Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 181 records · Page 10Linked to original sources

PubMed2001

Early peak creatine kinase activity is not always a marker of successful reperfusion with myocardial salvage in patients with reperfused anterior acute myocardial infarction.

BACKGROUND: Although early peak creatine kinase activity (peak CK) is considered a reliable marker of coronary reperfusion in patients with acute myocardial infarction (AMI), whether early peak CK indicates good myocardial salvage is unclear. Moreover, some patients have late peak CK despite successful reperfusion, and its clinical implication remains to be elucidated. METHODS AND RESULTS: We examined the association of the time to peak CK with predischarge left ventricular function in 124 patients with a first AMI who had successful reperfusion within 6 hours from symptom onset. Patients were classified according to the time from reperfusion to peak CK: group A, 61 patients with peak CK < 6 hours; group B, 42 with peak CK from 6 to 12 hours; and group C, 21 with peak CK > 12 hours. There were no differences among the 3 groups in age, sex, method of reperfusion, time from symptom onset to reperfusion, collateral circulation, or the extent of risk area estimated by number of leads with ST-segment elevation. Left ventricular ejection fraction measured by predischarge left ventriculography was lowest in group A, followed by group B, and highest in group C (median values, 43%, 52%, and 60%, P < .01). Left ventricular dysfunction (left ventricular ejection fraction < or = 40%) occurred in 26 (43%) patients in group A, 8 (19%) in group B, and none in group C (P < .01). CONCLUSIONS: We conclude that compared with early peak CK, late peak CK consistently reflects good myocardial salvage in patients with anterior AMI who had successful reperfusion within 6 hours from symptom onset.

Adult↗

PubMed2001

ST-segment depression in lead aVR predicts predischarge left ventricular dysfunction in patients with reperfused anterior acute myocardial infarction with anterolateral ST-segment elevation.

BACKGROUND: Patients with an anterolateral acute myocardial infarction (AMI) have a worse prognosis, and those with additional inferolateral wall involvement might be higher risk because of more extensive area at risk. Lead -aVR obtained by inversion of images in lead aVR has been reported to provide useful information for inferolateral lesion. METHODS: We examined the relation between ST-segment deviation in lead aVR on admission electrocardiogram (ECG) and left ventricular function in 105 patients with an anterolateral AMI undergoing successful reperfusion < or = 6 hours after onset. Patients were classified according to ST-segment deviation in lead aVR on admission ECG: group A, 23 patients with ST elevation of > or = 0.5 mm; group B, 47 patients without ST deviation; and group C, 35 patients with ST depression of > or = 0.5 mm. RESULTS: There were no differences among the 3 groups in age, sex, or site of the culprit lesion. In groups A, B, and C, the peak creatine kinase level was 3661 +/- 1428, 4440 +/- 1889, and 6959 +/- 2712 mU/mL, and the left ventricular ejection fraction (LVEF) measured by predischarge left ventriculography was 54% +/- 9%, 48% +/- 7%, and 37% +/- 9%, respectively(P < .01). During hospitalization, congestive heart failure occurred more frequently in group C than in groups A or B (P < .05). ST-segment depression in lead aVR had a higher predictive accuracy than other ECG findings in identifying patients with predischarge LVEF < or = 35%. CONCLUSIONS: We conclude that in patients with an anterolateral AMI, ST-segment depression in lead aVR on admission ECG is useful for predicting larger infarct and left ventricular dysfunction despite successful reperfusion.

Adult↗

PubMed2001

A radiologic analysis of dentigerous cysts and odontogenic keratocysts associated with a mandibular third molar.

OBJECTIVE: The purpose of this study was to discriminate radiographically between dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with a mandibular third molar. STUDY DESIGN: The material consisted of panoramic radiographs of dentigerous cysts (44 patients, 45 cysts) and odontogenic keratocysts (15 patients, 16 cysts), all of which were related to a mandibular third molar. The radiographic images were analyzed with reference to the patients' ages and symptoms. RESULTS: The mean age of patients in the OKC group was less than that of patients in the DC group. The mean area of the cysts in the OKC group was larger than that of those in the DC group. The mean distance from the second to the third molar in the DC group was greater than that in the OKC group. Although there was a significant correlation between the area and distance in the DC and OKC groups, the patients' ages did not significantly correlate to the area and distance of either cyst. CONCLUSIONS: The OKCs had a tendency toward rapid growth in the patient's youth but short movement of a third molar compared with the DCs. The DCs and OKCs do not appear to develop gradually from the period when follicles or dental lamina were formed but arise at various periods randomly.

Adolescent↗

PubMed2001

The role of nitric oxide in paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line.

