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Biomedical subjects

S Ikemoto

Publications and source records attributed to S Ikemoto.

At least 19 recordsLinked to original sources
PubMed2003

Thymidine phosphorylase levels as a prognostic factor in renal cell carcinoma.

OBJECTIVE: To investigate the relationship between thymidine phosphorylase (TP), a vascular growth factor, and established prognostic factors for renal cell carcinoma (RCC), e.g. histological grade or Tumour-Node-Metastasis (TNM) classification. PATIENTS AND METHODS: TP levels were measured in RCC tissue (tumour TP) and in adjacent non-neoplastic kidney tissue (normal tissue TP), using a sandwich-type enzyme-linked immunosorbent assay. The 59 patients, diagnosed with organ-confined RCC before surgery and who had undergone radical nephrectomy, were divided into two groups according to their prognosis after surgery. Group 1 (nine patients) had a poor prognosis and group 2 (50) had no evidence of disease within a 65-month follow-up. The relationships among TP level, TNM classification, histological subtypes, V factor and prognosis, and of tumour TP to normal tissue TP levels were investigated. Multiple regression analysis was used to determine the importance of factors associated with increased TP levels. RESULTS: Normal tissue TP levels correlated with histological grade (r = 0.31, P < 0.01); in patients with venous invasion or with a poor prognosis, the levels were significantly higher than in those without (P < 0.05 and < 0.001, respectively). The normal tissue TP levels were also significantly higher in the non-clear cell than in the clear cell subtype. Multiple regression analysis showed that the independent factor associated with elevated normal tissue TP levels was histological grade (R2 = 0.189, P < 0.01). There was no correlation between tumour TP and other factors. CONCLUSION: Normal tissue TP levels in localized hypervascular RCC were associated with histological grade. These data suggest that normal tissue TP levels could be a prognostic factor.

Adult↗
PubMed2002

Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma.

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and 0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor alpha level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor alpha may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.

Biomarkers, Tumor↗
PubMed2002

Ventral striatal anatomy of locomotor activity induced by cocaine, D-amphetamine, dopamine and D1/D2 agonists.

The ventral striatum appears to play a critical role in mediating motoric effects (i.e. ambulatory activity and rearing) of psychostimulants such as cocaine. We evaluated whether sub-regions of the ventral striatum play differential roles in locomotion and rearing induced by various dopaminergic drugs. Injections of D-amphetamine and dopamine stimulated locomotion and rearing with a similar potency at each of the sub-regions: the core, medial shell or medial tubercle. However, injections of mixtures of the D(1)- and D(2)-type agonists SKF 38393 and quinpirole or cocaine into the medial olfactory tubercle or the medial shell of the nucleus accumbens induced marked locomotion and rearing, while these injections into the core induced little or no locomotion or rearing. Furthermore, cocaine injections into the lateral or posterior tubercle produced marginal locomotion and rearing, while cocaine injections into regions just dorsal to these tubercle sites, the lateral portion of the shell or the ventral pallidum, did not produce any stimulating effect. We conclude that dopaminergic compounds induce vigorous locomotion and rearing in both core and shell; the relative roles of the core and shell differ depending on chemical compounds. Similar to the nucleus accumbens, the olfactory tubercle, particularly the medial portion, also mediates these behaviors induced by dopaminergic compounds. The medial ventral striatum (i.e. the medial tubercle and medial shell) plays a more important role in cocaine-induced locomotion and rearing than the lateral ventral striatum (i.e. the core, lateral shell and lateral tubercle). Moreover, the differential effects of cocaine between the medial and lateral portions of the shell on locomotion and rearing suggest more than two functional units (the core vs. the shell) within the accumbens.

Animals↗
PubMed2002

Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states in female subjects: susceptibility to psychotic states and implications for relapse of schizophrenia.

In this study, we examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). The subjects were 81 physically healthy females. Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had undergone frightening and stressful experiences during previous MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers, the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while the 11 with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization, and also noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model psychosis is a potential tool for validating basic neurobiological concepts thought to be related to the schizophrenia. A better understanding of the neurobiological mechanisms of susceptibility to recurrence could provide useful information in the development of strategies for preventing relapse.

Adult↗
PubMed2001

Susceptibility to subsequent episodes of spontaneous recurrence of methamphetamine psychosis.

