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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of insulin and heparin on glucose-induced vascular damage in cell culture.

BACKGROUND: Clinical trials have shown that tight glycemic control reduces the risk of diabetic microvascular complications, namely retinopathy, nephropathy, and neuropathy. The mechanism of these microvascular complications is not yet fully elucidated. The present study describes the effect of different concentrations of glucose on vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in cell culture. Our objective was to shed some light through this biological study on the mechanism and prevention of diabetic microvascular complications. METHODS: ECs and VSMCs were treated with 5 mmol/L (90 mg/dL) or 30 mmol/L (540 mg/dL) D-glucose or D-glucose plus insulin or D-glucose plus insulin and heparin in culture. ECs were studied with light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) for surface changes. The cultured ECs were treated with vimentin antibodies and VSMCs with actin antibodies for immunoflourescence microscopy (IFM) study. Endothelin-1 (ET-1) assay was done on ECs culture medium using enzyme-linked immunosorbent assay (ELISA). RESULTS: LM, SEM, and TEM of ECs treated with a physiological concentration (90 mg/dL) of D-glucose appeared the same as control. However, LM and SEM of ECs treated with a high concentration of D-glucose (540 mg/dL) showed pronounced intercellular gaps. This finding was further confirmed by TEM study. These gaps were minimally or not at all discernible when insulin, heparin, or a combination of both was added to the culture medium. IFM showed increased vimentin expression with a high concentration of D-glucose. Vimentin expression was attenuated with the addition of insulin or heparin in the medium and more markedly with combined insulin and heparin. Significant correlations were obtained between glucose levels, vimentin expression, and ET-1 levels. The higher the glucose level, the higher is the ET-1 production and the greater vimentin expression in ECs. Cultured VSMCs treated with a high concentration of D-glucose showed enhanced actin expression. Actin expression was blunted with the addition of insulin or heparin in the culture medium. CONCLUSIONS: These biological findings indicate the salutary effect of insulin or insulin and heparin in the mitigation of vascular disorganization caused by a high concentration of D-glucose.

Cell Line↗
PubMed2000

Effect of angiotensin-converting enzyme inhibitor on left ventricular parameters and circulating brain natriuretic peptide in elderly hypertensives with left venticular hypertrophy.

In the elderly, left ventricular hypertrophy (LVH) is a powerful risk factor for cardiovascular events and cardiovascular death. The purpose of the present study is to investigate the effect of long-term effective blood pressure control with the angiotensin-converting enzyme (ACE) inhibitor temocapril on left ventricular (LV) mass and function indices and the circulating concentration of the cardiac hormone brain natriuretic peptide (BNP) in elderly hypertensives with LVH. Temocapril treatment was administered for 1 year to 11 elderly hypertensives (mean age, 72 years) with LVH. Cardiac dimensions and circulating concentrations of BNP were monitored before initiation of treatment and after 1 year of treatment. At entry, BNP levels were positively correlated with the LV mass index, but were not correlated with the mean blood pressure, LV ejection fraction, or E/A ratio (the ratio of peak transmitral flow velocity in early diastole, peak E, to that in late diastole, peak A). After 1 year, temocapril treatment resulted in effective control of blood pressure. The treatment did not affect the LV ejection fraction, but modestly increased the E/A ratio. Temocapril significantly reduced septal and posterior wall thickness and the LV mass index. BNP significantly declined after 1 year. Changes in BNP were significantly related to changes in the LV mass index, but were not related to changes in the mean blood pressure, LV ejection fraction, or E/A ratio. The results suggest that long-term ACE inhibitor treatment with temocapril can induce the regression of LV mass and reduce elevated plasma BNP in elderly hypertensive patients with LVH. In this study, changes in BNP reflected the magnitude of regression of LVH.

Aged↗
PubMed2000

Estimation of critical points of branched polymers

The authors' theory of the gel point is applied to the gelation experiments in nonstoichiometric systems of Gordon and Scantlebury. Agreement between the theory and the observations is found to be excellent in every region examined, confirming the mathematical soundness of the theory. The theory is transposed to the site-bond problem. With the aid of a high dimension expansion of the ring distribution function, we derive an analytic expression for the bond percolation threshold. The resultant equation is in good conformity with the site-bond percolation simulation of Stauffer. The present theory is scrutinized over a wide range of dimensions for pure bond percolation; the result shows that the theoretical line abruptly merges with the observed points at d=8, consistent with the Lubensky-Isaacson excluded volume theory which predicts the critical dimension d(c)=8 for sol clusters on lattices.

Journal Article↗
PubMed2000

Neurovascular decompression for idiopathic tarsal tunnel syndrome: technical note.

