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Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 109 records · Page 6Linked to original sources

Type A behavior is associated with an increased risk of left ventricular hypertrophy in male patients with essential hypertension.

OBJECTIVE: To determine whether type A behavior, which is associated with a risk of coronary heart disease, affects left ventricular hypertrophy in patients with essential hypertension. DESIGN: Cross-sectional study of 88 untreated patients with mild to moderate essential hypertension (33 men, mean +/- SEM age 54 +/- 1 years). METHODS: We measured the type A behavior score using a standardized questionnaire, left ventricular mass index using M-mode echocardiography and 24 h mean ambulatory blood pressure (recorded every 30 min). Beat-to-beat blood pressure was also measured using a Finapres device in patients at rest and during mental stress (counting backward) to determine the blood pressure response to stress. RESULTS: The left ventricular mass index was correlated with the type A behavior score (r = 0.214, P < 0.05), age (r = 0.266, P < 0.05), 24 h mean systolic and diastolic blood pressures (r = 0.391, P < 0.001, and r = 0.382, P < 0.001, respectively), systolic blood pressure both at rest and during stress (r = 0.255, P < 0.05, and r = 0.215, P < 0.05, respectively), and the variability of both systolic and diastolic blood pressures at rest (r = 0.253, P < 0.05, and r = 0.321, P < 0.01, respectively). Stepwise multiple linear regression analysis demonstrated that age was associated with an increase in the left ventricular mass index for both sexes (P = 0.004 for males, P = 0.003 for females). The type A behavior score predicted a greater increase in left ventricular mass index in men (P = 0.018) but not in women. The 24 h mean systolic blood pressure was associated with a greater increase in left ventricular mass index in women (P < 0.001) but not in men. CONCLUSION: Type A behavior is an independent risk factor for left ventricular hypertrophy in male patients with essential hypertension.

Blood Pressure↗

Expression of protein p27 is associated with progression and prognosis in laryngeal cancer.

OBJECTIVE: A cyclin-dependent kinase inhibitor, p27kip1, is recognized as a negative regulator of the cell cycle. To clarify whether immunohistochemical detection of p27 might provide prognostic information, we investigated the expression of p27 in laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: A retrospective study of patients was performed in 109 cases of laryngeal SCC. In addition, we investigated the expression of p53 and granulocyte colony-stimulating factor receptor (GCSF-R) to examine the prognostic significance of them in the same samples. METHODS: Immunohistochemical staining by specific monoclonal antibodies was performed using the avidin-biotin-peroxidase complex technique. RESULTS: Advanced tumor size and clinical stage and the occurrence of lymph node metastasis were associated with the absence of p27 expression, but not correlated with p53 expression and GCSF-R expression. The overall 5-year survival rate in the p27-positive group was significantly higher than that in the p27-negative group. In the Cox proportional hazard model, p27 was demonstrated to be the most powerful prognostic factor among gender, tumor size, lymph node metastasis, stage of disease, and p53 and GCSF-R expression. CONCLUSIONS: We concluded that assessment of p27 expression is useful as a prognostic factor for laryngeal SCC and of value in selecting patients with laryngeal SCC for aggressive therapy.

Adult↗

Molecular epidemiology of rabies in Thailand.

For the purpose of making clear the dynamics of rabies viruses that are prevalent among dogs in Asia, especially Thailand, nucleoprotein (N) genes of isolates derived from Thailand were partially sequenced, and a phylogenetic analysis was performed on the basis of the sequencing data. Firstly, all 27 isolates from Thailand belonged to one group that was distantly related to an isolate from China and was separated into at least six lineages. On the other hand, the isolate from Japan was related to viruses from the Arctic. Secondly, in order to analyze the diversity of the N gene more conveniently, restriction fragment length polymorphism (RFLP) analysis was performed on the N gene of 27 isolates from Thailand. The RFLP analysis could distinguish the lineages of each isolate, and the lineages of additional 34 isolates were deduced by this method. On examination of the geographical distribution of the six lineages, based on the results of phylogenetic and RFLP analyses, it was clear that infection cycles of the rabies virus in Thailand have tended to be maintained endemically.

