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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 253 records · Page 14Linked to original sources
PubMed1998

PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis.

BACKGROUND: Except for Reye's syndrome, influenza-associated acute encephalopathy or encephalitis is not universally recognised. We did a multicentre study of laboratory and clinical data for patients with influenza-associated acute encephalopathy or encephalitis. METHODS: In Nagoya, Japan, ten patients with acute encephalopathy or encephalitis associated with influenza-like illness were admitted to our hospitals between April, 1996, and March, 1997. We collected clinical, laboratory and serological data and assessed cerebrospinal fluid samples by PCR for influenza A and B. FINDINGS: Seven patients, aged 22 months to 4 years, had evidence of recent influenza infection, six with type-A/Hong Kong (H3N2) and one with type B. The first sign in the central nervous system appeared within 2 days of fever in all but one patient. The first sign of involvement of the central nervous system was generalised convulsions in all patients. Two patients died, one had sequelae, and four survived without sequelae. PCR for influenza type A was positive for five patients. INTERPRETATION: The results of PCR suggest that at least part of the influenza type A genome existed in the central nervous system. Influenza-associated acute encephalopathy or encephalitis in young children deserves wider recognition.

Acute Disease↗
PubMed1998

Ouabain suppresses ATP elevation in response to fuel secretagogues in pancreatic islets.

The alterations of the ATP concentration in response to fuel secretagogues such as glucose, glyceraldehyde, and ketoisocaproate (KIC) were investigated in a single islet. The intraislet ATP concentration was transiently elevated and then decreased to a level slightly higher than basal. To asses the ATP content under conditions of reduced ATP consumption, the Na-K pump blocker ouabain was used. The elevation of ATP concentration was found unexpectedly to be suppressed under ouabain in the islet, even when incubated with any of the secretagogues. High glucose did not elevate the intracellular creatine phosphate during incubation with ouabain. Since the suppression rate for the intraislet ATP elevation was considerably smaller with KIC than with glyceraldehyde and glucose, we conclude that ouabain inhibits ATP production, at least in part, in the glycolytic pathway through a feedback mechanism.

Adenosine Triphosphate↗
PubMed1998

Vasorelaxant effect of olprinone, an inhibitor of phosphodiesterase 3, on mesenteric small artery and vein of rabbits.

The effects of olprinone, a cardiotonic agent that inhibits cyclic GMP (cGMP)-inhibited phosphodiesterase, was studied on isolated rabbit mesenteric small artery and vein. In the presence of indomethacin and propranolol, olprinone at concentrations of 10 nM to 10 microM and 1 microM to 100 microM relaxed norepinephrine-stimulated mesenteric artery and vein in a concentration-dependent manner, respectively. The relaxation was not endothelium-dependent in the artery. Removal of the endothelium, however, increased marginally the response of the vein to olprinone. Olprinone-induced relaxation was less pronounced in arteries contracted with high KCl solution + norepinephrine than in those contracted with norepinephrine alone. Nicardipine inhibited this attenuating effect of high KCl solution on the olprinone-induced relaxation. Olprinone (1 microM) enhanced the relaxation of artery and vein in response to a cAMP-increasing agent, 6-(3-dimethylaminopropionyl) forskolin (NKH477), but not to a cGMP- increasing agent, glyceryl trinitrate. Norepinephrine (10 microM) and caffeine (5 mM) elicited a transient, phasic contraction of the artery in Ca2+-free solution. Both olprinone and NKH477 attenuated more potently the norepinephrine-induced contraction than the caffeine-induced contraction. When norepinephrine (10 microM) and caffeine (5 mM) were successively applied in Ca2+-free solution, the contractile effect of caffeine was diminished compared to that in artery which had not been pretreated with norepinephrine. When the contraction in response to norepinephrine was partially attenuated by 1 microM olprinone, the following contraction evoked by caffeine was enlarged. It is concluded that olprinone relaxes the small artery more strongly than the vein via its direct action on smooth muscles. It is suggested that olprinone attenuates norepinephrine-induced contraction through inhibition of receptor-operated transmembrane Ca2+ influx and Ca2+ release from intracellular storage sites.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Regulation of the pAD1 sex pheromone response of Enterococcus faecalis by direct interaction between the cAD1 peptide mating signal and the negatively regulating, DNA-binding TraA protein.

