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Biomedical subjects

S Totsuka

Publications and source records attributed to S Totsuka.

At least 19 recordsLinked to original sources
PubMed1999

Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis.

BACKGROUND: Many studies have demonstrated in animal experiments that persistent inflammation may accelerate the development of carcinoma. In this article, the question of whether the persistent elevation of serum alanine aminotransferase (ALT) levels (which represents the inflammatory necrosis of hepatocytes) correlates with the development of hepatocellular carcinoma (HCC) was studied in patients with early stage hepatitis C virus (HCV)-associated cirrhosis. METHODS: Sixty-nine consecutive patients with biopsy proven HCV-associated cirrhosis (mostly Child's Stage A) who had been followed for >5 years for the development of HCC were studied. They were subdivided into 3 groups according to their serum ALT levels: Group A was comprised of 28 patients whose annual average serum ALT level was persistently high (>/= 80 IU) (high ALT group), Group B was comprised of 28 patients whose annual average serum ALT level was persistently low (< 80 IU) (low ALT group), and Group C was comprised of 13 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for > 5 years. RESULTS: In the high ALT group HCC developed in 71.4% of patients compared with 25.0% in the low ALT group over the observation period (P < 0.005). The 5-year rate of incidence of HCC in the high ALT group was as high as 53.6% compared with only 7.1% in the low ALT group (P < 0.001). The expected interval between the diagnosis of cirrhosis and the development of HCC was 6.0 +/- 0.7 years (mean +/- standard error) in the high ALT group and 12.7 +/- 1.2 years in the low ALT group (P < 0.001). CONCLUSIONS: The results of the current study demonstrated that the development of HCC was more rapid in the high ALT group with HCV-associated cirrhosis.

Aged↗
PubMed1998

Non-enzymatic, template-directed ligation of 2'-5' oligoribonucleotides. Joining of a template and a ligator strand.

Decauridylate containing exclusively a 2'-5' phospho-diester bond ([2'-5']U10) served as a template for the synthesis of oligoadenylates [oligo(A)s] from the 5'-phosphorimidazolide of 2'-5' diadenylate (ImpA-2'p5'A). Joining of [2'-5']U10and ImpA2'p5'A also took place in substantial amounts to yield long-chain oligoribonucleotides in the template-directed reaction. An unusual CD spectrum ascribed to helix formation between [2'-5']U10and [2'-5'](pA)2was observed under the same conditions as that of the template-directed reaction. The 3'-5' linked decauridylate ([3'-5']U10) also promoted the template-directed synthesis of oligo(A)s from ImpA2'p5'A, but more slowly compared with [2'-5']U10. The results indicate that short-chain RNA oligomers with a 2'-5' phosphodiester bond could lead to longer oligoribonucleotides by template-directed chain elongation.

Adenine Nucleotides↗
PubMed1998

Clinical evaluation of attention-deficit hyperactivity disorder by objective quantitative measures.

This study assessed the diagnostic potential of the actigraph, the Continuous Performance Test, and the Matching Familiar Figures Test in diagnosing attention-deficit hyperactivity disorder (ADHD). Twenty boys previously diagnosed with ADHD and 52 controls were examined. By these measures the boys with ADHD were differentiated from the controls with sensitivity and specificity above 75%. We were able to classify ADHD into eight subtypes by combining the scores of the actigraph and the CPT: "hyperactive-impulsive", "hyperactive-inattentive", "impulsive-inattentive", "hyperactive", "impulsive", "inattentive", "mixed", and "unspecified" type. These classifications may be useful in diagnosing ADHD.

Attention↗
PubMed1998

One-year prognosis of depressive illness in the elderly population in Japan.

A 1-year prospective study of 43 elderly depressed residents (13 men and 30 women) in Nagai City in Japan is described. An initial survey was carried out in 1993 to find depressed residents. The subjects of the survey were 2056 residents of 65 years of age and older. The Japanese version of the Geriatric Depression Scale (GDS) was employed as a screening tool in the first phase of the survey. In the second phase, screened subjects and control subjects were interviewed by psychiatrists using the Structured Interview for DSM-III-R (SCID). The diagnosis of depression was made by the psychiatrists on the basis of the results of the SCID. Forty-three persons were judged to be depressed. At follow-up, 10 were still depressed and 15 were well. Four were demented. Fourteen dropped out due to death, hospitalization, absence from home or refusal. The results showed that approximately half of the elderly depressed persons seemed to recover by the time of the 1-year follow-up. One-year prognosis of dysthymia was the worst. Some types of depression seemed to be a precursor for dementia. The concern is with how the findings may be used as an aid in understanding and planning community mental health services strategies. The results indicate that it is very important to pay close attention to patients with depressive illness who do not meet the criteria for major depression.

Aged↗
PubMed1998

Changes in regional brain activity in major depression after successful treatment with antidepressant drugs.

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state-related abnormality.

Adult↗
PubMed1997

Headache and stress in a group of nurses and government administrators in Japan.

