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Biomedical subjects

A Murata

Publications and source records attributed to A Murata.

At least 91 records · Page 5Linked to original sources
PubMed1995

Inhibitory effect of a synthetic protease inhibitor (gabexate mesilate) on the respiratory burst oxidase in human neutrophils.

We investigated the mechanism by which the synthetic protease inhibitor gabexate mesilate inhibits the production of the superoxide anion by human neutrophils. We found that gabexate mesilate suppressed SOD-inhibitable cytochrome c reduction in a dose-dependent manner in intact neutrophils activated with phorbol ester. Gabexate mesilate slightly scavenged the superoxide anion in the pyrogallol assay. The reagent also inhibited superoxide anion production in a dose-dependent manner in a cell-free oxidase-activating system. Translocation of the cytosolic respiratory burst oxidase components, the 47- and 65-kDa proteins, to membranes was suppressed by the reagent in intact cells stimulated with phorbol ester. Gabexate mesilate also reduced arachidonic acid-induced translocation of the components to the membrane fraction in the cell-free system. These results demonstrate that gabexate mesilate suppresses superoxide anion production by reducing the translocation of the 47- and 65-kDa proteins to the plasma membrane.

Cell Membrane↗
PubMed1995

Interleukin-1 receptor antagonist modifies the changes in vital organs induced by acute necrotizing pancreatitis in a rat experimental model.

OBJECTIVE: Interleukin-1 (IL-1) is a mediator in some critical conditions such as septic shock and multiple organ failure. Acute pancreatitis is one of the noted causes of multiple organ failure but the mechanism by which local inflammation progresses to systemic disease is unknown. In this study, we used an IL-1 receptor antagonist (IL-1ra) to investigate whether multiple organ failure due to acute pancreatitis is mediated by IL-1, as in other causes such as severe infection, trauma, and major surgery. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory of a university medical school. SUBJECTS: Specific pathogen-free male Wistar rats weighing 200 to 250 g. INTERVENTIONS: Necrotizing pancreatitis was induced by retrograde injection of deoxycholate solution into the biliopancreatic duct. IL-1ra was injected intravenously at a dose of 10 mg/kg 15 mins before induction of acute pancreatitis and then infused continuously at a rate of 5 mg/kg/hr for the following 24 hrs. MEASUREMENTS AND MAIN RESULTS: Although treatment with recombinant human IL-1ra did not affect the degree of local pancreatic insult, it significantly reduced mortality, improved urine output as an indicator of the state of shock, and ameliorated the accumulation of neutrophils into the lung in a rat experimental pancreatitis model. CONCLUSIONS: We concluded that multiple organ failure in severe pancreatitis is mediated, at least in part, by IL-1 through the activation of neutrophils. Furthermore, we concluded that circulatory collapse may also be important in the mechanism of the lethal effect of pancreatitis.

Acute Disease↗
PubMed1995

[Usefulness of endotoxin-specific limulus test for the measurement of endotoxin in cerebrospinal fluid in diagnosis of bacterial meningitis].

Using a new endotoxin-specific chromogneic limulus assay (Endoscopy test), endotoxin concentrations were measured in 93 specimens of cerebrospinal fluid (CSF) from 66 pediatric patients. Eighteen patients were diagnosed as having menigitios. Of these, 6 cases (group A) with gram-negative meningitis proven by culture had high CSF endotoxin concentrations of 115.3, (82-133) (median, range) pg/ml. Ten cases (group B) with gram-positive or aseptic meningitis had endotoxin concentrations of 2.15 (0.1-3.6) pg ml. Other 2 cases with bacterial meningitis (group C), in whom no pathogen was detected, had CSF endotoxin concentrations of more than 100 pg/ml. Four cases with encephalitis (group D) and 45 cases with non-meningitis or non- encephalitis (group E), had CSF endotoxin concentrations of less than 5 pg/ml. Despite a negative culture after antibiotic treatment in group A patients, endotoxin was cleared slowly from the CSF. A clearing of endotoxin from CSF was followed by alleviation of fever with a more gradual decline in CRP values. In 2 cases of group C, the negative bacterial culture appeared to be attributable to the previous treatment with antibiotics. However, these patients had high CSF endotoxin levels, indicating gram negative bacterial meningitis. In 17 CSF specimens from 5 patients of group A, in whom Haemophilus influenzae was detected on admission, an additional a latex agglutination test for the detection of H. influenzae polysaccharide antigen was performed. Only 3 specimens from 3 patients with CSF endotoxin concentrations of more than 80 pg/ml had a positive agglutination test. These results suggest that quantitation of endotoxin concentrations is useful for the diagnosis of gram-negative meningitis. And also, the clearance of endotoxin from CSF during treatment appears to be useful in determining the timing of when antibiotic should be stopped.

