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Biomedical subjects

S Miwa

Publications and source records attributed to S Miwa.

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

Molecular cloning and expression profile of rat myocilin.

Myocilin is known to be associated with the pathogenesis of juvenile-onset primary open angle glaucoma. The tissue distribution of myocilin transcripts has been analyzed in both humans and mice, and a high level of expression in the retina and skeletal muscle has been reported. The functions of myocilin in these tissues are unknown. We isolated rat myocilin cDNA and examined the expression pattern of myocilin, including its expression in endocrine organs, using Northern blot analysis. The rat myocilin cDNA sequence has two in-frame initiation codons, the upstream and downstream ATGs corresponding to the initiation codon of human and murine myocilin, respectively. It is most likely that the first ATG is a translational initiation codon, since 8 of 13 amino acid residues deduced from the rat cDNA sequence between the first and the second ATGs are the same as those in human myocilin. The open reading frame encodes 502 amino acids. Rat myocilin also has both a myosin-like domain and an olfactmedin-like domain, which have been identified in human and murine myocilin. Northern analysis of rat myocilin mRNA revealed substantial expression in the thyroid gland, as well as in the retina and muscle. No transcripts were detected in other endocrine glands, including the adrenal gland, pituitary, and testis. Myocilin may play an important role in thyroid function. Further study of the expression and role of myocilin in the thyroid is required.

Amino Acid Sequence↗
PubMed2000

Other erythrocyte enzyme deficiencies associated with non-haematological symptoms: phosphoglycerate kinase and phosphofructokinase deficiency.

Phosphoglycerate kinase (PGK) deficiency is associated with hereditary haemolytic anaemia and often with central nervous system dysfunction and/or myopathy. Twenty-three families have been discovered with this condition. Nine have manifested both symptoms, six only haemolysis, and seven central nervous system dysfunction and/or myopathy without haemolysis; one case is asymptomatic. Among them, the structural abnormalities of 14 mutants, including 11 missense mutations, 1 gene deletion, 1 gene insertion, and 1 splicing mutation, have been identified. The correlation between the phenotypic and structural differences in PGK deficiency remains to be defined. Splenectomy obviates transfusion in most patients but does not correct the haemolytic disorder. Phosphofructokinase (PFK) deficiency is associated with myopathy and/or haemolysis. More than half reported had the typical features of glycogen storage disease type VII (Tarui disease). The other cases exhibited myopathy alone, haemolytic anaemia alone, or no clinical symptom at all. Eight missense, 1 nonsense, 1 frameshift and 5 splicing mutations have been determined in the PFK-M gene. In classic PFK-M deficiency, the avoidance of undue exertion is the key to prevent muscle symptoms.

Anemia, Hemolytic, Congenital↗
PubMed2000

Endothelin-1-induced contraction of rat thoracic aorta depends on calcium entry through three types of calcium channel.

We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1-H-imidazoe l hydrochloride (SK&F 96365) (a blocker of NSCC-2 and SOCC) and (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma l)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]acetamide (LOE 908) (a blocker of NSCC-1 and NSCC-2). For our study we characterized Ca2+ channels involved in ET-1-induced contractions and increases in the intracellular free Ca2+ concentration ([Ca2+]i) using these blockers. Our results show that the response to lower concentrations of ET-1 involves only one Ca2+ channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2). In contrast, the response to higher concentrations of ET-1 involves two types of Ca2+ channel in addition to NSCC-2: one is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC), and the other is resistant to SK&F 96365 but sensitive to LOE 908 (NSCC-1). Furthermore, the percentage contribution of Ca2+ entry through NSCC-1, NSCC-2 and SOCC is calculated to be 10%, 50-60% and 30-40%, respectively.

Acetamides↗
PubMed2000

Pharmacological properties of calcium entry channels in A7r5 cells activated by endothelin-1.