Paraquat (PQ) is a well-known pneumotoxicant that exerts its toxic effect by elevating intracellular levels of superoxide. In addition, production of pro-inflammatory cytokines has possibly been linked to PQ-induced inflammatory processes through reactive oxygen species (ROSs) and nitric oxide (NO). However, the role of NO in PQ-induced cell injury has been controversial. To explore this problem, we examined the effect of NO on A549 cells by exposing them to the exogenous NO donor NOC18 or to cytokines; tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma, as well as PQ. Although the exogenous NO donor on its own had no effect on the release of lactate dehydrogenase (LDH), remarkable release was observed when the cells were exposed to high concentrations of NOC18 and PQ. This cellular damage caused by 1 mM NOC18 plus 0.2 mM PQ was ascertained by phase contrast microscopy. On the other hand, NO derived from 25-50 microM NOC18 added into the medium improved the MTT reduction activity of mitochondria, suggesting a beneficial effect of NO on the cells. Incubation of A549 cells with cytokines increased in inducible NO synthase (iNOS) expression and nitrite accumulation, resulting in LDH release. PQ further potentiated this release. The increase in nitrite levels could be completely prevented by NOS inhibitors, while the leakage of LDH was not attenuated by the inhibition of NO production with them. On the other hand, ROS scavenging enzymes, superoxide dismutase and catalase, inhibited the leakage of LDH, whereas they had no effect on the increase in the nitrite level. These results indicate that superoxide, not NO, played a key role in the cellular damage caused by PQ/cytokines. Our in vitro models demonstrate that NO has both beneficial and deleterious actions, depending on the concentrations produced and model system used.

Adenocarcinoma↗

PubMed2001

Virion-targeted viral inactivation: new therapy against viral infection.

BACKGROUND: Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. MATERIALS AND METHODS: To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. RESULTS: The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of scAb, scAbE-Vpr, or scAbE-WXXF, as determined by virion-associated reverse transcriptase assay and by immunoblot analysis, respectively. Because G418-selected HeLa clones carrying the expression plasmid for scAbE-WXXF were obtained much more frequently than those for scAbE-Vpr, scAbE-WXXF was inferred to be less toxic to cells than scAbE-Vpr. The result that scAbE-WXXF with viral incorporation achieved more than a 10-fold reduction in infectivity of the progeny virions than scAb without incorporation suggests that scAbE-WXXF is a potential antiviral molecule, inhibiting replication by neutralization of HIV IN activity both within cells and within virions. Moreover, it is nontoxic to human cells. We termed this gene therapy "virion-"targeted-viral inactivation" and these molecules "packageable antiviral therapeutics." CONCLUSION: This new gene therapy has the potential for wide application in many viral infectious diseases.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis.

To test the hypothesis that nucleotide excision repair (NER) plays a protective role in chemical carcinogenesis in internal organs, xeroderma pigmentosum group A gene-deficient (XPA(-/-)) mice, heterozygous (XPA(+/-)) and wild-type (XPA(+/+)) mice were orally administered 0.001% 4-nitroquinoline 1-oxide (4NQO) in their drinking water and compared. After 50 weeks of 4NQO exposure, tongue squamous cell carcinomas (SCCs) occurred in XPA(-/-) mice only, no tumors being observed in XPA(+/-) and XPA(+/+) animals. Of the XPA(-/-) mice 86% had tumors and 100% demonstrated multiple foci of dysplastic epithelium in the tongue. Accumulation of p53 protein was immunohistochemically detected in 56% of the SCCs. Mutational analysis of the p53 gene (exons 4-10) in carcinoma DNA revealed missense mutations in exons 5 and 9 in four of 20 samples. Our results clearly demonstrate that the NER gene XPA acts as a defensive factor against 4NQO-induced tongue carcinogenesis in vivo.

4-Nitroquinoline-1-oxide↗

PubMed2001

2'-O,4'-C-ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affinity for RNA.

Novel nucleosides, 2'-O,4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks for antisense oligonucleotides. The 2'-O,4'-C-ethylene linkage of these nucleosides, as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA), restricts the sugar puckering to the N-conformation. The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (delta Tm = degrees C/modification) and were approximately 400 and 80 times more nuclease-resistant than natural DNA and BNA/LNA, respectively. These results indicate that ENA have better antisense activity than BNA/LNA.

Base Sequence↗

PubMed2001

Production of a biologically active epidermal growth factor fusion protein with high collagen affinity.