Adolescent↗
PubMed1995

Interleukin 10 reduces mortality from severe peritonitis in mice.

Interleukin 10 (IL-10) is known to suppress the induction of proinflammatory cytokines such as tumor necrosis factor (TNF) and IL-1 and is itself induced by monocytes and macrophages during sepsis. We studied the therapeutic efficacy of IL-10 by testing its effect on the survival rate in the murine cecal ligation-and-puncture (CLP) model. Administration of 1 microgram or more of recombinant murine IL-10 6 h after induction of sepsis decreased lethality in septic mice significantly and also suppressed the elevation of circulating TNF after sepsis. However, treatment with the same dose of IL-10 simultaneously or 6 h before induction of CLP had no effect on survival, and treatment with anti-TNF antibody after induction of CLP had no effect on the survival rate. These data suggest that cytokine modulation with IL-10 is a potential candidate for the treatment of sepsis and sepsis-related multiple organ failure.

Animals↗
PubMed1995

Changes in serum granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) after surgical intervention.

To evaluate the physiological role of G-CSF following surgery, we measured the serum levels of immunoreactive IL-6 and G-CSF sequentially in nine patients after major elective thoracoabdominal surgery for esophageal carcinoma. Both G-CSF and IL-6 levels reached their maxima at the first postoperative day and decreased thereafter. There was a significant correlation between serum G-CSF (y) and IL-6 (x) levels (y = 3.273x + 3.991; r = 0.787, n = 78, p < 0.001). In the case that developed aspiration pneumonia and ARDS at the second postoperative day, the measured G-CSF level was less than half the predicted value. The relationship between serum G-CSF and IL-6 levels supports the central role of G-CSF as the host defense response modifier and, thus, low G-CSF levels in the circulation is one reason for the immunodeficient state after major surgery.

Aged↗
PubMed1994

Deficit of hand preshaping after muscimol injection in monkey parietal cortex.

In order to assess the functional role of the parietal hand movement region, the anterior part of the lateral bank of the intraparietal sulcus (IPS), area AIP, in the visual guidance of hand grasping, we reversibly inactivated several parts of this area with microinjections of Muscimol in a monkey trained to grasp objects of different shapes, sizes and orientations. During the local inactivation, some of the skilled patterns of finger movements were disrupted in the contralateral hand, due to the lack of preshaping to adjust the finger posture to the object; however, no major deficits in visual reaching were observed. The results suggest that area AIP plays a crucial role in the visual guidance of goal-directed hand movements.

Animals↗
PubMed1994

Effect of granulocyte-macrophage colony-stimulating factor on sepsis-induced organ injury in rats.

The administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with severe active infections has been questioned because activation of neutrophils may cause tissue injury. To identify the effect of GM-CSF administration on severe sepsis, we examined the survival rate and pathologic changes in vital organs using the rat lethal sepsis model. Rats received 20 micrograms of recombinant murine GM-CSF (rmGM-CSF) 3 hours after the onset of peritonitis induced by cecal ligation and puncture. After 48 hours, the survival rate did not improve, and earlier deaths than in the control group were observed. In addition, the inhibition of early leuko-sequestration in the peritoneal cavity was seen in animals treated with GM-CSF. These results suggested that the administration of rmGM-CSF after the onset of sepsis was not beneficial; thus, we concluded that care should be taken in the clinical use of GM-CSF in severe infection.

Animals↗
PubMed1994

Elevation of circulating monitor peptide/pancreatic secretory trypsin inhibitor-I (PSTI-61) after turpentine-induced inflammation in rats: hepatocytes produce it as an acute phase reactant.

Monitor peptide (MP) is a trypsin-sensitive cholecystokinin (CCK)-releasing peptide purified from rat pancreatic juice on the basis of its stimulatory activity toward pancreatic enzyme secretion and has been reported to exhibit cell growth-stimulating activity. Pancreatic secretory trypsin inhibitor (PSTI) prevents premature activation of trypsinogen in the pancreatic duct. There are two PSTIs (PSTI-61 and -56) purified from rat pancreatic juice on the basis of trypsin inhibitory activity as reported previously. Fushiki et al. (1989, FASEB J. 3, 121) showed that MP is structurally the same peptide as PSTI-61. We measured the serial changes of circulating MP/PSTI-61 in rat and those in the level of PSTI-61 mRNA in the rat liver to investigate another novel role of this peptide in the turpentine-induced acute inflammation model. The elevation of serum MP/PSTI-61 as well as the alpha 2-globulin fraction, which is known to include several acute phase reactants such as alpha 2-macroglobulin and haptoglobin, was observed after induction of the turpentine inflammation. The serum alpha 2-globulin fraction had increased approximately 3-fold over the initial level at 48 hr after the injection. In contrast, serum MP/PSTI-61 had increased approximately 17-fold over the initial level at 48 hr after the injection. The elevation of circulating MP/PSTI-61 was significantly related with that of the alpha 2-globulin fraction (r = 0.91, P < 0.01). Immunoreactive MP/PSTI-61 was detected in the liver after induction of the inflammation (152.5 +/- 16.5 ng/g wet weight), but in the normal rat liver there was no immunoreactive MP/PSTI-61.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1994

Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis-induced organ injury in rat.

Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and puncture-induced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.

Amino Acid Sequence↗
PubMed1994

Overexpression of pancreatic secretory trypsin inhibitor in pancreatic cancer. Evaluation of its biological function as a growth factor.

Four clones of pancreatic secretory trypsin inhibitor (PSTI)-overexpressing cells (TF-PANC clones 1, 6, 8, and 36) were established to evaluate the physiological function of PSTI secreted by cancer cells, by means of introducing a PSTI-expression vector (pRSV-PSTI) into the human pancreatic adenocarcinoma cell line (PANC-1). No obvious changes were observed in the histological features of these transplanted tumors in nude mice, in the growth of TF-PANC and PANC-1, or that of 3T3 fibroblasts when cocultured with them. Addition of recombinant human PSTI to the cultured media resulted in no increase in proliferation of fibroblasts (3T3 and WI-38) or of four pancreatic cancer cell lines (PANC-1, CAPAN-I, MIAPaCa-2, and Hs766T). These results suggest that the estimation of tumor-bearing PSTI as a paracrine or autocrine growth factor in recent studies should be given careful consideration.

3T3 Cells↗
PubMed1994

Enhanced attachment and elastase-releasing capacity of neutrophils after surgery.

Perioperative changes in neutrophil attachment level and neutrophil elastase-releasing capacity were examined in patients who underwent surgery for either esophageal or gastric cancer. The neutrophil attachment level was significantly increased in both groups to approximately three times that of the preoperative value. The elastase-releasing capacity of nonstimulated neutrophils was not significantly changed, but it was significantly increased in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). Moreover, both neutrophil attachment and elastase-releasing capacity of FMLP-stimulated neutrophils were more enhanced in patients with postoperative complications than in patients without complications. Peak levels of serum interleukin 6, serum alpha 1 proteinase inhibitor, and plasma neutrophil elastase were also significantly higher in patients with postoperative complications than in patients without. These results suggest that during the postoperative period, neutrophils may be primed and activated in response to inflammatory mediators such as cytokines, and that such an alteration of neutrophil functions may reflect the extent of inflammation and may, at times, be implicated in postoperative complications.

Aged↗
PubMed1994

Ipsilateral connections of the anterior cingulate cortex with the frontal and medial temporal cortices in the macaque monkey.

The present study was attempted to study ipsilateral corticocortical connections of the anterior part (area 24) of the cingulate cortex of the macaque monkey by means of wheat germ agglutinin-conjugated peroxidase (WGA-HRP) method. In 2 out of 4 Japanese monkeys (Macaca fuscata) that were injected with WGA-HRP into the anterior part of the cingulate cortex, the sites of injection were successfully localized within the cortical regions corresponding to areas 24a and 24b. The results obtained from these monkeys indicate that areas 24a and 24b in the anterior part of the cingulate cortex are reciprocally connected with the prefrontal, premotor, and motor cortical regions, and also with the medial temporal cortical regions. Areas 24a and 24b were strongly connected with the lateral and medial prefrontal cortices and area 6a beta of the premotor cortex, moderately with the remaining premotor cortex, and weakly with the motor cortex. In the medial temporal cortex, areas 24a and 24b were strongly connected with the prosubiculum, entorhinal cortex (area 28), and perirhinal cortex (areas 35 and 36), and weakly with areas TF and TH of the parahippocampal gyrus, throughout their rostrocaudal extent. In addition, areas 24a and 24b projected to the molecular layer of the CAI subfield of Ammon's horn and the external pyramidal layer of the presubiculum. Our findings suggest that areas 24a and 24b of the anterior cingulate cortex may constitute relays in the reciprocal pathways between the prefrontal cortex and the hippocampal, entorhinal and/or perirhinal cortical regions.

Animals↗
PubMed1994

Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus.

Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5; 0%), and rare in those infected with hepatitis C virus (1/9; 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus.

Adult↗
PubMed1994

Suppression of sex steroids by a gonadotrophin-releasing hormone agonist increases serum growth hormone-binding protein activity in girls with central idiopathic precocious puberty.

