Clinical effect of Fasudil hydrochloride for cerebral vasospasm following subarachnoid hemorrhage.
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Biomedical subjects
T Hayakawa
Publications and source records attributed to T Hayakawa.
Antioxidant changes in the hypertrophied heart due to energy metabolic disorder.
Oxidative stress has been implicated in the pathogenesis of both heart hypertrophy and heart failure. Hypertrophied heart, in response to pressure overload, is associated with an increase in antioxidant capacity and a decrease in oxidative stress. However, in the hypertrophied heart due to energy metabolic disorder, antioxidant capacity has not been investigated. Antioxidant changes in juvenile visceral steatosis (JVS) mice, a model of heart hypertrophy due to disorder of fatty-acid oxidation, were examined at 4 weeks (developing hypertrophy stage) and 8 weeks of age (established hypertrophy stage). Superoxide dismutase activity in the JVS mice was higher than that in control mice at 4 weeks of age and was not different from that in the control mice at 8 weeks of age. Glutathione peroxidase activity in the JVS mice at 8 weeks of age was lower than that in the control mice. Catalase activity showed no significant differences between the control and the JVS mice. Lipid peroxidation in the JVS mice was significantly reduced at 4 weeks of age and increased toward control levels at 8 weeks of age. The levels of vitamin E in the heart were increased in the JVS mice at 8 weeks of age. To determine whether antioxidants affect the pathogenesis of hypertrophy in this model, long-term treatments of vitamin E and 2-mercaptopropionyl glycine were performed. Vitamin E treatment partially reduced the heart hypertrophy in these mice. The present study shows that heart hypertrophy in the JVS mice is accompanied with increased antioxidant capacity as indicated in other animal models of heart hypertrophy. The precise mechanism of heart hypertrophy in JVS mice is still unknown, but oxidative stress may play a role in the pathogenesis of heart hypertrophy.
Animals↗
Tandem repetition of baculovirus ie1 promoter results in upregulation of transcription.
In order to improve a virus-independent gene expression system in insect cells, the effect of the repetition of the promoter sequence of a baculovirus immediate early gene, BmNPV ie1, on the gene expression activity was examined. Tandem repetition of ie1 promoter resulted in about a 4-fold increase of the reporter gene expression activity. Primer extension analysis revealed that the repetition increased not only the amount of transcripts (4 to 5-times) but also the number of sites of transcription initiation (at least 3 extra initiation sites). A mutational experiment demonstrated the involvement of independent cis-acting elements in these two different promoter-enhancing effects.
Animals↗
Cloning and sequencing of a novel human gene that encodes a putative target protein of Nesh-SH3.
By using a conventional two-hybrid technique with an Src homology 3 (SH3) domain of Nesh as the bait protein, a novel full-length cDNA was isolated and sequenced from a human placenta cDNA library. This cDNA consists of 3023 bp and has a predicted open reading frame that encodes 486 amino acids. It possesses an SH3 binding motif, a nuclear targeting sequence, and no catalytic domain. Overall, it has no similarity to known molecules involved in a signaling cascade. Polymerase Chair reaction-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels localized the gene on human chromosome 3q12 near the marker D3S1271.
Amino Acid Sequence↗
Subnuclear distribution of afferents from the oral, pharyngeal and laryngeal regions in the nucleus tractus solitarii of the rat: a study using transganglionic transport of cholera toxin.