OBJECTIVE: The surgical outcome of idiopathic tarsal tunnel syndrome (TTS) is reported to be worse than that attributable to ganglion, tarsal coalition, or tumour, and therefore further development in the surgical treatment for idiopathic TTS is considered to be necessary. Here the efficacy of neurovascular decompression for patients with idiopathic TTS is evaluated. METHODS: Twelve feet from nine patients with idiopathic TTS were treated. The patients were aged 52-78 years (mean 64.6 years), and all of them complained of pain or dysaesthesia of the sole of the foot. The posterior tibial nerve was freed from the attached arteriovenous complex (posterior tibial artery and veins). The dissected nerve had a flattened appearance in all of the patients, suggesting nerve compression by the adjacent arteriovenous complex and superficially by the flexor retinaculum. A graft of fat was inserted as both a cushion and an antiadhesive between the vessels and the nerve to achieve neurovascular decompression. RESULTS: Patients on whom neurovascular decompression was performed had resolution or lessening of symptoms in their feet. Neither wound infection nor recurrence of symptoms was found during the follow up period (mean 26.8 months). CONCLUSION: Neurovascular compression syndrome plays a part in idiopathic TTS, and adding neurovascular decompression to resection of the flexor retinaculum is effective.

Aged↗
PubMed2000

Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.

In tachycardia-induced heart failure (HF), positive lusitropic effects of milrinone or dobutamine were assessed by evaluating the time constant of left ventricular (LV) pressure decay (tau) and Ca(2+)-ATPase activity of the sarcoplasmic reticulum (SR). The peak value of the positive first derivative of LV pressure (+dP/dt) was less increased, either by dobutamine (2-10 microg x kg(-1) x min(-1)) or by milrinone (4-20 microg/kg), in HF than in control (P < 0.05), whereas tau was shortened to an extent similar to that in control with dobutamine [P = not significant (NS)] and to an even greater extent with milrinone (P < 0.05). Ca(2+)-ATPase activity increased similarly in HF and control with dobutamine (1 microM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 microM; +19% in HF vs. +11% in control, P < 0.05). Ca(2+)-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca(2+)-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.

Animals↗
PubMed2000

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum.

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.

Adrenergic beta-Agonists↗
PubMed2000

Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein- and lysophosphatidylcholine-induced human mesangial cell migration.

The objectives of the present study were (1) to determine whether oxidized LDL and lysophosphatidylcholine (lyso-PtdCho), a major phospholipid component of oxidized LDL, stimulate the migration of cultured human mesangial cells and (2) to investigate the possible effects on mesangial cell migration of the cardiac natriuretic peptides atrial and brain natriuretic peptide (ANP and BNP). Oxidized LDL (10 and 100 microg/mL) and lyso-PtdCho (10(-7) to 10(-5) mol/L) stimulated migration in a concentration-dependent manner. In contrast, the effects of native LDL and phosphatidylcholine were modest or nonexistent. Protein kinase C (PKC) inhibitor and downregulation of PKC activity by phorbol ester inhibited oxidized LDL- and lyso-PtdCho-induced migration. Human ANP(1-28) and human BNP-32 significantly inhibited oxidized LDL- and lyso-PtdCho-induced migration in a concentration-dependent manner. C-ANF (des-[Glu(18),Ser(19),Gly(20),Leu(21),Gly(22)]ANP(4-23)), a specific ligand for ANP clearance receptors, could not inhibit oxidized LDL- and lyso-PtdCho-induced migration. Inhibition by ANP and BNP of lyso-PtdCho-induced migration was paralleled by an increase in the cellular level of GMP. Oxidized LDL- and lyso-PtdCho-induced migrations were inhibited by 8-bromo-cGMP. The results suggest that oxidized LDL and lyso-PtdCho stimulate the migration of human mesangial cells, at least in part, through a PKC-dependent process and that ANP and BNP inhibit this stimulated migration, probably through a cGMP-dependent process.

Atrial Natriuretic Factor↗
PubMed2000

Aldose reductase inhibitor improves insulin-mediated glucose uptake and prevents migration of human coronary artery smooth muscle cells induced by high glucose.

