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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 739 records · Page 41Linked to original sources
PubMed1994

Molecular characterization and functional expression of squid retinal-binding protein. A novel species of hydrophobic ligand-binding protein.

The primary structure of squid retinal-binding protein (RALBP) was determined by cDNA and protein sequencing. Squid RALBP contains 342 amino acid residues in a single N-terminal-blocked chain with a molecular weight of 39,111. The N alpha-blocking group was identified as an acetyl moiety by mass spectrometry. The amino acid sequence revealed that the protein is highly hydrophilic and acidic, but it has several hydrophobic regions that are located mainly in the middle part of the polypeptide chain. It is also predicted that these hydrophobic regions form beta-sheet structures. The primary structure of RALBP is, however, quite distinct from those of other retinoid-binding proteins, showing that squid RALBP is a novel hydrophobic ligand-binding protein that functions in intracellular retinoid transport. Using the cloned cDNA, squid RALBP was expressed in vitro. By carrying out the translation at 20 degrees C in reticulocyte lysates, the protein having retinol binding activity was produced.

Amino Acid Sequence↗
PubMed1994

Synaptophysin and chromogranin A immunoreactivities of Lewy bodies in Parkinson's disease brains.

Lewy bodies commonly observed in brains with Parkinson's disease (PD) histochemically contain both protein and lipid as chemical components. Ultrastructurally, they are composed of filamentous, vesicular and granular structures. We investigated PD brains with light and electron microscopic immunohistochemistry using antibodies against two marker proteins for neuronal secretory vesicles, synaptophysin and chromogranin A. Both antibodies immunolabeled the peripheral zones and occasionally central cores of Lewy bodies of the classical and intraneuritic types. In addition, the diffuse immunolabeling was observed in Lewy bodies of the cortical type. Furthermore, the ultrastructural immuno-decoration was found mainly in the vesicular structures, and also in the filamentous and granular structures of Lewy bodies. Immuno-blot analysis of each antibody showed no difference between PD and normal control brains. The present observations suggest that vesicular profiles of Lewy bodies represent presynaptic and dense core secretory vesicles, and therefore that the lipid elements of Lewy bodies are derived from membrane lipids of these vesicles.

Aged↗
PubMed1994

Oxidation and keto reduction of 12-hydroxy-5,8,10,14-eicosatetraenoic acids in bovine corneal epithelial microsomes.

The R and S enantiomers of 12-hydroxyeicosatetraenoic acid (12-HETE) exhibit different biological activities. Although they appear to be produced by different enzymatic pathways, cytochrome P-450 monooxygenase and lipoxygenase, respectively, they display similar metabolism in both corneal epithelium and neutrophils. In corneal epithelial microsomes, both enantiomers are subject to oxidation and keto reduction reactions to form the dihydro metabolite, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE), via a keto intermediate. The apparent Km for the formation of 12-HETrE was 17.9 and 20 microM for 12(R)-HETE and 12(S)-HETE, respectively, and the apparent Vmax of the reaction was 17.4 and 8.2 pmol/mg per min, respectively. Chiral analysis of the dihydro metabolite demonstrated a product enantiospecificity. Arachidonic acid, 12(R)-HETE, 12(S)-HETE and the intermediate of this reaction, 12-oxo-ETrE, were metabolized predominantly to 12(R)-HETrE in a ratio [12(R)-HETrE: 12(S)-HETrE] of 7.3:1, 4.3:1, 1.5:1 and 2.3:1, respectively. 12(R)-HETrE is a potent vasodilator, chemotactic and angiogenic factor whose synthesis is induced in inflamed tissues; 12(S)HETrE is devoid of these properties. 12(R)-HETE, derived from NADPH-dependent cytochrome P-450 monooxygenases, and 12(S)-HETE, derived from 12-lipoxygenase, may both play an important role in regulating the inflammatory response by serving as substrates for the local synthesis of 12(R)-HETrE.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Alloreactive feature of HLA-DP-specific cytotoxic T-cell clone.

