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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 703 records · Page 39Linked to original sources
PubMed1994

Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse.

About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases.

Administration, Oral↗
PubMed1994

Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart.

Cyclic nucleotide-gated cation channels are essential in visual and olfactory signal transduction. An additional member of the cGMP-gated channel family, termed CNG-3, has been cloned from bovine kidney. Its deduced amino acid sequence is 60% and 62% identical with the CNG-channel proteins from bovine rod outer segment and bovine olfactory epithelium, respectively. Northern analysis and sequences amplified by the PCR showed that the CNG-3 mRNA is present in testis, kidney, and heart. Calcium permeated the expressed channel in the presence of extracellular Mg2+ and Na+ at membrane potentials from -100 to +45 mV. It is likely that CNG-3 protein is responsible for cGMP-induced Ca2+ entry in cells other than sensory cells.

Animals↗
PubMed1994

Role of type II phospholipase A2 in the inflammatory process of carrageenan-induced pleurisy in rats.

In order to investigate the role of type II phospholipase A2 (PLA2) in the inflammatory process, the effect of a monoclonal antibody specific to type II PLA2 on carrageenan-induced pleurisy was studied in rats. Intravenous injection of the antibody (MB5.2), which inhibits the catalytic activity of type II PLA2, significantly reduced both the pleural exudate volume and the intrapleural leukocyte count, while a control antibody did not have any appreciable effect. MB5.2 caused no change in the level of type II PLA2 in the pleural fluid. These results suggest that type II PLA2 generated at inflamed sites, at least in part, have a crucial role in the pathogenesis of acute inflammation.

Animals↗
PubMed1994

Craniosynostosis and hemizygosity for D7S135 caused by a de novo and apparently balanced t(6;7) translocation.

Craniosynostosis (CRS) is frequently seen in the del(7p) syndrome, and the gene for this cranial anomaly (CRS1) has been assigned to 7p21. We present a 3-year-old boy with CRS involving the sagittal and coronal sutures, who had a de novo and apparently balanced translocation, t(6;7)(q16.2;p15.3). Southern blot analysis of several loci on 7p14-->pter showed that the patient was heterozygous for HOX1I and IL6, possibly homozygous for D7S149, but hemizygous for D7S135 with a loss of the paternal allele. These findings suggest the localization of a candidate gene for CRS1 to be on 7p15.3 in the close proximity to the D7S135 locus.

Blotting, Southern↗
PubMed1994

Antigen-receptor cross-linking induces peritoneal B-cell apoptosis in normal but not autoimmunity-prone mice.

BACKGROUND: Programmed cell death (apoptosis) is an essential process in the development of various tissues and seems to be involved in the elimination of self-reactive immature T and B lymphocytes when they interact with self antigens. Indeed, signaling through the antigen receptor of immature T cells induces their apoptotic cell death. Immature B cells have also been shown to be eliminated when they interact with antigens, although the involvement of apoptosis has yet to be demonstrated. In contrast, little is known about the elimination of mature lymphocytes upon interaction with antigens. We have previously demonstrated that Ly1 B cells in the peritoneal cavity of transgenic mice undergo apoptotic cell death upon interaction with antigens. As Ly1 B cells constitute a B-cell lineage distinct from conventional B cells, it is important to know whether conventional B cells also undergo apoptosis upon antigen-receptor cross-linking. RESULTS: Our experiments show that, in vivo, strong cross-linking of cell-surface immunoglobulins induced apoptotic death of normal, mature B cells in the peritoneal cavity, regardless of whether they were conventional or Ly1 B cells. The same treatment did not kill, but rather activated, B cells in bcl-2-transgenic, apoptosis-resistant mice. Peritoneal B cells from autoimmune-disease-prone New Zealand mouse strains were also found to be resistant to cell death induced by surface immunoglobulin cross-linking. CONCLUSION: Self-reactive B cells are eliminated by the binding of antigen at both mature and immature stages. B-cell activation appears to require, in addition to antigen binding, a second signal that induces expression of rescue molecules such as the bcl-2 gene product. Resistance to B-cell apoptosis induced by antigen receptor cross-linking may play a crucial role in the production of autoantibodies and in the pathogenesis of the autoimmune diseases found in the strains of mice used here.