Using whole-cell recordings of patch-clamp and monitoring of the intracellular free calcium (Ca2+) concentration ([Ca2+]i), we characterized Ca2+ entry channels in A7r5 cells activated by endothelin-1 (ET-1). ET-1 activates three types of voltage-independent Ca2+ entry channels: two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). Furthermore, it was found that these channels can be discriminated pharmacologically using Ca2+ channel blockers such as 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1-H-imidazoe l hydrochloride (SK&F 96365) and (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma l)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethoxyl]acetamide (LOE 908). NSCC-1 is resistant to SK&F 96365 but sensitive to LOE 908, whereas NSCC-2 is sensitive to both drugs: SOCC is sensitive to SK&F 96365 but resistant to LOE 908. Using these channel blockers, we analyzed the Ca2+ entry channels involved in the ET-1-induced increase in [Ca2+]i of the cells. The increase induced by lower concentrations of ET-1 (< or = 0.1 nM) was unaffected by SK&F 96365 but it was abolished by LOE 908. In contrast, the increase caused by higher concentrations of ET-1 (> or = 1 nM) was suppressed by SK&F 96365 or LOE 908 to about 35% of controls, and abolished by combined treatment with SK&F 96365 and LOE 908. These results show that the increase in [Ca2+]i resulting from lower concentrations of ET-1 (< or = 0.1 nM) involves Ca2+ entry through only NSCC-1, whereas that resulting from higher concentrations of ET-1 involves Ca2+ entry through NSCC-1, NSCC-2 and SOCC, contributing 35%, 30% and 30%, respectively, to total Ca2+ entry.

Acetamides↗
PubMed2000

[Torsion of the spermatic cord in undescended testis: report of two cases].

We report two cases of torsion of the spermatic cord in undescended testis. Case 1: A 23-year-old man was admitted to our hospital with the complaints of fever and left inguinal pain. He had cerebral palsy in his past history. Tentative diagnosis of acute epididymitis of left undescended testis was made, and antibacterial drugs were given. Response was poor, and torsion of the spermatic cord was suspected strongly. Torsion of the spermatic cord in undescended testis and severe testicular infarction were seen in surgery after 13-day conservative treatment. Orchiectomy was performed. Case 2: A 6-year-old boy was admitted to our hospital with the chief complaints of left inguinal mass and pain. He had felt abdominal pain for 3 days. Scrotal contents were impalpable and the diagnosis of torsion of the spermatic cord was made. Orchiectomy was performed due to severe testicular infarction.

Adult↗
PubMed1999

Sphingosylphosphorylcholine induces cytosolic Ca(2+) elevation in endothelial cells in situ and causes endothelium-dependent relaxation through nitric oxide production in bovine coronary artery.

Sphingosylphosphorylcholine (SPC) increased intracellular Ca(2+) concentration ([Ca(2+)]i) and nitric oxide (NO) production in endothelial cells in situ on bovine aortic valves, and induced endothelium-dependent relaxation of bovine coronary arteries precontracted with U-46619. The SPC-induced vasorelaxation was inhibited by N(omega)-monomethyl-L-arginine, an inhibitor of both constitutive and inducible NO synthase (NOS), but not by 1-(2-trifluoromethylphenyl) imidazole, an inhibitor of inducible NOS (iNOS). Immunoblotting revealed that endothelial constitutive NOS, but not iNOS, was present in endothelial cells in situ on the bovine aortic valves. We propose that SPC activates [Ca(2+)]i levels and NO production of endothelial cells in situ, thereby causing an endothelium-dependent vasorelaxation.

Animals↗
PubMed1999

Retinoic acid stimulates development of adult-type chromatophores in the flounder.

Premetamorphic flounder larvae were administered different doses of 9-cis retinoic acid (9cRA). 9cRA at 25 nM (the highest dose) not only stimulated adult-type (ad-) chromatophore development on the ocular (eyed) side, but also induced the development of ad-chromatophores on the blind (non-eyed) side of the metamorphosed fish. The ad-chromatophore development was stimulated by 9cRA only when administered to the larvae that were at late premetamorphosis and at early prometamorphosis. Ad-chromatophores actually appear much later, at the end of metamorphosis. 9cRA was not effective at later stages of metamorphosis. These results suggest that 9cRA stimulated the development or determination of the developmental fate of neural crest cells for chromatophores. The present results also suggest the presence of immature chromatophores or neural crest cells on both sides of the larval body of the flounder and that the ad-chromatophore development is somehow inhibited on the blind side in spontaneous metamorphosis. All-trans retinoic acid (atRA) had a similar effect on the ad-chromatophore development. In addition, both types of RAs affected the development of fin rays of the fish, resulting in deformity of fins when administered at high doses early in metamorphosis. The teratogenic effect of atRA was greater than that of 9cRA.