The alloreactive feature of CD4+ cytotoxic T-cell clone that could specifically lyse the cells bearing DPB1*0202 sequence was described. The clone was generated from a mixed culture of peripheral blood lymphocytes derived from siblings who were HLA-A, B, C, DR, and DQ identical by serological typing and whose DNA sequence of the second exon of DPB1 was one-allele mismatched by oligonucleotide typing (responder, PDB1*0201/0402; stimulator, DPB1*0202/0402). Specific cytotoxic activity of the clone was strictly limited against the cells bearing DPB1*0202 and was not able to lyse the other tested cells bearing DPB1*0201, 0301, 0401, 0501, 0601, 0901, 1301, and 1601. The cytotoxic activity of the clone was blocked by treatment of target cells with anti-DP monoclonal antibodies (B7/21). On the other hand, treatment of target cells with blocking agents of endogenous or exogenous antigen transport pathway (brefeldin A (BFA), endogenous; chloroquine, exogenous) had no effect on the cytotoxic activity of the clone. These results strongly favor the view that the DP epitopes recognized by the clone are conformational epitopes conferred by specific amino acids in hypervariable regions of the HLA-DP second DPB1 exon and the contribution of peptides in the HLA grooves to the conformational epitope motif is less likely.

Acyclovir↗
PubMed1994

The presence of giant granules in the juxtaglomerular cells of beige rats may affect plasma renin activity and blood pressure.

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder, characterized histopathologically by giant granules in various cells. Since little is known about the juxtaglomerular (JG) cells of CHS, the present study was undertaken as a morphological investigation of the JG cell of Beige rats, which were found to be a new animal model of CHS. In addition, we measured the blood pressure and plasma renin activity. The blood pressure of Beige rats is similar to that of DA rats, the mother strain of Beige rats. However, the plasma renin activity of Beige rats increases with age, whereas that of DA rats decreases. Morphologically, JG cells of Beige rats gave no evidence of hyperplasia and hypertrophy. The most conspicuous change was a small number of giant JG granules. Ultrastructurally, JG granules of Beige rats were large, irregular, and varied in size at 2 months of age, but no age-dependent changes were detected. These results suggested that giant JG granule formation slightly increases renin release with age, but does not affect blood pressure.

Animals↗
PubMed1994

The presequence of the precursor to the nucleus-encoded 30 kDa protein of photosystem II in Euglena gracilis Z includes two hydrophobic domains.

A cDNA clone for the extrinsic 30 kDa protein (OEC30) of photosystem II in Euglena gracilis Z was isolated and characterized. The open reading frame of the cDNA encoded a polypeptide of 338 amino acids, which consisted of a long presequence of 93 amino acids and a mature polypeptide of 245 amino acids. Two hydrophobic domains were identified in the presequence, in contrast to the presence of a single hydrophobic domain in the presequence of the corresponding proteins from higher plants. At the N- and C-terminal regions, respectively, of the presequence, a signal-peptide-like sequence and a thylakoid-transfer domain were identified. The presence of a long and unique presequence in the precursor to OEC30 is probably related to the complexity of the intracellular processes required for the synthesis and/or transport of the protein in Euglena.

Algal Proteins↗
PubMed1994

Bundles of amyloid precursor protein-immunoreactive axons in human cerebrovascular white matter lesions.

Cerebral white matter lesions commonly observed in Binswanger's disease, multi-infarct encephalopathy and elderly people are neuropathologically characterized by diffuse incomplete demyelination and considered to be ischemic in nature. Arteriolosclerosis in the white matter is a common feature in these white matter lesions. To investigate a possible alteration of the distribution of amyloid precursor protein (APP), chromogranin A (CgA) and synaptophysin (Syn) in such white matter lesions, we examined 15 cases with white matter lesions and 5 without white matter lesions. Many bundles of axons with APP-like immunoreactivity (LI) were observed particularly in mild white matter lesions. Such bundles of axons showed similar but less intense CgA-LI and Syn-LI. They appeared to occur in areas with many ameboid or ramified microglia labeled with anti-leukocyte common antigen and few astrocytes labeled with anti-glial fibrillary acidic protein. In the center of moderate of severe white matter lesions bundles of axons with APP-LI were never observed. Since APP, CgA and Syn undergo fast axonal transport, and since following ischemic insults to central nervous system microglial reaction occurs earlier than astroglial changes, our results suggest that axonal damage, which induces disturbance of fast axonal transport, can occur even in the early stage of white matter lesions.

