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Biomedical subjects

N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 379 records · Page 21Linked to original sources
PubMed1994

Interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor gene expression in endotoxin-induced uveitis.

PURPOSE: To localize and determine the levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and tumor necrosis factor (TNF) gene expression in the process of endotoxin-induced uveitis (EIU) in rats. METHOD: EIU was induced by lipopolysaccharide (LPS) injection in male Lewis rats weighing 150 to 200 g. The levels of IL-1 alpha, IL-1 beta, and TNF gene expression in the iris-ciliary body (ICB) were quantified by a semiquantitative polymerase chain reaction (PCR) method; in situ hybridization histochemistry was carried out to localize the gene transcripts. RESULTS: Little expression of IL-1 alpha, IL-1 beta, and TNF genes was observed in normal ICB. IL-1 alpha gene expression began to increase (about 10-fold greater than that of the control) as early as 1 hour after the LPS treatment, reached a peak (about 100-fold) at 3 to 6 hours. A second peak (60-fold) was observed at 24 hours, and the expression returned to near basal levels (3-fold) at 48 hours. Expression of IL-1 beta and TNF genes showed a pattern similar to that of IL-1 alpha. Three hours after LPS treatment, IL-1 beta and TNF genes were found by in situ hybridization histochemistry to be expressed by "histiocyte-like" cells in the stroma of the ICB. None of these genes were detected in the control rats. CONCLUSIONS: Expression of IL-1 alpha, IL-1 beta, and TNF genes was dramatically up-regulated in the process of EIU. These genes were found to be expressed in "histiocyte-like" cells in the ICB, and may have an important role in EIU.

Animals↗
PubMed1994

[A successful surgical correction of the intermediate type of common atrioventricular orifice--report of an adult case].

A 42-year-old female was admitted to our hospital because of exertional dyspnea. Preoperative color Doppler echocardiogram revealed massive left to right shunt through the ostium primum defect, moderate mitral and tricuspid regurgitation, and trivial shunt via the small ventricular septal defect. Preoperative cardioangiogram also demonstrated goose neck deformity of the left ventricle. At the operation, the piece of atrioventricular valve fused on the summit of the small scooped ventricular defect was detected, and the total correction consisted of patch closure of the ostium primum defect and mitral and tricuspid valvuloplasty was performed. Postoperative course was uneventful. This is the first adult case reported in Japan who was operated on for the intermediate type of common atrioventricular orifice.

Adult↗
PubMed1994

Platelets-induced stimulation of endothelin-1 production and inhibition by phosphoramidon.

The effects of platelets on endothelin-1 (ET-1) production were examined by using cultured bovine pulmonary artery endothelial cells (ECs). Platelets (6 x 10(6) to 2 x 10(9) platelets/ml) prepared from rat peripheral arterial blood markedly stimulated immunoreactive (IR)-ET release from ECs into the culture medium, in a time-and platelet number-dependent manner. High-performance liquid chromatography analysis of the culture supernatant following exposure to platelets revealed one major IR-ET component corresponding to the elution position of synthetic ET-1. Northern blot analysis showed that platelets enhanced prepro ET-1 mRNA expression in the ECs. Increased IR-ET release was observed with the supernatant obtained after incubation of platelets, and this increment was significantly inhibited by transforming growth factor-beta 1 neutralizing antibody. Phosphoramidon, an ET converting enzyme inhibitor, significantly decreased the amount of IR-ET accumulating in the culture medium of ECs, incubated with or without platelets, and the decreasing effect of phosphoramidon in the presence of platelets was greater than that in their absence. A similar effectiveness of phosphoramidon was seen when transforming growth factor-beta 1 was used instead of platelets. Thus, platelets appear to stimulate the endothelial production of ET-1 in vitro, probably through a release of transforming growth factor-beta 1. We also suggest that the inhibition of ET converting enzyme by phosphoramidon is more effective in the augmented condition of ET-1 production than in the basal condition.

Animals↗
PubMed1994

[Minimum required number of anesthetists for general hospitals (41-1300 beds) in Japan--analysis of questionnaire, 1992].

