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Biomedical subjects

K Omori

Publications and source records attributed to K Omori.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibition of cardiac delayed rectifier K+ currents by an antisense oligodeoxynucleotide against IsK (minK) and over-expression of IsK mutant D77N in neonatal mouse hearts.

The IsK (minK or KCNE1) protein is known to co-assemble with the KvLQT1 (KCNQ1) protein to form a channel underlying the slowly activating delayed rectifier K+ current (IKs). Controversy remains as to whether the IsK protein assembles with ERG (the ether-a-go-go-related gene) products to form or modulate the channel-underlying the rapidly activating delayed rectifier K+ current (IKr). We investigated the effects of antisense oligodeoxynucleotides (AS-ODN) against IsK and its mutant D77N [which underlies a form of long QT syndrome (LQT5) in humans] on the delayed rectifier K+ current (IK) of neonatal mouse ventricular myocytes in primary culture. Patch-clamp experiments on these cells showed that IK consists of IKs and IKr. IK was not recorded from ventricular cells transfected with AS-ODN, while it was recorded from cells transfected with the corresponding sense oligodeoxynucleotides (S-ODN). IK was not recorded from cells transfected with the D77N mutant, and the action potential duration was much longer than in cells transfected with wild-type IsK. Furthermore, HERG could not induce currents in COS-1 cells co-expressed with the D77N mutant and HERG (the human form of ERG). These results indicate that the IsK protein associates with both KvLQT1 and ERG products to modulate IKr and IKs in cardiac myocytes.

Action Potentials↗
PubMed2001

Genetic polymorphisms in the promoter and 5' UTR region of the Fc alpha receptor (CD89) are not associated with a risk of IgA nephropathy.

The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc alpha receptor (FcalphaR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5'-untranslated region region of the FcalphaR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and T+56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcalphaR gene do not appear to be primarily involved in the susceptibility to IgAN.

5' Untranslated Regions↗
PubMed2001

Geomagnetic disturbance associated with decrease in heart rate variability in a subarctic area.

BACKGROUND: Physical environmental variables, such as the natural variation in the geomagnetic field in and around the earth, influence biological processes and human health. The effect of geomagnetic disturbances on heart rate variability (HRV) in healthy students in a subarctic area is studied herein. SUBJECTS AND METHODS: Seven-day records by Holter ECG were obtained from eight clinically healthy subjects in Alta, Norway (70 N). Frequency- and time-domain measures of HRV were compared between 24-hour spans of high geomagnetic disturbance versus quiet conditions. RESULTS: A 5.9% increase in the 24-hour average of HR (P = 0.020) and a 25.2% decrease in HRV (P = 0.002) were documented on days of high geomagnetic disturbance. The decrease in spectral power was found primarily at frequencies lower than 0.04 Hz and was not statistically significant around 3.6 sec. CONCLUSIONS: The physiological mechanism involved may be other than the parasympathetic, usually identified with spectral power centered around 3.6 sec, a spectral region wherein no statistically significant differences were found.

Adult↗
PubMed2001

An evaluation of elastomeric impression materials based on surface compressive strength.

The setting times of seven commercially available elastomeric impression materials were determined using Wilson's reciprocating rheometer at temperatures 23 +/- 0.5 or 32 +/- 0.5 degrees C. The surface compressive strength and depression of these materials after setting time were measured using a rheometer (Fudoh). Each material was mixed according to the mixing proportion (base/accelerator or catalyst ratio) recommended by the manufacturer. The surface compressive strength and the depression of each material were measured by using a method which pressed the material to the edge of a sensitive rod (2.0 mm in diameter) connected to a load cell. In the case of silicone impression materials (additional type) at a temperature of 23 +/- 0.5 degrees C, the surface compressive strength and the depression of these materials were extremely stable after the setting time. However, the surface compressive strength of other materials except additional type materials increased markedly after setting time and the depression corresponding to the surface compressive strength decreased. These increased largely with the increase, in pressing speed to the sensitive rod. At 450 s from the setting time of all materials, there was an adequate correlation (r = 0.84) between measured values and theoretical values derived using the theory of elasticity.

