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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 109 records · Page 6Linked to original sources

Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia.

The aim of this study was to investigate whether idiopathic pulmonary fibrosis (IPF) can be distinguished from rheumatoid arthritis (RA)-associated interstitial pneumonia (RA-IP) by means of quantitatively assessing myofibroblasts and S-100 protein positive dendritic cells. Seven patients with IPF and twelve with RA, in whom the pathological findings were consistent with usual interstitial pneumonia (UIP) were studied. Antibodies to vimentin, alpha-smooth muscle actin (alpha-SMA) and S-100 protein were used for immunohistochemical studies performed using the streptavidin/biotin/peroxidase complex method, applied to dewaxed sections from each case. In fibrosis of RA-IP, appearance of both vimentin- and alpha-SMA-positive cells, namely myofibroblasts, was widely observed, together with the pathological patterns of honeycombing, UIP and bronchiolitis obliterans-organizing pneumonia (BOOP). Fibrosis, in cases of chronic IPF, was found to be characterized mainly by vimentin-positive but alpha-SMA-negative fibroblasts. Pulmonary tissues from RA-IP patients especially when associated with a BOOP pattern, contained many cells positive for S-100 protein. However, such cells were generally hard to find in cases of IPF. These findings suggests that idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia can be differentiated from each other, to some extent, based on the appearance of myofibroblasts and the presence of S-100-positive dendritic cells.

Actins↗

Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats.

A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A2 (detected as thromboxane B2) and prostaglandin I2 (detected as 6-ketoprostaglandin F1alpha). Thromboxane B2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F1alpha level exceeded that of thromboxane B2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1alpha and -1beta detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1alpha into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-ketoprostaglandin F1alpha resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1alpha injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1alpha.

Animals↗

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Adolescent↗

Probucol suppresses ICAM-1 expression in rat mesangial cells: possible role of IL-1.

Interleukin-1 (IL-1) participates in the progression of glomerulonephritis by up-regulating intercellular adhesion molecule-1 (ICAM-1) expression in experimental glomerulonephritis. Probucol, an anti-hyperlipidemic agent, ameliorates some types of glomerulonephritis regardless of serum cholesterol levels, and is also reported to inhibit IL-1 release from macrophages in atherosclerotic lesions. However, little is known about the mechanism of this favorable action on glomerular injury. We examined whether or not probucol inhibits ICAM-1 expression by suppression of IL-1 action in cultured rat mesangial cells. In this brief report, we review the actions of probucol on IL-1 secretion and discuss the possible mechanism by which probucol may suppress the glomerular injury.

Animals↗

Effect of age on cerebrospinal fluid levels of metabolites of biopterin and biogenic amines.

We identified an age effect on biopterin and biogenic amine metabolites in the cerebrospinal fluid from 56 neurologically normal patients, aged 1 mo to 80 y. The levels of total and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were found to peak during the first year of life. The levels of these metabolites then gradually decreased, plateauing at the age of 20 y. We found significant correlations between biopterin, homovanillic acid, and 5-hydroxy-indoleacetic acid.

Adolescent↗

Oxidant mechanisms in toxic acute renal failure.

Over the last decade, there is accumulating evidence for a role of reactive oxygen metabolites in the pathogenesis of a variety of renal diseases, including gentamicin, glycerol, cisplatin, and cyclosporine A models of toxic acute renal failure. Gentamicin has been shown both in in vitro and in vivo studies to enhance the generation of reactive oxygen metabolites. Iron is important in models of tissue injury, presumably because it is capable of catalyzing free-radical formation. Gentamicin has been shown to cause release of iron from renal cortical mitochondria. Scavengers of reactive oxygen metabolites as well as iron chelators provide protection in gentamicin-induced nephrotoxicity. In glycerol-induced acute renal failure, an animal model of rhabdomyolysis, there is enhanced generation of hydrogen peroxide, and scavengers of reactive oxygen metabolites and iron chelators provide protection. Although the dogma is that the myoglobin is the source of iron, recent studies suggest that cytochrome P450 may be an important source of iron in this model. In addition, there are marked alterations in antioxidant defenses, such as glutathione, as well as changes in heme oxygenase. Several recent in vitro and in vivo studies indicate an important role of reactive oxygen metabolites in cisplatin-induced nephrotoxicity. Thus, catalytic iron is increased both in vitro and in vivo by cisplatin, and iron chelators as well as hydroxyl radical scavengers have been shown to be protective. Recent studies indicate that cytochrome P450 may also be an important source of the catalytic iron in cisplatin nephrotoxicity. Cyclosporine A has been shown to enhance generation of hydrogen peroxide in vitro and enhance lipid peroxidation in vitro and in vivo. Antioxidants have been shown to be protective in cyclosporine A nephrotoxicity. This collective body of evidence suggests an important role for reactive oxygen metabolites in toxic acute renal failure and may provide therapeutic opportunities of preventing or treating acute renal failure in humans.

