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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 631 records · Page 35Linked to original sources
PubMed1995

Histamine chloramines have a persistent stimulating effect on histamine H2 receptors and gastric acid secretion.

Histamine plays an important role in the control of gastric acid secretion. Recently, chlorinated derivatives of histamine have been identified as having multiple effects on the intestinal tract. The aim of this study was to investigate the role of histamine chloramines on gastric acid secretion. We compared the effects of histamine and histamine chloramines on the histamine H2 receptors in vitro using guinea pigs and on gastric acid secretion in rats. With respect to the effects on histamine H2 receptors, histamine monochloramine showed agonist effects similar to those seen with histamine, but the agonist effects of histamine dichloramine were about half those of histamine. Unlike histamine effects, the histamine H2 receptor agonist effects of histamine monochloramine and histamine dichloramine did not disappear after repeated washout. With respect to the stimulation of gastric acid secretion in vivo, histamine monochloramine was similar to histamine, while the effect of histamine dichloramine was 42.2-52.7% of that of histamine. The recovery time to the basal secretory level after completion of stimulation by histamine chloramines was significantly prolonged compared with histamine. These results suggest that histamine chloramines, which bind strongly with histamine H2 receptors, may delay the termination of gastric acid secretion and increase the burden on the gastric and duodenal mucosa.

Animals↗
PubMed1995

c-kit ligand mediates increased expression of cytosolic phospholipase A2, prostaglandin endoperoxide synthase-1, and hematopoietic prostaglandin D2 synthase and increased IgE-dependent prostaglandin D2 generation in immature mouse mast cells.

We have examined the cytokine regulation of IgE-dependent prostaglandin (PG) D2 generation in mouse mast cells by assessing the changes in the levels of the transcript, translated protein, and activity of the enzymes involved in the synthesis of PGD2 from endogenous arachidonic acid. When mouse mast cells, derived by culture of bone marrow cells with WEHI-3 cell-conditioned medium as a source of interleukin (IL)-3 (BMMC), were cultured in recombinant ckit ligand (KL), sensitized with IgE, and stimulated with antigen, PGD2 generation increased 3-fold; when KL was combined with IL-3, IL-9, or IL-10, PGD2 generation increased 6-8-fold above that produced by the cells cultured in IL-3 alone. The increased IgE-dependent PGD2 generation by BMMC was apparent after 1 day of culture, reached a maximum after 2-4 days of culture, and was dose-dependent for KL and for each of the accessory cytokines. IgE-dependent generation of leukotriene C4 increased 2-fold after the cells were cultured with KL and was not increased by the addition of IL-3, IL-9, or IL-10. Assays for steady-state transcripts by RNA blotting, for protein by SDS-PAGE/immunoblotting, and for function by enzymatic activities revealed that KL alone stimulated the increased expression of cytosolic phospholipase A2 (cPLA2), prostaglandin endoperoxide synthase (PGHS)-1, and the terminal enzyme, hematopoietic PGD2 synthase, without a change in expression of 5-lipoxygenase. IL-3, IL-9, and IL-10 each enhanced the KL-induced expression of PGHS-1. In contrast, transcripts for PGHS-2, which were detected transiently after the cells had been cultured for 5 h in KL+IL-3, were not expressed during the period of subsequent increase in IgE-dependent PGD2 generation. These findings demonstrate that KL up-regulates expression of cPLA2, PGHS-1, and hematopoietic PGD2 synthase, leading to a relatively selective increase in IgE-dependent production of PGD2 from endogenously released arachidonic acid in BMMC, and they provide the first example of cytokine regulation of hematopoietic PGD2 synthase.

Animals↗
PubMed1995

fra-2 promoter can respond to serum-stimulation through AP-1 complexes.

fra-2 (fos-related antigen-2) expression is detected at a basal level even in growth-arrested chicken embryo fibroblasts (CEF), but upon serum-stimulation high levels of its transcripts are transiently observed. This induction is delayed and prolonged compared to that of c-fos. Transient expression experiments in CEF using a series of constructs of chicken fra-2 promoter region linked to the CAT reporter gene indicated previously that serum response element (SRE) is not required for full serum inducibility. In this report, we show that constructs in which the CRE-like sequence and both AP-1 binding sites are disrupted lack serum inducibility, suggesting that either of these enhancers is important in serum induction of fra-2. In growth-arrested CEF, small amounts of Fra-2/c-Jun complex bind to the AP-1 consensus sequences in fra-2 promoter, while a significant part of the enhanced AP-1 binding activity after 60-120 min of serum stimulation is attributable to c-Fos/c-Jun heterodimer. At later times Fra-2/c-Jun again becomes the main complex. Transient expression assays in F9 cells indicated that c-Fos/c-Jun heterodimers have strong stimulatory effects on fra-2 promoter activity, while Fra-2/c-Jun complex has lower transcriptional activity than that of c-Jun homodimer. These results suggest that c-Fos (induced at earlier times) and c-Jun proteins are at least partly responsible for serum-induced expression of fra-2.