BACKGROUND: We have elucidated the deficit of anesthetists in general hospitals excluding university hospitals by assessing the results of questionnaires from 204 institutions in Japan. METHODS: Answers to the questionnaire were computed in average, maximum, and minimum values, using MS-Excel soft ware for statistical analysis. RESULTS: The 204 hospitals were classified into 4 groups; G-1(46)-more than 640 beds, G-2(53)-more than 500 beds, G-3(53)-more than 360 beds, and G-4(52)-less than 359 beds, respectively (parenthesis indicate hospital numbers). The number of cases of anesthesia performed by anesthesiologists were 2055(G-1), 1516(G-2), 1177(G-3) and 959(G-4), respectively. The number of anesthetists per operating table were as follows; 0.62(G-1), 0.62(G-2), 0.58(G-3) and 0.74(G-4), but remarkably low compared to the number of operating theater nurses: 5.49(G-1), 2.96(G-2), 2.82(G-3) and 3.07(G-4). Moreover, the number of emergency cases were as follows; 235(G-1), 187(G-2), 134(G-3) and 125(G-4), respectively. In prolonged surgery over 6 hours, patients were anesthetized with an exchange system or two anesthetists system in 74% of the institutions in G-1. Also, 28-50% of anesthetists in the 4 groups were concerned with intensive care medicine and 0.94-1.54 anesthetists worked in pain clinics with combined operation-theater tasks 1.37-2.49 days per week. In G-1-G-4 institutions, we found that anesthesia cases per year were equivalent to 5 times their bed numbers. CONCLUSION: We concluded that the number of anesthetists should be at least 50% of that of operation-theater nurses. Without increasing anesthesiologists, we cannot expect sophisticated medical care in the 21st century.

Anesthesiology↗
PubMed1994

[Probable Bickerstaff's brainstem encephalitis associated with anti-GQ1b antibody].

We presented a case of probable Bickerstaff's brainstem encephalitis. A 39-year-old woman developed easy falling, progressive consciousness disturbance, total ophthalmoplegia, and bilateral pyramida tract sign. In serum anti-ganglioside antibody assay using enzyme-linked immunosorbent assay, high anti-GQ1b antibody was found. Electroencephalography was dominated by alpha activity, superimposed with occasional theta wave bursts. Brain MRI showed abnormal signal hyperintensities in the tegmentum of the midbrain to the upper pons on T2 weighted images and swelling of the midbrain and pons on T1 weighted images. Five days after the onset of the disease, she had respiratory arrest, which necessitated artificial ventilation for a few days. Then, she began to recover. However, she gained only partial recovery, leaving upward gaze palsy, right abducens nerve palsy, pseudbulbar palsy and quadriplegia.

Adult↗
PubMed1994

Endothelin-mediated cell signaling and proliferation in cultured rabbit corneal epithelial cells.

PURPOSE: To determine if there is endothelin-mediated regulation of cell signaling and proliferation in rabbit corneal epithelium. METHODS: Endothelin-1 (ET-1) gene and protein expression by the rabbit corneal epithelial (RCE) cells were analyzed by polymerase chain reaction, sequence analysis, and enzyme immunoassay. DNA synthesis was characterized by [3H]-thymidine uptake. Endothelin receptor linkage to cell signaling pathways was determined based on measurements of the dose dependent effects of ET-1, ET-2, and ET-3 on intracellular Ca2+ concentration ([Ca2+]i) transients in fura-2-loaded cells, and of ET-1 on phosphoinositide turnover and cAMP accumulation in the isolated rabbit corneal epithelium. RESULTS: The authors detected the mRNA for prepro ET-1 in RCE cells, and ET-like immunoreactivity was identified in conditioned culture medium. ET-1 (1 nM) maximally stimulated [3H]-thymidine uptake by twofold (EC50 = 0.3 nM). Endothelins elicited transient increases in [Ca2+]i with a rank order of potency of ET-1 > or = ET-2 >> ET-3. These increases consisted of both intracellular Ca2+ mobilization and influx of Ca2+ from the bathing solution. Intracellular mobilization was linked to increases in IP3 turnover because 1 microM ET-1 increased IP3 content by 48% from its control value (EC50 = 23 nM), whereas Ca2+ influx occurred through a non-L-type Ca2+ channel because preexposure to 1 microM nicardipine did not affect either the height or the duration of a [Ca2+]i transient. One micromolar of ET-1 was required to elicit a significant increase in cAMP accumulation of 69% from its control value. This increase was dependent on the presence of Ca2+ in the bathing solution and was comparable to and nonadditive with that of the Ca2+ ionophore, A23187 (1 microM). CONCLUSION: These data suggest that endothelin production by primary cultures of RCE cells can mediate an increase in cell proliferation through an ETA receptor subtype. This receptor subtype appears to be involved based on the rank order of potency of ETs to elicit [Ca2+]i transients, increases in phosphoinositide turnover, and cAMP accumulation.

