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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 505 records · Page 28Linked to original sources

Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode.

1. Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed. 2. Basal glutamate levels were below detection limits (approximately 0.1 microM). An increase in extracellular KCl (from 2.7 to 50 and 100 mM) increased extracellular hippocampal glutamate levels to 9.2+/-1.4 and 20.0+/-2.6 microM, respectively, calculated from the area under curve (AUC) for 60 min. 3. This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises. 4. An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 12.4+/-2.1 and 5.8+/-0.9 microM. 5. Perfusion with 100 microM CBZ or 1 mM ZNS inhibited both the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2+/-1.4 to 5.5+/-1.1 and to 5.8+/-1.3 microM, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release. 6. These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.

Animals↗

Decreased hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis.

Recent studies of the stratum corneum (SC) in patients with atopic dermatitis (AD) have disclosed various functional impairments even in clinically unaffected skin. However, it has not been clear whether the presence of atopic background itself has any influence on the function of the SC. In this study, we conducted functional studies of the SC in the mid-portion of the flexor surface of the forearm of 49 skin lesion-free patients with allergic rhinitis to Japanese cedar pollen (atopic respiratory disease; ARD) in early spring, their disease-active season, by comparing the findings obtained with those in 28 patients with AD and 57 age-matched healthy control subjects. The results showed that the patients with ARD had significantly lower skin surface hydration levels assessed by high-frequency conductometry than those of the healthy control subjects. These levels were, however, not as low as those noted in moderately or severely affected patients with AD. Moreover, by measuring the amounts of water-soluble amino acids contained in the superficial portions of the SC, we found that these are also decreased at a marginal level (P = 0.051) in patients with ARD compared with levels in healthy control subjects. In contrast, the water barrier function of the SC evaluated by measurements of transepidermal water loss in patients with ARD was not different from that of the healthy control subjects. These results suggest that, although their skin appears normal clinically, the SC of the patients with ARD has functional deficiency in water-holding capacity.

Adult↗

Significance of trilineage myelodysplasia in de novo acute myeloid leukaemia during remission rather than at diagnosis.

Patients with trilineage myelodysplasia (TMDS) in de novo acute myeloid leukaemia (AML) at diagnosis and remission were clinically evaluated between 1983 and 1996. AML with TMDS (AML/TMDS) was observed in 20 (12%) of 162 patients with de novo AML at diagnosis. Complete remission (CR) was achieved with combination chemotherapy in 12 (67%) of 18 AML/TMDS cases. This CR rate was relatively worse than the rate of 78% (106/136 cases) of AML without TMDS, but this difference was not significant. Disease-free survival curves also showed no difference between AML/TMDS and AML without TMDS. During remission, eight (67%) of 12 AML/TMDS cases had myelodysplastic remission marrow (AML/MRM). AML/MRM was also seen in seven (7%) of 106 AML cases without TMDS. The actuarial disease-free survival was significantly lower in AML/MRM than in AML without MRM (P = 0.0003). All of the AML/MRM cases exhibited early leukaemic relapse; median remission duration was only 9 months. Clonal changes occurred in two cases of AML/TMDS and five cases of AML/MRM at the time of relapse. These findings suggest that TMDS during remission predicts a poorer prognosis and early leukaemic relapse when compared with the absence of TMDS.

Acute Disease↗

A modified human ureter graft tanned by a new crosslinking agent polyepoxy compound for small diameter arterial substitutions: an experimental preliminary study.

The effectiveness of human ureter grafts tanned by polyepoxy compound for small diameter arterial substitution was examined in 8 carotid arteries of rabbits, followed by an observation period of either 1 month (n = 6) or 6 months (n = 2). In this model there was no evidence of rejection, aneurysm formation, or infection. The modified human ureter showed excellent patency in all cases as well as excellent function, and the histological evaluation revealed monolayer endothelial-like cells covering all of the surface of the graft as was expected. No intimal hyperplasia was demonstrated at either anastomotic site. This study suggests that our newly designed polyepoxy compound fixed human ureter could serve as a satisfactory blood conduit with good long-term patency for substitution.

Anastomosis, Surgical↗

Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine.

