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T Oka

Publications and source records attributed to T Oka.

At least 37 records · Page 2Linked to original sources

Clinical implications of cardiac (123)I-meta-iodobenzylguanidine scintigraphy and cardiac natriuretic peptides in patients with heart disease.

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

3-Iodobenzylguanidine↗

Factors predicting compensatory vascular remodelling of the carotid artery affected by atherosclerosis.

OBJECTIVE: To investigate factors predicting the development of outward remodelling of the carotid artery in patients with atherosclerosis. DESIGN: 130 patients with carotid artery stenosis (15-85% of the vessel diameter) were divided into two groups, based on the presence or absence of outward remodelling of the sclerotic carotid segment on high resolution ultrasonography. Logistic regression analysis was used to evaluate the contribution of haemodynamic, laboratory, and clinical measurements on the development of remodelling, including age, sex, type of stenosis, extent of plaque, per cent diameter stenosis, underlying disease, selected drug treatment, and plasma concentrations of total cholesterol, high density lipoprotein cholesterol, triglyceride, and uric acid. RESULTS: 64 patients (49%) had outward remodelling. Multivariate regression analysis showed that hypertension, the type of plaque, the thickness of the plaque, and the extent of stenosis were independent factors predicting remodelling. The odds ratios of hypertension, unstable shape of plaque, thickness of plaque, and the extent of the stenosis were 6.70, 3.02, 2.04, and 1.05, respectively. Other measurements did not contribute significantly to the estimation of remodelling. CONCLUSIONS: Compensatory enlargement of the vessel occurs in about 50% of carotid artery segments with a diameter stenosis of 15-85%. Hypertension and the shape of the plaque are major determinants of the development of outward remodelling.

Aged↗

Serum level of cartilage oligomeric matrix protein (COMP) in equine osteoarthritis.

This study was designed to assay and compare cartilage oligomeric matrix protein (COMP) in horse sera, in samples from normal and joint diseased horses, and to investigate the relationships between COMP in sera and synovial fluids (SF) with keratan sulphate (KS) data. Sera from 38 horses free of any joint pathology (controls) and from horses with aseptic joint disease (AJD horses, n = 40) were assayed for COMP and KS concentrations. Of the 78 horses in the study, 53 were also assayed for COMP and KS concentrations in SF. COMP and KS were measured by inhibition ELISA, using monoclonal antibodies 12C4 and 5D4, respectively. The COMP concentration in sera from AJD horses (mean +/- s.d. 10.7 +/- 7.4 microg/ml) was significantly (P<0.02) lower than in control sera (14.8 +/- 7.8 microg/ml). The joint disease sera also had significantly lower (P<0.01) KS levels (180.5 +/- 61.8 ng/ml) than controls (237.1 +/- 116.1 ng/ml). A significant correlation (r = 0.52, n = 53, P<0.001) was seen between serum and SF in COMP levels; no such relationship was seen in KS levels. It is possible that serum COMP concentration could be a more specific marker of equine joint disease than any other described to date.

Animals↗

Long-term results of chronic hemodialysis patients with isolated coronary artery bypass grafting performed by the same surgeon. A comparative study.

BACKGROUND: The aim of this study was to examine the long-term results of isolated coronary artery bypass grafting (CABG) patients who required chronic hemodialysis. METHODS: From May 1990 to June 2000, 23 hemodialysis patients received isolated CABG performed by the same surgeon. Postoperative follow-up was completed with maximum duration of 122 months. RESULTS: Operative deaths (n=2) were due to acute circulatory failure related to hemodialysis. The most frequent cause of late deaths (n=10) was infection. Five (50%) patients died of sepsis, and 80% of sepsis was caused by leg infection associated with arteriosclerosis obliterans. There were 6 late cardiac events including 3 cardiac deaths. The actual survival rates 1, 3, 5 and 7 years after CABG were 68.6%, 42.5%, 35.4% and 35.4%, respectively. And the actual cardiac event free rates 1, 3, 5 and 7 years after CABG were 77.6%, 77.6%, 46.6% and 46.6%, respectively. Operative mortality (p=0.019), long-term survival (p<0.001) and cardiac event free rate (p=0.002) were significantly poorer in hemodialysis patients than in non-hemodialysis patients. However, the long-term survival rate of our hemodialysis patients receiving isolated CABG was almost similar to that in dialysis patients without CABG. The etiology of chronic renal failure did not significantly affect long-term RESULTS. Using internal thoracic artery graft significantly (p=0.02) decreased the late cardiac event in hemodialysis patients, although it did not improve late survival. CONCLUSIONS: Primary CABG followed by aggressive re-intervention have the benefit of preventing late cardiac death in hemodialysis patients. However, prevention of sepsis and treatment of arteriosclerosis obliterans are important for improving the late survival in hemodialysis patients receiving isolated CABG.