Acute Kidney Injury↗

Ophthalmomyiasis caused by Sarcophaga crassipalpis (Diptera: Sarcophagidae) in a hospital patient.

Nine sarcophagid larvae were found on the right eyelid, cornea, and bulbar conjunctiva of a debilitated patient in a hospital in Osaka, Japan. Inflammation of the right eyelid and conjunctival congestion, probably initiated or aggravated by the larvae, were found. The larvae were removed and reared for accurate identification, and, on the basis of the characteristics of the 3rd instar and adult flies, the species was identified as Sarcophaga crassipalpis Macquart. This is a report of ophthalmomyiasis caused by this facultative parasite in a human. Patients with diminished consciousness in hospitals need protection from flies.

Aged↗

Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

BACKGROUND: With progressive renal disease, structural derangement increasingly encompasses the tubulointerstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important contributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of differentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial cell activation in IgA nephropathy patients. METHODS. We studied whether the expression of caldesmon in interstitium of the kidney was enhanced in the process of glomerular disease and whether it would be a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. Interstitial caldesmon expression were compared with histological changes and clinical parameters. RESULTS: Caldesmon expression was enhanced where interstitial cell infiltration and fibrosis were found. Immunoelectron microscopy revealed that caldesmon staining in the renal interstitium was cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon expression was more prominent in the intense CD68 infiltrated group than in the low positive cells infiltrated group. Patients showing high intensity of interstitial caldesmon expression had significantly higher urinary protein excretion than those showing low intensity of caldesmon expression. Next, 15 patients were treated with glucocorticoid and heparin for 4-8 weeks and re-biopsies were performed. Caldesmon expression was reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 months) revealed a significant suppression of urinary protein excretion and significant improvement of creatinine clearance. CONCLUSION: These results suggest that the interstitial caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid--heparin therapy may reverse the phenotypic change of interstitial cells during the disease process of glomerulonephritis.

Actins↗

Hearing loss with a mitochondrial gene mutation is highly prevalent in Japan.

OBJECTIVES/HYPOTHESIS: Mutations in the mitochondrial genome may predispose people to sensorineural hearing loss. An adenine to guanine point mutation in the tRNA(Leu(UUR)) gene at nucleotide 3,243 is one of the deaf-related mutations. This mutation is reported to be associated with 0.9% of diabetes mellitus patients. However, the prevalence of this mutation in hearing-impaired patients still remains unknown. The aim of this study was to determine the prevalence of this mutation among bilaterally sensorineural hearing-impaired patients in Japan. STUDY DESIGN: Retrospective survey of 100 patients with bilateral sensorineural hearing loss without any evident causes. METHODS: Mitochondrial DNA fragments from the patients were amplified by polymerase chain reaction, followed by a restriction enzyme fragment length polymorphism method. RESULTS: Three patients with this mutation were identified. Their clinical profiles were different from the category which had been considered as hearing loss caused by this mitochondrial gene mutation. CONCLUSIONS: The mutation is associated with approximately 3% of bilateral sensorineural hearing loss cases of unknown origin and is possibly distributed widely in sensorineural hearing-impaired patients in Japan.

Adult↗

Radiofrequency catheter ablation of left ventricular outflow tract tachycardia from the coronary cusp: a new approach to the tachycardia focus.

INTRODUCTION: Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. Previously reported were two cases of LVOT tachycardia which were treated with radiofrequency (RF) catheter ablation through endocardial aortomitral continuity. We report here a case of a repetitive LVOT tachycardia in which the QRS morphology during VT exhibited an atypical left bundle branch block and inferior axis. Pace mapping revealed that the origin of this VT was very close to the left sinus of Valsalva. Transcoronary cusp RF catheter ablation abolished the VT in this patient and is a new approach for the treatment of this kind of VT. The application of this approach to the other types of VT has yet to be determined.

Adult↗

Incidence and risk factors of benign creatine phosphokinase elevations in chronic psychiatric patients.