Because of its potential for chronic nephrotoxicity, the long-term use of cyclosporine A (CsA) as treatment for nephrotic syndrome (NS) is controversial. The clinical outcome of patients with NS treated with CsA is unclear. We retrospectively evaluated 35 children with idiopathic NS, 24 with steroid-dependent NS (SDNS), and 11 with steroid-resistant NS (SRNS), who received CsA therapy for more than 12 months (median, 23 months) at the dosage maintaining 50 to 120 ng/mL in trough level. For SDNS patients, CsA was added to prednisolone after complete remission was achieved. For SRNS patients, CsA was used in combination with alternate-day prednisolone. Initial renal histology showed minimal changes (MC) in 28 patients (including all of the patients with SDNS) and focal segmental glomerulosclerosis (FSGS) in seven patients. The patients were followed up for 2 to 10.5 years (median, 6.5 years) after the termination of the CsA therapy. In SDNS patients, the relapse rate, dosage of prednisolone, standard deviation score for height, and body mass index significantly improved during CsA treatment. The follow-up study showed the proportion of SDNS decreased to 13 of 24 (54%) patients. In SRNS patients, CsA therapy induced remission in 8 of 11 patients (73%) (complete remission in seven and incomplete remission in one). Six of 11 patients (55%) then became steroid sensitive. Post-therapy biopsies, performed in 13 patients (10 with SDNS and three with SRNS), showed mild stripped interstitial fibrosis in two SDNS patients (15%). Long-term CsA therapy in moderate doses was effective to the patients with SDNS and SRNS and low in incidence of nephrotoxicity. The long-term use of CsA appears to result in a decrease in the proportion of SDNS and acquisition of subsequent steroid responsiveness in SRNS.

Adolescent↗

Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.

In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influenced neuronal activities of the medial vestibular nucleus (MVN) using chloral hydrate-anesthetized rats and dissociated MVN neurons, respectively. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each micropipette was filled with 20-HE, glutamate, bicuculline or 2 M NaCl. These chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. Microiontophoretically applied 20-HE (20-80 nA) dose-dependently decreased rotation-induced firings of both type I and II neurons, which were identified according to their responses to horizontal sinusoidal rotations. Microiontophoretically applied bicuculline, a GABAA receptor antagonist, inhibited 20-HE-induced decreases in neuronal firing of MVN. These findings suggest that 20-HE potentiates the action of GABA, probably by acting directly on the GABAA receptor of MVN neurons. In addition, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was also antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investigated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 microM)-induced currents were potentiated in the presence of 20-HE (100 microM). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion channel complexes to potentiate GABA inhibition.

Animals↗

Homozygosity mapping of a gene responsible for gelatinous drop-like corneal dystrophy to chromosome 1p.

Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disorder characterized clinically by grayish corneal deposits of amyloid and by severely impaired visual acuity. Most patients require corneal transplantation. To localize a gene responsible for GDLD, we performed linkage analysis of 10 consanguineous Japanese families with a total of 13 affected members. Homozygosity mapping provided a maximum LOD score of 9.80 at the D1S2741 marker locus on the short arm of chromosome 1. Haplotype analysis further defined the disease locus within a region of approximately 2.6 cM between D1S2890 and D1S2801.

Chromosome Mapping↗

Experimental and clinical studies on transmyocardial laser revascularization (TMLR).

The number of patients with coronary artery disease has been increasing and several kinds of treatments have been performed to alleviate their conditions. In patients with small branches or diffuse stenotic lesions of the coronary arteries, on whom coronary artery bypass grafting and intracoronary intervention cannot be carried out, it has been shown possible to supply arterial blood from the left ventricular cavity to the ischemic myocardium through laser channels. Arterial blood can be supplied hemodynamically from the left ventricular cavity to the ischemic myocardium. In trials on dogs laser channels 0.2 mm in diameter have been found to be histologically patent even 3 years after transmyocardial laser revascularization (TMLR). Thus, this procedure could be used as an alternative method of transmyocardial revascularization. We used TMLR on a 55-year-old male patient with severe angina pectoris who had undergone pericardiectomy 7 years ago. He is still alive more than 12 years after TMLR. This patient was among the first successful clinical cases in the world treated by TMLR alone. Therefore, this procedure should be recommended for the patients with end-stage coronary artery disease.

Angina Pectoris↗

Clinical experience of endovascular laser intervention in cardiovascular disease.

OBJECTIVE: The authors studies laser angioplasty for patients with obstructive arterial diseases since the 1980s. SUMMARY BACKGROUND DATA: Usefulness of laser angioplasty for endovascular surgery was recognized especially for patients having short segments of severe atherosclerotic changes in vessels. METHODS: The authors retrospectively reviewed clinical experience of angioplasty by argon laser for 113 patients (103 peripheral, 10 coronary artery). Using an argon laser optimal conditions were (a) 6W in output and 3 sec in irradiation time or (b) metal tip temperature of 200 degrees C and 5 sec of ablation time for the peripheral artery. On the other hand, 4-5 W in output and 2 sec in irradiation time were optimal conditions for the same procedure on the coronary artery. RESULTS: The initial success rate of laser angioplasty for the peripheral artery was 92% in the stenotic lesions and 73% in the occlusive lesions. However, cumulative patency rate was 85% in the stenotic lesions and 74% in the occlusive lesions in the long-term follow-up study of 106 months among the patients with clinical success. On the basis of the excellent results in the peripheral arterial diseases, coronary laser angioplasty and coronary artery bypass grafting was intraoperatively performed in 10 patients with anginal attack. Patency rate was 90% in this series. CONCLUSIONS: Laser angioplasty for endovascular surgery was a useful procedure for patients with stenotic and occlusive changes of the peripheral and coronary arteries. Consequently, this method should be recommended especially for high-risk patients with atherosclerosis.