Animals↗
PubMed1994

Characterization of glucose transporter in cultured human retinal pigment epithelial cells: gene expression and effect of growth factors.

PURPOSE: To investigate gene and protein expression of glucose transporter isoforms in cultured human retinal pigment epithelial cells. To investigate growth factor-dependent stimulation of glucose transport and the effect of growth factors on the gene and protein expression in retinal pigment epithelial cells. METHODS: Glucose transport activity was analyzed by [3H]2-deoxyglucose uptake studies. Gene and protein expression of glucose transporter isoforms were analyzed by polymerase chain reaction, Northern blot analysis, and Western blot analysis. RESULTS: Polymerase chain reaction, nucleotide sequencing, and Southern blot analyses revealed that the retinal pigment epithelial cells express GLUT-1, -3, and -5 genes. Northern and Western blot analysis detected only GLUT-1 transcripts and protein. A 24-hour exposure to fetal bovine serum (15%), basic fibroblast growth factor (50 ng/ml), platelet-derived growth factor (10 ng/ml), epidermal growth factor (50 ng/ml), and insulin-like growth factor-1 (50 ng/ml) significantly stimulated [3H]2-deoxyglucose uptake in cultured human retinal pigment epithelial cells. Western blot analysis showed that serum and platelet-derived growth factor induced an increase of GLUT-1 protein in the membrane preparation in the cells. Serum, fibroblast growth factor, platelet-derived growth factor, and insulin-like growth factor-1 did not increase GLUT-1 gene expression to an appreciable level, as shown by Northern blot analysis. CONCLUSION: Cultured human retinal pigment epithelial cells dominantly express GLUT-1 gene and protein with minor expression of GLUT-3 and -5 genes. Fetal bovine serum, fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, and insulin-like growth factor-1 significantly, although modestly, increase glucose transport activity of the cells.

Base Sequence↗
PubMed1993

A novel immunosuppressant, IR-1116, which has a different biological mechanism from that of cyclosporine A.

The effects of an epifumagillol derivative, IR-1116, on human lymphocytes in vitro, mouse antibody production in vivo and rat renal and cardiac transplantation were investigated. IR-1116 suppressed the human primary mixed lymphocyte reaction (MLR) in a dose-dependent manner with a value of the dose required for 50% suppression of 0.32 microM. IR-1116 suppressed the antibody production by human B lymphocytes activated with pokeweed mitogen or Epstein-Barr virus, but did not affect the interleukin-2 production by human lymphocytes stimulated with phytohemagglutinin. Furthermore, IR-1116 did not have any effect on the proliferation of B or T lymphocytes. IR-1116 is thought to have a different mechanism from cyclosporine A (CsA). BALB/c mice were immunized by s.c. injection of bovine gamma-globulin (BGG) and then received IR-1116 or CsA by i.p. injection at a dose of 20 mg/kg every other day for 2 weeks. IR-1116 suppressed the production of serum antibodies against BGG as strongly as CsA. In this experiment, IR-1116 apparently showed no adverse effects, while CsA-treated mice suffered from diarrhea and appeared to be irritated. Histological studies showed that IR-1116 suppressed the formation of germinal centers in the spleen of immunized mice. Flow cytometric analysis showed that IR-1116 caused a reduction of B lymphocyte population in splenocytes. On the other hand, CsA caused a marked reduction of helper T lymphocyte population in splenocytes and thymocytes. Furthermore, the i.p. administration of IR-1116 prolonged the survival time in a rat renal allograft model and the vital period of grafted hearts in rats. Based on the above, IR-1116 seems to be a new type of immunosuppressant acting via novel mechanisms different from those of immunosuppressants such as CsA, a potent T lymphocyte suppressant.

Adult↗
PubMed1993

The effect of spermine on the disaccharidase activities in suckling rats of different age.