We surveyed a group of 311 nurses and 283 mid-level government administrators in Yamagata Prefecture, Japan, to determine the prevalence and character of their headaches. We investigated the relationship of headaches to the subjects' stress, and their behavior and coping patterns. The questionnaire we administered explored background factors, as well as the state of the respondents' mental health, life events, work motivation, support system, and interpersonal relationships. The questionnaire was completed by 76.8% of nurses and 100% of administrators. Of these, 40.6% of nurses and 19.1% of the administrators reported recurrent headaches. Furthermore, the number of headache sufferers among the women administrators was significantly higher than in the men. The nurses and the administrators who reported headache scored significantly higher than the nonheadache groups on the questions measuring symptoms of burnout, General Health Questionnaire, and learned helplessness. The group of nurses with headache had higher scores for life events, decreased work motivation, and nervous behavior than the nonheadache group; the administrators with headache scored higher for daily hassles than those of the nonheadache groups. In this study of a Japanese sample, the character of the subjects' headache and the possible inducing factors are consistent with those reported in studies of Europeans and Americans using similar testing methods. However, the high prevalence of headache among nurses and women administrators seems to be related to psychological stress, particularly work stress, which may be characteristic in Japan.

Administrative Personnel↗
PubMed1997

Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy.

The relationship between the genetic polymorphism of S-mephenytoin 4'-hydroxylation catalyzed by CYP2C19 and the N-demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S-mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2-hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N-demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine.

Adult↗
PubMed1997

Stress and psychiatric disorders in local government officials in Japan, in relation to their employment level.

In order to explore an association between psychiatric disorders and employment level, 283 local government officials in Japan were asked to complete a questionnaire consisting of a series of psychometric scales. The Daily Hassles Scale, General Health Questionnaire and Burnout Scale were used to measure stress, psychiatric disorders and burnout syndrome, respectively. As a result of canonical correlation analysis, the first canonical correlation indicated that the higher the level of stress under poorer support systems, the greater the likelihood of burnout syndrome. The second canonical correlation indicated that the stronger the support system, the smaller the tendency toward depression. Officials in higher levels of employment were supported less and were more severely depressed than officials at lower levels of employment.

Adult↗
PubMed1996

Chronic dexamethasone administration decreases noradrenaline-stimulated, but not serotonin-stimulated, phosphoinositide metabolism in the rat brain.

The present study was undertaken to investigate the effects of chronic administration of dexamethasone on the noradrenaline- and serotonin-stimulated (5-HT-stimulated) phosphoinositide metabolism in hippocampus and frontal cortex of the rat brain. For determination of phosphoinositide metabolism, slices from selected regions of the rat brain (hippocampus or frontal cortex) were loaded with myo- [3H] inositol and stimulated with the agonists (noradrenaline or 5-HT) in the presence of LiCl (7.5 mM). Administration of dexamethasone (1 mg/kg/day) every 2nd day for 14 days markedly reduced the noradrenaline-stimulated phosphoinositide metabolism in the rat hippocampus (IP1: 60% of the control value). In the rat frontal cortex, the noradrenaline-stimulated phosphoinositide metabolism was less depressed by the chronic administration of dexamethasone (IP1: 84% of the control value). However, the chronic administration of dexamethasone did not affect the 5-HT-stimulated phosphoinositide metabolism in the rat brain. The binding characteristics of alpha 1 -adrenoceptors and 5-HT2A receptors were unaffected by the chronic treatment with dexamethasone. These results indicate that chronic administration of dexamethasone induces regional and neurotransmitter-specific changes of phosphoinositide metabolism in rat brain. The results suggest that the reduction of noradrenaline-stimulated phosphoinositide metabolism is due to modification of the intracellular signal transduction system.

Animals↗
PubMed1996

Steady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4'-hydroxylation status in Japanese depressive patients.

The steady-state plasma concentrations of imipramine and desipramine were measured after a more than 2-week treatment with 0.39 to 1.39 mg/kg/day of imipramine hydrochloride in 28 Japanese patients with major depression who had been phenotyped simultaneously with mephenytoin (for CYP2C19-related status) and with metoprolol (for CYP2D6-related status) before initiating the antidepressant therapy. Patients consisted of five poor metabolizers (PMs) of CYP2C19 with an extensive metabolizer (EM) phenotype of CYP2D6, whereas the remainder were EMs for both of the phenotypes. The mean respective concentrations (corrected by mg/kg) of imipramine and the sum of imipramine plus desipramine were 2.4 and 1.8 times greater in the CYP2C19-related PM than in the EM group, and these two variables correlated with the log10 urinary excretion of 4'-hydroxymephenytoin (rs = -0.73 and -0.64, both p < 0.01, respectively), but not with the metabolic ratio (MR) of metoprolol/alpha-hydroxymetoprolol. The mean N-demethylation index (MR of desipramine/imipramine) was significantly (p < 0.01) less in the PM than in the EM group. This index correlated with the 4'-hydroxylation of S-mephenytoin (rs = -0.51, p < 0.01), but not with the alpha-hydroxylation of metoprolol, implying that imipramine N-demethylation is under a coregulatory pharmacogenetic control of CYP2C19, but not of CYP2D6. In conclusion, by taking into account that the incidence of the PMs of CYP2C19 is much greater (18-23%) than that of CYP2D6 (< 1%) in Japanese population, the individually predetermined assessment of the CYP2C19-mediated metabolic capacity of imipramine would be more valuable than that of the CYP2D6-mediated capacity for forecasting the steady-state concentrations of imipramine and desipramine in Japanese depressive patients, thereby attaining an individualized optimization of imipramine therapy. Obviously, a pharmacodynamic assessment study conducted simultaneously with predetermined CYP2C19 status is required for supporting this contention.