We examine susceptibility to subsequent spontaneous recurrences of methamphetamine psychosis (i.e. flashbacks) in 11 flashbackers with a single episode and in nine flashbackers with subsequent episodes. All had undergone frightening stressful experiences during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks, the nine flashbackers with subsequent episodes had more markedly increased norepinephrine levels, with slightly increased 3-methoxytyramine levels. The duration of imprisonment in this subgroup approached significantly long levels than in the 11 flashbackers with a single episode. Robust noradrenergic hyperactivity with slightly increased dopamine release may therefore predict subsequent flashbacks. Longer exposure to distressing situations may also contribute to robust noradrenergic hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

A head-attachable device for injecting nanoliter volumes of drug solutions into brain sites of freely moving rats.

We describe a head-mounted micropump-injection system designed for the infusion of nanoliter volumes of drug solutions into discrete brain regions of the freely moving rats. Using a miniature step motor, the micropump-injection system can be readily constructed from commercially available supplies. In calibrating the micropump-injection system, we found that it will deliver a reliable volume of 50 nl per infusion over a 1-h period, with an infusion given every 1 min. From in vivo testing, we also found that rats readily self-administered up to 100 infusions of D-amphetamine into the nucleus accumbens at regular intervals, suggesting that this system can deliver constant volumes of infusions over time in freely moving rats. It (1) attaches easily to an implanted guide, (2) is compact and durable, (3) weighs only 10 g, and (4) is well tolerated with no apparent discomfort to the animal. This system overcomes some of the weaknesses of currently used intracranial self-administration systems.

Amphetamine↗
PubMed2001

Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.

Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue.

Age Factors↗
PubMed2001

Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz ultrasonic vocalizations in rats.

The authors have hypothesized that, in adult rats, 50-kHz ultrasonic vocalizations (USVs) index a state characterized by high arousal and expectations of reward. This study was conducted to investigate whether dopamine agonism of the nucleus accumbens (NAcc) could evoke such an appetitive state, by examining the effects of NAcc amphetamine (AMPH) microinjections on USVs. Intra-NAcc AMPH injections (0.3, 1.0, 3.0, 10.0 microg unilaterally) produced robust, dose-dependent increases in 50-kHz USVs, which could not be accounted for by concomitant increases in locomotor activity (LA). However, AMPH injections into dorsal control caudate putamen sites produced a modest, dose-dependent increase in LA without significant increases in 50-kHz USVs. These findings indicate that NAcc AMPH microinjections selectively evoke 50-kHz USVs in rats, supporting the notion that dopamine elevations in the NAcc may unconditionally elicit a state of reward anticipation.

Amphetamine↗
PubMed2001

Are tobacco use and urine pH indicated as risk factors for bladder carcinoma?

BACKGROUND: Many case-control and cohort studies have shown a positive relationship between bladder carcinoma and tobacco use. Recently, urine pH has been reported to influence aromatic amine carcinogenesis, which have been implicated as potent carcinogens in bladder carcinoma patients. Herein the correlation between bladder carcinoma, tobacco use and urine pH is reported. METHOD: One hundred and forty-one patients with bladder carcinoma and 128 patients with benign prostatic hyperplasia or urolithiasis as controls were selected. All patients were admitted to Osaka City University Hospital for the purpose of surgical treatment. Urine pH was checked by a test tape. RESULTS: Of the patients with bladder carcinoma, 106 were smokers and 35 were non-smokers. In contrast, the number of smokers in the control group was 76 and that of non-smokers was 52. The odds ratio in the bladder carcinoma group calculated for the smoker patients was 2.07, showing a significant correlation between bladder carcinoma and tobacco use. Regarding urine pH, acidic urine was found in 126 patients in the bladder carcinoma group and in 116 patients in the control group. The odds ratio in the bladder carcinoma group for acidic urine was 0.87, showing no significant relationship between bladder carcinoma and urine pH. CONCLUSION: The study found a positive relationship between bladder carcinoma and tobacco use; however, it could not establish a clear relationship between bladder carcinoma and urine pH, even in the smoker group.

Aged↗
PubMed2001

Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy--a randomized controlled trial.