The central distributions of afferents from the oral cavity, the pharynx, the larynx and the esophagus to the nucleus tractus solitarii (NTS) were examined by using transganglionic anterograde transport of the cholera toxin B subunit (CT-b). Injections of CT-b into the body of the tongue and the hard palate resulted in heavy labeling of the lateral subnucleus (l-NTS) of the NTS rostral to the area postrema. Injection into the root of the tongue resulted in heavy labeling of the l-NTS, the dorsal half of the medial (m-NTS), the intermediate (im-NTS) and the interstitial (is-NTS) subnuclei rostral to the area postrema. Injections into the soft palate and the pharynx resulted in a similar labeling pattern in the is-NTS, im-NTS and m-NTS to that in the case of the root of the tongue, but this labeling extended rostrocaudally. Heavy labeling of the medial aspect of the l-NTS was found in the case of the soft palate, but the labeling was sparse in the case of the pharynx. Moderate labeling was also found in the commissural subnucleus (co-NTS). Injection into the larynx resulted in labeling of the is-NTS throughout the NTS, and of the rostral half of im-NTS. Injection into the esophagus resulted in heavy labeling of the central subnucleus, and moderate labeling of the co-NTS and the caudal half of im-NTS. A few but consistent anterogradely labeled terminals were found to appose retrogradely labeled small neurons in the rostral tip of the dorsal motor nucleus of vagus in the cases of injections into the root of the tongue, the soft palate, the pharynx, and the larynx. These results have characterized the viscerotopic representation of afferent projections from the oral and the cervical visceral organs to the subnuclei of the NTS.
Afferent Pathways↗
U73122 inhibits the dephosphorylation and translocation of cofilin in activated macrophage-like U937 cells.
Cofilin, an actin-binding protein, plays an important role in the migration, phagocytosis, and superoxide production of activated phagocytes through cytoskeletal reorganization. In unstimulated phagocytes, cofilin is a major phosphoprotein. However, upon activation, the phosphoprotein is dephosphorylated and translocated from cytosol to plasma membranes. Only the unphosphorylated form of cofilin is an active form that binds actin, whereas the regulatory mechanisms of cofilin have not been elucidated. We found that 1-[6-[[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), an inhibitor of phospholipase C (PLC), suppressed both opsonized zymosan (OZ)-induced dephosphorylation and translocation of cofilin in macrophage-like U937 cells at 4 microM concentration. OZ triggered an increase in inositol 1,4,5-trisphosphate (IP3), and U73122 inhibited it. 1-[6-[[17beta-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-pyrrodione-dione (U73343), which was employed as an inactive analogue, had no such inhibitory activities as did U73122. Furthermore, herbimycin A, an inhibitor of src-type tyrosine kinase, also inhibited OZ-triggered IP3 formation. These results suggest that the activity and localization of cofilin are regulated by PLC at the downstream of src-family tyrosine kinase.
Actin Depolymerizing Factors↗
Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum.
The mechanisms by which Dai-kenchu-to (TJ-100), a kampo medicine, enhances gastrointestinal motility was investigated using isolated guinea pig ileum. TJ-100 induced contractions accompanied by autonomous contraction at a concentration of more than 3 x 10(-4) g/ml in a dose-related manner. The TJ-100-induced ileal contraction was suppressed by atropine and tetrodotoxin, but not by hexamethonium. This effect was partially suppressed in the presence of high concentrations of ICS 205-930, a serotonin 4 (5-HT4) receptor antagonist. In addition, TJ-100 showed an acetylcholine (ACh)-releasing action in the smooth muscle tissues of ileum. These results suggest that contractile response induced by TJ-100 is partially mediated by ACh released from the cholinergic nerve endings and that 5-HT4 receptors would be involved in the effect of TJ-100.
Acetylcholine↗
Isolation and characterization of a Na+/H+ antiporter gene from the halophyte Atriplex gmelini.
With a homologous gene region we successfully isolated a Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini, and named it AgNHX1. The isolated cDNA is 2607 bp in length and contains one open reading frame, which comprises 555 amino acid residues with a predicted molecular mass of 61.9 kDa. The amino acid sequence of the AgNHX1 gene showed more than 75% identity with those of the previously isolated NHX1 genes from glycophytes, Arabidopsis thaliana and Oryza sativa. The migration pattern of AgNHX1 was shown to correlate with H+-pyrophosphatase and not with P-type H+-ATPase, suggesting the localization of AgNHX1 in a vacuolar membrane. Induction of the AgNHX1 gene was observed by salt stress at both mRNA and protein levels. The expression of the AgNHX1 gene in the yeast mutant, which lacks the vacuolar-type Na+/H+ antiporter gene (NHX1) and has poor viability under the high-salt conditions, showed partial complementation of the NHX1 functions. These results suggest the important role of the AgNHX1 products for salt tolerance.
