Images in cardiovascular medicine. Differential color imaging technique of helical CT angiography in the diagnosis of total anomalous pulmonary venous drainage.
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Color↗
Biomedical subjects
H Satoh
Publications and source records attributed to H Satoh.
KB-R7943 block of Ca(2+) influx via Na(+)/Ca(2+) exchange does not alter twitches or glycoside inotropy but prevents Ca(2+) overload in rat ventricular myocytes.
BACKGROUND: The Na(+)/Ca(2+) exchange (NCX) extrudes Ca(2+) from cardiac myocytes, but it can also mediate Ca(2+) influx, load the sarcoplasmic reticulum with Ca(2+), and trigger Ca(2+) release from the sarcoplasmic reticulum. In ischemia/reperfusion or digitalis toxicity, increased levels of intracellular [Na(+)] ([Na(+)](i)) may raise levels of intracellular [Ca(2+)] ([Ca(2+)](i)) via NCX, leading to cell injury and arrhythmia. METHODS AND RESULTS: We used KB-R7943 (KBR) to selectively block Ca(2+) influx via NCX to study the role of NCX-mediated Ca(2+) influx in intact rat ventricular myocytes. Removing extracellular Na(+) caused [Ca(2+)](i) to rise, due to Ca(2+) influx via NCX, and this was blocked by 90% with 5 micromol/L KBR. However, KBR did not alter [Ca(2+)](i) decline due to NCX. Thus, we used 5 micromol/L KBR to selectively block Ca(2+) entry but not efflux via NCX. Under control conditions, 5 micromol/L KBR did not alter steady-state twitches, Ca(2+) transients, Ca(2+) load in the sarcoplasmic reticulum, or rest potentiation, but it did prolong the late low plateau of the rat action potential. When Na(+)/K(+) ATPase was inhibited by strophanthidin, KBR reduced diastolic [Ca(2+)](i) and abolished the spontaneous Ca(2+) oscillations, but it did not prevent inotropy. CONCLUSIONS: In rat ventricular myocytes, Ca(2+) influx via NCX is not important for normal excitation-contraction coupling. Furthermore, the inhibition of Ca(2+) efflux alone (as [Na(+)](i) rises) may be sufficient to cause glycoside inotropy. In contrast, Ca(2+) overload and spontaneous activity at high [Na(+)](i) was blocked by KBR, suggesting that net Ca(2+) influx (not merely reduced efflux) via NCX is involved in potentially arrhythmogenic Ca(2+) overload.
Animals↗
The sustained inward current and inward rectifier K+ current in pacemaker cells dissociated from rat sinoatrial node.
1. Myocytes were dissociated from the sinoatrial (SA) node of rat heart using a new enzymatic dissociation technique. Only a small number of isolated SA node myocytes showed regular rhythmic contractions and spontaneous action potentials, and these were used in the present study. 2. The spontaneous action potential was resistant to TTX, and the action potential parameters were similar to those of rabbit and guinea-pig pacemaker cells. Major time- and voltage-dependent currents were the delayed rectifier K+ current IKr, the L-type Ca2+ current ICa,L and the sodium current INa. The hyperpolarization-activated cation current (If) was recorded from approximately 50 % of the cells with hyperpolarization beyond -90 mV. 3. The instantaneous current jump at the onset of a hyperpolarizing pulse showed inward rectification and was largely blocked by Ba2+. This Ba2+-sensitive current corresponded well to the inward rectifier K+ current (IK1), although it was much smaller in amplitude than in the ventricle. 4. A sustained inward current was activated on depolarization from -80 mV to the voltage range of slow diastolic depolarization. The current was blocked by nicardipine, enlarged by isoprenaline and was insensitive to removal of external Ca2+. These characteristics were similar to the sustained inward current, Ist, previously described in the rabbit and guinea-pig SA node cells. 5. The role of Ist was considered by constructing empirical equations, which were applied to the experimental record of the action potential. It is demonstrated that the voltage-dependent activation of Ist constitutes a positive feedback loop with the depolarization of the membrane.
Action Potentials↗
Tetrodotoxin-sensitive persistent current boosts the depolarization of retinal amacrine cells in goldfish.