There have been few studies focusing on the creatine phosphokinase (CPK) elevations in chronic psychiatric patients. The survey was conducted prospectively to investigate the incidence and risk factors of CPK elevations in chronic psychiatric patients during a 2-year follow-up period. Sixteen of 32 (50%) patients had maximums of more than 230 U/l (upper limit of our normal range) and 7 (22%) patients had maximums of more than 500 U/l. Surprisingly, 4 (13%) patients had maximums of more than 1,000 U/l after exercises such as swimming and walking. Nonetheless, none of the 16 patients with the CPK elevations developed severe conditions such as rhabdomyolysis despite an absence of therapeutic intervention, and their CPK elevations were proven to be benign. According to the path analysis, usual physical activity and neuroleptic doses seemed to underlie CPK elevations directly. The present findings suggest that not a few chronic psychiatric inpatients may have at least one CPK elevation per 2 years. Patients engaging in more physical activity or receiving higher neuroleptic doses are at greater risk of developing such CPK elevations. However, most of these increases are benign, and it is not considered necessary to treat them.

Adult↗

Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells.

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has been implicated in the etiology of localized juvenile periodontitis (LJP), and produces a multiplicity of tissue-damaging products. Among those products, the capsular-like polysaccharide antigen (CPA) from A. actinomycetemcomitans is a potent mediator of bone resorption. In fact, this CPA (serotype b) is known to promote osteoclast-like cell formation via interleukin (IL)-1alpha production in mouse marrow cultures. Although osteoblasts complete bone formation, there are few reports focusing on the effect of CPA in bone-forming activity of osteoblasts in inflammatory disease sites. We hypothesized that CPA plays a mediating role in osteoblastic cells. Therefore, the purpose of this study was to examine the effect of CPA from A. actinomycetemcomitans on the mouse osteoblastic cell line MC3T3-E1 and human osteosarcoma SaOS-2 cells. A. actinomycetemcomitans serotype c resulted in a potent dose-dependent inhibition of cell proliferation of both cell lines. Characterization of the antiproliferative activity in the CPA demonstrated that it was not cytotoxic for MC3T3-E1. A 20-hour incubation with CPA-c resulted in a significant increase in apoptotic cell death in the cells, as evaluated by both cellular DNA fragmentation ELISA and FACS analysis. In contrast to the results obtained with a cytokine mixture (tumor necrosis factor-alpha, IL-1beta, and interferon-gamma), no inducible nitric oxide (NO) synthase gene expression or NO release could be detected in MC3T3-E1 after incubation with CPA-c. Further, both CPA-b and -c caused potent induction of apoptosis-related modifiers, e.g., Fas mRNA, whereas bcl-2 mRNA levels were unchanged. Therefore, this study has shown that CPA from A. actinomycetemcomitans contains a potent antiproliferative polysaccharide whose activity is associated with apoptotic cell death in MC3T3-E1, and that CPA per se is an inducer of apoptosis mediated by the Fas system but not by NO.

Aggregatibacter actinomycetemcomitans↗

Heart rate variability analysis of patients with idiopathic left ventricular outflow tract tachycardia: role of triggered activity.

There have been several reports with respect to idiopathic ventricular tachycardias (VTs) originating from the left ventricular outflow tract (LVOT). A previous report suggested that triggered activity plays a partial role in idiopathic LVOT tachycardia from the electrophysiological as well as the electropharmacological viewpoint. However, the exact role of triggered activity in this type of VT remains unknown. In the present study the relationship of the frequency of premature ventricular contractions (PVCs) and heart rate was examined and heart rate variability (HRV) was analyzed in 2 cases of LVOT tachycardia using 24-h Holter electrocardiographic (ECG) monitoring. The relation between the PVCs frequency and heart rate showed a persistently positive correlation, indicating frequent PVCs as heart rate increased. In HRV analysis, NN50(%), a time-domain variable of parasympathetic activity, showed no change prior to ventricular arrhythmias. In frequency-domain analysis of HRV, the high frequency (HF) component tended to fall prior to repetitive PVCs and VTs. The ratio of the low frequency to high frequency (LF/HF) components increased prior to single PVCs, repetitive PVCs and VTs. Sympathetic predominance predisposes the genesis of these kinds of arrhythmias originating from the LVOT and it is suggested that triggered activity plays an important role in LVOT tachycardia, at least in its initiation.

Electrocardiography↗

[Hemostatic effect of a novel sheeted fibrin adhesive agent, TO-193, on experimental incision models].