Aged↗

Selection of surgical methods for infected infrarenal abdominal aortic aneurysms.

BACKGROUND: There is no standard treatment for patients with infected abdominal aortic aneurysm (AAA). To determine the basis for selection of a surgical method, we reviewed our experiences with all patients who underwent surgery for infected infrarenal AAA. METHODS: Between 1993 and 2000, 6 patients with infected infrarenal AAA underwent surgery. Extra-anatomic bypass grafting was performed in 2 of 3 patients with infection extending into the retroperitoneum. In situ grafting was performed in 3 patients with localized infection and in 1 patient with extended infection. RESULTS: Severe peritonitis occurred in 2 patients with extended infection in the early postoperative phase. One patient, who had undergone in situ grafting, died of sepsis. The other patient, who had undergone extra-anatomic bypass grafting, was treated by continuous irrigation with an electrolyzed strong acid aqueous solution (ESAAS). He recovered gradually and was discharged. After a follow-up period with a mean of 40 months (range: 17-102 months), all 5 patients who survived surgery are alive and asymptomatic. CONCLUSIONS: It was suggested that the method used for revascularization should be selected based on the degree of diffusion of infection. For a patient with extended infection, postoperative continuous irrigation with ESAAS appears to be effective in eradicating retroperitoneal infection.

Aged↗

Pyridoxal 5'-phosphate inhibits DNA binding of HNF1.

An efficient Escherichia coli expression system was constructed for the production of a variant form of HNF1 protein having the additional five amino acid residues (Asp-Arg-Trp-Gly-Ser) at the NH(2)-terminal. The cDNA encoding HNF1 was ligated to 6 x His tag and inserted into an inducible bacterial expression vector pRSET A. After expression in E. coli, the recombinant product was purified by Ni-NTA affinity column chromatography. The purified product showed expected NH(2)-terminal sequence and specific binding to the HNF1 site. The effect of pyridoxal 5'-phosphate and its analogues on the binding activity of recombinant HNF1 was examined and found that only pyridoxal 5'-phosphate effectively inhibited the DNA binding. The concentration of pyridoxal 5'-phosphate that inhibited 50% of DNA binding was around 100 microM. Furthermore, we identified Lys197 of HNF1 molecule as the essential residue of DNA binding. These observations suggest that pyridoxal 5'-phosphate directly interacts with tissue-specific transcription factor HNF1 and modulates the binding to DNA.

Amino Acid Sequence↗

Native-like tertiary structure formation in the alpha-domain of a hen lysozyme two-disulfide variant.

Structure formation in two species of the two-disulfide variant of hen lysozyme was investigated by means of CD spectroscopy, disulfide exchange measurement, and 1H-NMR spectroscopy. One species, 2SS [6-127, 30-115], which contained the two disulfide bonds found in the alpha-domain of authentic lysozyme, had amounts of secondary and tertiary structures, and bacteriolytic activity comparable to those of authentic lysozyme, and showed a cooperative thermal unfolding. By contrast, the other species, 2SS [64-80, 76-94], which contained the beta-domain disulfide bond as well as the inter-domain one, had a limited amount of secondary structure and little tertiary structure. Disulfide-exchange did not occur for 2SS [6-127, 30-115], whereas it occurred for 2SS [64-80, 76-94], indicating that the protein main-chain fold coupled with the formation of two disulfide bonds is relatively stable for the former variant, while unstable for the latter. 1H-NMR spectra of 2SS [6-127, 30-115] showed that native-like local environment is present within the region that corresponds to the alpha-domain, while it is absent within the region that corresponds to the beta or inter-domain. These results indicate that the alpha-domain of hen lysozyme can be an independent folding domain at equilibrium. Although the bipartite nature in the structure formation of hen lysozyme is similar to that reported for alpha-lactalbumin, differences exist between the disulfide-intermediates of the two proteins in terms of the structural domain that accomplishes tertiary structure.

Animals↗

Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium.

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell-cell contacts in PrlR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5-null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy.

Animals↗

Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide-induced hyperalgesia in rats.