The Enterococcus faecalis conjugative plasmid pAD1 (60 kb) encodes a mating response to the recipient-produced peptide sex pheromone cAD1. The response involves two key plasmid-encoded regulatory proteins: TraE1, which positively regulates all or most structural genes relating to conjugation, and TraA, which binds DNA and negatively regulates expression of traE1. In vitro studies that included development of a DNA-associated protein-tag affinity chromatography technique showed that TraA (37.9 kDa) binds directly to cAD1 near its carboxyl-terminal end and, as a consequence, loses its affinity for DNA. Analyses of genetically modified TraA proteins indicated that truncations within the carboxyl-terminal 9 residues significantly affected the specificity of peptide-directed association/dissociation of DNA. The data support earlier observations that transposon insertions near the 3' end of traA eliminated the ability of cells to respond to cAD1.

Bacterial Outer Membrane Proteins↗
PubMed1998

Bcl-2 expression and prognosis of patients with endometrial carcinoma.

Bcl-2 protein inhibits apoptosis, reduces the requirement for growth factors, and thereby extends the survival of cells. Recent findings of Bcl-2 in several solid tumors suggest that it might contribute to the genesis of some types of cancer. Over-expression of Bcl-2 might play a role in carcinogenesis and malignant progression of endometrial carcinoma. The aims of this study were to determine Bcl-2 expression in endometrial carcinoma in relation to other histopathologic prognostic factors, and to test its prognostic significance in patients with endometrial carcinoma. A total of 61 endometrioid-type endometrial carcinomas were immunohistochemically investigated for Bcl-2 expression on cryostat sections. Bcl-2 localization was observed in cytoplasm in 18 tumors, in nucleus in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl-2 was observed neither in cytoplasm nor in nucleus. There was not a statistically significant relationship between grade of tumor and Bcl-2 expression. Cytoplasmic Bcl-2 became less frequently expressed as the tumor invaded the myometrium deeper (p < 0.025). Retroperitoneal lymph-node dissection was performed in 57 patients. Multiple-regression analysis showed that lymph-vascular space invasion and nuclear expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001 and < 0.05 respectively). Univariate Cox regression analysis revealed that nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a significant prognostic factor for patients who underwent systematic retroperitoneal lymph-node dissection. Cox multivariate-regression analysis revealed that pelvic node metastasis and cervical invasion were the most important prognostic factors in this series of patients. When the analysis was made after exclusion of pelvic node metastasis, histologic grade (hazard ratio = 2.4), cervical invasion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard ratio = 11.5) were shown to be significant predictors of survival of the patients. These results indicate that aberrant Bcl-2 expression might be involved in malignant progression of endometrioid-type endometrial carcinoma. Site of Bcl-2 localization may be an important predictor of prognosis for patients with endometrioid-type endometrial carcinoma.

Adult↗
PubMed1998

Alteration of myo-inositol monophosphatase in Alzheimer's disease brains.

myo-Inositol monophosphatase (E.C.3.1.3.25) catalyzes the hydrolysis of myo-inositol 1-phosphate in the presence of Mg2+ at a physiologic pH to form free myo-inositol, maintaining a supply that represents the precursor for inositol phospholipid second messenger signaling systems. In the present study the activity and protein level of myo-inositol monophosphatase were investigated in samples from normal human and Alzheimer's disease (AD) postmortem brains. The separation profile on Sephadex G-100 gel filtration chromatography revealed one major form of myo-inositol monophosphatase in crude extracts from both normal human and AD brains. In AD brains myo-inositol monophosphatase activity and its protein level were significantly higher than in control brains. The activity of myo-inositol monophosphatase per enzyme molecule was similar in control and AD brains. These results suggest that myo-inositol monophosphatase is upregulated in AD, probably reflecting compensatory mechanisms concerned with phospholipid metabolism.

Aged↗
PubMed1998

Analysis of the murine Hoxa-9 cDNA: an alternatively spliced transcript encodes a truncated protein lacking the homeodomain.

Hoxa-9 is one of the homeo box (Hox) genes exhibiting similarity to the Drosophila Abdominal B gene. So far, only partial nucleotide sequences have been reported for mouse Hoxa-9 cDNA (Rubin et al., (1987) Mol. Cell. Biol. 7, 3836-3841). Here, we have determined the nucleotide sequence of the 5'-region of mouse Hoxa-9 cDNA and its genomic structure. Mouse Hoxa-9 cDNA contains a complete ORF encoding a protein of 271aa exhibiting 96.7% identity to its human counterpart. Interestingly, an alternatively spliced transcript (Hoxa-9T) was identified by RT-PCR. Sequence analysis revealed that 173bp within the Hoxa-9 ORF was missing from the Hoxa-9T cDNA. This additional splicing would potentially result in a frameshift, leading to the production of a truncated protein lacking the homeobox. Northern blot analysis revealed that the probe containing the homeodomain hybridized to two major transcripts (2.5 and 1.9kb) in the trunk region of 12.5 dpc embryos, and adult kidney and large intestine. On the other hand, the probe containing the additional intron detected only 2.5kb transcript in the same tissues, indicating that 1.9kb transcript corresponds to Hoxa-9T mRNA. We have also determined the transcriptional start site of Hoxa-9T.