Animals↗
PubMed1995

Human prochymase activation. A novel role for heparin in zymogen processing.

Human prochymase is packaged with heparin in mast cell granules and appears to be activated by dipeptidylpeptidase I. We show that a high affinity interaction between heparin and prochymase allows the 2-residue propeptide to be cleaved by dipeptidylpeptidase I. A conserved Glu in the propeptide is necessary for this heparin effect. Following propeptide cleavage, capture of the newly generated NH2 terminus by an "activation groove" on the enzyme activates the enzyme and concurrently prevents a progressive degradation of the NH2 terminus by dipeptidylpeptidase I. Surrogate peptide studies show that the activation groove is unoccupied in prochymase and is specific for the chymase NH2 terminus. These observations indicate that heparin is an important cofactor in the prochymase activation process and explain how dipeptidylpeptidase I, a nonspecific processing enzyme, can effect a specific cleavage of the zymogen propeptide.

Amino Acid Sequence↗
PubMed1995

Administration of interleukin-5 or -10 activates peritoneal B-1 cells and induces autoimmune hemolytic anemia in anti-erythrocyte autoantibody-transgenic mice.

Activation mechanisms of B-1 (Ly-1 B) cells have been suggested to be different from those of conventional B cells. To assess the role of various interleukins (IL) in the activation of B-1 cells, we injected IL-4, IL-5 or IL-10 into nonanemic anti-red blood cells (RBC) autoantibody-transgenic mice, in which conventional B cells are clonally deleted but peritoneal B-1 cells persist without secreting Ig. Intraperitoneal or intramuscular injection of IL-5 or IL-10, but not IL-4, increased the number of antibody-producing peritoneal B-1 cells by four- to five-fold, resulting in increased anti-RBC serum autoantibody and induction of hemolytic anemia. These results suggest that IL-5 or IL-10 may play an important role in the terminal differentiation of B-1 cells into antibody-producing cells in vivo.

Anemia, Hemolytic, Autoimmune↗
PubMed1995

Species-specific mechanism in rat Leydig cell tumorigenesis by procymidone.

To clarify the mechanism of species difference in the induction of testicular interstitial cell tumor (ICT, Leydig cell tumor) between rats and mice, male Sprague-Dawley rats and ICR mice were fed procymidone at dietary concentrations of 700, 2000 or 6000 ppm and 1000, 5000, or 10,000 ppm, respectively, for 3 months. The Leydig cell functions were evaluated by serum testosterone and luteinizing hormone (LH) levels, testosterone levels in the testis, LH levels in the pituitary, the capacity of the testis to respond to gonadotropin stimulation, i.e., the production of testosterone in vitro, and by the testicular binding of labeled human chorionic gonadotropin (hCG). Measurement of testosterone and LH levels in rat serum, the testis, or the pituitary showed that both hormones were enhanced throughout the 3-month treatment period. The hypergonadotropism was associated with the increase of interstitial cell response to hCG in vitro for up to 3 months. As with rats, both serum and pituitary LH were increased in mice at 4 weeks but not at 13 weeks. However, in contrast to rats, no significant increase in testosterone was observed in mice either in vivo or ex vivo during the course of the study. This suggests a difference between the rat and mouse in the response of the Leydig cell to the LH stimulation associated with procymidone administration. These differences in the response of interstitial cells to procymidone may be the basis for the distinct species responses to procymidone-induced Leydig cell tumorigenesis. The sustained response of the Leydig cells to stimulation in the rat results in chronic hyperplasia and subsequent benign tumor formation, while the attenuated response of Leydig cells in the mouse is associated with neither hyperplasia nor neoplasia.

Administration, Oral↗
PubMed1995

Tetraethylammonium-insensitive, Ca(2+)-activated whole-cell K+ currents in rat submandibular acinar cells.

Using whole-cell patch-clamp techniques, we demonstrate, for the first time, that rat submandibular acinar cells contain a tetraethylammonium (TEA)-insensitive, Ca(2+)-activated K+ conductance which is not attributable to large conductance, voltage-sensitive, Ca(2+)-dependent K+ channels (maxi-K+ channels). Taken together with our recent K+ efflux and fluid secretion studies in intact rat submandibular gland, we postulate that the K+ conductance reported here may be involved in the basolateral K+ efflux pathway activated by cytosolic Ca2+ concentration during secretion by this gland.