Amino Acid Sequence↗
A seroepidemiological study of the risks of Q fever infection in Japanese veterinarians.
The causative agent of Q fever, a widespread zoonotic disease, is the bacteria Coxiella burnetii. Although cases of Q fever have been documented in countries throughout the world, the prevalence of the disease in Japan is not yet known. Q fever is a demonstrated occupational hazard to those employed in zoological professions, but the risk to Japanese veterinarians has not yet been quantified. In order to evaluate the risk to Japanese veterinarians, we performed a serological survey using serum samples from 267 veterinarians. Two control groups consisting of 352 medical workers and 2003 healthy blood donors were also evaluated. The antibody titers of the serum samples were measured by indirect immunofluorescence assay (IFA) using phase II C. burnetii Nine Mile strain as the antigen. The positive rate of IgG antibody was 13.5% in the veterinarians, which was higher than in the blood donors (3.6%, p < 0.001) and medical workers (5.1 %,p < 0.001). These findings suggest that Japanese veterinarians have a higher risk of infection by C. burnetii than other members of the Japanese population. An interesting finding of this study was that positive rates of IgG and IgM antibodies in the blood donor group were higher in younger individuals. The IgM antibody positive rate was the highest in females under 30 years old.
Antibodies, Bacterial↗
Protamine augments stretch induced calcium increase in vascular endothelium.
1. Human umbilical vein endothelial cells cultured on a transparent silicone chamber were subjected to a short stretch pulse (ca. 1 s, 5-25% stretch) of their substrate and following increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured by fluorescence intensity ratiometry using fura-2. 2. In response to mechanical stretch, the cells in HEPES buffered saline exhibited a Ca(2+) transient in a dose dependent way. The response was completely dependent on external Ca(2+) and inhibited by gadolinium (Gd(3+)), suggesting that it was mediated by the activation of a stretch activated cation channel (SACatC). 3. Interestingly, the stretch induced Ca(2+) transient was significantly augmented in the presence of basic polypeptide, protamine. This augmented Ca(2+) response was inhibited neither by Gd(3+) nor by the deprivation of external Ca(2+), indicating that the SACatC is not responsible for this phenomenon. 4. In contrast, this augmentation was inhibited by depletion of intracellular Ca(2+) stores with thapsigargin or by the pretreatment with phospholipase inhibitors such as U73122 and manoalide. 5. These results suggest the presence of a metabotropic mechanoreceptor distinct from the SACatC in vascular endothelium. This augmented [Ca(2+)](i) increase may contribute to the vasodilating response induced by protamine during heparin neutralization in cardiac surgery.
Calcium↗
Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system.
In this article, we evaluated the feasibility of the restricted replication-competent adenoviruses for treatment of anaplastic thyroid carcinomas (ATCs), which are very aggressive and difficult to treat. Because ATCs very often harbor p53 mutations, we used wt-p53 as a regulatory factor to restrict virus replication and cytopathic effect to p53-mutated cells. The recently reported "gene inactivation strategy" using p53-regulated Cre/loxP system was employed; this system consists of two recombinant adenoviruses. One has an expression unit of the synthetic p53 - responsive promoter and the Cre recombinase gene (Axyp53RECre), and another contains two expression units; the first consists of E1A gene flanked by a pair of loxP sites downstream of the constitutive CAG promoter and the second E1B19K gene under the control of the CMV promoter (AdCALE1AL). We expected that coinfection of these two adenoviruses into the cells with wt-p53 would lead to expression of the Cre, which excises E1A gene and switches off E1A expression resulting in no virus replication, whereas in the cells with mutant p53 E1A could be expressed that leads to virus replication and cell lysis. Our in vitro data demonstrate that although infection of AdCALE1AL alone led to E1A expression, viral replication and cytolysis in all the thyroid cells examined irrespective of their p53 status, the double infection did so in FRO cells (p53-null ATC) but not in FRO cells stably expressing wt-p53 and normal thyroid cells with wt-p53. These data indicate that our double infection method may have a potential for treatment of ATC and probably also other p53-defective cancer cells.