Aged↗
PubMed1994

Corticobasal degeneration: a disease with widespread appearance of abnormal tau and neurofibrillary tangles, and its relation to progressive supranuclear palsy.

The neuropathological findings, including immunohistochemistry and electron microscopy, of two patients with clinical findings consistent with corticobasal degeneration (CBD) are reported. Both patients showed degeneration of the precentral cortex, the substantia nigra, the pallidum, and the thalamus. Many ballooned neurons were seen in the cerebral cortex, and argentophilic, skein-like inclusions suggesting neurofibrillary tangles (NFTs) were found in the brain stem and precentral cortex in patient 1. In contrast, patient 2 clearly showed NFTs in the brain stem and dentate nucleus which were indistinguishable from those seen in progressive supranuclear palsy (PSP), while only a few ballooned neurons were found in the cerebral cortex. Gallyas silver stain showed many argentophilic inclusions suggesting NFTs in the brain stem, subcortical nuclei, and cerebral cortex in both patients. Immunohistochemistry for tau showed tau-positive neurons in the cerebral cortex, brain stem, subcortical nuclei and spinal cord, and tau-positive glial cells were seen in the cerebral cortex, white matter and subcortical nuclei, and thread-like structures were seen in the cerebral cortex and white matter. Electron microscopy of the brain stem showed NFTs consisting of paired helical filaments in patient 1, and paired helical filaments and straight tubules in patient 2. Immunoelectron microscopy revealed parallel tau-positive filaments in the cerebral cortex in patient 1. From the two patients, the wide-spread appearance of abnormal tau and NFTs is one of the essential pathological features in CBD, and it also appears that CBD and PSP have some common underlying pathological processes. Patient 2 is closer to PSP than patient 1 and suggests CBD would link to PSP.

Aged↗
PubMed1994

Cloning and sequence analysis of a Streptomyces cholesterol esterase gene.

Streptomyces lavendulae H646-SY2 produces cholesterol esterase (CHE; EC 3.1.1.13) extracellularly. A genomic library of the strain, prepared in plasmid pUC119, was screened with probes based on the amino acid sequence of the protein. A plasmid, designated as pKX101 and identified by hybridization with the probes, contained a 2.7-kb insert from Streptomyces DNA. We determined the 17-N-terminal amino acid sequence of mature CHE and the nucleotide sequence of the 0.9-kb segment containing the CHE gene (che). We found that the N-terminal of the mature CHE was Ala39 and an open reading frame consisting of 681 bp starts at ATG and ends at TGA, suggesting that a precursor and a mature CHE consist of 227 and 189 amino acids, with a calculated relative molecular mass of 24,362 and 20,650, respectively. The leader peptide extends over 38 amino acids and has the characteristics of a signal sequence, including basic amino acids near the N-terminus and a hydrophobic core near the signal cleavage site.

Amino Acid Sequence↗
PubMed1994

Effects of membrane lipid peroxidation by tert butyl hydroperoxide on the sodium current in isolated feline ventricular myocytes.