Animals↗
PubMed1995

Carmofur-induced leukoencephalopathy: MRI.

Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an infrequent but serious association with leukoencephalopathy. To our knowledge, there has been no report of early MRI findings in this leukoencephalopathy. We describe a case in which diffuse high signal intensity of the entire cerebral white matter, including the corpus callosum, was seen on T2-weighted magnetic resonance images. Although similar findings can be seen in many other diseases, carmofur-induced leukoencephalopathy should be suspected in a patient treated with carmofur. It is important to know the clinical and MRI characteristics of this condition, for early diagnosis and better prognosis.

Antineoplastic Agents↗
PubMed1995

Critical amino acids responsible for conferring calcium channel characteristics are located on the surface and around beta-turn potentials of channel proteins.

Calcium ion is thought to be one of the initial signals in the process of synaptic modification. Various reports have described that the critical amino acids responsible for determining calcium permeability of ion channels are glutamic acid, glutamine, arginine, and asparagine. By using a computational method (MacPROT) distinguishing transmembrane, globular, and surface sequences of proteins, the present work predicts that the critical amino acids exist within surface regions of the proteins. Furthermore, occurrence of beta-turn probabilities can be predicted around these critical residues by the protein conformational prediction method of Chou and Fasman. The results suggest that the critical amino acids exist at hydrophilic spaces or canals of membranous channel proteins and that the redirection potential of the protein chain induced by the turn structures provides the conformational change requisite for the ion selectivity and gating (opening/closing) of the channels.

Amino Acid Sequence↗
PubMed1995

Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage.

Recent studies have indicated that ammonia is involved in the pathophysiology of Helicobacter pylori-associated gastric mucosal damage. Helicobacter pylori-associated chronic active gastritis is characterized by an invasion of neutrophils. We investigated the interrelationship among hypochlorous acid (oxidant produced by neutrophil), ammonia (product of Helicobacter pylori urease), and monochloramine (product of ammonia and hypochlorous acid) in the development of gastric mucosal damage in rats. Gastric mucosal lesions were produced by exposure of the gastric mucosa to ammonia, urea with urease, or urea with Helicobacter pylori in rats subjected to ischemia. Pretreatment with taurine (scavenger of hypochlorous acid) or antineutrophil serum significantly attenuated gastric mucosal lesions induced by the above test agents. Ammonia-induced gastric mucosal lesions were exacerbated in the presence of hypochlorous acid with concomitant generation of monochloramine. These results suggest that the ammonia, hypochlorous acid, and monochloramine triad may be important in Helicobacter pylori-mediated gastric mucosal damage.

Ammonia↗
PubMed1995

Mechanism of Helicobacter pylori-associated gastric mucosal injury.

Helicobacter pylori infection is associated with gastric mucosal damage and the infiltration of neutrophils. Myeloperoxidase from neutrophils produces hypochlorous acid, which yields monochloramine in the presence of ammonia produced by urease enzyme of Helicobacter pylori. The target cells of gastric mucosal damage are gastric mucosal cells and endothelial cells. We therefore tested the hypothesis that ammonium, hypochlorous acid, and monochloramine damage the target cells. We studied the in vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and activated neutrophils on the target cells. Cytotoxicity was measured by a 51Cr-release assay. Ammonium chloride, sodium hypochlorite, and monochloramine were toxic to labeled cells in a concentration dependent manner. The toxicity of these agents was in the order monochloramine > sodium hypochlorite >> ammonium chloride. Incubation of labeled cells with activated neutrophils, Helicobacter pylori, and urea resulted in cytolysis. These cytotoxicities were significantly inhibited by the scavenger of hypochlorous acid, taurine. Monochloramine is more toxic to the target cells than ammonium chloride. Although ammonium chloride at neutral pH by itself has little direct damaging effect on the gastric mucosa, it is damaging to the gastric mucosa through a reaction with hypochlorous acid, suggesting that it plays a role in Helicobacter pylori-associated gastric damage.

Animals↗
PubMed1995

Regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method.

By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO2) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear-unplugged resting condition. Regional CBF was measured by the autoradiographic method after intravenous administration of H2(15)O. Regional OEF and rCMRO2 were measured by the single inhalation of 15O2. With MR T1-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO2 images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO2 values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO2 values among the cortical gyri. Regional OEF for the pontine nuclei (0.34 +/- 0.04), the midbrain (0.35 +/- 0.05), the parahippocampal gyri (0.35 +/- 0.04 for the right and 0.37 +/- 0.05 for the left), and the thalami (0.37 +/- 0.05 for the right and 0.36 +/- 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 +/- 0.04) (p < 0.05 or less). The global CBF and CMRO2 were consistent with those obtained by the Kety-Schmidt method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Angiotensin-converting enzyme gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.