Adenovirus E1A Proteins↗
A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob.
The use of recombinant adenovirus (Ad) vectors containing genetically modified capsid proteins is an attractive strategy for achieving targeted gene transfer. The HI loop of the fiber knob is a promising candidate location for the incorporation of foreign ligands for achieving this goal. However, the method of constructing an Ad vector containing a foreign ligand in the HI loop of the fiber knob has proved difficult. In this study, we developed a simple system to construct fiber-modified vectors. To do this, a vector plasmid containing a complete E1/E3-deleted Ad type 5 genome and a unique Csp45I and/or ClaI site between positions 32679 and 32680 of the Ad genome (residues threonine-546 and proline-547 of the fiber protein) was constructed. Oligonucleotides corresponding to the Arg-Gly-Asp (RGD) or Asn-Gly-Arg (NGR)-containing peptide motif (as a model) and containing a Csp45I and/or ClaI recognition site, were ligated into the Csp45I and/or ClaI-digested plasmid. The foreign transgene expression cassette was inserted into the E1 deletion site of the vector plasmid and the fiber-mutant Ad vector was produced by transfection of the PacI-digested plasmid into 293 cells. The virus containing the RGD or NGR peptide on the fiber knob was able to infect human glioma cells, which do not express coxsackievirus and adenovirus receptor (CAR), one of the Ad virus receptors, about 100-1000 times more efficient than the virus containing wild-type fiber. This suggested that the mutant virus mediated CAR-independent cell entry pathway. The simplicity of this method allows not only for easy construction of fiber-mutant Ad vectors, but also for screening of the peptides that target the vector to the desired cells and tissues.
Adenoviridae↗
Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats.
1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.
Age Factors↗
Analysis of hepatocellular carcinoma tumor growth detected in sustained responders to interferon in patients with chronic hepatitis C.
BACKGROUND: By analyzing a tumor growth of hepatocellular carcinoma (HCC) detected in sustained responders (SR) to interferon (IFN) therapy for chronic hepatitis C, we sought to determine the duration of follow up in SR that would be sufficient to detect HCC. In addition, we sought to elucidate the presence of HCC, which truly developed after the eradication of hepatitis C virus (de novo HCC development). METHODS: Tumor volume doubling time (DT) was calculated in a total of 46 cases of HCC detected in SR after IFN therapy. Based on DT, the annual growth rate was estimated for each tumor. Survival was compared between patients with HCC < or = 30 mm and patients with HCC > 30 mm in diameter. RESULTS: Doubling time in SR was similar to the previously reported DT of HCC irrespective of IFN therapy. However, extensive DT was observed in three HCCs despite relatively poor differentiation, which may represent de novo HCC development. In the analysis of tumor growth, all HCCs grew to exceed 20 mm in estimated diameter between 6 months and 7 years after the end of IFN therapy. Better survival was observed in patients with HCC < or = 30 mm in diameter compared with patients with HCC > 30 mm (P = 0.0107). In surviving patients, recurrences of HCC were very infrequent. CONCLUSIONS: We may be able to detect most HCC in SR between 6 months and 7 years after IFN therapy. However, we cannot neglect the presence of de novo HCC development after the eradication of HCV, which makes it difficult to determine completely sufficient follow-up duration after IFN therapy in this population.
Antiviral Agents↗
Transperineal 12-core systematic biopsy in the detection of prostate cancer.
