Search PubMed⌕ Search

Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 181 records · Page 10Linked to original sources

[Clinical significance of (1-->3)-beta-D-glucan in pleural effusion and liquor].

The Measurement of serum (1-->3)-beta-D-glucan (beta-glucan) has been considered to be useful in the early diagnosis of deep mycosis. In this study, we investigated the clinical significance of beta-glucan in pleural effusion or liquor from patients with various conditions. beta-glucan was measured in 29 samples of pleural effusion from 27 patients (male: 17, female: 10 median age: 62.1). Two patients undergoing hemodialysis treatment were excluded from the study of normal range of beta-glucan in these samples. beta-glucan was also measured in 39 samples of liquor from 23 inpatients (male: 15, female: 8 median age: 48.4) with certain neurological disorders. In these cases, only two patients had deep mycosis. beta-glucan in the pleural effusion from a patient with Aspergillus pyothorax showed an extremely high value of more than 1100 pg/ml. Slight elevation of beta-glucan was observed in the spinal fluid from a patient with cryptococal, meningitis. In the other cases with no mycotic infection or any factor influencing the value of beta-glucan, beta-glucan in pleural effusion and spinal fluid were generally lower than the normal range of serum samples. However, there is false positive elevation of beta-glucan in pleural effusion. The above results indicated that measurement of beta-glucan in pleural effusion or spinal fluid may be useful for the diagnosis of mycotic infection as the cause of pleuritis or meningitis.

Adult↗

Characteristics of the clinical findings in patients with idiopathic thrombocytopenic purpura who are positive for anti-phospholipid antibodies.

It has been reported that anti-phospholipid antibodies are detected in some patients with idiopathic thrombocytopenic purpura (ITP). To study the significance of determination of anti-phospholipid antibodies in patients with ITP, clinical and laboratory findings were compared between patients whose sera were positive for these antibodies (Group A) and non-positive patients (Group B). Anti-cardiolipin antibody (aCL) was determined by enzyme-linked immunosorbent assay and lupus anticoagulant (LA) was determined by activated partial thromboplastin time (aPTT) and thromboplastin time inhibition test. Seven out of 27 cases of ITP belonged to Group A and 3 of the 7 were confirmed to have anti-phospholipid antibody syndrome (APS). There was a tendency for habitual abortion, and thrombosis, megakaryocytes in the bone marrow and platelet-associated IgG (PAIgG)-positive cells were more frequent in Group A than in Group B. However, it was difficult to discriminate APS from ITP alone, when there were no symptoms or signs of APS. Therefore, measurement of anti-phospholipid antibodies in ITP was thought to be useful for the differential diagnosis of APS and subsequently for the prevention of thrombosis.

Adolescent↗

[Clinical analysis of adjuvant chemotherapy using 5-fluorouracil, leucovorin and cis-diamminedichloroplatinum for patients with advanced and recurrent gastric cancer].

The chemotherapy combining 5-FU, CDDP, and LV was conducted in 17 patients with advanced and recurrent gastric cancer. The regimen consisted of 5-FU (by continual infusion 600 mg/m2/day for 5 days), CDDP (low-dose consecutive drip infusion, 2 hours 20 mg/m2/day for 3 days) and LV (by bolus infusion 20 mg/ m2/day for 5 days). Advanced gastric cancer was found in 12 cases (operation performed in 9 cases and 7 cases resectable) and recurrent in 5 cases. Macroscopic judgment of efficacy in 10 recurrent and inoperable cases revealed CR in 1 patient, PR in 5 patients, NL in 2, and PD in 2 patients. The overall response rate was 60.0%. There were 7 resectable cases, 4 PR patients, 1 MR and 2 NC patients. The overall response rate was 57.1%. Operations were done in 9 of 12 patients with advanced gastric cancer. The histological effects in 7 cases with resectable cases were as follows: 1 patient of grade 0, 2 patients of grade 1a, 3 patients of grade 1b, and 1 patient of grade 2. The main adverse reactions were gastrointestinal symptoms, but in 3 cases thrombocytopenia was found. This chemotherapy for advanced and recurrent gastric cancer shows excellent clinical efficacy.

Adenocarcinoma↗

Receptor tyrosine kinases involved in hematopoietic progenitor cells.

