Search PubMed⌕ Search

Biomedical subjects

A Murakami

Publications and source records attributed to A Murakami.

At least 163 records · Page 9Linked to original sources

Visual function and gene analysis in a family with Oguchi's disease.

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.

Adult↗

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

Amino Acid Sequence↗

Relaxation and activation of graviresponses in Paramecium caudatum.

The kinetics of gravitaxis and gravikinesis in Paramecium caudatum were investigated by employing (1) step transitions from normal gravity (1 g) to weightlessness (microgravity) and (2) turns of the experimental chambers from the horizontal to the vertical position at 1 g. The transition to microgravity left existing cell orientations unchanged. Relaxation of negative gravitaxis under microgravity took longer than 10 s and may be described by the time constant of the decay of orientation coefficients. Gravitaxis was started at 1 g by turning the experimental chamber from a horizontal to a vertical position. Gravitaxis activated rapidly during the turning procedure and relaxed to an intermediate level after the turning had stopped. Gravity-induced regulation of swimming speed (gravikinesis) at 1 g had reached a steady state after 1 min; at this point, gravikinesis counteracted the effects of sedimentation (negative gravikinesis). A step transition to microgravity initially reversed the sign of the gravikinesis (positive gravikinesis). The relaxation of this kinetic response was not completed during 10 s of microgravity. The data suggest that gravikinesis is functionally unrelated to gravitaxis and is strongly affected by the rate of change in acceleration. We present a model explaining why gravikinesis reverses sign upon the onset of a step from 1 g to microgravity.

Animals↗

Increased anticoagulant activity of recombinant thrombomodulin modified with glycosaminoglycan.

Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface, effective as an anticoagulant by changing procoagulant thrombin to an anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent anticoagulant activity than that without GAG, we expressed recombinant GAG-modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an additional GAG chain on anticoagulant activity was investigated in comparison with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of fibrinogen by thrombin or prothrombinase activity was more potently depressed by GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin complex was accelerated by GAG modification. The acceleration of antithrombin III-dependent anticoagulant activity was shown only by GAG-UTM. Parameters like thrombin time, prothrombin time and activated partial thromboplastin time in human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM significantly reduced the decrease in fibrinogen and platelet number induced by endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time induced by endotoxin, while r-UTM accelerated it. These results suggest that the addition of a GAG chain may increase availability as an anticoagulant.

Angiotensin III↗

[Recent development of nucleic acid drug].

Oligonucleotides and their analogs have been utilized for the regulation of gene expression since mid-1970. The so-called antisense strategy has recently acquired its reality of the application to clinical therapeutic uses. In the course of the development, it has been found that nucleic acids might have broad variety of abilities to regulate gene expression. The abilities are classified as ribozymes, antigenes, decoy DNAs (or RNAs) and aptamers, and they can be applied to clinical uses as nucleic acid drugs in the near future.

Antigens↗

[Pterygium and mast cells--expression of basic fibroblast growth factor increase in mast cells of the pterygium].

We examined the expression of basic fibroblast growth factor (bFGF) protein immunohistochemically, and bFGF specific messenger RNA (bFGF-mRNA) by in situ hybridization in the excised tissue of 5 cases of pterygium and 4 cases of normal conjunctiva. Immunohistochemical staining for bFGF showed strong positive staining in metachromatic mast cells stained with toluidine blue in the pterygium and in normal conjunctival specimens. The mean metachromatic mast cell count in pterygium specimens was increased significantly when compared with normal conjunctiva. In mast cells, bFGF positive rate was 84% in pterygium specimens, and 69% in normal conjunctival specimens. In situ hybridization indicated that the bFGFmRNA is located in most mast cells in pterygium specimens, but in only a few mast cells in normal conjunctival specimens. These results suggest that increased bFGF protein produced and stored by mast cells in the pterygium may contribute to its progression.

Female↗

[Two cases of spontaneous hemopeumothorax].