To examine the contribution of the angiotensin-converting enzyme (ACE) gene to hypertrophic cardiomyopathy (HCM), we determined the ACE insertion/deletion (I/D) polymorphism in 80 patients with HCM and 88 of their unaffected siblings and children. Patients were divided into familial or solitary HCM (FHCM or SHCM) groups with or without affected family members. Genotypes were identified by the polymerase chain reaction (PCR) with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene to amplify template DNA prepared from peripheral leukocytes. D-allele frequencies were 0.38 in all subjects, 0.42 in patients with HCM, and 0.35 in relatives (p < 0.05). The probability ratios were 1.98, 1.46, and 2.97 in patients with HCM, FHCM, and SHCM, respectively. The D allele frequency was higher in SHCM than in FHCM (p < 0.05). The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. Findings imply that the ACE D allele is one of the genetic contributing factors associated with cardiac hypertrophy in HCM.

Aged↗
PubMed1995

Primary intracranial plasma-cell granuloma: a case report and review of the literature.

BACKGROUND: Plasma-cell granulomas, which are characterized by the non-neoplastic proliferation of plasma cells, are primarily found in the lungs and upper respiratory tracts, and are extremely rare in the central nervous system. METHODS: An intracranial tumor of an 11-year-old boy was evaluated by histologic and radiologic examination. RESULTS: An 11-year-old boy had a 2-month history of mild headache and nausea. A computed tomography scan showed a round, slightly high-density mass surrounded by marked edema in the left frontal lobe. On magnetic resonance imaging (MRI), the mass had a slightly high signal intensity on the T1-weighted image and marked low signal intensity on the T2-weighted image. It was heterogenously enhanced with gadolinium-DTPA. Microscopic examination demonstrated a non-neoplastic mixed cell population with a predominance of plasma cells. Immunohistochemical staining revealed that it was characterized by a polyclonal plasma cell population. CONCLUSION: Our extensive search of the literature indicated this to be the ninth reported case of intracranial plasma cell granulation. The MRI was very useful for evaluating the extent of the intracranial lesions. The tumor was removed surgically and did not recur during a 2-year follow-up with no radiation therapy.

Brain Diseases↗
PubMed1995

Neutrophil-independent myocardial dysfunction during an early stage of global ischemia and reperfusion of isolated hearts.

The effect of global ischemia and reperfusion on the expression of cytokine genes and cell adhesion molecules by myocardial tissues and neutrophils was studied by using the Langendorff model. Although cardiac function deteriorated after reperfusion of ischemic hearts, there was no evidence of inflammation and myocardial degeneration, which is in contrast to previous findings that neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion injury in regional ischemia. Flow cytometry analysis demonstrated that the global ischemia and reperfusion did not affect the expression of adhesion molecules on neutrophils. We also examined the expression of various cytokines which are involved in inflammatory responses. Only interleukin 1 alpha was induced after the reperfusion of the ischemic hearts. These results suggest that neutrophils barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in post-ischemic myocardial dysfunction during the early stage of reperfusion.

Animals↗
PubMed1995

The rat neutrophil low-affinity Fc receptor for IgG: molecular cloning and functional characterization.

A complementary DNA (cDNA) clone encoding rat Fc gamma receptor II (Fc gamma RII) was isolated from rat neutrophils and characterized. The cDNA encodes a type I transmembrane protein with 285 amino acids having an extracellular domain consisting of two immunoglobulin-like domains (179 amino acids), a transmembrane domain (26 amino acids), and a cytoplasmic domain (47 amino acids). The nucleotide sequences are identical to that of recently cloned Fc gamma RII from rat mast cells. This protein was expressed on FcR-negative Chinese hamster ovary (CHO) cells. The characterization of cDNA-transfected CHO cells clearly indicated that the protein encoded by the cDNA clone binds guinea-pig IgG1 and IgG2 complexes and unexpectedly binds monomeric rat IgG1, but not IgG2. Furthermore, the affinity for immune complexes was significantly augmented by protease treatment of transfectants. In addition, endocytosis of immune complex was noted in transfectants.

Animals↗
PubMed1995

Involvement of B-1 cells in mucosal immunity and autoimmunity.

B-1 cells are distinguished from conventional B cells by their anatomical localization, surface phenotypes and functional characteristics. The physiological functions and pathological roles of these cells remain controversial. In this review, Masao Murakami and Tasuku Honjo summarize recent evidence for the involvement of B-1 cells in mucosal immunity and autoimmunity, and discuss the relationship between these phenomena.

Animals↗