The influence of the age of the rat on the maturation of disaccharidase activities induced by spermine was studied. Three-day- and 9-day-old rats were used in the experiment. Spermine was administered orally or directly into the stomach using thin tubing daily for 3 days, and disaccharidase activities in the jejunum were measured. While spermine caused maturation of not only lactase activity but also maltase and sucrase activities in 9-day-old rats, it only caused maturation of lactase activity in 3-day-old rats. Histological studies showed no significant changes in the jejunum of 3-day-old rats treated with spermine.

Age Factors↗
PubMed1993

Polylysine stimulated protein phosphorylation in rabbit ciliary processes: casein kinase activities.

Protein phosphorylation in response to polylysine was investigated in vitro in rabbit ciliary process homogenates by SDS-PAGE autoradiography. The degree of phosphorylation was greater in the soluble/cytoplasmic fraction than in the particulate fraction and was antagonized by heparin. Time and dose-dependent studies indicated several different kinetic patterns of phosphorylation/dephosphorylation among the approximately 15 significantly 32P-labeled bands found in each fraction. These results are consistent with phosphorylation of endogenous substrates by casein kinase II, and dephosphorylations by type I and type II phosphoprotein phosphatase enzymes. The presence of EGF receptors in ciliary processes was indicated by high affinity (kD < 0.5 nM) binding sites and by intraocular pressure and blood-aqueous barrier responses to injection of low doses of EGF (100 ng per eye). EGF did not stimulate protein phosphorylation in ciliary process homogenates in vitro. The results show that casein kinase II is a significant kinase activity in ciliary processes and may have a modulatory role on signal transduction proteins involved in cellular response to hormones.

Animals↗
PubMed1993

Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease--a multi-center study.

The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE1 (0.08 microg.kg(-1).min(-1)) decreased systolic blood pressure from 125 +/- 29 to 106 +/- 22 mmHg (mean +/- SD) in the deliberate hypotension group (n = 158) and from 155 +/- 34 to 125 +/- 32 mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 +/- 15 to 85 +/- 18 beats.min(-1) in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20 min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20 min. No rebound hypertension was observed. PGE1 significantly increased the urine flow in patients who had a low urine flow before PGE1 infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE1 infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE1 can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.

Journal Article↗
PubMed1993

Long-term palliation after systemic-to-pulmonary artery shunt using an internal mammary artery.

We report the long-term results after systemic-to-pulmonary artery shunts using the internal mammary arteries in 2 patients. The systemic-to-pulmonary artery shunts using the internal mammary arteries were created in 2 children. Both of them are doing well 11 years and 7 years after operation. This procedure could be a reasonable alternative to classic Blalock-Taussig shunt for patients with diminutive pulmonary arteries as it offered good long-term palliation.

Angiography↗
PubMed1993

The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

A pharmacological study using monkeys, in which parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was undertaken to elucidate the mechanism underlying urinary bladder dysfunctions in Parkinson's disease. Under ketamine anesthesia, cystometrograms showed that, in MPTP-treated monkeys, a contraction of the urinary bladder was induced with smaller bladder volume than that in normal monkeys. In MPTP-treated monkeys, subcutaneously injected SKF 38393, a dopamine D1 receptor agonist, significantly increased the bladder volume and pressure thresholds for inducing the micturition reflex without affecting those in normal monkeys. In contrast, subcutaneous injections of quinpirole, a dopamine D2 receptor agonist, and apomorphine, a dopamine D1 and D2 receptor agonist, slightly, but significantly reduced the volume threshold of the bladder for the micturition reflex in both normal and MPTP-treated groups. These results indicate that, in parkinsonism, the degeneration of dopaminergic neurons in the substantia nigra leads to the detrusor hyperreflexia, probably due to a failure of activation of dopamine D1 receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Local immunosuppressive therapy with monoclonal anti-T cell antibody on renal allograft survival in the rat.