We experienced two cases of spontaneous hemopeumothorax. One case was a 17-year-old male with a complaint of back pain. A chest tube for rapid pleural evacuation disclosed hemorrhage as much as 3,000 ml, with drainage volume being gradually decreased. He needed about two month's admission because of complication of pyothorax. The other case was a 46-year-old male with a complaint of chest pain. Chest X-P gave the diagnosis of right hemopeumothorax. Thirty minutes later, he became shock, and five hours later, we performed an emergency intervention of video-assisted thoracoscopic surgery (VATS). Bleeding site of a funicular structure from the parietal pleura was stopped by clipping, with excellent postoperative results. Spontaneous hemopeumothorax is often indicated for early surgical intervention because of association with a high risk of hemorrhagic shock. In such a case, VATS is very helpful.

Adolescent↗

[Neuronal cell death mechanism in glaucomatous optic neuropathy].

Apoptosis of retinal ganglion cells has been observed in experimental glaucomatous models and human glaucomatous eyes in recent pathological studies. It seems that retinal ganglion cells in glaucomatous optic neuropathy die by a process similar to programmed cell death. Deprivation of neurotrophic factors, ischemia, chronic elevation of glutamate, and disorganized NO metabolism are suspected to be factors affecting neuronal loss in glaucoma, and most of these factors are known to activate the mechanism of cellular suicidal death. One of the common switches for the death mechanism seems to be in the mitochondria and to be controlled by Bcl-2 family proteins. A major goal of neuronal cell death research in glaucomatous neuropathy is to identify its molecular components and mechanisms of regulation. This information will lead to therapeutic agents that can modulate the cell death process in the treatment of glaucomatous neuropathy.

Animals↗

Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension.

Combined administration of inhaled nitric oxide and beraprost sodium resulted in a more intense decrease in pulmonary vascular resistance than nitric oxide given alone (mean -33% vs -45%, p <0.05), without serious systemic hypotension. Combined therapy with nitric oxide and beraprost sodium is highly desirable in treating primary and secondary pulmonary hypertension in children.

Child↗

The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E feeding or indomethacin treatment suppressed the urethane-induced increase in ODC activity, while exogenous PGE2 overcame the effect of vitamin E on ODC activity. Furthermore, the amount of PGE, and the level of ODC activity were well correlated. These results indicate that the vitamin E-induced decrease in PGE2 level probably contributes to the inhibition of ODC induction and the prevention of tumor development in the lung.

Animals↗

The inhibitory effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice.

We investigated the modulating effect of vitamin E on pulmonary polyamine biosynthesis, cell proliferation and carcinogenesis in mice treated with urethane. Pulmonary ornithine decarboxylase induction and subsequent polyamine accumulation were observed during the initiation and promotion phases of the urethane-induced lung carcinogenesis in mice. The increases of ODC activity and polyamine level during both phases were almost inhibited when a high vitamin E diet was provided. The urethane-increased level of pulmonary proliferating cell nuclear antigen as a marker of cell proliferation during the carcinogenesis was inhibited by vitamin E treatment. Also, vitamin E suppressed the urethane-induced elevation of pulmonary cyclooxygenase activity as a marker of tumor promotion. In conjugation with these events, vitamin E reduced the development of lung tumors in mice treated with urethane. These results indicated that vitamin E could act as a useful chemopreventive agent against lung carcinogenesis in mice due to the regulation of cell proliferation.

Animals↗

The inhibitory effect of vitamin E on K-ras mutation at an early stage of lung carcinogenesis in mice.

In this study, we investigated the effect of vitamin E on the activation of the K-ras oncogene with a 61st codon A-->T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K-ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer.

Animals↗

Inhaled nitric oxide after lung ischemia reperfusion; effect on hemodynamics and oxygen free radical scavenger system.