To light illumination retinal amacrine cells respond with graded depolarization accompanied by a spike discharge. It has been assumed that the graded depolarization is produced solely by the excitatory synaptic inputs from bipolar cells. Here we demonstrate that a tetrodotoxin (TTX)-sensitive persistent current also contributes to the graded depolarization. This current was isolated in amacrine cells of the goldfish retinal slice preparations by the whole-cell patch clamp technique. The activation threshold of the persistent current was about -50 mV, approximately 10 mV more positive than the membrane potential in the dark. Therefore, it is highly likely that the TTX-sensitive persistent current is a booster of the excitatory postsynaptic potential in amacrine cells.
Action Potentials↗
Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.
The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect disease-causing mutations, to clarify their frequency and distribution, to determine whether genotype correlates with phenotype, and to determine the rate of abnormal findings in heterozygotes for the WD gene. We analyzed 41 unrelated Japanese WD families, including 47 patients. Twenty-one mutations, including nine novel ones, were identified. 2871delC (15.9%), 1708-5T-->G (11. 0%), and Arg778Leu (13.4%) were the most common mutations. 2871delC was detected mainly in eastern Japan and 1708-5T-->G in western Japan. The homozygotes for the 1708-5T-->G, 2871delC, or Arg778Leu mutations did not show a correlation with their phenotypes. Ceruloplasmin and copper levels were abnormally low in 28.6% and 35. 0% of heterozygotes, respectively. When patients and their families are screened for WD, a high rate of abnormal laboratory data in heterozygotes must be taken into account.
Adenosine Triphosphatases↗
Isolation of Campylobacter species from zoo animals and polymerase chain reaction-based random amplified polymorphism DNA analysis.
A total of 104 fecal specimens from 30 mammals, 12 birds, and 3 reptiles at the Phoenix Zoological Gardens, Miyazaki City, Japan, were examined for the presence of Campylobacter species. All the animals examined were healthy with no fecal abnormality. Twenty-three (22.1%) thermophilic campylobacters, (9 C. jejuni, 11 C. hyointestinalis, 2 C. coli, and 1 C. lari), were isolated from 11 animals (7 mammals and 4 birds). C. jejuni and C. hyointestinalis were the predominant species isolated from these zoo animals and C. hyointestinalis was isolated frequently from simians. As selective media influence the numbers and species of campylobacters isolated, the agar medium was not supplemented with cephalothin. Campylobacters were isolated most frequently when a combination of enrichment culture and selective agar plating was performed at 42 degrees C. For the epidemiological study, a polymerase chain reaction (PCR)-based randomly amplified polymorphic DNA (RAPD) method was used as a tool to detect the heterogeneity of amplified DNAs of Campylobacter spp. isolated from zoo animals. The two arbitrary primers used in this study enabled even closely related strains of the same Campylobacter spp. to be differentiated. RAPD analysis revealed considerable diversity among the strains, suggesting that the transmission of Campylobacter spp. among animals in a defined area occurred through different mechanisms. Examination of the genotypic diversity among the multiple clones from the same host also revealed differences between clones. These results demonstrate that campylobacter populations in zoo animals are highly divergent.
Animals↗
Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure.
The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.
Adult↗
Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama study.
The polymorphism of the angiotensin-converting enzyme gene is considered to be associated with increased risk for stroke, but there is a diversity in the results obtained. The genetic involvement of the renin-angiotensin system in stroke also remains unclear. To predict the genetic risk of lacunar infarction, we conducted an association study in an Ohasama population, which is the cohort in a rural region of northern Japan. A total of 134 subjects without major neurological, cardiovascular, or metabolic disorders were recruited. Using brain magnetic resonance imaging, the number of lacunae in each of four brain regions were calculated, and periventricular hyperintensity was classified into five grades. We used the following four candidate gene polymorphisms: angiotensin converting enzyme (ACE)/Insertion(I)-Deletion(D), angiotensinogen (AGT)/M235T, angiotensin II type 1 receptor (AT1)/ A1166C, type 2 receptor (AT2)/C3123A, to examine the association between polymorphisms and the severity of lacunar infarction. AGT/M235T was significantly associated with the number of lacunae in the brain stem, the basal ganglia (P < .05), and whole brain (P < .005) regions. The AT1 polymorphism was also significantly associated with the number of lacunae in the basal ganglia and whole brain regions (P < .05), and with periventricular hyperintensity grade (P < .005) in the younger population. However, ACE and AT2 polymorphisms failed to show an association with either the number of lacunae or the PVH grade. We concluded that AGT and AT1 polymorphisms are independent genetic risk factors for lacunar infarction.