Alternative Splicing↗
PubMed1998

Expression of three calpain isoform genes in human skeletal muscles.

Calpain is thought to be involved in muscular degradation in progressive muscular dystrophy (PMD), especially Duchenne and Becker muscular dystrophies. To assess the expression of calpain genes in skeletal muscles of patients with myopathies, we examined mRNA levels of three calpain isoforms by the quantitative reverse transcriptase-polymerase chain reaction method in biopsied muscles from control, PMD and amyotrophic lateral sclerosis (ALS) patients. There was a statistically significant increase in calpain 1 and calpain 2 mRNA levels in PMD and ALS patients as compared to controls. In contrast, there was a decrease in expression of calpain 3 mRNA in PMD, but it was not statistically significant. Expression of calpain 1 and calpain 2 positively correlated with each other, but not with calpain 3. These results indicate that expression of calpain 1 and calpain 2, but not calpain 3, are upregulated in diseased human muscles, likely playing a regulatory role in the process of myofibrillar degradation at the transcriptional as well as posttranslational level.

Adolescent↗
PubMed1998

Necessity of endogenous GTP derived from glucose-6-phosphate for insulin secretion augmented by glucose under protein kinase A activation.

To investigate the possible involvement of some intracellular metabolic signaling other than the ATP derived from glucose metabolism under protein kinase A (PKA) activation, we measured the insulin secretory capacity stimulated by glucose and other fuel secretagogues using diazoxide-treated pancreatic islets. Under these conditions, we found a signal from a site proximal to glyceraldehyde-3-phosphate (GA-3-P) in the glycolysis to be necessary for glucose-induced insulin secretion. By using several different glycolytic enzyme inhibitors, we found that this proximal signal is derived from glucose-6-phosphate (G-6-P), and that metabolic signaling distal to GA-3-P also is necessary. Mycophenolic acid completely inhibited the augmented glucose-induced insulin secretion, which guanosine could reverse, indicating that the proximal signaling is coupling with endogenous GTP production. In this novel system of metabolic signaling, endogenous GTP derived from G-6-P in the glycolysis elicits the augmentation of glucose-induced insulin secretion under PKA activation in diazoxide-treated pancreatic islets.

Animals↗
PubMed1998

Differential expression of rat brain phospholipase C isozymes in development and aging.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. In the present study we examined developmental and aging changes in three PLC isozymes (beta 1, gamma 1, and delta 1) in the rat brain. Enzyme assays and immunoblot analyses after gel filtration chromatography of brain extracts from embryonic day 19 and postnatal 4- and 48-week rats indicated that gamma-specific activity was highest in fetal brain and decreased with aging, that beta 1-specific activity was high at 4 weeks but essentially undetected in fetal brain, and that delta 1-specific activity was high at both 4 and 48 weeks with faint detection in fetal brain. Our results suggest that the gamma 1 isozyme may be particularly involved in cell division and growth during the histo-genesis of the central nervous system, while beta 1 and delta 1 isozymes may take part in processes of its maturation and maintenance.

Aging↗
PubMed1998

Indication of a protein kinase C-independent pathway for NADPH oxidase activation in human neutrophils.

A potent tyrosine phosphatase inhibitor, pervanadate, induced (i) translocation of the cytosolic NADPH oxidase factors, p47-phox and p67-phox, to the plasma membrane; and (ii) O2- production in human neutrophils. However, the translocation of p47-phox and p67-phox was inhibited by H-7, a protein kinase C (PKC) inhibitor without markedly affecting O2- production in whole neutrophils. Results from the plasma membrane fraction showed that NADPH oxidase activity in neutrophils treated with pervanadate did not vary in the presence or absence of H-7, despite a lower content of p47-phox and p67-phox in H-7-treated neutrophils. These findings suggest that in addition to the well-known PKC-dependent pathway, there may exist another PKC-independent pathway to activate NADPH oxidase in human neutrophils. This pathway involves protein tyrosine phosphorylation but does not seem to necessitate translocation of p47-phox and p67-phox to the plasma membrane.

Enzyme Activation↗
PubMed1998

Prenatal identification of mos 45,X/46,X,+mar in a normal male baby by cytogenetic and molecular analysis.