Monotherapy with sulfonylurea may result in the exhaustion of pancreatic beta-cell function, fat accumulation, and dyslipidemia. We examined the possibility of dose reduction by administering sulfonylurea together with troglitazone, and investigated changes in insulin secretion and fat deposition. Seventy-eight patients with type 2 diabetes adequately controlled with glibenclamide were randomly allocated to a troglitazone (400 mg/d)-added group (n = 40) or a control group without placebo (n = 38) and monitored for 24 weeks. The daily dose of glibenclamide was adjusted to maintain stable HbA(1c) levels. Fat accumulation to the liver and thigh muscle were measured in mean Hounsfield units determined on computed tomography (CT) scan. Visceral fat accumulation (V), subcutaneous fat accumulation (S), and the V/S ratio were also determined by CT scan. The daily dose of glibenclamide and serum fasting insulin level in the troglitazone-added group significantly decreased (from 4.05 +/- 2.50 mg/d to 1.84 +/- 1.65 mg/d and from 8.47 +/- 4.62 microU/mL to 6.49 +/- 3.28 microU/mL, respectively) during the observation period compared with the control group (P < .01 and P < .01, respectively). Serum triglyceride and homeostasis model insulin resistance index (HOMA-R) in the troglitazone-added group decreased significantly in comparison to the control group (P < .05 and P < .01, respectively). The mean Hounsfield units of liver significantly decreased in the control group compared with the troglitazone-added group (P < .05). Visceral fat area and the V/S ratio significantly increased in the control group compared with the troglitazone-added group (P < .01 and P < .01, respectively). Glibenclamide monotherapy resulted in fat accumulation accompanied by dyslipidemia. An alternate conclusion is that troglitazone reversed type 2 diabetes (not sulfonylurea)-associated fat accumulation. The addition of troglitazone decreased daily doses of glibenclamide, preserved fasting insulin secretion, improved fat accumulation in liver, and prevented dyslipidemia.

Adipose Tissue↗
PubMed2001

Angiotensin converting enzyme genetic polymorphism is not associated with hypertension in a cross-sectional sample of a Japanese population: the Shibata Study.

BACKGROUND: The studies on the association of deletion/ insertion (D/I) polymorphism of angiotensin converting enzyme (ACE) gene with blood pressure and hypertension reported contradictory results. Because there was no population-based study in Japan, we examine the hypothesized association in a cross-sectional sample of a Japanese cohort. METHODS AND RESULTS: The blood pressure of 464 men and 876 women aged 40-80 years was measured, and their DNA was analyzed for ACE D/I genotypes. The prevalence of the D allele was 38.7 and 39.2% in men and women, respectively (overall 39%). There was a tendency for higher covariate (age, body mass index, albuminuria, hematocrit, alcohol consumption, smoking, diabetes mellitus, ischemic heart disease and antihypertensive medication) adjusted mean levels of diastolic blood pressure for the DD genotype in men but not in women. However, this tendency disappeared after dichotomization of blood pressure into diagnostic categories (normotension and hypertension). Results did not differ when the subjects were divided into two age groups (< or = 59 and > or = 60 years). Covariate-adjusted odds ratios for hypertension for presence of the D allele were close to the null value of one. ACE genetic variation accounted for only 0.1 and 0.7% of the inter-individual variation in systolic and diastolic blood pressure in men. These estimates were 0.2 and 0.1%, respectively, in women. CONCLUSION: Although there is a tendency of higher diastolic blood pressure in men with DD genotypes, there is no convincing evidence that ACE genotypes are associated with hypertension in this Japanese population.

Adult↗
PubMed2001

Molecular cloning of a cDNA coding for feline liver xanthine dehydrogenase.

A cDNA coding for feline liver xanthine dehydrogenase (XDH, EC 1.1.204) was amplified by RT-PCR and cloned for determining the sequence. The clones contained an open reading frame of 4002 base pairs encoding 1333 amino acid residues. The calculated molecular weight and isoelectric point were approximately 146 kDa and 7.0. Comparison of the deduced amino acid sequences indicated remarkable high homology, i.e., the amino acid residues of feline XDH shared approximately 90%, 87%, 87% and 86% identity with those of human, bovine, rat and mouse, respectively. The anino acid sequences of two putative iron-sulfur centers, one NAD binding site and one molybdenum binding site were well conserved among mammalian animals.

Amino Acid Sequence↗
PubMed2001

Microsatellite polymorphism in intron 14 of the canine BRCA1 gene.

Microsatellite polymorphism due to differences in CT dinucleotide repeats was demonstrated in intron 14 of the canine BRCA1 gene. Genotype analysis of 103 unrelated dogs from 30 different breeds detected the presence of five alleles, including 10 of the expected 15 genotypes. Gene frequencies were biased and all alleles with the exception of one were below 0.1. This polymorphism, which occurs at the intron of canine BRCA1 should prove to be a useful marker for detecting the loss of heterozygosity (LOH). One of the more notable findings of the present study was the detection of homozygotes of rare alleles. This finding identified an accumulation of rare alleles in specific canine breeds and demonstrated the usefulness of this characteristic for the biological study of dog evolution.