Adult↗
PubMed1996

An epidemiological study of eating disorders in a northern area of Japan.

A total of 97 patients with eating disorders who visited the Department of Neuro-Psychiatry, Yamagata University Hospital, between 1978 and 1992 were studied. According to the diagnostic criteria of DSM-III-R, there were 48 cases of anorexia nervosa (AN). 38 cases of bulimia nervosa (BN) and 11 cases with both AN and BN. Both the number of patients and the ratio to all out-patients in each year increased four times during the period 1988-1992 compared to the previous period. With regard to their places of residence, the number of patients with AN and with BN from every district appeared to increase at almost the same rate, although the majority of the patients were from medium-sized cities. These findings may indicate that eating disorders are influenced by urbanization.

Adolescent↗
PubMed1995

Enhancement of 5-hydroxytryptamine-stimulated phosphoinositide hydrolysis in the rat cerebral cortex by repeated immobilization stress.

The present study was undertaken to investigate the influence of repeated immobilization stress on phosphoinositide hydrolysis induced by 5-hydroxytryptamine (5-HT) and noradrenaline in the rat cerebral cortex. Three groups of rats subjected to stress intervention were immobilized for 2 h per day for 3, 7, and 14 days. The stress intervention of any duration did not alter noradrenaline-stimulated phosphoinositide hydrolysis. The 3- and 7-day repeated immobilization enhanced 5-HT-stimulated phosphoinositide hydrolysis, whereas the characteristics of 5-HT2 receptor binding did not change. Chronic treatment with imipramine partially, but significantly, suppressed the increase in 5-HT-stimulated phosphoinositide hydrolysis, induced by the 3-day repeated immobilization. These findings imply that modulation of 5-HT-stimulated phosphoinositide hydrolysis occurs in stressful situations and that the therapeutic effects of tricyclic antidepressant drugs might be related to the modulation of phosphoinositide hydrolysis mediated by 5-HT receptors.

Animals↗
PubMed1992

Influence of stress and antidepressant treatment on 5-HT-stimulated phosphoinositide hydrolysis in rat brain.

The aim was to elucidate the role of 5-hydroxytryptamine (5-HT)-stimulated phosphoinositide (PI) metabolism in stress situations and in the behavioral improvement produced by chronic antidepressant treatment. Rat cerebral cortex slices were used for the purpose. Forced swimming for 15 min and longer induced changes in behavioral activities of rats associated with a significant reduction of 5-HT-stimulated PI metabolism, without any changes in density and affinity of 5-HT2 receptors. This suggests that modulation of the receptor coupling process but not of the 5-HT2 receptor binding characteristics may be responsible for the significant reduction of 5-HT-stimulated PI metabolism in stress situations. Chronic antidepressant treatment tended to reduce 5-HT-stimulated PI metabolism. This treatment improved significantly the behavioural activities during forces swimming, and prevented the forced swimming-induced reduction of 5-HT-stimulated PI metabolism. It is postulated that chronic antidepressant treatment may improve behavioral activities in relation to PI metabolism in stress situations.

Animals↗
PubMed1992

Influence of the acute stress on agonist-stimulated phosphoinositide hydrolysis in the rat cerebral cortex.

1. The present study was carried out in order to elucidate the influence of the acute stress on alpha 1-adrenergic, serotonin-2 (5-HT2) and muscarinic cholinergic (M-Ach) receptors-mediated phosphoinositide (PI) hydrolysis in rat cerebral cortex slices. 2. In rat cerebral cortex slices, noradrenaline (NA), serotonin (5-HT) and carbachol stimulated [3H]inositol-monophosphate (IP1) accumulation in a concentration-dependent manner. 3. The forced swimming test (FST) for 15 min induced a significant reduction of 5-HT-stimulated [3H]IP1 accumulation, but this stress situation did not produce a significant alteration of NA- and carbachol-stimulated [3H]IP1 accumulation. 4. The FST for 15 min did not affect the density and affinity of alpha 1-adrenergic, 5-HT2 and M-Ach receptors. 5. In a mild acute stress situation, the intracellular signal transduction mediated by 5-HT was promptly inhibited as compared to the signal transduction mediated by NA or carbachol. This inhibition may be induced by an acute uncoupling of 5-HT2 receptor-mediated intracellular signal transduction.

Adrenergic alpha-Agonists↗