We report a case of mos 45,X/46,X,+mar, diagnosed prenatally by amniocentesis, whose physical examination, including external and internal organs, along with serum testosterone values were normal five years after delivery. The mosaic karyotype was seen in 146 of 240 cells examined (amniotic fluid cells, 110/65; placental chorionic villi: 5/4; cord blood, 21/81; cultured skin fibroblasts, 10/90) from 386 metaphases, and the marker chromosome appeared as a small non-fluorescent acrocentric chromosome. All autosomes appeared normal, and no normal Y chromosome could be demonstrated. Analysis of 26 Y-chromosome loci by molecular techniques such as PCR, Southern analysis using multiple Y-specific DNA probes, and Hae III restriction endonuclease assessment of male-specific repeated DNA in the heterochromatic region of the Y chromosome, and fluorescence in situ hybridization (FISH), revealed the marker was derived from a Y chromosome including p terminal to q11.23, and paracentric inversion in the remaining Y long arm. The formation of testes can be considered as existence of SRY (sex-determining region of Y) as a testis-determining factor. The present report illustrates the importance of FISH and molecular techniques as a complement to cytogenetic methods for accurate identification and characterization of chromosome rearrangements in prenatal diagnosis.

Adult↗
PubMed1998

Estimation of coronary flow reserve by intracoronary administration of nicorandil: comparison with intracoronary administration of papaverine.

We investigated the usefulness of the intracoronary administration of nicorandil (NIC) compared with that of papaverine (PAP) in the evaluation of coronary flow reserve (CFR) in 17 patients, including 10 patients with old myocardial infarction and 7 patients with angina pectoris. CFR was measured with a Doppler guidewire inserted into the distal site of the left anterior descending coronary artery during intracoronary administration of 10 mg PAP, and of 0.5 mg, 1.0 mg, 2.0 mg, and 3.0 mg NIC. We examined the changes in heart rate (HR), mean blood pressure (mBP), the total score of QTc interval on a 12-lead electrocardiogram (sigma QTc), and ST-T segment, before and after drug administration. CFR was significantly lower during administration of 0.5 mg (1.9 +/- 0.9) and 1.0 mg (2.2 +/- 0.9) NIC than during administration of PAP (2.6 +/- 1.1) (P < 0.01). There was no significant difference in the CFR during administration of 2.0 mg (2.6 +/- 1.0) or 3.0 mg (2.5 +/- 1.0) NIC and that observed during administration of PAP. The CFR during administration of PAP was significantly correlated with that during administration of 2.0 mg NIC (r2 = 0.72, P < 0.0001) and 3.0 mg NIC (r2 = 0.70, P < 0.0001). PAP, but not NIC, significantly altered the HR, mBP, and sigma QTc. Inverted T waves were observed in 14 patients, and elevation of the ST segment was observed in 4 patients during administration of PAP (including 1 patient with ventricular tachycardia). The administration of 0.5 mg to 2.0 mg NIC was not associated with ST-T segment changes, except in 1 patient, but inverted T waves were observed in 2 patients and depression of the ST segment was observed in 2 patients during administration of 3.0 mg NIC. Intracoronary administration of NIC is useful and safe for evaluating the CFR. The appropriate dose for measuring CFR is 2.0 mg nicorandil.

Angina Pectoris↗
PubMed1998

Magnetic resonance velocity mapping of transtricuspid velocity profiles in dilated cardiomyopathy.

To investigate the velocity profiles and jet sizes of transtricuspid inflow by magnetic resonance imaging (MRI), we examined seven dilated cardiomyopathy (DCM) patients (mean age 37 +/- 15 years) and 20 normal subjects (mean age 32 +/- 7 years). We used a Siemens Magnetom Impact Expert (1.0 T) together with a surface receiver coil. Electrocardiographic gating, triggered by the R wave, was performed. Cine gradient echo images were obtained in the short axis of the right ventricle. Velocity mapping of right ventricular inflow was obtained at peak early diastolic filling. Velocity profile curves across the tricuspid inflow were obtained at 1-cm intervals from the tricuspid ring up to 3 cm into the cavity. Maximum/mean velocities in both groups were 1.1 +/- 0.1 at the ring level, unchanged at 1 cm from the tricuspid ring, and thereafter increased to 1.4 +/- 0.3 at 2 cm and 1.5 +/- 0.3 at 3 cm as peak velocity fell. Jet cross-sectional area was 10.4 +/- 2.1 cm2 at the ring level, and was unchanged at the 3-cm level in the normal subjects. However, in patients with DCM it was smaller than that in normals, and decreased in proportion to the distance from the tricuspid ring. Thus, tricuspid inflow velocity showed a relatively flat profile at the tricuspid ring and tip levels, becoming more dispersed at 2 and 3 cm from the ring. The cross-sectional area of the right ventricular inflow jet in the DCM patients was small and decreased in proportion to the distance from the tricuspid ring, although it appeared to be relatively constant in normal subjects.