Animals↗
PubMed1994

Coronary spasm in patients with coronary ectasia.

The incidence of coronary ectasia (CE) and the relationship between CE and coronary spasm that was said not to be apt to occur in patients with CE were studied. The study consisted of 1,373 patients (including 1,008 patients with ischemic heart disease) who underwent cardiac catheterization. In 74 patients with CE, coronary spasm was tested in 33 patients subjected to acetylcholine (ACh) provocation and in 17 patients subjected to ergonovine (Ergo) provocation. CE was found in 74 patients (5.4%), and its incidence was significantly higher (6.7%) in patients with ischemic heart disease. In addition, ACh and Ergo provocation tests gave positive results in 12 (36%) and 4 patients (24%), respectively. Spasm was not provoked as frequently in the ectatic portion as elsewhere. In addition, spasm was often found at the borders of the ectatic portion in both provocation tests. The incidence of coronary ectasia was higher than that described in previous reports, and coronary spasm was more often observed at the borders between ectatic and normal portions than elsewhere.

Acetylcholine↗
PubMed1994

The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid.

Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid). In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined. In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks. A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels. Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid. Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation. Serum prolactin levels were decreased by the administration of oxolinic acid. The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg). In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study. These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Administration, Oral↗
PubMed1994

A method to quantitate cerebral blood flow using a rotating gamma camera and iodine-123 iodoamphetamine with one blood sampling.

A method has been developed to quantitate regional cerebral blood blow (rCBF) using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique requires only two single-photon emission tomography (SPET) scans and one blood sample. Based on a two-compartment model, radioactivity concentrations in the brain for each scan time (early: t(e); delayed: td are described as: [formula: see text] respectively, where x denotes the convolution integral; Ca(t), the arterial input function; f, rCBF; and Vd, the regional distribution volume of IMP. Calculation of the ratio of the above two equations and a "table look-up" procedure yield a unique pair of rCBF and Vd for each region of interest (ROI). A standard input function has been generated by combining the input functions from 12 independent studies prior to this work to avoid frequent arterial blood sampling, and one blood sample is taken at 10 min following IMP administration for calibration of the standard arterial input function. This calibration time was determined such that the integration of the first 40 min of the calibrated, combined input function agreed best with those from 12 individual input functions (the difference was 5.3% on average). This method was applied to eight subjects (two normals and six patients with cerebral infarction), and yielded rCBF values which agreed well with those obtained by a positron emission tomography H2(15)O autoradiography method. This method was also found to provide rCBF values that were consistent with those obtained by the non-linear least squares fitting technique and those obtained by conventional microsphere model analysis. The optimum SPET scan times were found to be 40 and 180 min for the early and delayed scans, respectively. These scan times allow the use of a conventional rotating gamma camera for clinical purposes. Vd values ranged between 10 and 40 ml/g depending on the pathological condition, thereby suggesting the importance of measuring Vd for each ROI. In conclusion, optimization of the blood sampling time and the scanning time enabled quantitative measurement of rCBF with two SPET scans and one blood sample.

Aged↗
PubMed1994

Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography.

The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [14C]clorgyline in normal, conscious rat brain. [14C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [14C]methyliodide. Sixty minutes after [14C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.

Animals↗
PubMed1994

Basolateral K+ efflux is largely independent of maxi-K+ channels in rat submandibular glands during secretion.