Collagen is generally incapable of capturing polypeptides such as growth factors in a specific manner. In this study, we established a collagen-binding growth factor (FNCBD-EGF) consisting of epidermal growth factor (EGF) and the fibronectin collagen-binding domain. A typical yield of FNCBD-EGF was approximately 200 microg/ml culture in an Escherichia coli expression system. This fusion protein bound to gelatin and fibrillar collagen sponges, and the bound protein was not effectively eluted even with 2 M NaCl. In addition, FNCBD-EGF bound to type I, II, III, or IV collagen-coated plates, and the specificity of binding was confirmed by competitive inhibition using fibronectin. FNCBD-EGF substantially stimulated cell growth after binding to collagen-coated culture plates, whereas EGF had no effect, indicating that this fusion protein acted as a collagen-associated growth factor. In an animal model of impaired wound healing, FNCBD-EGF, but not EGF, was retained with collagen sponges at wound sites 4 d after implantation, and repair of epidermis was observed underneath the sponges. These results suggested that our fusion protein with high collagen affinity would be useful for wound healing.

Animals↗

PubMed2001

Demonstration of the pH sensitive binding of multivalent carbohydrate ligands to immobilized Shiga-like toxin 1 B subunits.

The cytotoxic effects of Shiga-like toxins from enterohemorrhagic Escherichia coli O157:H7 depend on the recognition of carbohydrate determinants by B subunits. As a specific carbohydrate ligand, globotriaosylceramide has been characterized. We developed an alternative binding assay using multivalent carbohydrate ligands. We prepared globotriose-conjugated poly-lysine, and measured their binding to immobilized recombinant B subunits by an ELISA format. The signals representing ligand binding were dependent on the amount of immobilized B subunits as well as on the concentration of the ligands. The ligand binding activity was lost in an acidic environment, in which changes in the local conformation of the B subunits have been reported. Furthermore, pH dependent dissociation of the ligands from the B subunits was observed. We also demonstrate that antiserum from mice immunized with the B subunits specifically interferes with ligand binding. This suggests further potential for an assay to screen for blocking antibodies that could inhibit toxin internalization into host cells.

Animals↗

PubMed2001

5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients.

Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.

Alleles↗

PubMed2001

Analysis of tumor necrosis factor-alpha gene promoter polymorphisms in anorexia nervosa.

Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.

Adult↗

PubMed2001

Delayed onset of systemic bacterial dissemination and subsequent death in mice injected intramuscularly with Streptococcus pyogenes strains.

Streptococcus pyogenes causes severe invasive diseases in humans, including necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome (STSS). We found that mice infected intramuscularly (i.m.) with S. pyogenes strains developed bacteremia and subsequent sudden death after at least 10 days of a convalescent period. Mostly, it occurred more than 21 days after muscle infection. We provisionally designate this phenomenon as "delayed death." Just after muscle infection, all the mice lost weight and activity, but recovered completely within 3 days. They had kept good activity and a fine coat of fur till one or two days before their death. Some of the dead mice were found to have soft-tissue necrosis. There was no correlation between the virulence leading to the delayed death and the severity of diseases from which strains were isolated. It was also found that the production of neither streptococcal pyrogenic exotoxin (SPE) A nor B correlated to the virulence leading to delayed death. The bacteria obtained from the organs of the mice with delayed death expressed capsule. We suggest that the mice with delayed onset of systemic bacterial dissemination and subsequent death after muscle infection with S. pyogenes are the animal models of STSS, because the pathophysiology is extremely similar to that of human STSS.

Animals↗

PubMed2001

Expression of Bub1 gene correlates with tumor proliferating activity in human gastric carcinomas.

Bub1 plays an important role at the spindle assembly checkpoint to prevent cell cycle progression following spindle damage. We examined the expression of human Bub1 mRNA in 20 gastric carcinoma tissues and corresponding nonneoplastic mucosas by reverse transcriptase-polymerase chain reaction and analyzed the relation with proliferative activity monitored by the expression of proliferating cell nuclear antigen (PCNA) on Western blotting as well as Ki-67 labeling index by immunohistochemistry. Increased expression of Bub1 mRNA was detected in 8 (40%) of the gastric carcinomas in comparison with their nonneoplastic counterparts, while 4 (20%) expressed Bub1 at lower levels. The expression of Bub1 mRNA was confirmed by in situ hybridization. The expression levels of Bub1 mRNA were well correlated with the levels of PCNA protein in 16 (80%) gastric carcinoma cases. The examination of Ki-67 labeling indices proved the close correlation between the expression levels of Bub1 and proliferating activity. These findings suggest that mRNA expression of human Bub1 gene is closely associated with the tumor-proliferating activity. Since genetic alterations of human Bub1 rarely occur in gastrointestinal cancers, the functional machinery of Bub1 to prevent cell cycle progression into anaphase might be well preserved in gastric carcinomas even with high proliferative activity.