Adult↗
PubMed1998

Production of trehalose synthase from a basidiomycete, Grifola frondosa, in Escherichia coli.

The genomic DNA and cDNA for a gene encoding a novel trehalose synthase (TSase) catalyzing trehalose synthesis from alpha-D-glucose 1-phosphate and D-glucose were cloned from a basidiomycete, Grifola frondosa. Nucleotide sequencing showed that the 732-amino-acid TSase-encoding region was separated by eight introns. Consistent with the novelty of TSase, there were no homologous proteins registered in the data-bases. Recombinant TSase with a histidine tag at the NH2-terminal end, produced in Escherichia coli, showed enzyme activity similar to that purified from the original G. frondosa strain. Incubation of alpha-D-glucose 1-phosphate and D-glucose in the presence of recombinant TSase generated trehalose, in agreement with the enzymatic property of TSase that the equilibrium lay far in the direction of trehalose synthesis.

Amino Acid Sequence↗
PubMed1998

Risk factors for neonatal thrombocytopenia in pregnancy complicated by idiopathic thrombocytopenic purpura.

The aim of this study was to evaluate risk factors for the occurrence of fetal/neonatal passive immune thrombocytopenia (PIT) in pregnancy complicated with ITP. We studied 52 pregnancies with ITP and the 54 neonates retrospectively. Neonatal platelet counts were compared with maternal platelet counts, platelet-associated IgG (PAIgG) values and the presence of antiplatelet antibody in maternal circulation, history of previous PIT, maternal treatments for ITP, and other maternal/neonatal factors including gestational age and birth weight. Logistic regression analysis for multivariables was performed. PIT (platelet counts < 100 x 10(3)/microl) without neonatal mortality or any morbidity was observed in eight (15.4%) of 52 pregnancies. The presence of circulating antiplatelet antibodies in maternal blood, splenectomy prior to pregnancy, and a history of previous PIT were observed more frequently with statistical significance in women giving birth to neonates who developed PIT. By logistic regression analysis, splenectomy prior to pregnancy was found to be the single significant variable (p=0.017, odds ratio 9.33) among the risk factors for PIT. Thus, splenectomy prior to pregnancy is related to increased risk for PIT in ITP-complicated pregnancy.

Adolescent↗
PubMed1998

Does increased QT dispersion in the acute phase of anterior myocardial infarction predict recovery of left ventricular wall motion?

QT dispersion has been recognized as an undesirable marker because of its association with arrhythmogenicity in patients with myocardial infarction, but the relation between QT interval dispersion and wall motion abnormalities has not been clarified. After the introduction of reperfusion therapy, it was recognized that T waves were inverted twice in the course of myocardial infarction. An investigation was made of the clinical significance of QT dispersion in relation to the presence of inverted T waves and left ventricular wall motion abnormalities in 34 patients (mean age, 59 years) with acute anterior myocardial infarction who underwent successful reperfusion therapy. The amplitude of the deepest inverted T waves occurring within the first 3 days (T1) and after 3 days (T2) of myocardial infarction were measured in electrocardiographic (ECG) lead V3. On the ECGs on which T1 and T2 were recorded, QT dispersion was calculated (QTd1, QTd2), and T1 and T2 were correlated with QTd1 (r = .65) and QTd2 (r = .47), respectively. The difference between the extent of asynergy in the acute phase and the chronic phase, which was evaluated by the centerline method, was correlated with T1 (r = .63) and QTd1 (r = .67). Patients with a QTd1 of 0.1 second or longer showed a greater change in the extent of asynergy (23.4 +/- 13.1% vs 4.9 +/- 9.8%, P < .01) and less asynergy in the chronic phase (19.9 +/- 15.6% vs 46.5 +/- 14.0%, P < .01) than patients with a QTd1 of less than 0.1 second. Thus, QT dispersion in the acute phase of anterior myocardial infarction indicates recovery of left ventricular wall motion. Prolongation of the local action potential duration of the myocardium that recovers from severe ischemia may be a contributor to the increased QT dispersion that results in inversion of T waves in the acute phase of myocardial infarction.

Electrocardiography↗