To analyze the molecular mechanisms of the proliferation and differentiation of hematopoietic cells, we have cloned PTKs from sorted stem cells. We discuss the expression and function of receptor tyrosine kinases, STK/RON, TIE, TEK and HTK which have been cloned from these cells. STK and its ligand, MSP contributed to the motility and phagocytosis of peritoneal macrophages and bone absorption of osteoclasts. Apoptosis was induced in an erythroid cell line by the binding of MSP(MacrophageStimulating Protein). TIE, TEK and HTK were interestingly expressed in the subpopulations of stem cells and related to the myeloid differentiation. These study will indicate the heterogeneity of stem cells and their diverse differentiation.

Animals↗

[Gene Polymorphism of 5, 10-methylenetetrahydrofolate reductase as a coronary risk factor].

Hyperhomocysteinemia has been identified as a possible risk factor for coronary artery disease. The association of the alanine/valine (A/V) polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing re-methylation of homocysteine, with coronary artery disease was examined in 362 Japanese males with a diagnosis of coronary artery disease confirmed with coronary angiography. The A/V polymorphism was analyzed with PCR followed by Hinf I digestion. The screening of 778 male volunteer controls revealed that the frequency of V allele in Japanese was 0.33, comparable to that in the French Canadian population. The VV genotype, which correlates with increased plasma homocysteine levels due to reduced activity and increased thermolability of this enzyme, was significantly more frequent in patients with coronary artery disease (15.7%, n = 362) than in controls (10.2%, n = 778; p = 0.0067). The association of the VV genotype with coronary artery disease was further increased in patients with > or = 99% stenotic lesion (p = 0.0010). In these patients, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). The fasting plasma homocysteine levels in VV subjects were higher than those in AV or AA subjects. The VV genotype of MTHFR associated with increased plasma homocysteine levels may represent an important genetic risk factor for coronary artery disease, especially with the occurrence of myocardial infarction.

Adult↗

[Echocardiographic prediction of risk for embolism in patients with infective endocarditis].

The relationship between two-dimensional echocardiographic findings of vegetation and embolic events was investigated in 26 patients with infective endocarditis (17 males and 9 females, mean [+/-SD] age 51 +/- 17 years). The size and the other morphologic characteristics of vegetation (mobility, extent and consistency) were analyzed retrospectively according to the criteria by Sanfilippo, et al., and parameters were assigned scores from 1 to 4 to provide a total score. Patients with a maximum vegetation diameter > 10 min had a significantly higher incidence of embolic events than those with < or = 10 mm (p < 0.05). Each parameter of vegetation showed no significant difference between patients with and without embolic events; but the total score was significantly higher in patients with embolic events (p < 0.05). Particularly, all patients with a total score > or = 10 had embolic events, whereas those without embolic events had a total score < or = 9. There were no significant differences in the frequency of emergent valve replacement between patients with aortic value and mitral valve endocarditis. However, the incidence of heart failure was higher, but not significantly, in patients with aortic valve (67%) and combined valve endocarditis (67%) than in those with mitral valve endocarditis (36%). The maximum size and total score reflecting mobility, extent and consistency of vegetation using two-dimensional echocardiography provide useful information to predict the occurrence of embolic events in patients with infective endocarditis.

Adult↗

Structure-activity relationships of spontaneous nitric oxide releasers, FK409 and its derivatives.

(+/-)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) shows both potent in vitro vasorelaxant and antiplatelet activities via nitric oxide (NO) generated spontaneously from the compound. In this study, we measured spontaneous NO-releasing rates of a series of FK409 derivatives, of which chain lengths or substituents were systematically modified, in sodium-phosphate buffer solution at pH 7.4. Furthermore, we studied their in vitro antiplatelet and vasorelaxant effects to evaluate relationships between spontaneous NO-releasing activities of FK409 analogs and their biological activities. FK409 derivatives were found to possess different spontaneous NO-releasing rates and biological activities according to their structural modification. In addition, these studies revealed a close correlation between NO-releasing rates of FK409 derivatives and their in vitro antiplatelet activities in human platelet-rich plasma, whereas the in vitro vasorelaxant activities of these compounds in isolated rat aorta did not correlate with the rates of NO liberation. The vasorelaxant effects were supposed to be affected by the structural properties of FK409 derivatives as well as their NO-releasing abilities.

Animals↗

[Ischemic heart disease and apoptosis].