Adult↗

Depolarization-induced tyrosine phosphorylation of p130(cas).

KCl-treatment of PC12 cells induces depolarization of the plasma membrane and Ca2+ influx into the cells. We have previously shown that KCl induced tyrosine phosphorylation of cellular proteins of 120, 110, 68, 44, and 42 k, and that the 68 k protein was paxillin. In the present study, we found that the 120 k protein was a Crk-associated Src substrate, p130(cas). KCl-induced tyrosine phosphorylation of p130(cas) was not observed in EGTA-containing medium, suggesting that it was due to Ca2+ influx into the cells. Time course experiments showed that tyrosine phosphorylation of p130(cas) peaked at 5 min after stimulation and returned to the basal level at 60 min, while mobility shift of p130(cas) was observed within 2 min and lasted over 60 min, indicating that serine or threonine residues, in addition to tyrosine, were phosphorylated on KCl stimulation. In vitro kinase assay of immunoprecipitates with anti-p130(cas) antibody suggested that some protein-tyrosine kinases were associated with p130(cas). Using the substrate region of p130(cas) as the substrate, we found that Fyn and Src were activated on stimulation with KCl. These results indicate that tyrosine phosphorylation of p130(cas) may be involved in Ca2+-dependent events in neuronal and neuroendocrine cells.

Animals↗

Comparison of survival-promoting effects of brain-derived neurotrophic factor and neurotrophin-3 on PC12h cells stably expressing TrkB receptor.

We obtained two PC12h cell lines, PC-pAB1 and PC-pAB2, stably expressing TrkB receptor and investigated the effects of BDNF and NT-3 in these cell lines. The cells differentiated into neuron-like cells in response to BDNF as well as NGF, neurite extension being more rapid in the former case. These TrkB-expressing cells also extended neurites in response to NT-3, which is a nonpreferred ligand of TrkB. Next, we examined the survival-promoting effects of NGF, BDNF, and NT-3 under apoptotic conditions of oxygen toxicity in naive cells and NGF deprivation in differentiated cells. In both cases, BDNF prevented cell death similarly to NGF. NT-3 prevented cell death induced by oxygen toxicity in naive cells, but not that induced by NGF deprivation in differentiated cells. NT-3 induced the tyrosine phosphorylation of TrkB in naive cells, but not in differentiated cells. These results indicate that NT-3 has survival-promoting effects on naive TrkB-expressing PC12h cells, but not on differentiated cells because of its inability to induce the tyrosine phosphorylation of TrkB.

Animals↗

A muscular fatigue index based on the relationships between superimposed M wave and preceding background activity.

A practical muscle fatigue index is studied in this paper using the correlation between the instantaneous frequencies (IF's) of the superimposed M wave and the mean power frequency (MPF) of the preceding background activity. A superimposed M wave is an M wave elicited during a sustained contraction and was recently introduced for studying muscle fatigue. We investigated the details of the distribution of a feature vector (mpf, if) in two-dimensional space. Our experimental results showed that MPF and IF's were closely correlated during the first phase of a short-term high-level sustained voluntary contraction and then became uncorrelated or sometimes showed negative correlation as muscular fatigue progressed. Combining the correlation coefficients and conventional myoelectric (ME) parameters, such as the MPF and the average rectified value of ME signals, we propose a fuzzy rule based muscular fatigue index that can be used for managing the inevitable variability among individual subjects collected as a group. Introducing fuzzy inference seemed effective, but further studies including detailed investigation of the level of voluntary effort, the muscle fiber type composition, and metabolic by-products will be needed to customize the membership functions and fuzzy rules more appropriately in each practical field.

Adult↗

Correlation between endoscopic severity and the clinical activity index in ulcerative colitis.