The systemic administration of lipopolysaccharide (LPS), an experimental model of systemic bacterial infection is known to modulate nociception. It increases the prostaglandin E(2) (PGE(2)) levels in the preoptic area of the hypothalamus (POA) and the microinjection of PGE(2) into the POA and the neighboring basal forebrain induces hyperalgesia. We, therefore, hypothesized that the PGE(2) synthesized in these regions mediates intravenous (i.v.) LPS-induced hyperalgesia. To test this hypothesis, we microinjected cyclooxygenase (COX) inhibitors into several sites in the rat hypothalamus and observed their effects on the LPS (0.1-100 microg/kg, i.v.)-induced changes in nociceptive behavior as assessed by a plantar test. LPS (10 and 100 microg/kg, i.v.) reduced the paw-withdrawal latency at 90 min and 45-60 min after injection, respectively, both thus indicating a hyperalgesic effect. This hyperalgesia was observed only in the period before the development of fever which started 120-135 min after the LPS injection. The LPS (100 microg/kg, i.v.)-induced hyperalgesia was completely abolished by pretreatment with the microinjection of diclofenac (an inhibitor of COX-1 and 2) at 1.0 ng into the bilateral POA. Furthermore, it was also blocked by the microinjection of NS-398 (a selective COX-2 inhibitor) at 1.0 ng into the bilateral POA and the horizontal limb of the diagonal band of Broca (DBB), but not the lateral hypothalamic area, the paraventricular hypothalamic nucleus, and the ventromedial hypothalamic nucleus. These findings suggest that LPS (i.v.)-induced hyperalgesia is mediated predominantly through a COX-2 induced prostanoids in the POA and the DBB in rats.

Animals↗

a4, a unique kidney-specific isoform of mouse vacuolar H+-ATPase subunit a.

The vacuolar-type H+ -ATPase (V-ATPase) translocates protons across membranes. Here, we have identified a mouse cDNA coding for a fourth isoform (a4) of the membrane sector subunit a of V-ATPase. This isoform was specifically expressed in kidney, but not in the heart, brain, spleen, lung, liver, muscle, or testis. Immunoprecipitation experiments, together with sequence similarities for other isoforms (a1, a2, and a3), indicate that the a4 isoform is a component of V-ATPase. Moreover, histochemical studies show that a4 is localized in the apical and basolateral plasma membranes of cortical alpha- and beta-intercalated cells, respectively. These results suggest that the V-ATPase, with the a4 isoform, is important for renal acid/base homeostasis.

Acid-Base Equilibrium↗

Cost effectiveness of reducing dioxin emissions from municipal solid waste incinerators in Japan.

The main sources of dioxin emissions are municipal solid waste incinerators. The Japanese national government has set an emission standard for dioxins to reduce dioxin exposure levels. In this study, cost-effectiveness analyses are carried out regarding countermeasures that were recently taken and are being taken at municipal solid waste incinerators in Japan. Annual costs were estimated by telephone survey and model calculations. Annual decrease in the incidence of cancer was estimated in three steps. First, the annual decrease in the volume of dioxin emissions was estimated. Next, using a mathematical model, the annual decrease in human exposure was estimated. Finally, the annual decrease in the incidence of cancer was estimated by applying the cancer slope factor. When annual costs are divided by the annual number of life-years saved, cost per life-year saved (CPLYS) was obtained. CPLYS was estimated to be 7.9 million yen for emergency countermeasures and 150 million yen for long-term countermeasures. However, it must be noted that these obtained CPLYSs are highly dependent on the cancer slope factor and should be considered as an upper limit since there may be a cancer effect threshold.

Air Pollution↗

Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell-specific expression during development.

We have identified four genes (vha-5, vha-6, vha-7, and unc-32) coding for vacuolar-type proton-translocating ATPase (V-ATPase) subunit a in Caenorhabditis elegans, the first example of four distinct isoforms in eukaryotes. Their products had nine putative transmembrane regions, exhibited 43-60% identity and 62-84% similarity with the bovine subunit a1 isoform, and retained 11 amino acid residues essential for yeast V-ATPase activity (Leng, X. H., Manolson, M. F., and Forgac, M. (1998) J. Biol. Chem. 273, 6717-6723). The similarities, together with the results of immunoprecipitation, suggest that these isoforms are components of V-ATPase. Transgenic and immunofluorescence analyses revealed that these genes were strongly expressed in distinct cells; vha-5 was strongly expressed in an H-shaped excretory cell, vha-6 was strongly expressed in intestine, vha-7 was strongly expressed in hypodermis, and unc-32 was strongly expressed in nerve cells. Furthermore, the vha-7 and unc-32 genes were also expressed in the uteri of hermaphrodites. RNA interference analysis showed that the double-stranded RNA for unc-32 caused embryonic lethality similar to that seen with other subunit genes (vha-1, vha-4, and vha-11) (Oka, T., and Futai, M. (2000) J. Biol. Chem. 275, 29556-29561). The progenies of worms injected with the vha-5 or vha-6 double-stranded RNA became died at a specific larval stage, whereas the vha-7 double-stranded RNA showed no effect on development. These results suggest that V-ATPases with these isoforms generate acidic compartments essential for worm development in a cell-specific manner.

Amino Acid Sequence↗

Purification, characterization and developmental expression of rat brain PSP protein.