BACKGROUND: The present study was designed to determine the clinical value of transperineal 12-core systematic prostate biopsy guided by transrectal ultrasonography (TRUS) in the detection of prostate cancer. METHODS: A total of 679 consecutive patients underwent systematic prostate biopsies because of abnormal results on digital rectal examination and/or TRUS and/or an elevated serum prostate-specific antigen level. Systematic six- and 12-core biopsies were taken in 138 patients between April 1994 and February 1995 and in the remaining 541 between March 1995 and February 2000, respectively. Twelve-core biopsy included two samples from the lateral portion of the peripheral zone and four from the anterior portion of the transition zone in addition to the conventional six-core biopsy. RESULTS: In the series overall, systematic biopsy revealed 156 cases of prostate cancer (23.0%). The detection rate increased by 5.2%, although this was statistically not significant, from 18.8% (26/138) by six-core biopsy to 24.0% (130/541) by 12-core biopsy. Out of 130 patients in whom prostate cancer was detected by 12-core biopsy, it was supposed that conventional six-core biopsy would have missed 18 cases (13.8%). CONCLUSIONS: Systematic 12-core biopsy might improve the detection rate for prostate cancer. However, further studies are needed to determine its clinical value in the diagnosis of the disease.
Adult↗
Interactions among gastric somatostatin, interleukin-8 and mucosal inflammation in Helicobacter pylori-positive peptic ulcer patients.
BACKGROUND: To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin-8 (IL-8), histological inflammation through eradication therapy, and interactions among these parameters. METHODS: Twenty-eight H. pylori-positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and 13C-urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL-8 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Histology was assessed by the Sydney system. RESULTS: H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients' backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL-8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL-8. CONCLUSIONS: These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide-immune interactions in the gastric mucosa exist in H. pylori infection.
Adult↗
Infection of hepatitis A virus in Japanese haemophiliacs.
OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have been reported from many countries. The aim of this study was to determine the prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs. METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV infection. We also compared the rate of HAV infection with that of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus (HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb. Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV, HCV, and HGV were not statistically different between HAVAb positive and HAVAb negative haemophiliacs. We suggest that the use of clotting factor concentrates is closely associated with HAV infection, but HAV infection does not have an effect on clinical course. CONCLUSIONS: Administration of clotting factor concentrates may increase risk of HAV infection in haemophiliacs.
Adolescent↗
Relative importance of calcium-activated potassium channels in nipradilol-induced aortic relaxation in rats.
Nipradilol (CAS 81486-22-8), a vasodilatory beta-blocker, has been shown to dilate smaller vessels than nitroglycerin does, and the vasodilative effects of nipradilol have been reported to be less mediated by cyclic GMP (guanosine monophosphate) than those of nitroglycerin. To test the hypothesis that cyclic GMP-independent potassium channels have a larger role in nipradilol-induced aortic relaxation than cyclic GMP-dependent mechanisms, the effects of a potassium channel blocker, tetraethylammonium (TEA, CAS 56-34-8), and of a guanylate cyclase inhibitor, methylene blue (MB, CAS 61-73-4), on nipradilol-induced aortic relaxation were investigated and compared with those on nitroglycerin-induced aortic relaxation in isolated rat aortic rings. Relaxation response was expressed as percent relaxation, which is a percentage of the tension developed by 10(-7) mol/l norepinephrine. Nitroglycerin and nipradilol similarly relaxed the aortic ring in a concentration-dependent manner (10(-9)-10(-4) mol/l). In contrast, desnitronipradilol, a nipradilol analogue which has no nitroxy group, induced almost no aortic relaxation. TEA at 10(-3) mol/l, which is selective for calcium-activated potassium channels, inhibited the aortic relaxation induced by nipradilol (10(-5) mol/l) to a significantly greater extent than that induced by nitroglycerin (10(-5) mol/l) (% relaxation: 30.0 +/- 6.8 vs. 51.1 +/- 6.1%, p < 0.05). MB (10(-5) mol/l) suppressed the relaxation by nitroglycerin slightly but not significantly more than that by nipradilol. (% relaxation: 54.7 +/- 9.9 vs. 64.6 +/- 5.7%). The combination of TEA and MB almost completely eliminated the relaxation induced by nipradilol as well as by nitroglycerin. Thus, cyclic GMP-independent calcium activated potassium channels may be more involved in the aortic relaxation by nipradilol than that by nitroglycerin in rats.
Adrenergic beta-Antagonists↗