Compressive Strength↗
PubMed2001

Genomic organization of the human phosphodiesterase PDE11A gene. Evolutionary relatedness with other PDEs containing GAF domains.

PDE11A is a dual-substrate, cAMP and cGMP, cyclic nucleotide phosphodiesterase (PDE). Presently four unique variants carrying distinct GAF sequences in the N-terminal region have been identified. While human PDE11A3 and PDE11A4 are known to be specifically expressed in testis and prostate, respectively, PDE11A1 was mainly detected in skeletal muscle. The human PDE11A gene was investigated and revealed to span > 300 kb, contain 23 exons and be mapped on chromosome 2q31. The transcription start sites of PDE11A1, PDE11A3 and PDE11A4 were determined, and the promoter sequences were revealed. Although 5' flanking genomic regions of PDE11A1 and PDE11A3 had a consensus TATA motif, that of PDE11A4 was a TATA-less but contained CCAAT box and Sp1-binding sequence. Interestingly, we found that the exon 2 sequence for N-terminal region of PDE11A3 encoded an N-terminal sequence of the cytochrome c pseudogene in an alternate reading frame, and that C-terminal region of the cytochrome c pseudogene in intron 2 was disrupted by the insertion of Alu repetitive sequence. Furthermore, we examined the exon-intron organization of the PDE2A gene and compared the exon organization among GAF-PDE family. The exon organization of the PDE11A catalytic domain was very similar to those of PDE5A and PDE6B. However, other GAF-PDEs, PDE2A and PDE10A, displayed different exon organization from PDE11A although these three PDEs are similar in their amino-acid sequences to each other. The findings suggested that PDE11A has a common ancestral gene with PDE5A and PDE6s, whereas PDE2A and PDE10A are generated separately from these three GAF-PDEs.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): comparison of rat and human PDE11A splicing variants.

We have isolated and characterized rat cyclic nucleotide phosphodiesterase (PDE)11A, which exhibits properties of a dual-substrate PDE, and its splice variants (RNPDE11A2, RNPDE11A3, and RNPDE11A4). The deduced amino-acid sequence of the longest form of rat PDE11A splice variant, RNPDE11A4, was 94% identical with that of the human variant (HSPDE11A4). Rat PDE11A splice variants were expressed in a tissue-specific manner. RNPDE11A4 showed unique tissue distribution distinct from HSPDE11A4, which is specifically expressed in the prostate. Rat PDE11A splice variants were expressed in COS-7 cells, and their enzymatic characteristics were compared. Although the Km values for cAMP and cGMP were similar for all of them (1.3-1.6 and 2.1-3.9 microM, respectively), the Vmax values differed significantly (RNPDE11A4 >> RNPDE11A2 > RNPDE11A3). Human PDE11A variants also displayed very similar Km values and significantly different Vmax values (HSPDE11A4 >> HSPDE11A2 > HSPDE11A3 >> HSPDE11A1). The Vmax values of HSPDE11A4 for cAMP and cGMP were at least 100 times higher than those of HSPDE11A1. These observations indicate unique characteristics of PDE11A splicing variants.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Antidesmoglein autoantibodies in silicosis patients with no bullous diseases.

BACKGROUND: Pemphigus is an autoimmune bullous disease characterized by the presence of antidesmoglein autoantibodies. However, the mechanism of its autoantibody production remains unknown. In previous reports, we have described rare cases of pemphigus and pemphigoid associated with silicosis. It is well known that during long-term silicosis, some autoimmune diseases, such as systemic sclerosis, systemic lupus erythematosus or rheumatoid arthritis, can occur. OBJECTIVE: The aim of this study was to explore the presence of pemphigus or pemphigoid autoantibodies in silicosis patients without clinical bullous diseases or collagen diseases. METHOD: The presence of pemphigus antibodies was examined in 54 silicosis patients with no associated bullous diseases, using immunofluorescence, the enzyme-linked immunosorbent assay (ELISA) for desmoglein 1 and 3, and immunoblotting methods. In the antibody-positive cases, HLA genotyping of peripheral lymphocytes was performed with PCR-RFLP. RESULTS: Seven out of the 54 patients were found to be positive for pemphigus antibodies and 1 for bullous pemphigoid by immunofluorescence. In addition, by ELISA, 6 patients were found to be positive against the desmoglein 1 antigen, 2 against the desmoglein 3 antigen and 2 against both desmoglein 1 and desmoglein 3. CONCLUSION: The results of the present study strongly suggest the occurrence of pemphigus and pemphigoid autoantibodies in patients with silicosis. It remains unclear whether such patients will develop an autoimmune bullous disease in the future. Accordingly, long-term follow-up of antibody-positive patients is required.