We examined involvement of the polyol pathway in high glucose-induced human coronary artery smooth muscle cell (SMC) migration using Boyden's chamber method. Chronic glucose treatment for 72 hours potentiated, in a concentration-dependent manner (5.6 to 22.2 mol/L), platelet-derived growth factor (PDGF) BB-mediated SMC migration. This potentiation was accompanied by an increase in PDGF BB binding, because of an increased number of PDGF-beta receptors, and this potentiation was blocked by the aldose reductase inhibitor epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited high glucose-potentiated (22.2 mmol/L), PDGF BB-mediated migration. Epalrestat at 100 nmol/L inhibited a high glucose-induced increase in the reduced/oxidized nicotinamide adenine dinucleotide ratio and membrane-bound protein kinase C (PKC) activity in SMCs. PKC inhibitors calphostin C (100 nmol/L) and chelerythrine (1 micromol/L) each inhibited high glucose-induced, PDGF BB-mediated SMC migration. High glucose-induced suppression of insulin-mediated [(3)H]-deoxyglucose uptake, which was blocked by both calphostin C (100 nmol/L) and chelerythrine (1 micromol/L), was decreased by epalrestat (100 nmol/L). Chronic high glucose treatment for 72 hours increased intracellular oxidative stress, which was directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by epalrestat (100 nmol/L). Antisense oligonucleotide to PKC-beta isoform inhibited high glucose-mediated changes in SMC migration, insulin-mediated [(3)H]-deoxyglucose uptake, and oxidative stress. These findings suggest that high glucose concentrations potentiate SMC migration in coronary artery and that the aldose reductase inhibitor epalrestat inhibits high glucose-potentiated, PDGF BB-induced SMC migration, possibly through suppression of PKC (PKC-beta), impaired insulin-mediated glucose uptake, and oxidative stress.

Aldehyde Reductase↗
PubMed2000

15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.

Animals↗
PubMed2000

Liver dysfunction due to apoptosis in a patient with systemic lupus erythematosus.

We report on a 23-year-old Japanese female with a 13-year history of systemic lupus erythematosus (SLE), and two episodes of deterioration followed by treatment with high dose prednisolone. Although she had been recently treated with prednisolone (12.5 mg daily), her liver function became worse in July 1998. Results of a liver biopsy revealed multi-focal hepatic cell death in a severe fatty liver, without any inflammatory cell invasion. The biopsy also showed a positive TUNEL (Tdt-catalysed DNA nick end labelling) reaction indicating apoptosis. Her liver function recovered rapidly following steroid pulse therapy. Serum soluble Fas ligand (sFasL) was found to be elevated to a concentration of 0.395 ng/ml at the time of liver damage, but was less than 0.03 ng/ml before liver damage and after prednisolone treatment. The liver damage in this case appeared to be involved with apoptosis induced by sFasL. Although hepatitis associated with SLE is rare, apoptosis directly related to elevated sFasL levels might cause this complication.

Adult↗
PubMed2000

Electron spin resonance studies of dipalmitoylphosphatidylcholine liposomes containing soybean-derived sterylglucoside.

The effects of soybean-derived sterylglucoside (SG) on the fluidity of liposomal membrane composed of dipalmitoylphosphatidylcholine (DPPC) were investigated compared with those of soybean-derived sterol (SS) and cholesterol (Ch) using an electron spin resonance spectrometer. Three kinds of liposomes were prepared in the molar ratio of DPPC/X=7/4, where X is SS, Ch or SG. The fluidity close to the polar head groups increased with an increase of temperature in the DPPC membrane containing SS, Ch and SG in the range 35 to 45 degrees C. Those near the hydrophobic end changed with an increase in temperature in liposomes containing SS, Ch and SG, which had a fluidizing effect on the DPPC membrane below the transition temperature (Tm, 41.9 degrees C) and a condensing effect over the Tm. The fluidizing effects of these compounds around 37 degrees C near the polar head group and the hydrophobic end increased in the following order: Ch < SG < or = SS and SS < Ch < SG, respectively. SG increased the fluidity of liposomal membrane dramatically above the Tm (35.4 degrees C). These results suggest that the high fluidity close to the hydrophobic end of the liposomal membranes around 37 degrees C, the decrease of Tm, and the sigmoidal nature of fluidity vs. temperature are important factors in the effectiveness of liposomes containing SG as a carrier of drugs.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

[A nationwide survey of anesthesia for laparoscopic and thoracoscopic surgeries].

This is the report the first nationwide survey of anesthetic management for laparoscopic and thoracoscopic surgeries. We mailed a questionnaire to anesthetists of 133 hospitals in Japan and 74 completed questionnaires were returned. The number of intra-abdominal and thoracic surgical procedures has been increasing. General anesthesia was used in all cases for endoscopic surgery. The double lumen tube was selected in 79% of patients with pneumothorax for the endobronchial intubation. Patients for the laparoscopic cholecystectomy (LC) were given various types of anesthetics. Thirty-two percent of patients who underwent LC was anesthetized with inhalation anesthetics combined with epidural anesthesia for the early ambulance and postoperative pain control. The maximum length of time for LC surgery was 12.5 hr. Complications related to laparoscopic surgery included bile duct injuries in 72 patients, postoperative bleeding in 32 patients, vascular injuries in 29 patients, pneumothorax in 26 patients, bronchial intubation in 17 patients, gas embolism in 11 patients, bowel injuries in 9 patients and postoperative ileus in 7 patients. Administering anesthesia for endoscopic procedures requires precise knowledge of the surgical procedures, physiologic changes and complications of the pneumoperitoneum, and one lung ventilation.