OBJECTIVE: The high-affinity growth hormone (GH)-binding protein corresponds to the extracellular domain of GH receptor. The direct role of sex steroids in pubertal bone growth may be an increased GH receptor-coupled GH action. We examine the GH-binding protein (GHBP) activity before and after the suppression of female sex steroids and the relation of GHBP to pubertal growth. PATIENTS: We studied six girls with central idiopathic sexual precocity without any prior gonadal suppression therapy. DESIGN: We measured GHBP activity before and 12, 24 and 48 weeks after the treatment with s.c. injection of a GnRH agonist (leuprolide acetate) every 4 weeks. MEASUREMENT: GHBP activity was measured by immunoprecipitation using anti-GH receptor monoclonal antibody. RESULTS: The treatment caused a decrease in the LH and FSH responses to GnRH test and plasma oestradiol, which resulted in decreased urinary GH excretion, plasma IGF-I levels, height velocity and bone age maturation. GHBP activity before the start of the treatment was normal (75 +/- 27% relative to adult pooled serum, mean +/- SD), and it was increased above adult level (122 +/- 29% at 48 weeks, P < 0.01) by the suppression of the pituitary-gonadal axis. There were significant negative correlations between GHBP and oestradiol (r = 0.452, n = 24, P < 0.05) and between GHBP and urine GH excretion (r = -0.462, n = 24, P < 0.05). CONCLUSIONS: The high-affinity GHBP is increased by the withdrawal of female sex steroid. The clinical significance of this finding may be interference with the binding of GH to its receptor resulting in a reduced IGF-I level and decreased height velocity. The mechanism warrants further study.

Body Height↗
PubMed1994

Two cases of insulin-dependent diabetes mellitus under insulin treatment with slow height velocity: relationship of growth hormone-binding protein, metabolic control and growth.

Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth. High affinity growth hormone-binding protein (GHBP), which is identical to the extracellular domain of growth hormone (GH) receptor, is present in the human sera. We have determined GHBP activity in two cases of poorly controlled IDDM with low height velocity in relation to metabolic control in order to determine the mechanism of resistance to GH in this condition, as indicated by low levels of GH-dependent growth factor IGF-I in the face of high serum GH levels. GHBP activity was within the normal range in two cases of IDDM with slow height velocity, low IGF-I and high hemoglobin-A1. In both cases, improved blood sugar control normalized IGF-I to result in accelerated height velocity without a major change in GHBP levels. These results may indicate either normal peripheral GH receptor or normal free portion of serum GH, and may suggest that the major defect in slow growth in poorly controlled diabetes is due to the post GH receptor.

Body Height↗
PubMed1994

Attainment of normal height in severe juvenile hypothyroidism.

Prolonged juvenile hypothyroidism results in a permanent loss in height that is related to the duration of thyroxine deficiency before adequate thyroxine replacement treatment. A 13 year old girl with severe juvenile hypothyroidism was studied prospectively. She had an undetectable serum thyroxine concentration, a height SD score of -6.6 SD, and a bone age of 5.8 years. The enlarged pituitary gland involuted with thyroxine treatment to produce an empty sella. In addition to thyroxine the girl was treated with a gonadotrophin releasing hormone agonist to avoid the progression of puberty for 18 months and with growth hormone to achieve normal adult height.

Adolescent↗
PubMed1994

[A case of Cushing's disease: hallucinatory paranoid state preceding physical symptoms].

A 39-year old woman presented with hallucinatory paranoid state, particularly with erotomania, around September, 1988 (at the age of 39), and was hospitalized in a mental hospital for 9 days from May 1, 1989, to receive major tranquilizer therapy. At admission, the leukocyte count was 10,400/mm3 showing a mild leukocytosis, and there was temporary adynamia in the upper extremities. Thereafter, mild leukocytosis persisted intermittently. On May 12, 1989, the patient visited the Department of Neuropsychiatry, Kansai Medical University, and clinical examinations revealed mental symptoms including insomnia and erotomania, delusion of reference and auditory hallucination without persecutory taint. She showed clear consciousness and well understanding. Characteristically, her expression and behavior were smooth and emotional communication was available. There were neither alterations in her basic mood, nor flaccid association of idea. No abnormalities were seen in the hair and skin, and buffalo hump was not observed. Blood examination revealed a leukocyte count of 10,700/mm3, suggesting a mild leukocytosis. According to the patient, the menses have been regular. Although major tranquilizer therapy has been maintained, she gradually developed emotional instability, and tended to show fatigue and regressive changes in her personality. She was hospitalized in a mental hospital from October 25, 1989 to July 24, 1991. Since 1990, when she was in the hospital, she gradually developed obesity, hypertension, acne, and diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