We have isolated a perchloric acid-soluble protein designated as B-PSP1 from the postmitochondria supernatant fraction of rat brain. It was purified by gel filtration and anti-PSP1 affinity chromatography. Immunoblotting, peptide mapping, partial amino acid sequencing and reverse transcriptase-polymerase chain reaction showed that the amino acid sequence of B-PSP1 was identical with that of PSP isolated from rat liver. B-PSP1 was expressed in all regions including frontal cortex, posterior cortex, cerebellum, hippocampus, olfactory bulb, striatum, thalamus, midbrain, entorhinal cortex, pons, medulla and spinal cord. Immunohistochemical study showed that the expression of B-PSP1 was observed in ependymal cells of choroid plexus and glial cells of the other region. The expression of B-PSP1 in brain increased gradually from the first day to the 60th day of postnatal age, but the expression of B-PSP1 was slower than that of GFAP which is a marker protein of glial cells. The expression of PSP may be related to the cellular function rather than the developmental regulation of the glial cells. Thus, our findings are the first report on the presence of a PSP in rat brain which may be involved in the regulation of cellular function.

Animals↗

A novel myocyte-specific gene Midori promotes the differentiation of P19CL6 cells into cardiomyocytes.

Although several cardiac-specific transcription factors have been shown to play vital roles in various steps during the heart formation, the precise mechanism of the early stage of cardiogenesis has yet to be elucidated. By differential display technique, we tried to identify molecules that are expressed earlier than cardiac transcription factors such as CSX/NKX2-5 and GATA-4 and are involved in cardiomyocyte differentiation using the P19CL6 cell line, which efficiently differentiates into cardiomyocytes when treated with dimethyl sulfoxide. We isolated a novel gene designated Midori. Its deduced amino acid sequence contained an ATP/GTP-binding site, Ig-like domain, and Kringle-like domain. Northern blot analysis revealed that expression of Midori was restricted to the fetal and adult heart and adult skeletal muscle in mice. In whole mount in situ hybridization, Midori was expressed in cardiac crescent and developing heart but not in somites. The MIDORI protein was localized in the nucleus and overexpression of Midori induced expression of endogenous Midori itself, suggesting that MIDORI may act as a transcriptional regulator. Permanent P19CL6 cell lines overexpressing Midori more efficiently differentiated into cardiomyocytes than did parental cells, whereas those overexpressing the antisense Midori less efficiently differentiated. These results suggest that Midori may promote the differentiation of P19CL6 into cardiomyocytes.

Amino Acid Sequence↗

Sharp spectral lines observed in gamma-ray ionized parahydrogen crystals.

We have observed sharp infrared spectral lines ( Deltanu approximately 60 MHz FWHM) in gamma-ray ionized para- H2 crystals. The lines are assigned to the Q1(0) transition of H2 near H+3 and H-, which becomes optically active and Stark shifted by the Coulomb fields of the ions. A simple model calculation gives a spectrum which agrees approximately with the observation. The spectrum stays the same over many days, demonstrating the stability of the ionized system. The remarkable sharpness and reproducibility of the line positions indicate uniformity of the local structure surrounding the charges.

Journal Article↗

Dendritic aberrations in the hippocampal granular layer and the amygdalohippocampal area following kindled-seizures.

Amygdaloid kindling is a model of human temporal lobe epilepsy, in which excitability in limbic structures is permanently enhanced by repeated stimulations. We report here dendritic aberrations occurring in mice following kindled-seizures. Adult mice received a biphasic square wave pulse [495+/-25.5 (S.E.M.) microA 60 Hz, 200 micros duration, for 2 s] unilaterally in the basolateral amygdaloid complex once a day and mice with electrophysiologically and behaviorally verified seizures were used in the experiments. The hippocampus and amygdaloid complex contralateral to the lesions were observed by immunofluorescence histochemistry with a somatodendritic marker, microtubule-associated protein 2 (MAP2), showing that kindled-seizures caused hypertrophy of proximal dendrites in the granule cells of the dentate gyrus and in neurons of the amygdalohippocampal area. To further characterize the morphological changes of the dendrites, electron micrographic analysis was performed on the contralateral side. (1) In the granular layer of the dentate gyrus and the amygdalohippocampal area, kindled-seizures generated an increase in the number of dendrites containing polymerized microtubules and width of dendritic profiles showing the increase was in the range 0.2-3.0 and 0.2-1.4 microm, respectively. (2) In the granular layer, bundles between dendrites separated by the puncta adhaerentia increased. (3) In the granular layer, the seizure-induced dendritic aberration was more severe in the rostral than the caudal region. These results suggested that growth of dendrites with enriched-stable microtubules is part of the structural plasticity in response to seizure activity in specific areas of the adult brain.

Amygdala↗