Aged↗
Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma.
BACKGROUND: In eukaryotic cells, nucleolar processing of preribosomal RNAs (prerRNAs) is assisted by a large number of small nucleolar RNAs (snoRNAs) that function in the 2'-O-methylation or the pseudouridylation of rRNAs. Most snoRNAs so far characterized are encoded and processed from introns of premRNAs. RESULTS: We found a novel intronic snoRNA gene, named U50HG, located on chromosome 6q15, at the breakpoint of chromosomal translocation t(3;6)(q27;q15). The U50HG gene is composed of six exons, whose spliced transcripts have little potential for coding a protein, and its introns produce both U50 and U50-like (U50') snoRNAs that are localized in nucleoli. It possesses an oligopyrimidine tract that is characteristic of the 5'-terminal oligopyrimidine (5'TOP) class of genes which have been shown to be coordinately regulated in response to cell growth. CONCLUSIONS: U50HG is a member of the nonprotein-coding multiple snoRNA host gene family, as well as of the 5'TOP gene family similar to UHG (U22 host gene), U17HG (U17 host gene), U19HG (U19 host gene) and gas5 (growth arrest-specific transcript 5 gene). It is novel to find that the snoRNA gene is located at the breakpoint of chromosomal translocation t(3;6)(q27;q15) involved in human B-cell lymphoma.
Alternative Splicing↗
Automated high throughput human CYP isoform activity assay using SPE-LC/MS method: application in CYP inhibition evaluation.
1. A high throughput screening (HTS) method for the evaluation of the seven major human hepatic CYP isoform activities was developed on a 96-well format, with automation. The method utilized pooled human liver microsomes and seven probe substrates, generic conditions for incubation, reaction termination and metabolite extraction with solid phase extraction (SPE) plates. Metabolites from the seven reactions were pooled and quantified using a generic liquid chromatography and tandem mass spectrometry (LCMS/MS) method. 2. The HTS method was validated based on Km values obtained, which were in agreement with literature data. 3. The isoform inhibition profiles of ketoconazole, quinidine, sulfaphenazole, tranylcypromine, alpha-naphthoflavone, and 4-methylpyrazole against CYPs 3A4, 2D6, 2C9, 2A6 land 2C19), 1A2 and 2E1, respectively, were obtained by this HTS method. Graphically obtained IC50 values are in agreement with literature reported values. 4. The HTS method represents a significant efficiency and selectivity improvement over traditional methods, and can be used for CYP inhibition assay and can be extended for liver activity profiling.
Automation↗
Characterization of a zebra mutant of rice with increased susceptibility to light stress.
The rice zebra mutant TCM248 is a single recessive mutant. This mutant develops transverse-striped leaves with green and white sectors under alternate light/dark growth conditions. Mutants that were grown under a higher light intensity during the light period showed a more intense striped phenotype. The white tissues contained abnormal chloroplasts with few internal membrane structures, while the green tissues in the mutants contained normal chloroplasts. The white tissue contained only trace amounts of Chls and carotenoids, and mRNA accumulation of nuclear genes encoding chloroplast proteins (rbcS, cab) was strongly suppressed compared to that in the wild type plants. A series of growth condition shift experiments demonstrated that the mutant displayed the striped phenotype only if it was exposed to the alternate light/dark growth conditions during a limited stage of early leaf development. These data suggest that the zebra gene is involved in the acquisition of photoprotective capacity of the plants and that this gene functions at an early stage of chloroplast differentiation.
Carotenoids↗
Effects of a selective inhibitor of Na+/Ca2+ exchange, KB-R7943, on reoxygenation-induced injuries in guinea pig papillary muscles.