Membrane lipid peroxidation is known to play a pivotal role in the genesis of coronary reperfusion arrhythmias in both experimental and clinical settings. To elucidate the electrophysiological mechanisms underlying these arrhythmias, the effects of tert butyl hydroperoxide (TBH) on the Na+ current (INa) in isolated feline ventricular myocytes were studied using whole-cell patch clamp techniques under 100% O2 bubbling. This agent at 20 mM inhibited INa from 2.2 +/- 1.3 to 1.7 +/- 1.0 nA (P < 0.01, n = 7) without changing time courses of INa inactivation. Twenty millimoles TBH shifted the steady-state inactivation curve for INa from -77.4 +/- 1.7 to -81.3 +/- 1.8 mV when measured at INa half inhibition voltage (P < 0.01, n = 7), but did not affect the slope factor. The kinetics of INa recovery from inactivation remained unchanged. These findings suggest that lipid peroxidation in the membrane by TBH reduces INa conductance and voltage-dependent INa availability, most likely as a result of structural damage to the Na+ channels.

Animals↗
PubMed1994

Myocardial protective effect and its mechanism of leukocyte-depleted reperfusion in neonatal rabbit hearts.

Thirty-six isolated blood-perfused hearts from newborn rabbits (age range, birth to 2 days) were subjected to 2 hours of cold global ischemia (15 degrees C), with an initial infusion of cold crystalloid cardioplegic solution, followed by 30 minutes of reperfusion (37 degrees C). The hearts were divided into two groups: those reperfused with whole blood (n = 18) and those reperfused with leukocyte-depleted blood (n = 18) obtained by the passage of blood through a leukocyte removal filter. At 30 minutes of reperfusion, the group of hearts reperfused with leukocyte-depleted blood showed significantly higher percentages of recovery in terms of the left ventricular developed pressure, the maximum rate of increase of left ventricular pressure, the rate pressure product, coronary sinus flow, and the adenosine triphosphate content in myocardium than did the group of hearts reperfused with whole blood. The hearts reperfused with leukocyte-depleted blood also showed significantly lower levels of malondialdehyde, chemiluminescence in the coronary sinus effluent, and counts of intracapillary neutrophils in myocardium than did the group of hearts reperfused with whole blood. The ultrastructural semiquantitative assessment in the myocardium showed that the mitochondrial and endothelial cell damages after 30 minutes of reperfusion were significantly less in the hearts reperfused with leukocyte-depleted blood than those in the hearts reperfused with whole blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Role of pulmonary intravascular macrophages in anti-platelet serum-induced pulmonary hypertension in sheep.

It has been reported that an injection of anti-sheep platelet serum (AsPS) induces transient pulmonary hypertension in sheep, but the mechanism by which this occurs has not been well explained. To examine the hypothesis that pulmonary intravascular macrophages (PIMs) are involved in this phenomenon, we investigated the morphological features of PIMs from sheep that received three different kinds of AsPS injections. The pulmonary arterial pressure response was examined not only in sheep that have many PIMs in the lung and had received AsPS, but also in rats that reportedly have few PIMs and had received an injection of anti-rat platelet serum. The pulmonary arterial pressure responses of the two species were quite different in quality and quantity. In sheep whose pressure response was definitely positive in association with production of thromboxane in the pulmonary circulation, PIMs were found by fluorescent microscopy and electron microscopy to phagocytize aggregated platelets that bound AsPS. These results suggest that PIMs significantly contribute to AsPS-induced transient pulmonary hypertension in sheep.

Animals↗
PubMed1994

Spinal cord blood flow during prostaglandin E1 induced hypotension.

To evaluate the effect of prostaglandin E1 (PGE1) induced hypotension on spinal blood flow (SBF) during spinal surgery, SBF was measured under isoflurane anaesthesia by the heat clearance method in 10 patients with spinal tumour. An initial dose of 0.1 microgram/kg/min of PGE1 was administered intravenously after spinal opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. PGE1 was discontinued at the completion of the operative produces. After starting PGE1, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the hypotensive effect of PGE1 remained constant at 60 min after its discontinuation. Heart rate (HR) did not change throughout the study. SBF showed no change over the course of PGE1 induced hypotension (preinfusion: 47.8 +/- 21.7 ml/100 g/min, at 15 min: 41.2 +/- 16.9 ml/100 g/min, at 30 min: 40.4 +/- 16.8 ml/100 g/min, and at 60 min: 46.1 +/- 16.3 ml/100 g/min, respectively). These results suggest that PGE1 may be a useful drug for hypotensive anaesthesia in surgery for spinal cord tumours because PGE1 maintained SBF.