Animals↗
PubMed2001

[Apolipoprotein D].

Explore the source record for details and available documents.

Alzheimer Disease↗
PubMed2000

Stress induced spontaneous recurrence of methamphetamine psychosis: the relation between stressful experiences and sensitivity to stress.

We examined increased sensitivity to stress in relation to spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). Plasma monoamine metabolite levels were assayed in: 26 flashbackers, of whom 11 were on neuroleptics before and during the study, and the other 15 received neuroleptics in the course of the study; 18 non-flashbackers with a history of MAP psychosis; eight subjects with persistent MAP psychosis; and 23 MAP user and 11 non-user controls. The 26 flashbackers had experienced stressful events and/or MAP-induced fear-related psychotic symptoms during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks plasma norepinephrine levels increased markedly; among the flashbackers, those with a history of stressful events, whether or not they had experienced fear-related symptoms, showed a further increase in 3-methoxytyramine levels. Stressful experiences, together with MAP use, may therefore induce sensitization to stress associated with noradrenergic hyperactivity, involving increased dopamine release, and so triggering flashbacks.

Adult↗
PubMed2000

Intra-medial prefrontal cortex injections of scopolamine increase instrumental responses for cocaine: an intravenous self-administration study in rats.

The present experiments examined the effects of muscarinic cholinergic receptor blockade in the nucleus accumbens (NAC) and medial prefrontal cortex (MPC) on intravenous cocaine self-administration. Adult male Sprague-Dawley rats were implanted with chronic indwelling jugular catheters and guide cannulae stereotaxically aimed at the NAC or MPC. The rats were then given the opportunity to intravenously self-administer cocaine (0.8 mg/kg/infusion) during daily 2-h sessions. Intra-NAC microinjections of methyl-scopolamine (2, 4, 8, 16, and 32 microg/side) or vehicle did not affect either the number of lever presses made or infusions delivered. On the other hand, intra-MPC injections of scopolamine significantly increased responding, although there was only a trend for an increase in the number of cocaine infusions. The effects of intra-MPC injections of scopolamine (8 and 16 microg/side) on locomotor activity were also evaluated. Intra-MPC injections of scopolamine (16 microg/side) produced significant increases in locomotor activity. However, these same microinjections decreased locomotor activity when the animals also received cocaine (15 mg/kg, i.p.). These results suggest that cholinergic neurotransmission at muscarinic receptors in the MPC is involved in regulating cocaine-maintained responding.

Animals↗
PubMed2000

Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines.

OBJECTIVES: To investigate the antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on human bladder cancer cell lines (KU-1 and EJ-1) and a murine bladder cancer cell line (MBT-2). METHODS: Bladder cancer cells were incubated with various concentrations of the agents. Antiproliferative activity against the bladder cancer cell lines was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diplenyl tetrazolium bromide assay. In an in vivo experiment, the mice were subcutaneously injected with MBT-2 cells, and Scutellariae radix was orally administered at a dose of 2 or 10 mg per mouse one time daily for 10 days from day 11 to day 20. RESULTS: All the drugs inhibited cell proliferation in a dose-dependent manner, but baicalin exhibited the greatest antiproliferative activity. The concentration of baicalin necessary to obtain 50% inhibition was 3.4 microg/mL for KU-1, 4.4 microg/mL for EJ-1, and 0.93 microg/mL for MBT-2. For KU-1 and MBT-2, the percentage of cell survival significantly decreased (P <0.05) at a baicalin concentration of 1 microg/mL. In an in vivo experiment, antitumor effects of Scutellariae radix on C3H/HeN mice implanted with MBT-2 were investigated. All the control mice showed a progressive increase in tumor volume, reaching 2.81 +/- 0.18 cm(3) on day 20 and 5.36 +/- 0.44 cm(3) on day 25. However, when Scutellariae radix was orally administered at a dose of 10 mg per mouse one time daily for 10 days from day 11 to day 20, the tumor volume was 1.99 +/- 0.19 cm(3) on day 20 and 3.86 +/- 0.26 cm(3) on day 25, a significant inhibition of tumor growth (P <0.05). Conclusions. These results suggest that Chinese herbal medicines may become an attractive and promising treatment for bladder cancer.

Animals↗