The effects of a novel agent that is reported to selectively block Ca2+ influx by Na+/Ca2+ exchange (NCX), KB-R7943, on the reoxygenation-induced arrhythmias and the recovery of developed tension after reoxygenation, were investigated in guinea pig papillary muscles. KB-R7943 dose-dependently suppressed the contracture tension during low-sodium (21.9 mM) perfusion (23+/-8% of steady-state developed tension at 10 microM vs. 56+/-11% in control; n = 6, p<0.05), but did not change action potential and contractile parameters. During the reoxygenation period after 60-min substrate-free hypoxia, KB-R7943 (10 microM) significantly decreased the incidence of arrhythmias (44 vs. 100% in control; n = 9, p <0.05) and shortened the duration of arrhythmias (16+/-11 vs. 72+/-14 s; p<0.01). KB-R7943 (10 microM) significantly enhanced the recovery of developed tension after reoxygenation (83+/-4 vs. 69+/-3% in control; p<0.05). We conclude that KB-R7943 (10 microM) selectively inhibits the reverse mode of NCX, and that it attenuates reoxygenation-induced arrhythmic activity and prevents contractile dysfunction in guinea pig papillary muscles. These results suggest that Ca2+ influx by NCX may play a key role in reoxygenation injury.
Action Potentials↗
Assignment of rat estrogen sulfotransferase gene (Ste) to rat chromosome band 14p21.3-->p21.2.
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Animals↗
Assignment of desert hedgehog (DHH) to human chromosome bands 12q12-->q13.1 by in situ hybridization.
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Chromosomes, Human, Pair 12↗
Expression of hnRNP A2/B1 proteins in human cancer cell lines.
The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.
Heterogeneous-Nuclear Ribonucleoprotein Group A-B↗
[Chromophobe cell renal carcinoma: a case report].
Chromophobe cell renal carcinoma is an uncommon subtype of renal cell carcinoma and the number of cases studied is still limited in Japan. We here report a case of chromophobe cell renal carcinoma in a 41-year-old Mexican male. He visited our branch hospital with the symptom of upper abdominal pain. Ultrasound examination showed a left renal mass. He was admitted to our hospital for treatment of a left renal mass. Radiological examinations revealed a hypervascular tumor in the left kidney. Under the clinical diagnosis of possible renal cell carcinoma, left radical nephrectomy was performed. This tumor was diagnosed as chromophobe cell renal carcinoma with a microscopic examination of H & E stained specimens, histochemical staining using Hale's colloidal iron and an ultrastructural study.
Adult↗
Increased cytosolic Ca(2+) concentration in endothelial cells by calmodulin antagonists.
Many functions of endothelial cells are Ca(2+)/calmodulin dependent, whereas the role of calmodulin in the regulation of cytosolic Ca(2+) ([Ca(2+)](i)) remains largely unexplained. In the present study, effects of various calmodulin antagonists on [Ca(2+)](i) were investigated in cultured aortic endothelial cells loaded with the Ca(2+)-sensitive dye fura-2/AM, and were compared with those of calmodulin-dependent protein kinase II (CaM kinase II) inhibitors. The calmodulin antagonists W-7, calmidazolium and fendiline provoked dose-dependent increases in [Ca(2+)](i). However, the CaM kinase II inhibitors KN-93 and lavendustin C had no effect on [Ca(2+)](i). In the absence of extracellular Ca(2+), pretreatment of cells with bradykinin (BK) and thapsigargin completely prevented W-7-stimulated increase in [Ca(2+)](i). Alternatively, pretreatment with W-7 also completely blocked BK- and thapsigargin-stimulated increases in [Ca(2+)](i). The time course of the Ca(2+)-response in W-7 treated cells was identical to that in thapsigargin-treated cells, but not that in BK-stimulated cells, suggesting that calmodulin antagonists could share a common signaling pathway with thapsigargin to increase [Ca(2+)](i) in endothelial cells. These findings indicate that calmodulin is involved in the regulation of [Ca(2+)](i), and may play an important role in the uptake of Ca(2+) to intracellular stores.
Animals↗
Comparison of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine with gemcitabine in its antitumor activity.
The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D arabinofuranosyl)cytosine (4'-thio-FAC) was compared with that of 2'-deoxy-2',2'-difluorocytidine (gemcitabine). 4'-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4'-thio-FAC. However, 4'-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4'-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4'-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4'-thio-FAC is expected.
Animals↗