TO-193 (TachoComb) is a new fibrin adhesive agent that consists of a collagen sheet coated with fibrin glue. We compared the hemostatic effect of TO-193 in several experimental models with Beriplast P as a fibrin adhesive agent, Avitene and Novacol as a microfibrillar collagen hemostat, and a sponge-like collagen sheet as the constitutional parts of TO-193. In the in vitro bleeding model in which blood leaks out through cotton cloth, the pressure of TO-193 when blood leakage was observed was higher than those of Beriplast P, Avitene, Novacol and the collagen sheet, indicating that TO-193 possessed a strong adhesive effect on the bleeding surface. On the kidney resection surface, TO-193 showed a more potent adhesive effect than those of Beriplast P and the collagen sheet, suggesting that TO-193 has a potent hemostatic effect. In the liver resection, TO-193 significantly reduced the bleeding volume compared with that of Novacol in normal rats. Furthermore, the bleeding volume of TO-193 was about half that of Beriplast P and equivalent to that of Novacol even in anticoagulant-treated rats. From these data, it is expected that TO-193 would be a valuable hemostatic agent for clinical use since TO-193 possesses a potent adhesive ability on the bleeding resection surface and would certainly stop bleeding in both patients with normal coagulation and those with a low blood coagulation condition.

Animals↗

Experimental ablation study using a new long linear probe in isolated porcine hearts.

We studied a new technique for creating long linear lesions in hearts using a custom-made linear probe. Radiofrequency (RF) energy applications using a 25-mm long stainless steel linear probe and a corresponding 500-kHz energy generator were tested, creating 90 lesions in isolated porcine hearts. The RF current was applied between the linear probe and a large patch electrode attached to the back of the specimen. Three parameters, comprising the power of the delivered energy, the pressure of contact between the probe and the specimen, and the duration of energy delivery were changed independently and the size of the resulting lesions was measured. All 90 lesions were transmural, well demarcated and created by a single stationary RF application. Lesion length and width increased with: 1) increasing power, when the other two parameters were maintained at constant levels, 2) increasing contact pressure, when the other two parameters were maintained at constant levels, and 3) increasing duration of energy delivery when the other two parameters were maintained at constant levels. The maximum width of the lesions was 3.7 mm. No overheating of any of the specimens was observed. In conclusion, the new original long linear probe used in this study was effective for creating transmural linear lesions, presenting the possibility of a worthwhile contribution to the maze surgical procedure applied to atrial fibrillation.

Animals↗

Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes.

OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm.

Adult↗

Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by metered-dose inhaler with InspirEase to relieve acute asthma attack.

Although the inhalation of beta2-agonists has frequently been used to relieve acute asthma attacks, the efficacy of anticholinergic agents for acute asthma attacks still remains unclear. This study was designed to compare the inhalation of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by a metered-dose inhaler with holding chamber (InspirEase) to relieve acute asthma attacks. To accomplish this, 69 patients who had presented with an acute asthma attack were randomized to receive either fenoterol (1 puff [200 microg/puff] every 1 min for 5 min; total 1000 microg) or fenoterol plus oxitropium bromide (2 puffs [100 microg/puff] every 1 min for 5 min; total 1000 microg). The peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) values were measured before treatment, and 1, 15, 30, and 60 min after the inhalation therapy. The ratios of improvement, PEF (or FEV1) after treatment divided by PEF (or FEV1) before treatment, were also calculated. Thirty-three patients were evaluated in the combination group and 31 patients were evaluated in the fenoterol group. The PEF value at 60 min after inhalation therapy of the fenoterol plus oxitropium bromide group (261 +/- 18 L/min, mean +/- standard error) was significantly higher compared to that of the fenoterol group (210 +/- 17 L/min). In addition, the ratios of improvement of PEF at 1, 15, 30, and 60 min after inhalation therapy were significantly higher in the fenoterol plus oxitropium bromide group compared with the fenoterol group.

Acute Disease↗

Radiofrequency catheter ablation of idiopathic right ventricular tachycardia near the His bundle.

There are only a few reports on successful radiofrequency catheter ablation of idiopathic right ventricular tachycardia (VT) originating from other sites than right ventricular outflow tract. We report here a case of VT which exhibited an inferior-axis and a left bundle branch block pattern and originated near the His bundle. Using the temperature-controlled ablation catheter, prudent observation of the fluoroscopy and intracardiac electrograms during pacemapping, we successfully ablated the origin of the VT without any conduction disturbance. However, further study is required to determine the effectiveness of catheter ablation and the long term prognosis for this type of VT.

Adult↗