Aged↗
PubMed1994

Low dose intrathecal morphine and pain relief following caesarean section.

Healthy women who underwent caesarean section under spinal anaesthesia were studied to determine the extent of postoperative analgesia and side-effects produced by low doses of intrathecal morphine. Patients were randomly allocated to receive, in double-blind fashion, 0 mg (group 1: control group), 0.05 mg (group 2), 0.1 mg (group 3), or 0.2 mg (group 4) of morphine, with 10 mg tetracaine in 10% dextrose 2.5 ml. (n = 20 x 4 groups). The effect of intrathecal morphine was examined in terms of the duration until the first supplemental analgesic was needed and the numbers of the doses within the first postoperative 48 h. Pain relief was significantly greater in groups 3 and 4 than in group 1. The incidence of nausea, vomiting and pruritus increased in a dose-dependent manner. No patient developed respiratory depression. Our results suggest that postoperative analgesia lasts more than 24 h with 0.1 mg or 0.2 mg of intrathecal morphine. Since the incidence of side-effects was higher at 0.2 mg, 0.1 mg may be the optimum dose for caesarean section.

Journal Article↗
PubMed1994

Chediak-Higashi syndrome in rats: light and electron microscopical characterization of abnormal granules in beige rats.

Chediak-Higashi syndrome (CHS) is a rare disease occurring in several animal species. Recently, mutant beige rats with CHS were found among DA strain rats in Japan. In the present study, histological examination of beige rats revealed giant granules in the hepatocytes, renal proximal tubules, submandibular ducts, thyroid follicular cells, granulocytes, mast cells, melanocytes, retinal pigment epithelial cells and globular leucocytes. Ultrastructurally, these granules varied from enlarged lysosomes, which were amorphous, granular or filamentous, to giant mast cell granules, crystalloid granules of eosinophils and slightly enlarged neutrophil granules. These findings bore many similarities to those in the beige mouse, which is a well known animal model for CHS, but some differences were apparent. Thus the giant granules of beige rats were larger and more easy to observe than those in beige mice. The study indicated that the beige rat may prove useful as an animal model for CHS.

Acid Phosphatase↗
PubMed1994

Distribution of nitric oxide synthase in the human cerebral blood vessels and brain tissues.

The distribution of nitric oxide synthase was investigated in human cerebral blood vessels and brain tissues. NADPH-diaphorase histochemistry, which is a marker for nitric oxide synthase in neurons and endothelial cells, revealed periadventitial nerve fibers in the arteries of the circle of Willis and their cortical branches, as well as the common carotid and subclavian arteries. The fibers were mostly nonvaricose in the periadventitial nerve trunk and were varicose within the adventitia. Patchy reaction products were distributed in the perinuclear region of each endothelial cell. Smooth muscle cells in the tunica media were weakly stained. Staining was particularly intense in regions with atherosclerotic changes, which consist of macrophage infiltration and proliferation of fibroblasts. In the neural parenchyma, two types of NADPH-diaphorase reactive neurons were differentiated. Type I neurons were intensely stained, medium-sized, and bipolar or multipolar. They were distributed in the cerebral cortex and white matter, mostly in the subcortical white matter. Type II neurons were lightly stained, small oval neurons with fine processes and were distributed in the cerebral cortex. Endothelial cells were intensely reactive for NADPH-diaphorase in the arteries, arterioles, and capillaries but weakly in veins. Immunohistochemistry for neural nitric oxide synthase labeled perivascular nerves in the larger arteries and those in the neural parenchyma. Both type I and type II neurons were labeled. Nitric oxide synthase in endothelial cells and the nerve encircling blood vessels further suggests a dual control of cerebral circulation by nitric oxide in human brain.

Aged↗
PubMed1994

CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1.

We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat-number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD.

Adult↗