Animals↗

Organ-dependent modifying effects of caffeine, and two naturally occurring antioxidants alpha-tocopherol and n-tritriacontane-16,18-dione, on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis in female F344 rats.

Modifying effects of caffeine, alpha-tocopherol, and n-tritriacontane-16,18-dione (TTAD) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis were investigated in female F344 rats. Groups of 20 rats, 6 weeks old, were given 0.02% PhIP (in diet) alone, or together with 0.1% caffeine (in drinking water), 0.5% alpha-tocopherol (in diet) or 0.1% TTAD (in diet) for up to 54 weeks. Groups of 10 females receiving basal diet or one of the test chemicals without PhIP supplementation were also maintained. The final combined incidences (adenomas plus adenocarcinomas) and multiplicity (No./rat) of mammary adenomas and adenocarcinomas were significantly lowered in the PhIP plus caffeine group (10%, 0.10) as compared to the PhIP alone value (40%, (1.50). Incidences of mammary tumors in the PhIP plus alpha-tocopherol or TTAD groups tended to be decreased while their multiplicities were significantly lowered. With regard to colon tumor development, on the other hand, rats given PhIP plus caffeine exhibited an elevated incidence (75% versus 15% in the control), whereas alpha-tocopherol and TTAD had no effect. Surprisingly, metabolic activation of PhIP was inhibited by addition of caffeine in an in vitro assay. The results indicate that caffeine exerts a potent chemopreventive action against PhIP-induced mammary carcinogenesis, but acts as a co-carcinogen for PhIP-induced colonic carcinogenesis.

Adenocarcinoma↗

Unidirectional olfactory hallucination associated with ipsilateral unruptured intracranial aneurysm.

PURPOSE: We describe a patient with complex partial seizure with unidirectional olfactory aura associated with ipsilateral unruptured aneurysm. METHODS AND RESULTS: The patient felt a sweet pleasant smell coming from behind her right side every time before the attack. Cranial magnetic resonance imaging (MRI) and three-dimensional computed tomography (CT) angiography revealed a large aneurysm at the bifurcation of the right middle cerebral artery and compression of the right orbitofrontal cortex. Small spikes were recorded from the right orbitofrontal and superior temporal gyri and from the uncus by the cortical electrodes during clipping of the aneurysm. CONCLUSIONS: The orbitofrontal cortex may have a function related to the ipsilateral directional olfactory sensation.

Electroencephalography↗

Diacylglycerol delays pH(i) overshoot after reperfusion and attenuates contracture in isolated, paced myocytes.

Although protein kinase C (PKC) plays a pivotal role in ischemic preconditioning, it is not clear what the end effector is that protects the myocardium. In isolated, paced (1.25 Hz, 36-37 degrees C) adult rat cardiomyocytes, the effects of PKC preactivation by diacylglycerol on cell motion, intracellular Ca(2+) concentration ([Ca(2+)](i); indo 1), and intracellular pH (pH(i); seminaphthorhodafluor-1) during simulated ischemia-reperfusion (I/R) were investigated. The degree of reperfusion-induced contracture was significantly attenuated in the myocytes pretreated with 10 microM 1, 2-dioctanoyl-sn-glycerol (DOG; n = 19) compared with the untreated myocytes (n = 23, P < 0.02). There were no differences in twitch amplitude, end-diastolic [Ca(2+)](i), or peak-systolic [Ca(2+)](i) during I/R between the DOG-pretreated and untreated myocytes. Although there were no differences in pH(i) during ischemia, the pH(i) overshoot during reperfusion was significantly delayed in the DOG-pretreated myocytes compared with the untreated myocytes (n = 17 for each, P < 0.01). Chelerythrine completely abolished the favorable effects of DOG on the reperfusion-induced contracture and the pH(i) overshoot. These data suggest that diacylglycerol attenuates I/R injury in isolated, paced cardiomyocytes, which may be related to the slower pH(i) overshoot during reperfusion.