Alitretinoin↗
PubMed1999

Lack of repetition priming effect on visual event-related potentials in schizophrenia.

BACKGROUND: The present study was designed to assess, using event-related potentials, whether aberrant semantic processing reported in schizophrenia results from primary semantic overactivation or contextual dysregulation. METHODS: The visual event-related brain potentials were compared between 9 schizophrenic subjects and 16 normal control subjects performing two kinds of semantic categorization tasks with different nontarget stimuli: 1) nontargets comprising words, pseudowords, and unpronounceable foreign letters and 2) nontargets comprising initial presenting words, immediate repetition words, and delayed repetition words. RESULTS: Schizophrenic subjects showed no evidence suggestive of a greater negative potential associated with words and pseudowords, but they did show a lack of amplitude change associated with immediately repeated words relative to that in control subjects. CONCLUSIONS: These results suggest that aberrant semantic activation in schizophrenia results mainly from a failure to utilize information from preceding words or context, and could explain the increased N400 to the congruent or related words recently reported in this disease.

Adult↗
PubMed1999

Subcellular mechanisms of endothelin action in vascular system.

To elucidate the role of endothelin in the regulation of vascular function, the cellular and subcellular mechanisms for the synthesis of endothelin and the function of endothelin-receptors have been studied extensively. In this article, recent results regarding these problems are reviewed. (1) Oxidatively modified low-density-lipoprotein (LDL) reduces nitric oxide (NO) release via inhibition of the high-affinity arginine transporter of endothelial cells. (2) Endothelin-1-induced vasoconstriction is mediated by Ca2+ influx through a non-selective cation channel sensitive to 1-[beta-[3-(4-methoxyphenyl) propoxyl]-4-methoxyphenethyl]-1H-imidazole HCl (SK & F96365). (3) A distinct domain of the endothelin-receptor is required for the coupling of different G(alpha)-proteins. (4) Endothelin ET(A) receptor-mediated mitogenic activity is mediated by two pathways, one classical protein kinase C(PKC)-dependent, and the other phosphoinositide 3-kinase dependent. Both stimulate mitogen-activated protein kinase (MAPK). Endothelin ET(B) receptor-mediated mitogenic activity is also mediated by the PKC-dependent pathway. In contrast, endothelin ET(B) receptor-mediates differentiation and apoptosis via G(alpha)i coupling.

Animals↗
PubMed1999

Erythrocyte enzyme activities in cord blood of extremely low-birth-weight infants.

To investigate the features of erythrocyte metabolism in extremely immature infants, we assayed 21 enzyme activities and glutathione level in cord erythrocytes from 28 extremely low-birth-weight infants (ELBWI; defined as birth weight <1,000 g). The results were compared with those from normal adults and non-neonatal reticulocyte-rich controls. Statistical analysis revealed that activities of six enzymes (glucosephosphate isomerase, phosphoglycerate kinase, monophosphoglycerate mutase, enolase, glucose-6-phosphate dehydrogenase (G6PD), and glutathione reductase) were significantly higher, and those of eight other enzymes (phosphofructokinase, 6-phosphogluconate dehydrogenase (6PGD), glutathione peroxidase, adenylate kinase, adenosine deaminase, acetylcholinesterase, NADH methemoglobin reductase, and catalase) were lower in ELBWI taking their marked reticulocytosis into consideration. The 6PGD/G6PD ratio, which is consistently unchanged under various physiological and pathological conditions, was markedly reduced in ELBWI. Our results support the previous reports that neonatal erythrocytes have a unique metabolic pattern which is different from that of adult erythrocytes, and also suggest that the 6PGD/G6PD ratio might be an index for the developmental immaturity of fetal erythrocytes. This is the first report describing the pattern of erythrocyte enzyme activities in ELBWI.