Aged↗
PubMed2001

Isolation and analysis of lipase-overproducing mutants of Serratia marcescens.

We have isolated a lipase-overproducing mutant, GE14, from Serratia marcescens 8000 after three rounds of N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutant GE14 produced 95 kU/ml of extracellular lipase in the lipase medium, which was about threefold higher than that of produced by the original strain 8000. Enzymatic characteristics including specific activity of purified lipases from culture supernatants of GE14 and 8000 were almost same. The lipase gene (lipA) of GE14 contained two base substitutions; one in the promoter region and another in the N-terminal region of the lipA gene without an amino acid substitution. Promoter analysis using lipA-lacZ fusion plasmids revealed that these substitutions were responsible for the increase in the lipA expression level, independently. In contrast, no base substitution was found in the genes encoding the lipase secretion device, the Lip system. In addition, the genes coding for metalloprotease and the cell surface layer protein which are both secreted through the Lip system and associated with extracellular lipase production, also contained no base substitution. The strain GE14 carrying a high-copy-number lipA plasmid produced a larger amount of the extracellular lipase than the recombinant strains of 8000 and other mutants also did, indicating that GE14 was not only a lipase-overproducing strain, but also an advantageous host strain for overproducing the lipase by a recombinant DNA technique. These results suggest that the lipase-overproducing mutant GE14 and its recombinant strains are promising candidates for the industrial production of the S. marcescens lipase.

Journal Article↗
PubMed2001

[Special categories of elderly patients with intractable neurological diseases (NANBYO) in Toyama, Japan].

The purpose of this study was to elucidate special categories of elderly patients with intractable neurological diseases (NANBYO) in Toyama, Japan. This goal was accomplished through comparisons of data gathered in 1991 and 1997. Forty-eight (20 males, 28 females) with such diseases were recruited for the study and agreed to be interviewed. The surveys were performed by three public health center nurses. The same questionnaire was used in both years. The surveys show that the number of jobless patients and those who needed total support increased by approximately 20% from 1991 to 1997. In addition, it appears that the ratio of hospitalized patients and those who needed medical equipment installed at home increased considerably. The number of patients with caregivers increased by approximately 30%. As the caregivers got older, it was observed that the patients became more anxious about their health condition. Also, in both years, both patients and caregivers showed the highest concern about a sudden change in the patients' conditions. In conclusion, an assessment of patient and family needs is important for the development of a community health care system. It is also essential for all the parties in the field of health, medicine, and welfare, as well as volunteer groups, to have a good understanding of each other's services and to have a cooperative relationship coordinated by health centers through discussion of each individual case.

Adult↗
PubMed2001

Rational, effective metyrapone treatment of ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH).

Standard therapy for ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), a rare form of Cushing's syndrome, is bilateral adrenalectomy. Patients with AIMAH are usually elderly, with a variety of complications, and at risk for surgery. Postoperatively, they must receive lifelong corticosteroids and spend the remainder of their lives avoiding adrenal crisis. Therapy using metyrapone, a potent inhibitor of steroidogenesis, provides the advantages of avoiding the surgery. Its effectiveness is further anticipated because adrenal steroidogenic enzymes are reportedly weak in AIMAH. Treatment with metyrapone thus appears a good therapy for AIMAH, but its effectiveness has not, to our knowledge, been studied. We treated a 59-year-old man with AIMAH with metyrapone. At a low dose of metyrapone (500 to 750 mg/day), his plasma cortisol levels decreased to the normal range, and hypertension and diabetes mellitus were ameliorated. Therapy using metyrapone thus appears effective in treating AIMAH, and can be recommended for high risk AIMAH patients as an alternative therapy.