The involvement of large-conductance, voltage- and Ca(2+)-activated K+ channels (maxi-K+ channels) in basolateral Ca(2+)-dependent K(+)-efflux pathways and fluid secretion by the rat submandibular gland was investigated. Basolateral K+ efflux was monitored by measuring the change in K+ concentration in the perfusate collected from the vein of the isolated, perfused rat submandibular gland every 30 s. Under conditions in which the Na+/K(+)-ATPase and Na(+)-K(+)-2Cl- cotransporter were inhibited by ouabain (1 mmol/l) and bumetanide (50 mumol/l) respectively, continuous stimulation with acetylcholine (ACh) (1 mumol/l) caused a transient large net K+ efflux, followed by a smaller K+ efflux, which gradually returned to the basal level within 10 min. These two components of the K+ efflux appear to be dependent on an increase in cytosolic Ca2+ concentration. The initial transient K+ efflux was not affected by charybdotoxin (100 nmol/l) or tetraethylammonium (TEA) (5 mmol/l) but the smaller second component was strongly and reversibly inhibited by charybdotoxin (100 nmol/l) and TEA (0.1 and 5 mmol/l). The initial K+ efflux transient induced by ACh was inhibited by quinine (0.1-3 mmol/l), quinidine (1-3 mmol/l) and Ba2+ (5 mmol/l), but not by verapamil (0.1 mmol/l), lidocaine (1 mmol/l), 4-aminopyridine (1 mmol/l) or apamin (1 mumol/l). Ca(2+)-dependent transient large K+ effluxes induced by substance P (0.01 mumol/l) and A23187 (3 mumol/l) were not inhibited by TEA (5 mmol/l or 10 mmol/l). A23187 (3 mumol/l) evoked a biphasic fluid-secretory response, which was not inhibited by TEA (5 mmol/l). Patch-clamp studies confirmed that the whole-cell outward K+ current attributable to maxi-K+ channels obtained from rat submandibular endpiece cells was strongly inhibited by the addition of TEA (1-10 mmol/l) to the bath. It is concluded that maxi-K+ channels are not responsible for the major part of the Ca(2+)-dependent basolateral K+ efflux and fluid secretion by the rat submandibular gland.

Acetylcholine↗
PubMed1994

Sulfamethizole capsule method. A new method for assessing gastric emptying of solids.

We have developed a new method that is capable of assessing gastric emptying in humans. This method is based on the rapid absorption of sulfamethizole in the upper small intestine. Sulfamethizole capsules are gelatin capsules that are filled with a solid composed of egg albumin and sulfamethizole. After subjects ingested of 15 capsules with ham and bread, blood concentrations of sulfamethizole were measured and the areas under the sulfamethizole concentration-time curve (AUC) were calculated as an index of gastric emptying. After ingestion of 99mTc-labeled sulfamethizole capsules, there was a statistically significant correlation between the percentage of radioactivity remaining in the stomach at 120 min and AUC for 120 min (r = -0.82, P < 0.01). This method yielded a reliable value for gastric emptying of a solid meal as estimated by AUC. This method can be considered safe and is easily applicable to human subjects for assessment of gastric emptying.

Adult↗
PubMed1994

Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction.

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)]fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.

Aged↗
PubMed1994

Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy: a comparative study with C-terminal(109-141)- and N-terminal(1-86)-region-specific PTHrP radioassay.

We evaluated the circulating forms of immunoreactive PTHrP in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109-141) fragment of PTHrP (C-RAS) and for the N-terminal(1-86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C) of PTHrP was calculated to be about 1: 14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) HHM patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1: 70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r = 0.86). The values also showed a close correlation with serum Ca; r = 0.75 for C-RAS and r = 0.81 for N-RAS. In addition, the correlations between the PTHrP reading obtained with the different RASs and serum Cr were: r = 0.42 with C-RAS and r = 0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP(109-141). In contrast, circulating concentrations of the PTHrP(1-86) fragment are very low, but detection of the PTHrP(1-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PTHrP(109-141) fragment with C-RAS.

Adolescent↗
PubMed1994

Precipitations of thyrotropin receptor-related peptides by immunoglobulin G of patients with Hashimoto's thyroiditis.