Alkaloids↗

Dose-dependent induction of carcinomas and glutathione S-transferase placental form negative eosinophilic foci in the rat liver by di(2-ethylhexyl)phthalate after diethylnitrosamine initiation.

The dose-dependence of di(2-ethylhexyl)phthalate (DEHP) hepatocarcinogenicity was investigated in male F344 rats which were initially injected with diethylnitrosamine (200 mg/kg, i.p.) and subjected to partial hepatectomy at week 3. The animals were administered DEHP in the diet at concentrations of 30, 300, 3,000, or 12,000 ppm starting 2 weeks after the DEN injection for up to 46 weeks and killed at weeks 8, 24, 48 and 52. Additional groups were given clofibrate (3,000 ppm in diet) or basal diet instead of the DEHP diet. Incidences of hepatocellular carcinomas were 75% (9/12, P < 0.01) for 12,000 ppm, 10% (1/10) for 3,000 ppm, 7% (1/14) for 300 ppm, 0% (0/13) for 30 ppm, 15% (2/13) for clofibrate, and 8% (1/13) for the basal diet group at week 52, 4 weeks after cessation of chemical feeding. Development of glutathione S-transferase placental form (GST-P) positive foci was only slightly increased by clofibrate-administration at week 52 and consistently lower than the control level in the DEHP-treated groups after 24 weeks. In contrast, GST-P negative eosinophilic foci were dose-dependently increased in the more than 300 ppm DEHP and clofibrate treated groups. At the 30 ppm dose level, however, no morphological changes were apparent in the liver. Thus, the non-observed effect level regarding the promotional activity of hepatocarcinogenesis was demonstrated at 30 ppm, the effects being predictable on the basis of development of GST-P negative eosinophilic foci.

Adenoma, Liver Cell↗

[Validity analysis of Sapporo Medical University-sexual function questionnaire].

BACKGROUND: We evaluated the validity of the Sapporo Medical University-sexual function questionnaire, comparing the response to each question of patients having sexual dysfunction with those of normal volunteers as controls. PATIENTS AND METHODS: Responses from 335 patients with sexual dysfunction and 490 normal volunteers aged from 20 to 39 years old were evaluated. We compared mean scores of each question for patients having sexual dysfunction with those for controls. Discriminant analysis was used for evaluating which questions contributed more strongly to discriminating patients having the disease from controls. The analysis was also used for validating the questionnaire. RESULTS: Mean scores for patients with sexual dysfunction were significantly lower than those for controls in all questions. Nine of the 11 questions were statistically useful to discriminate these two groups with discriminant analysis. The analysis also revealed that questions about frequency of erection, rigidity of the erectile penis and duration of erection highly contributed to discriminate these two groups. The discriminant analysis achieved high sensitivity and specificity for classifying the groups. CONCLUSION: These results suggest that the use of the Sapporo Medical University-sexual function questionnaire is valid for discriminating patients with sexual dysfunction from subjects with normal sexual function.

Adult↗

[Clinical results of selective laser trabeculoplasty].

PURPOSE: Selective laser trabeculoplasty (SLT) is a new laser procedure using a frequency-doubled Q-switched Nd: YAG laser (wavelength: 532 mm). The laser parameters are set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or non-pigmented cells. We investigated the safety and efficacy of SLT in lowering intraocular pressure (IOP). SUBJECTS AND METHOD: Sixty-seven eyes of 67 patients with uncontrolled open angle glaucoma were treated with the Coherent Selecta 7000 (Coherent Inc., Palo Alto, CA). Nineteen of 67 patients had previously received argon laser trabeculoplasty (ALT). A total of approximately 60 non-overlapping spots were placed over 180 degrees of the TM ranging from 0.5 to 1.0 mJ per pulse. The maximum energy level at which no bubble formation was observed determined choice. RESULTS: The average preoperative IOP was 22.4 mmHg. Six months after the operation, mean IOP reduction was 4.4 mmHg, and mean outflow pressure (OP) reduction was 38.1%. One month after the operation 68.7% of patients responded to treatment with an OP reduction of at least 20% ("responders"). Transient IOP elevation of 5 mmHg or greater was seen in 25.4% of patients. The success rate at 6 months after operation was 64.6% for all patients (67 eyes) and 78.2% for the responders (46 eyes). An analysis using a Cox proportional hazard model showed that a low preoperative IOP was the significant determinant for success, and the hazard ratio for the IOP increase of 5 mmHg was 2.12. Other factors such as age, gender, past history of ALT, and goniopigment were not significantly related to success. CONCLUSION: SLT appears to be a safe and effective way to lower IOP.