Acetylcholinesterase↗
PubMed1999

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.

Adolescent↗
PubMed1999

Human HKR isozyme: organization of the hexokinase I gene, the erythroid-specific promoter, and transcription initiation site.

We previously described a cDNA for the human HKR isozyme, whose sequence is identical to that of the ubiquitous HKI isozyme, except for a unique 5' end sequence. Screening a human genomic library with a DNA fragment containing an erythroid-specific sequence we found one clone including 5' ends for both HKR and HKI genes. The first HKR exon was located 3 kb 5' of the first HKI exon. These results confirmed that HKR is produced from the HKI gene by alternate promoter and splicing. The HKI gene consisted of 19 exons. All exon-intron boundaries are conserved among the genes for hexokinase and glucokinase. The HKI gene length was estimated at over 67 kb. The initiation site for the HKR was identified by primer extension. Its promoter did not have a canonical TATA box, but an inverted GATA at nt -177 (i.e., 36 nt 5' to the transcription initiation site). In the HKR promoter a DNA fragment spanning nt -275 to nt -107 exhibited erythroid-specific activity. However, this was absent in shorter promoter fragments (nt -206 to -107 or nt -229 to -107). The sequence nt -275 to -229, which appeared critical for the erythroid-specific expression of the HKR gene, contained a consensus motif for Sp-1 and GATA, CCAAT, and GGAA motifs. The electrophoretic mobility shift assay (EMSA) suggested erythroid-specific cooperative protein-protein interaction in this region. Deletion of the GATA sequence as well as reaction with a specific antibody identified GATA-1 as one of the interacting proteins.

5' Untranslated Regions↗
PubMed1999

Pharmacological characterization of receptor-mediated Ca2+ entry in endothelin-1-induced catecholamine release from cultured bovine adrenal chromaffin cells.

To clarify the mechanism for the endothelin-1 (ET-1)-induced release of catecholamines from the adrenal gland, we examined the effects of removal of extracellular Ca2+, blockers of L-, N-, P- and Q-types of voltage-operated Ca2+ channels (VOCC) such as nifedipine (L-type), omega-conotoxin GVIA (N-type), omega-agatoxin IVA (P-type) and omega-conotoxin MVIIC (Q-type) and blockers of voltage-independent Ca2+ entry channel such as SK&F 96365 and LOE 908 on release of catecholamines, the cytosolic free Ca2+ concentration ([Ca2+]i), and 45Ca2+ uptake in cultured bovine adrenal chromaffin cells. ET-1 but not ET-3 induced increases in release of catecholamines, [Ca2+]i, and 45Ca2+ uptake. The responses to ET-1 were abolished by the antagonist for ET(A) receptors, BQ-123, but not by the antagonist for ET(B) receptors, BQ-788, and they were abolished by removal of extracellular Ca2+. The increases were only partially inhibited (to about 65% of control) by nifedipine but unaffected by any of the omega-toxins. The nifedipine-resistant increase was inhibited by SK&F 96365 (to about 40%) and abolished by LOE 908 alone. These results indicate that ET-1 augments the release of catecholamines from adrenal chromaffin cells through ET(A) receptors, by activating two types of Ca2+ entry channels in addition to L-type VOCC: one (nonselective cation channel-1; NSCC-1) is sensitive to LOE 908 but resistant to SK&F 96365, whereas the other (NSCC-2) is sensitive to both LOE 908 and SK&F 96365.

Acetamides↗
PubMed1999

First case of cadaveric liver transplantation in Japan.

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.

Adult↗
PubMed1999

Activation of three types of voltage-independent Ca2+ channel in A7r5 cells by endothelin-1 as revealed by a novel Ca2+ channel blocker LOE 908.