In order to study whether specific binding sites for Hashimoto's IgG exist in TSH receptor, we have examined the TSH receptor binding activity of IgG of patients with Hashimoto's thyroiditis using synthetic peptides corresponding to the amino acid sequences in the extracellular domain of human TSH receptor. Eight different peptides were synthesized, radiolabeled and examined by immunoprecipitation assay. Among the peptides studied, peptide (352-378) was significantly precipitated by IgG of patients with Hashimoto's thyroiditis compared with control subjects. Ten out of twenty patients with Hashimoto's thyroiditis showed more precipitations of peptide (352-378) than mean + 2SD of those of control subjects. Peptide (352-378) was precipitated by IgG in a dose dependent manner and the binding of peptide (352-378) to IgG was displaced by the addition of increased amount of cold peptide (352-378). Precipitations of peptide (352-378) positively correlates with both TGHA and MCHA titers. Two out of fourteen patients with Graves' disease, one out of seven patients with subacute thyroiditis and none of eleven patients with thyroid tumor showed more precipitations of peptide (352-378) than mean + 2SD of those of control subjects. These results suggest that one of binding sites for Hashimoto's IgG is present in the amino acid sequence of 352-378 in the extracellular domain of TSH receptor.

Amino Acid Sequence↗
PubMed1994

Susceptibility of ebiratide to proteolysis in rat intestinal fluid and homogenates and its protection by various protease inhibitors.

In order to estimate the intestinal stability of ebiratide [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], a novel adrenocorticotropic hormone (ACTH) analogue, after oral administration, the hydrolytic properties of ebiratide were determined in the rat small intestinal fluid and mucosal homogenates. Ebiratide was extremely stable in the rat small intestinal fluid, while it was degraded in various intestinal mucosal homogenates. Regional differences were observed in its proteolytic properties; e.g., the hydrolytic rates of ebiratide in jejunal and ileal mucosal homogenates were 2-3 times faster than that in duodenal and colonic homogenates. Degradation of ebiratide was markedly inhibited by aminoprotease inhibitors such as sodium glycocholate, puromycin, bestatin and bacitracin. These results suggest that co-administration of certain protease inhibitors are useful to improve the stability of ebiratide in the intestine.

Adrenocorticotropic Hormone↗
PubMed1994

Carcinogenicity studies of oxolinic acid in rats and mice.

A chronic feeding study was conducted to determine the carcinogenic potential of oxolinic acid, an antimicrobial agent, in rats and mice. Oxolinic acid was administered in the diet to Wistar rats (0, 30, 100, 300 or 1000 ppm; 50 rats/dose/sex) for 104 wk and to ICR mice (0, 50, 150 or 500 ppm; 50 mice/dose/sex) for 78 wk. Clinical signs, body weight, food consumption, autopsy findings and histopathological data were noted. Mortality was unaffected by oxolinic acid administration in neither species. In rats, body weight gain was suppressed in both sexes at 1000 ppm. Histopathological examinations conducted after autopsy at 104 wk revealed a slight increase in benign Leydig cell tumours of the testis at 1000 ppm, which did not appear until late in the lifetime of rats. No other treatment-related neoplastic lesions were observed in rats. Non-neoplastic lesions in males at 1000 ppm included Leydig cell hyperplasia and tubular atrophy of the testes. In mice, decreased body weight gain was observed in both sexes at 500 ppm, but no non-neoplastic or neoplastic lesions attributable to the treatment with oxolinic acid occurred in either sex. In conclusion, oxolinic acid induced benign Leydig cell tumours of the testis in rats at the highest dose level tested (1000 ppm). The no-effect level for tumour induction was confirmed to be 300 ppm (10.9 mg/kg/day) in rats. None was induced in mice.

Animals↗
PubMed1994

Isolated oculomotor nerve palsy following midbrain infarction.

A 62 year-old male patient presented with isolated oculomotor nerve palsy following a small infarction of the medial ventral midbrain, documented by magnetic resonance imaging. There was a 12-year history of hypertension, but no diabetes mellitus. Angiography revealed atherosclerosis of the paramedian mesencephalic arteries. Magnetic resonance imaging may be useful in patients with small brain stem infarctions.

Cerebral Angiography↗