In the last three years, apoptosis has been reported to be associated with cell death in ischemic heart diseases, for examples, acute ischemic cardiomyocyte death in acute myocardial infarction; death of the salvaged cardiomyocytes in old myocardial infarction; death of infiltrated leukocytes and granulation tissue cells after myocardial infarction. Apoptosis-related proteins such as Bcl-2, Bax and Fas are expressed in the salvaged cardiomyocytes edging the infarct area. In vitro experiment using cultured cardiomyocytes suggested hypoxia causes apoptosis in them. Thus, apoptosis may play important roles in ischemic heart diseases. For detecting apoptosis, however, all of the previous studies on acute ischemic cardiomyocyte death depended exclusively on DNA fragmentation (biochemical marker of apoptosis) by a DNA ladder on gel electrophoresis and in situ nick end labeling (TUNEL), but never documented the ultrastructural changes characteristic of apoptosis (morphological marker of apoptosis). Then, we examined the ultrastructure and DNA fragmentation of cardiomyocytes in rabbit myocardial infarction using electron microscopy combined with TUNEL (EM-TUNEL) which allows simultaneous observation of both markers in the same cell. Rabbits underwent 30-min ischemia followed by 0-, 30-min, 2-, 4- and 24-h reperfusion of a left coronary artery. In the infarcted tissue, EM-TUNEL revealed oncotic necrosis of cardiomyocytes with or without DNA fragmentation in the 2-h, 4-h, and 24-h reperfusion groups, but no apoptotic cardiomyocytes in ultrastructure in any groups. Thus, so-called apoptotic cardiomyocytes after ischemia/reperfusion may belong to a different category from apoptosis.

Animals↗

Gastrointestinal absorption of recombinant human insulin-like growth factor-I in rats.

The GI absorption of recombinant human insulin-like growth factor-I (rhIGF-I) and its improvement were investigated in rats. The 125I-rhIGF-I rapidly degraded to the trichloroacetic acid-soluble form in the small-intestinal contents, but it was relatively stable in the gastric and large-intestinal contents and in the subcellular fraction of the small-intestinal mucosa. To protect rhIGF-I from degradation in the small-intestinal contents, the effect of some adjuvants was examined and their degradation was markedly inhibited by the presence of aprotinin or casein. After p.o. administration of 125I-rhIGF-I at the dose of 1.0 mg/kg, trichloroacetic acid-precipitable radioactivity in the plasma was periodically determined. We found that a considerable amount of rhIGF-I was absorbed into the systemic circulation and that the bioavailability was 9.3%, which is much greater than that of insulin. The coadministration of aprotinin and that of casein enhanced the bioavailability further: 46.9% and 67.0%, respectively. Radioimmunoassay using a monoclonal antibody for rhIGF-I confirmed the high bioavailability of immunoreactive rhIGF-I. From gel chromatography of plasma, the radioactivity in the plasma was found to be in the form of high-molecular-weight complexes. The mechanism for the uptake of rhIGF-I by intestinal mucosa may be absorptive-mediated endocytosis.

Animals↗

[A case of adult meningitis with bilateral sensorineural hearing loss at the onset].

Here we report a case of pneumococcal meningitis with bilateral sensorineural hearing loss at the onset. The patient was a 60-year-old man who a few days before visiting our hospital experienced common cold-like symptoms, and then he suddenly developed bilateral hearing loss. Examination of the cerebrospinal fluid (CSF) on the day of admission revealed pleocytosis and his CSF culture demonstrated pneumococci. Otorhinolaryngological examinations disclosed bilateral severe sensorineural hearing loss due to cochlear impairment. Many cases of bacterial meningitis concomitant with hearing loss have been reported, but a case of meningitis starting with sudden hearing loss is rare.

Hearing Loss, Sensorineural↗

D-cycloserine, a glycine site agonist, reverses working memory failure by hippocampal muscarinic receptor blockade in rats.

D-Cycloserine, a partial agonist at the glycine binding site on the NMDA receptor/channel complex, did not affect the number of errors (attempts to pass through two incorrect panels of the three-panel gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 1 or 10 microg/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine (3.2 microg/side) significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal 3.2 microg/side scopolamine was significantly reduced by concurrent infusion of 1 and 10 microg/side D-cycloserine. These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine site can compensate dysfunction of hippocampal cholinergic neurotransmission involved in working memory function.

Animals↗

Working memory failure by stimulation of hippocampal adenosine A1 receptors in rats.

THE highly selective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 0.3 and 1.0 microgram per side into the dorsal hippocampus. Pretreatment with the selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 1 mg kg-1, i.p.) prevented the increase in working memory errors induced by intrahippocampal administration of CHA (1.0 microgram per side). CGS-21680, a highly selective agonist for adenosine A2 receptors, had no effect on the number of working memory errors, when administered intrahippocampally at a dose of 1.0 microgram per side. These results suggest that activation of hippocampal adenosine A1 receptors interferes with neural processes involved in working memory function.