Considerable interest in the experimental and clinical use of MoAbs as potential therapeutic agents in allograft rejection has been generated by the recent reports of striking prolongation. In this study we investigated the efficacy of the local administration of MoAb OX-19 which is directed to the rat CD5 equivalent, through the renal artery using a rat kidney transplant model, in order to develop a potent method for modifying rejection while minimizing the systemic side effects. Untreated Lewis rats (LEW, RT-1(1)) rejected Brown-Norway rat (BN, RT-1n) kidney at 7.8 +/- 0.2 days (n = 10). Mean survival time (MST) of recipients treated with OX-19 (75 micrograms/kg per day) as single bolus injections via the dorsal penile vein for 7 days was 7.0 +/- 0.2 days (n = 5, NS). LEW hosts receiving OX-19 (75 micrograms/kg per day) continuously for 7 days via a femoral vein by using an osmotic minipump (IV-treated group) showed a slight prolongation of graft survival (MST = 8.8 +/- 0.9 days, n = 5), but this was not statistically significant. On the other hand, local continuous intrarenal arterial infusion of OX-19 (75 micrograms/kg per day) for 7 days (RA-treated group) significantly prolonged the graft survivals (MST = 16.8 +/- 1.3 days, n = 8, P < 0.01). Histological examination of MoAb-treated LEW hosts on day 6 post-grafting revealed that kidney grafts from RA-treated hosts showed a slight tubular necrosis, but reduced mononuclear cell infiltration, whereas kidney grafts from IV-treated hosts displayed a severe mononuclear cell infiltration around the artery with interstitial oedema. Moreover, the local intrarenal administration of OX-19, even when the dose is delayed until day 4 after renal grafting, has a therapeutic effect for on-going acute allograft rejection (MST = 11.4 +/- 0.8 days, n = 8) compared with administration of OX-19 intravenously from day 4 after grafting (MST = 7.6 +/- 0.2 days, n = 5, P < 0.01) or with no treatment (MST = 7.8 +/- 0.2 days, P < 0.01). The phenotype of graft infiltrating cells (GIC) was investigated on day 6 post-grafting. There was a significantly lower percentage of cells positive for OX-19, OX-8, OX-26 (transferrin receptor), and OX-39 (IL-2 receptor) in the RA group than in the IV group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Complete recovery of cytochrome oxidase and superoxide dismutase activities in the brain of brindled mice receiving copper therapy.

To elucidate the roles played by copper-containing enzymes in the brain degeneration associated with Menkes disease, the brains of brindled mouse hemizygotes (BMs) were studied histochemically and biochemically before and after copper therapy. Light and electron microscopic histochemistry revealed that, while neuronal mitochondria in BM brains demonstrate only a weak diaminobenzidine reaction for cytochrome oxidase, these exhibit strong activity after therapy and in control mice. Biochemical assays of enzyme activity revealed only 30% of the normal level before a single subcutaneous application of 50 micrograms of CuCl2, whereas neuronal mitochondria of BMs surviving 8 months after the copper therapy displayed essentially no difference from the controls. Similar results were also gained for superoxide dismutase activity, although the reduction was less marked. The present findings provide direct support for decreased activities of copper-containing enzymes being responsible for the mitochondrial abnormalities and brain degeneration associated with Menkes disease.

Animals↗
PubMed1993

Surgical treatment for aneurysms of the descending aorta using temporary perfusion by a centrifugal pump: clinical analysis of 33 cases.

Since 1987, 33 patients have undergone surgery at Kobe University Hospital for aneurysm of the descending aorta using left heart bypass with a heparin-coated centrifugal pump and heparin-coated tubes. Sixteen patients had true aneurysms of the descending thoracic aorta, 7 had thoracoabdominal aneurysms, and 10 had aortic dissection (DeBakey's Type III). Heat exchangers and oxygenators were not included in the bypass circuit in any of the cases. Perfusion time was from 42 to 205 min (average 90 min). Left heart bypass was established with 1 mg/kg of systemic heparinization in 5 cases, 0.5 mg/kg in 5 cases, and 0 mg/kg in 23 cases. There were no complications such as perioperative embolism, acidosis, or hypothermia. During aortic cross-clamping, the arterial pressure of the lower extremity was maintained above 70 mm Hg, but there was no relationship between the distal perfusion pressure and bypass flow. The urine output during left heart bypass was related to the distal perfusion flow by centrifugal pump. Of 23 patients who underwent bypass with less than 40 ml/kg/min of distal perfusion flow, 7 showed transient renal dysfunction postoperatively, and 1 developed postoperative renal failure. The other patients who were bypassed with over 40 ml/kg/min of pump flow stayed in the normal range of renal function. Postoperative paresis occurred in 2 patients, who were also perfused with less than 40 ml/kg/min of bypass flow. It could be concluded that left heart bypass by centrifugal pump is safe and acceptable as a circulatory support in the surgical treatment of aneurysm of the descending aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