OBJECTIVE: The aim of this study was to examine the relationship between a new activity index and the endoscopic severity assessed by sigmoidoscopy in patients with ulcerative colitis. METHODS: We evaluated the sigmoidoscopic severity and Activity Index (AI) in 37 patients with distal colitis, 23 with left-sided colitis, and 36 with total colitis, in which the severity was divided into three categories: grade 1 = mildly active, grade 2 = moderately active, and grade 3 = severely active. We examined the relationship between the AI or clinical parameters and the endoscopic severity in all 96 cases. RESULTS: The AI was found to be significantly correlated with the degree of sigmoidoscopic activity in all cases, as well as in those with distal colitis, left-sided colitis, or total colitis. When patients with both grade 1 sigmoidoscopic activity and AI values of less than 150 were regarded to have mild colitis and patients with either grade 2 or grade 3 sigmoidoscopic activity and AI values of more than 150 were regarded to have moderate or severe colitis, 10 of 37 (27%) in the distal colitis, one of 23 (4.3%) in the left-sided colitis, and four of 36 (11.1%) in the total colitis groups were thus misclassified regarding the distinction between mild colitis and moderate or severe colitis. Three of four patients with severity of grade 1, indicating AI values of more than 150, had total colitis, whereas the remaining one had left-sided colitis. On the other hand, 10 of 11 patients with severity of grades 2 or 3 with AI values of less than 150 had distal colonic involvement. When the endoscopic activity was equivalent, the highest mean AI values occurred in total colitis whereas the lowest mean AI values were found in distal colitis. CONCLUSIONS: The AI well reflects the sigmoidoscopic activity. High AI values with a low sigmoidoscopic severity are thus considered to reflect extensive involvement, whereas a high sigmoidoscopic severity with low AI values is thought to indicate the involvement of the distal colon.

Adolescent↗

Analysis of the expression of CagA and VacA and the vacuolating activity in 167 isolates from patients with either peptic ulcers or non-ulcer dyspepsia.

OBJECTIVES: The goals of this study were: 1) to examine the prevalence of cytotoxin-associated protein (CagA), vacuolating cytotoxin (VacA), and the vacuolating cytotoxin activity (VCA) in vitro of infecting Helicobacter pylori isolates and 2) to clarify the relation between the expression of these virulence factors and the occurrence of peptic ulceration. METHODS: One hundred sixty-seven clinical isolates of H. pylori from patients with peptic ulcer disease (gastric ulcer, 62 cases; duodenal ulcer, 48 cases) and nonulcer dyspepsia (57 cases) were studied regarding their genetic and phenotypic properties. RESULTS: Type 1 bacteria, which had both CagA and VCA, and type 2 bacteria, which did not express either CagA or VCA, represented 62.9% and 7.8%, respectively; the remaining 29.4% had an intermediate phenotype, expressing either CagA independent of the presence of VCA (CagA+VCA-) or vice versa (CagA-VCA+). CagA+VCA- and CagA-VCA+ bacteria represented 17.4 % and 12.0%, respectively, both of which were more numerous than the type 2 category. The proportion of the CagA-positive isolates was significantly higher in both the duodenal ulcer (97.9%) and gastric ulcer (83.9%) patients than in the non-ulcer dyspepsia patients (61.4%) (p < 0.01). On the other hand, the proportion of VacA/VCA-positive isolates was not significantly different between peptic ulcer disease and non-ulcer dyspepsia. CONCLUSIONS: The currently used classification of this bacterium based on the concomitant expression of CagA and VacA/VCA into the two major types is not adequate. The CagA-positive phenotype thus may be important as a virulence marker for peptic ulcer disease independent of the presence of VacA/VCA.

Adult↗

Cutaneous malakoplakia in pigs inoculated with Rhodococcus equi.

Cutaneous malakoplakia was observed in pigs inoculated intramuscularly with Rhodococcus equi strains of intermediate virulence. Macroscopically, the inoculation sites showed the indurated swelling of the skin. Histopathologically, abscess formation with histiocytic granulomatous reaction was observed. Many macrophages contained target or owl-eye shaped hematoxyphil intracytoplasmic inclusions or calcosherites (Michaelis-Gutmann bodies) of various sizes. The Michaelis-Gutmann bodies were also seen outside of the macrophages. Histochemically, most Michaelis-Gutmann bodies stained positively with the von Kossa silver method and periodic acid Schiff. Immunohistochemically, some of Michaelis-Gutmann bodies were stained by two rabbit polyclonal antibodies (rabbit anti-A5 serum and rabbit anti-ATCC 33701 serum) and a mouse monoclonal antibody (anti-20-kDa antigen monoclonal antibody). This is the first report of cutaneous malakoplakia in domestic animals, which also revealed the relationship between R. equi infection and malakoplakia immunohistochemically. This experimental swine model is useful to investigate the morphogenesis of Michaelis-Gutmann bodies in malakoplakia through chronological skin biopsies.

Actinomycetales Infections↗