OBJECTIVE: Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. Recent studies have suggested that ischemia followed by reperfusion impairs release of endothelium-derived nitric oxide (NO). We investigated the acute effect of inhaled NO on hemodynamics and the oxygen free radical scavenger system after reperfusion following lung ischemia. METHODS: Fourteen anesthetized mongrel dogs were ventilated mechanically. After median sternotomy the left lung was rendered ischemic by totally clamping the left pulmonary hilum. After 90 min, the left lung was reperfused for 150 min by unclamping of the left hilum and clamping the right pulmonary hilum so that all pulmonary blood flow was directed to the left lung. Seven dogs inhaled 30 parts per million (ppm) NO during reperfusion (NO group); the other seven dogs were ventilated without NO inhalation (control group). Hemodynamics, gas exchange, superoxide dismutase activity and lipid peroxide of pulmonary venous blood, and wet/dry ratio of reperfused lung were measured. RESULTS: Neither of the two groups showed any change in systemic blood pressure prior to or following reperfusion. Immediately after reperfusion, mean pulmonary arterial pressure was significantly less (23.2 +/- 4.2 mmHg) in the NO group than in the control group (32.7 +/- 5.8 mmHg), as had been throughout reperfusion. Pulmonary vascular resistance and right ventricular end diastolic pressure were lower after reperfusion in the NO group. Superoxide dismutase activity after reperfusion in the control group significantly decreased to 41% of preischemic value. In the NO group, however, no decrease was seen and a significantly higher value was observed. The wet/dry ratio of reperfused lung was 5.47 +/- 0.52 in the control group and 4.72 +/- 0.36 in the NO group, with decreased pulmonary moisture noted in the NO group. There was no difference in lipid peroxide between the two groups. CONCLUSION: NO inhalation suppressed pulmonary hypertension after reperfusion following lung ischemia without affecting systemic arterial pressure. As superoxide dismutase activity was not depressed in the NO group, NO inhalation might enhance suppression of oxygen free radicals. These findings suggest that NO inhalation may be therapeutically useful after lung transplantation.

Administration, Inhalation↗

Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy.

We assessed the therapeutic significance of systematic aortic and pelvic lymphadenectomy followed by adjuvant therapy in node-positive endometrial carcinoma. Among 173 stage I-III patients, 30 (17%) had positive nodes: ten in the pelvic region alone (group P) and 20 in the aortic region alone or in both regions (group A). The adjuvant therapy was administered as follows: subjects in group P received 50 Gy pelvic radiation, including three post-surgical T3 (pT3) patients who received either one or three cycles of cisplatin-based chemotherapy before radiation. Subjects in group A were given three cycles of chemotherapy followed by 50 Gy pelvic and 50 Gy extended field periaortic radiation using a four-field or conformational technique. Five-year survival was 95% for 143 patients with negative nodes and 84% for 30 patients with positive nodes (100% for group P and 75% for group A). In group A, 5-year survival was 38% for eight patients with both pT3 and histology other than endometrioid type G1, and 91% for the remaining 12 patients. Either way, both group P and group A patients had a better prognosis than previously reported. In summary, aortic and pelvic lymphadenectomy and subsequent chemotherapy and radiation therapy based on node status seem to improve the survival of endometrial cancer patients with positive nodes.

Adenocarcinoma, Clear Cell↗

Prevention of heartburn relapse by low-dose famotidine: a test meal model for duration of symptom control.

AIM: To establish whether patients taking famotidine 10 mg to treat an episode of heartburn were protected from a recurrence of symptoms after a subsequent test meal. METHODS: Frequent heartburn sufferers (n = 366) were randomized to receive double blind treatment with famotidine 10 mg or 2 x 250 mg chewable alginate tablets within 30 min of a spontaneous episode of heartburn. After 4 h, patients with no or slight residual symptoms consumed a meal likely to induce heartburn. Over the next 4 h patients recorded the severity of heartburn and any consumption of 'rescue' antacids. At the end of this time they rated the global efficacy of their treatment in controlling meal-induced symptoms. RESULTS: Study groups were well matched for all baseline characteristics. Of the 366 randomized patients, 276 took study medication and data from 269 patients (132 famotidine, 137 alginate) were analysed for efficacy. Compared to the alginate control group famotidine treated patients reported better global efficacy following the test meal (P < 0.001; relative odds for a more favourable response: 2.26 [95% CI: 1.45-3.53]). Fewer patients receiving famotidine resorted to antacid rescue (P = 0.038; relative odds for a more favourable response: 2.24 [95% CI: 1.04-4.79]) and peak heartburn was significantly less severe with famotidine treatment (P < 0.001: relative odds for a more favourable response: 2.90 [95% CI: 1.85-4.53]). Eleven famotidine-treated patients (8%) and 13 alginate patients (9%) reported adverse events. CONCLUSION: Compared to patients receiving an alginate preparation, patients self medicating with famotidine 10 mg for heartburn are better protected against a recurrence of their symptoms when they next eat. This suggests that the duration of acid control (9 h) previously demonstrated with this dose translates into a similar duration of measurable symptom control during the day.

Adolescent↗