Anesthesia↗
PubMed2000

[Perforation of small intestinal during hematologic recovery in an elderly man after induction therapy for acute lymphoblastic leukemia L3].

A 67-year-old man with a 7-month history of dilated cardiomyopathy was admitted to our hospital because of general fatigue, shortness of breath, and anemia on laboratory examination. Increased blasts were observed in the bone marrow. The blasts were characterized by large cells with abundant, intensely basophilic, vacuolated cytoplasm, round nuclei, and prominent nucleoli. Chromosome analysis revealed a nonrandom t(8;22)(q24;q11) chromosomal abnormality, and surface-marker analysis disclosed a positive immunophenotype for CD10, CD19, CD20, CD38, HLA-DR, FMC7, and IgM-lambda. These findings yielded a diagnosis of L3 acute lymphoblastic leukemia. The patient was treated with chemotherapeutic agents. On the 39th hospital day, during hematologic recovery after induction therapy, abdominal pain developed. Abdominal X-ray films disclosed ileus with dilatation of the small bowel and Kerckring's folds. Conservative treatment was begun but the patient died. At autopsy, intestinal perforations were observed at a site 55 cm proximal to the ileocecal junction. A specimen of perforated tissue revealed a diffuse infiltration of leukemic cells through the small bowel wall. However, bone marrow specimens showed no signs of aggravation of leukemia.

Aged↗
PubMed2000

[Two cases of classical polyarteritis nodosa associated with a low titre of MPO-ANCA].

We studied two autopsy cases, each with a low titre of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated with systemic vasculitis. It was difficult to distinguish these cases from classic polyarteritis nodosa. The patients had suffered from continuous fever, malaise, and weight loss: however, their renal insufficiency was clinically mild over the course of their disease. The patients were diagnosed initially as having MPO-ANCA-associated vasculitis and were treated with prednisolone. Their clinical status improved, but unfortunately, they died of an infectious disease. Autopsies revealed systemic vasculitis in small arteries with no signs of necrotizing and crescentic glomerulonephritis. Our pathologist subsequently diagnosed both cases as classic polyarteritis nodosa. Systemic vasculitis associated with MPO-ANCA is usually considered to be a microscopic polyarteritis. However, classic polyarteritis nodosa should always be considered as a possibility for those patients with mild renal insufficiency and a low titre of MPO-ANCA.

Aged↗
PubMed2000

Evaluation of the Space Collaboration System: its history, image quality and effectiveness for joint case conference.

A joint case-conference was conducted between the Departments of Radiology at Nagoya and Kobe Universities using the Space Collaboration System (SCS), which connects 39 national universities and institutes by communication satellite. In the conference, both sides presented cases using medical images such as those from CT, MRI, and DSA, and the cases were discussed between participants at the two universities. After the final conference, we distributed a questionnaire to solicit responses from the 43 participating radiologists on the quality of the transferred images and their overall impression of the conference. The responses showed that the CT, MRI, and DSA images were clear enough to allow discussion, whereas the plain X-ray images were not. Hence from the standpoint of image quality, the SCS may be unsuited for medical image diagnosis, but useful for presentation of case images in joint conferences and seminars.

Evaluation Studies as Topic↗
PubMed2000

Cephalometric comparisons of craniofacial and upper airway structures in young children with obstructive sleep apnea syndrome.

We studied 15 children of preschool age who had obstructive sleep apnea syndrome to evaluate their dentofacial morphology in relation to the pharyngeal airway space. We found that (1) sleep apnea was often associated with mandibular retrognathia, (2) the lower incisors tended to exhibit a retrocline, (3) there were no significant differences in angular and linear measurements in the cranial base between patients with sleep apnea and a control group of 30 nonapneic children, and (4) the apneic children had a narrower epipharyngeal airway space than did the controls. These findings suggest that obstructive sleep apnea is probably caused by both adenoidal hypertrophy and abnormal development of the facial skeleton. We highly recommend cephalometric analysis as a valuable tool for conducting the presurgical evaluation of sleep apnea in children of preschool age.

Adenoids↗