Aged↗

PubMed2001

Potent and long-lasting action of lafutidine on the human histamine H(2) receptor.

BACKGROUND/AIM: Based on animal models, lafutidine, a novel histamine H(2) receptor (H(2)R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H(2)R-mediated effects. However, no reports have been published concerning its direct interaction with the human H(2)R. This study aims at characterizing its interaction with human H(2)R. METHODS: Chinese hamster ovary cell lines stably expressing human H(2)Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [(3)H]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 x 10(-7) M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [(3)H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the C(max) of lafutidine (10 mg p.o.) and above the C(max) of famotidine (20 mg p.o.). RESULTS: Lafutidine inhibited [(3)H]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. CONCLUSION: Lafutidine shows a potent and long-lasting antagonism on the human H(2)R.

Acetamides↗

PubMed2001

Successful left trisegmentectomy for polycystic liver disease accompanied by jaundice.

BACKGROUND: We report a case of severe polycystic liver disease (PLD) with jaundice in a 57-year-old woman who underwent successful left trisegmentectomy. METHOD: She was admitted for the first time in February 1992 to our hospital with a 7-year history of PLD, and became jaundiced in June 1995. Because normal liver parenchyma was confirmed mainly to the posterior segment, left trisegmentectomy was performed. RESULTS: No postoperative complication occurred. The serum bilirubin level decreased promptly after the operation, but postoperative endoscopic retrograde cholangiography showed that the root of the posterior hepatic duct remained thin. Thus, the elimination of jaundice was presumed to have been caused by a decrease of intra-abdominal and peripheral biliary pressure, since a large volume of tissue had been removed from the peritoneal cavity. She has since remained well without any symptoms. CONCLUSION: This procedure is useful for severe PLD, because it can be performed safely and the symptoms disappear dramatically. However, further follow-up is needed to determine the long-term effects of this procedure, because the remaining liver has shown some increase in size.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed2001

The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.

The lipid mediator prostaglandin E2 (PGE2) has diverse biological activity in a variety of tissues. Four different receptor subtypes (EP1-4) mediate these wide-ranging effects. The EP-receptor subtypes differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To identify the physiological roles for one of these receptors, the EP1 receptor, we generated EP1-deficient (EP1-/-) mice using homologous recombination in embryonic stem cells derived from the DBA/1lacJ strain of mice. The EP1-/- mice are healthy and fertile, without any overt physical defects. However, their pain-sensitivity responses, tested in two acute prostaglandin-dependent models, were reduced by approximately 50%. This reduction in the perception of pain was virtually identical to that achieved through pharmacological inhibition of prostaglandin synthesis in wild-type mice using a cyclooxygenase inhibitor. In addition, systolic blood pressure is significantly reduced in EP1 receptor-deficient mice and accompanied by increased renin-angiotensin activity, especially in males, suggesting a role for this receptor in cardiovascular homeostasis. Thus, the EP1 receptor for PGE2 plays a direct role in mediating algesia and in regulation of blood pressure.

Animals↗

PubMed2001

GH inhibits interferon-gamma-induced signal transducer and activator of transcription-1 activation and expression of the inducible isoform of nitric oxide synthase in INS-1 cells.

Interferon-gamma and TNFalpha synergistically induce the inducible isoform of nitric oxide synthase and elicit severe cytotoxicity in pancreatic beta-cells. We demonstrate here that GH, the well known beta-cell mitogen, inhibits nitric oxide production by reducing inducible nitric oxide synthase gene induction by the two cytokines and counteracts their cytotoxic effect in insulin-secreting INS-1 cells. To elucidate the underlying mechanism, we examined activation of the transcription factors implicated in the induction of inducible nitric oxide synthase, signal transducer and activator of transcription-1, and nuclear factor-kappa B. GH inhibited tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription-1 promoted by interferon-gamma, whereas nuclear factor-kappa B activation by TNFalpha was not affected by GH. GH was found to induce suppressor of cytokine signaling-1 and -3, both of which are able to inhibit interferon-gamma activation of signal transducer and activator of transcription-1, suggesting that they are likely to mediate the inhibitory action of GH. Finally, exposure of INS-1 cells to interferon-gamma resulted in the impairment of insulin secretion in response to glucose, which was restored by the addition of GH. These results indicate that GH counteracts the effect of interferon-gamma through the inhibition of signal transducer and activator of transcription-1. This action of GH may be sufficient to suppress the synergistic induction of inducible nitric oxide synthase by interferon-gamma and TNFalpha, thereby preventing the cytotoxicity to beta-cells.

Animals↗

PubMed2001

Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis.

Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.

Amino Acid Sequence↗