1. We have shown that in addition to voltage-operated Ca2+ channel (VOC), endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channel (NSCC) in A7r5 cells: its lower concentrations (< or = 1 nM; lower [ET-1]) activate only an SK&F 96365-resistant channel (NSCC-1), whereas its higher concentrations (> or = 10 nM; higher [ET-1]) activate an SK&F 96365-sensitive channel (NSCC-2) as well. 2. We now characterized the effects of a blocker of Ca2+ entry channel LOE 908 on NSCCs and store-operated Ca2+ channel (SOCC) in A7r5 cells, and using two drugs, clarified the involvement of these channels in the ET-1-induced increase in the intracellular free Ca2+ concentrations ([Ca2+]i). Whole-cell recordings and [Ca2+]i monitoring with fluo-3 were used. 3. LOE 908 up to 10 microM had no effect on increases in [Ca2+]i induced by thapsigargin or ionomycin, but SK&F 96365 abolished them. 4. In the cells clamped at -60 mV, both lower and higher [ET-1] induced inward currents with linear iv relationships and the reversal potentials of -15.0 mV. Thapsigargin induced no currents. 5. In the presence of nifedipine, lower [ET-1] induced a sustained increase in [Ca2+]i, whereas higher [ET-1] induced a transient peak and a sustained increase. The sustained increases by lower and higher [ET-1] were abolished by removal of extracellular Ca2+, and they were suppressed by LOE 908 to 0 and 35%, respectively, with the LOE 908-resistant part being abolished by SK&F 96365. 6. These results show that LOE 908 is a blocker of NSCCs without effect on SOCC, and that the increase in [Ca2+]i at lower [ET-1] results from Ca2+ entry through NSCC-1 in addition to VOC, whereas the increase at higher [ET-1] involves NSCC-1, NSCC-2 and SOCC in addition to VOC.

Acetamides↗
PubMed1999

Pharmacological characterization of Ca2+ entry channels in endothelin-1-induced contraction of rat aorta using LOE 908 and SK&F 96365.

We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. Here we characterized Ca2+ entry channels involved in ET-1-induced contractions of rat thoracic aortic rings and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of single smooth muscle cells using these blockers. LOE 908 or a blocker of voltage-operated Ca2+ channel nifedipine had no effect on the contractions and increases in [Ca2+]i induced by thapsigargin or ionomycin, whereas SK&F 96365 abolished them. The contractions and increases in [Ca2+]i induced by ET-1 depended on extracellular Ca2+ but were resistant to nifedipine. The responses to lower concentrations (< or =0.1 nM) of ET-1 were abolished by either SK&F 96365 or LOE 908. The responses to higher concentrations (> or = 1 nM) were abolished by SK&F 96365, but were partially resistant to LOE 908. SK&F 96365 inhibited the LOE 908-resistant contractions induced by higher concentrations of ET-1 with IC50 values similar to those for contractions induced by thapsigargin or ionomycin. These results show that the contractions and increases in [Ca2+]i of rat aortic smooth muscles at lower concentrations of ET-1 involve only one Ca2+ entry channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those at higher concentrations of ET-1 involve another Ca2+ entry channel which is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC) in addition to the former channel.

Acetamides↗
PubMed1999

Tissue-specific somatic mosaicism in spinal and bulbar muscular atrophy is dependent on CAG-repeat length and androgen receptor--gene expression level.

The factors influencing the tissue-specific pattern of somatic mosaicism in CAG-repeat diseases have not yet been fully resolved. We performed a detailed analysis of the degree of somatic mosaicism in various tissues from 20 patients with spinal and bulbar muscular atrophy (SBMA), including 4 who were deceased. The most outstanding feature was the prominent somatic mosaicism observed in the cardiac and skeletal muscles, composed predominantly of postmitotic cells, and in the skin, prostate, and testis. The CNS tissues, liver, and spleen showed the least mosaicism. The tissue distribution of somatic mosaicism in patients with SBMA was markedly different from that in patients with Huntington disease (HD) and from that in patients with dentatorubral-pallidoluysian atrophy (DRPLA). The degree of somatic mosaicism correlated with the CAG-repeat number but not with age at examination. Furthermore, tissues with a higher mosaicism level corresponded well to those with a higher expression level of androgen receptor protein. The tissue-specific pattern of somatic mosaicism related not only to cell composition with different cell turnover rates but to repeat size and gene expression levels, and postnatal cell division is unlikely to be a major cause of somatic mosaicism probably because of the relative stability of CAG repeat in SBMA.

Adult↗