Adult↗

Cytotoxic large T-cell lymphoma with fulminant clinical course, CD8+ and CD56- phenotype, and its relation to Epstein-Barr virus: a report of two cases.

Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.

Adult↗

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

Amides↗

Use of polyclonal antibodies against carcinogen-DNA adducts in analysis of carcinogenesis.

Polyclonal antibodies against 3,2'-dimethyl-4-aminobiphenyl (DMAB)- and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts were raised for their immunohistochemical demonstration in paraffin-embedded sections. Both carcinogens target multiorgans in rats with colon, mammary glands and prostate as common tumor sites. PhIP is particularly important because it is a cooked food-derived carcinogen to which man is exposed on a daily bases. Dose-related nuclear staining in various tissue of rats was observed 24 h after single applications of both carcinogens but no observable decrease in staining intensity was evident in most organs by 168 h. Staining specificity in terms of sites of tumor development was lacking. However, in target organs, semiquantitative data on adduct formation correlated with alteration in tumor response by modifying factor(s). Furthermore, human prostate tissue implanted into nude mice showed positive staining. Thus, the antibodies can be applied as tools to clarify tissue or cell-specific carcinogenesis, carcinogen-exposure levels and metabolic activation in various species, including man after tissue transplantation.

Aminobiphenyl Compounds↗

Atrial natriuretic peptide has different effects on contractility and intracellular pH in normal and hypertrophied myocytes from pressure-overloaded hearts.

BACKGROUND: Atrial natriuretic peptide (ANP) depresses contractility in left ventricular myocytes. Its expression is upregulated in pressure-overloaded hypertrophied hearts; however, the effects of ANP on contractility in hypertrophied myocytes are not known. Our aims were (1) to examine the cellular mechanisms of this depression in contractility in normal myocytes and (2) to test the hypothesis that the effects of ANP on contractility differ in hypertrophied myocytes from rats with ascending aortic stenosis. METHODS AND RESULTS: We measured the myocyte shortening as an index of contractility, [Ca2+]i with fluo 3, and pHi with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (n=26), ANP caused a concentration-dependent depression of contractility and reduction in pHi. In the presence of 10(-6) mol/L ANP, fractional cell shortening was 78+/-5% of baseline (P<0.05) and pHi was reduced by 0.16+/-0.04 U from baseline (P<0.01) without changes in [Ca2+]i. The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH4Cl pulse. The effects of ANP on contractility and pHi were prevented in the presence of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), which inhibits the Na+/H+ exchanger. In hypertrophied myocytes (n=23), ANP did not depress either myocyte contractility or pHi at concentrations of either 10(-8), 10(-7), or 10(-6) mol/L. ANP caused no change in pHi or the [Ca2+]i transient in hypertrophied myocytes. The cGMP level was increased and Na+/H+ exchanger mRNA levels were normal in left ventricles from aortic stenosis rats compared with controls. CONCLUSIONS: ANP directly depresses contractility in normal myocytes via intracellular acidification, which decreases myofilament [Ca2+]i sensitivity. In contrast, ANP causes no effects on contractility and pHi in hypertrophied myocytes, suggesting a suppression in the coupling of the ANP-cGMP intracellular signaling pathway to the Na+/H+ exchanger.