Adrenal Glands↗
PubMed2001

[Depression in late life].

Depression in the elderly is one of the most important psychotic disorder as well as dementia. In this report, at first we described the relation between brain-organic disorder and depression in late life. It is very interesting that depression in late life has often comorbid process with vascular dementia and dementia of the Alzheimer type. In biological treatments for depression in late life, pharmacotherapy and modified electroconvulsive therapy are useful. We must be aware of the adverse side effects from the use of antidepressant, then SSRIs are selected for clinical depression of late life, because the SSRIs produce fewer side effects. Psychotherapeutic medication, such as cognitive behavioral therapy and reminiscence or life, review is useful for depression in late life.

Age of Onset↗
PubMed2000

Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat.

Ca(2+), which enters cardiac myocytes through voltage-dependent Ca(2+) channels during excitation, is extruded from myocytes primarily by the Na(+)/Ca(2+) exchanger (NCX1) during relaxation. The increase in intracellular Ca(2+) concentration in myocytes by digitalis treatment and after ischemia/reperfusion is also thought to result from the reverse mode of the Na(+)/Ca(2+) exchange mechanism. However, the precise roles of the NCX1 are still unclear because of the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene targeting to determine the in vivo function of the exchanger. Homozygous Ncx1-deficient mice died between embryonic days 9 and 10. Their hearts did not beat, and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the Na(+)/Ca(2+) exchange activity was detected in null mutant hearts. The Na(+)-dependent Ca(2+) exchange activity as well as protein content of NCX1 were decreased by approximately 50% in the heart, kidney, aorta, and smooth muscle cells of the heterozygous mice, and tension development of the aortic ring in Na(+)-free solution was markedly impaired in heterozygous mice. These findings suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in embryos and plays critical roles in Na(+)-dependent Ca(2+) handling in the heart and aorta.

Animals↗
PubMed2000

Characterization and effects of methyl-2- (4-aminophenyl)-1, 2-dihydro-1-oxo-7- (2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel potent inhibitor of cGMP-binding cGMP-specific phosphodiesterase (PDE5).

An isoquinolone derivative, methyl-2-(4-aminophenyl)-1, 2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), was found to be a novel potent inhibitor of cyclic GMP (cGMP)-binding cGMP-specific phosphodiesterase (PDE5). We investigated the inhibitory effects of T-1032 on six PDE isozymes isolated from canine tissues. T-1032 specifically inhibited the hydrolysis of cGMP by PDE5 partially purified from canine lung, at a low concentration (IC(50) = 1.0 nM, K(i) = 1.2 nM), in a competitive manner. In contrast, the IC(50) values of T-1032 for PDE1, PDE2, PDE3, and PDE4 were more than 1 microM. T-1032 also inhibited PDE6 from canine retina with an IC(50) of 28 nM, which is of the same order of magnitude as the IC(50) of sildenafil. cGMP hydrolytic activities of two alternative splice variants of canine PDE5 expressed in COS-7 cells were inhibited by this compound to a similar extent. T-1032 increased the intracellular concentration of cGMP in cultured rat vascular smooth muscle cells in the presence and absence of C-type natriuretic peptide, an activator of membrane-bound guanylate cyclase, whereas the compound did not change cyclic AMP levels. These data indicated that T-1032, which belongs to a new structural class of PDE5 inhibitors, is a potent and selective PDE5 inhibitor. This compound may be useful in pharmacological studies to examine the role of a cGMP/PDE5 pathway in tissues.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression.

cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were isolated by a combination of reverse transcriptase-polymerase chain reaction using degenerate oligonucleotide primers and rapid amplification of cDNA ends. Their catalytic domain was identical to that of PDE11A1 (490 amino acids) reported during the course of this study. However, the cDNAs we isolated had N termini distinct from PDE11A1, indicating two novel N-terminal variants of PDE11A. PDE11A3 cDNA encoded a 684-amino acid protein including one complete and one incomplete GAF domain in the N-terminal region. PDE11A4 was composed of 934 amino acids including two complete GAF domains and shared 630 C-terminal amino acids with PDE11A3 but had a distinct N terminus containing the putative phosphorylation sites for cAMP- and cGMP-dependent protein kinases. PDE11A3 transcripts were specifically expressed in testis, whereas PDE11A4 transcripts were particularly abundant in prostate. Recombinant PDE11A4 expressed in COS-7 cells hydrolyzed cAMP and cGMP with K(m) values of 3.0 and 1.4 microm, respectively, and the V(max) value with cAMP was almost twice that with cGMP. Although PDE11A3 showed the same K(m) values as PDE11A4, the relative V(max) values of PDE11A3 were approximately one-sixth of those of PDE11A4. PDE11A4, but not PDE11A3, was phosphorylated by both cAMP- and cGMP-dependent protein kinases in vitro. Thus, the PDE11A gene undergoes tissue-specific alternative splicing that generates structurally and functionally distinct gene products.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Identification of human PDE7B, a cAMP-specific phosphodiesterase.

We isolated a human cAMP-specific phosphodiesterase (PDE7B) cDNA from human caudate nucleus. The human PDE7B was composed of 450 amino acid residues with a molecular mass of 51,835 Da. The deduced amino acid sequence of human PDE7B was 64.1% identical to that of human PDE7A (67.1% identity in the catalytic region). Northern blot analysis demonstrated that PDE7B transcripts were abundantly expressed in the putamen, caudate nucleus, and heart followed by skeletal muscle, pancreas, and occipital pole. Recombinant PDE7B expressed in transfected COS-7 cells had a low cAMP K(m) value of 0. 13 microM, which is similar to the K(m) value of recombinant human PDE7A expressed in transfected COS-7 cells. Interestingly, the relative V(max) value of recombinant PDE7B was half to one-third of recombinant PDE7A. The PDE7B activity was inhibited by dipyridamole and SCH51866, with IC(50) values of 1.1 microM and 1.5 microM, respectively. Thus, the PDE7B exhibited unique tissue distribution in humans and kinetic profiles. Human PDE7B showed the lowest K(m) values compared to the other cAMP-hydrolyzing PDEs which have been reported to be expressed in the brain. Therefore, human PDE7B may be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

The chloride channel ClC-2 contributes to the inwardly rectifying Cl- conductance in cultured porcine choroid plexus epithelial cells.

1. The contribution of ClC-2 protein to the inwardly rectifying Cl- conductance in cultured porcine choroid plexus epithelial cells was investigated using Western analysis and whole-cell current recordings. 2. Inwardly rectifying currents were elicited by hyperpolarizing voltage at a potential more negative than -50 mV in the presence of intracellular protein kinase A (PKA). The relative halide selectivity estimated from the shift in the reversal potential (Erev) was I- > Br- > Cl- > F-. 3. Extracellular vasoactive intestinal peptide (VIP) activated the same currents in a dose-dependent manner with a half-maximal concentration of 167.3 nM. H-89 (a PKA inhibitor) interfered with the current activation by VIP. 4. The Cl- channel was inhibited by external Cd2+, Ba2+or H+, but only weakly inhibited by known Cl- channel blockers including glibenclamide, NPPB, DIDS and anthracene-9-carboxylic acid (9AC). 5. A specific antibody to ClC-2 detected a 79 kDa protein in porcine choroid plexus cells, which was reduced in cells treated with antisense oligodeoxynucleotide for ClC-2. Both PKA and VIP failed to activate the inwardly rectifying Cl- currents in cells transfected with the antisense oligodeoxynucleotide, while they activated the currents in cells transfected with GFP alone or the control oligodeoxynucleotide randomized from antisense oligonucleotide. 6. It is concluded that ClC-2 protein contributes to the inwardly rectifying Cl- conductance in porcine choroid plexus epithelial cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