve fibers innervate mainly the stroma.

Adrenergic Fibers↗