Animals↗

Immunohistochemical demonstration of carcinogen-DNA adducts in tissues of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): detection in paraffin-embedded sections and tissue distribution.

A polyclonal antibody against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts was raised for their immunohistochemical demonstration in paraffin-embedded sections. Specificity of this antibody was confirmed by competitive ELISA. Positive signals were immunohistochemically detected in acetone-fixed but not in formalin- or ethanol-fixed sections from F344 rats treated by gavage with a single dose of PhIP at 37.5-300 mg/kg and killed at 1, 2, and 7 days thereafter. Dose-dependent positive staining was observed in almost all organs of both sexes, including the colon, prostate, and mammary gland but largely independent of the tumor response. Repair activity, judged by disappearance of adducts with time, differed according to the organ or cell type. One exception was hepatocytes, the liver incidentally being a nontarget organ. The results suggest that the generated antibody is applicable for detection of cells targeted by PhIP in paraffin-embedded sections and also for the investigation of the mechanisms of PhIP-carcinogenesis.

Administration, Oral↗

Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules.

Receptor tyrosine phosphorylation is crucial for signal transduction by creating high affinity binding sites for Src homology 2 domain-containing molecules. By expressing the intracellular domain of Flt-1/vascular endothelial growth factor receptor-1 in the baculosystem, we identified two major tyrosine phosphorylation sites at Tyr-1213 and Tyr-1242 and two minor tyrosine phosphorylation sites at Tyr-1327 and Tyr-1333 in this receptor. This pattern of phosphorylation of Flt-1 was also detected in vascular endothelial growth factor-stimulated cells expressing intact Flt-1. In vitro protein binding studies using synthetic peptides and immunoblotting showed that phospholipase C-gamma binds to both Y(p)1213 and Y(p)1333, whereas Grb2 and SH2-containing tyrosine protein phosphatase (SHP-2) bind to Y(p)1213, and Nck and Crk bind to Y(p)1333 in a phosphotyrosine-dependent manner. In addition, unidentified proteins with molecular masses around 74 and 27 kDa bound to Y(p)1213 and another of 75 kDa bound to Y(p)1333 in a phosphotyrosine-dependent manner. SHP-2, phospholipase C-gamma, and Grb2 could also be shown to bind to the intact Flt-1 intracellular domain. These results indicate that a spectrum of already known as well as novel phosphotyrosine-binding molecules are involved in signal transduction by Flt-1.

3T3 Cells↗

Differential regulation of lipopolysaccharide (LPS) activation pathways in mouse macrophages by LPS-binding proteins.

LPS binding to its receptor(s) on macrophages induces the synthesis of inflammatory mediators involved in septic shock. While the signaling mechanism(s) remains to be fully defined, the human LPS-binding protein (LBP) is known to regulate responses to LPS by facilitating its binding to CD14 on human monocytes. The structurally related bactericidal permeability increasing protein (BPI) differs from LBP by inhibiting LPS-induced human monocyte activation. We have demonstrated that, unlike the human monocyte response to LPS, both LBP and BPI inhibited LPS-stimulated TNF-alpha production in mouse peritoneal macrophages. In contrast, LPS-dependent nitric oxide release was not affected by LBP. LPS induces the phosphorylation of a number of proteins in a dose and time-dependent manner, however, the pattern of LPS-induced phosphorylation was not reduced by either LBP or BPI under conditions that result in selective TNF-alpha inhibition. Further, activation of the transcription factor NF-kappaB in response to LPS was also not modified by either LBP or BPI. Finally, no differences were detected in TNF-alpha or inducible nitric oxide synthase mRNA accumulations induced by LPS in the presence or absence of either protein, whereas a slight decreased mRNA stability was observed in the group with LPS treatment. These results would suggest that many of the early signaling events contribute to LPS-induced macrophage signaling at a point preceding the divergence of pathways that differentially regulate TNF-alpha and NO production.

Acute-Phase Proteins↗