Adenosine↗

Accelerated evolution of crotalinae snake venom gland serine proteases.

Eight cDNAs encoding serine proteases isolated from Trimeresurus flavoviridis (habu snake) and T. gramineus (green habu snake) venom gland cDNA libraries showed that nonsynonymous nucleotide substitutions have accumulated in the mature protein-coding regions to cause amino acid changes. Southern blot analysis of T. flavoviridis genomic DNAs using two proper probes indicated that venom gland serine protease genes form a multigene family in the genome. These observations suggest that venom gland serine proteases have diversified their amino acid sequences in an accelerating manner. Since a similar feature has been previously discovered in crotalinae snake venom gland phospholipase A2 (PLA2) isozyme genes, accelerated evolution appears to be universal in plural isozyme families of crotalinae snake venom gland.

Amino Acid Sequence↗

Blockade of 5-HT1A receptors compensates loss of hippocampal cholinergic neurotransmission involved in working memory of rats.

NAN-190, a selective 5-HT1A receptor antagonist, had no effect on the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterlly at 0.32 or 1.0 micrograms/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine at 3.2 micrograms/side or the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side significantly increased the number of working memory errors. The increase in working memory errors induced by intrahippocampal scopolamine (3.2 micrograms/side) was reduced by concurrent infusion of 0.32 and 1.0 microgram/side NAN-190, an effect that reached significance only for the 1.0 microgram/side dose. In contrast, NAN-190 at 1.0 micrograms/side did not affect the increase in working memory errors when infused intrahippocampally together with 32 ng/side CPP. These results suggest that blockade of hippocampal 5-HT1A receptors does not affect impairment of working memory resulting from block of NMDA receptor-mediated neurotransmission, but that it can compensate deficiency of septohippocampal cholinergic activity involved in working memory performance of rats.

Animals↗

Effect of cholinergic activation by physostigmine on working memory failure caused in rats by pharmacological manipulation of hippocampal glutamatergic and 5-HTergic neurotransmission.

The muscarinic receptor antagonist scopolamine significantly increased the number of errors in the working memory task with a three-panel runway setup, when injected bilaterally at 3.2 micrograms/side into the dorsal hippocampus. The increase in working memory errors induced by intrahippocampal 3.2 micrograms/side scopolamine was reduced by concurrent injection of the cholinesterase inhibitor physostigmine (1.0 and 3.2 micrograms/side. However, physostigmine (3.2 micrograms/side) did not affect an increase in working memory errors induced by intrahippocampal injection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist (+/)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) at 32 ng/side. Likewise, physostigmine (3.2 micrograms/side) was ineffective in reducing an increase in working memory errors caused by intrahippocampal administration of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-pro-pylamino)tetralin (8-OH-DPAT) at 10 micrograms/side. These results suggest that the septohippocampal cholinergic activity is necessary for normal working memory processes, but that cholinergic activation neither compensates loss of hippocampal NMDA receptor-mediated neurotransmission nor counteracts the overstimulation of hippocampal 5-HT1A receptors in terms of working memory function.

Acetylcholine↗

Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction.

BACKGROUND: In general, myocyte death in myocardial infarctions (MIs) is attributed to necrosis, but recently the involvement of apoptosis has been suggested. The ratio of bcl-2 protein, an inhibitor of apoptosis, to Bax protein, an inducer of apoptosis, determines survival or death after an apoptotic stimulus. We speculated that bcl-2 or Bax expression is induced by ischemia and that it may be related to myocyte death in human hearts. METHODS AND RESULTS: We studied immunohistochemically 37 autopsied human hearts (acute MI, n = 15; old MI, n = 12; normal hearts as a control, n = 10) with the use of bcl-2 and Bax antibodies. There were no myocytes with positive bcl-2 immunoreactivity in the controls or hearts with old MI. However, myocytes with positive bcl-2 immunoreactivity were seen in 9 of 15 hearts (60%) with acute MI, in that it was localized only in salvaged areas surrounding the infarcted tissues. Myocytes with slightly positive Bax immunoreactivity were observed in the control hearts. In the salvaged myocytes surrounding the infarcted tissues, Bax was overexpressed in 2 of 15 hearts (13%) with acute MI but in 10 of 12 hearts (83%) with old MI. CONCLUSIONS: bcl-2 protein is induced in salvaged myocytes at the acute stage of infarction, but Bax protein is overexpressed at the old stage. The expression of bcl-2 and the overexpression of Bax may play an important pathophysiological role in the protection or acceleration of the apoptosis of human myocytes after ischemia and/or reperfusion.

Adult↗