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Biomedical subjects

R Yoshimura

Publications and source records attributed to R Yoshimura.

At least 19 recordsLinked to original sources

A retrospective analysis of the use of brachytherapy in relation to early stage squamous cell carcinoma of the oropharynx and its relationship to second primary respiratory and upper digestive tract cancers.

The purpose of this study was to retrospectively evaluate brachytherapy for early stage squamous cell carcinoma of the oropharynx (SCO) in relation to second primary respiratory and upper digestive tract cancers (RUDT). Between 1976 and 2001, 111 previously untreated patients with stage I or II SCO were treated with Au-198 seed brachytherapy alone (36 cases) or Au-198 seed brachytherapy plus external irradiation (75 cases). Of the 111 patients, 28 patients had stage I disease and 83 patients had stage II disease. Each patient was evaluated for therapeutic efficacy, post-treatment quality of life (QOL) and a second cancer. The 5-year and 10-year cause-specific actuarial survival rates for stage I and II SCO were 87% and 86%, respectively. We found that the 5-year and 10-year survival rates for all SCOs combined with second primary RUDT cancers were 71% and 45%, respectively. 51 second primary RUDT cancers occurred successively in 41 patients following treatment for early stage oropharyngeal cancer and this was the sole prognostic factor by the multivariate analysis. Au-198 seed brachytherapy with or without ipsilateral external irradiation of up to 30 Gy was associated with fewer late complications in the oral cavity and salivary gland. We concluded that our treatment policy of brachytherapy with or without external irradiation for patients with early stage SCO was effective and acceptable from the standpoint of tumour control and post-treatment QOL.

Adult↗

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests.

RATIONALE: Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. OBJECTIVE: The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. SUBJECTS AND METHODS: Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 A: .M: . Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. RESULTS: As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. CONCLUSION: The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.

Administration, Oral↗

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Animals↗

Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.

Animals↗

High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.

Adult↗

Two cases of bipolar disorder successfully stabilized for five years with a low dose of risperidone and lithium.

Two patients with bipolar I disorder were successfully treated with a combination of risperidone and lithium in their acute manic states and maintenance periods. Although lithium monotherapy alone could not prevent relapse in these patients, the addition of a low dose of risperidone was well tolerated and effective for preventing recurrence over the long term. Plasma levels of HVA and MHPG were found to be elevated during the manic episodes and gradually decreased after the risperidone treatment. These results indicate that a low dose of risperidone to the lithium regimen was an effective and well tolerated means for treatment in the acute manic state and the later maintenance period in parallel with decreasing plasma levels of HVA and MHPG.

Adult↗

Expression of peroxisome proliferator-activated receptor-gamma in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Peroxisome proliferator-activated receptor (PPAR)-gamma is considered an important immunomodulatory factor as well as a fatty acid regulator. In this study, we researched the expression of PPAR-gamma in renal ischemia-reperfusion injury of the rat. The right kidney was harvested and left renal artery and vein were clamped under laparotomy. The kidney was reperfused after 90 minutes of ischemia, and rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. PPAR-gamma expression was analyzed by immunohistochemical staining using monoclonal antibody. In normal kidney, PPAR-gamma staining was weak on endothelial cells, including mesangial cells. On the other hand, PPAR-gamma staining was weak on interstitial cells and strong on collecting ducts of medulla. From 1.5 to 5 hours after reperfusion, PPAR-gamma staining was strong on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. Twelve hours after reperfusion, PPAR-gamma staining was weak on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. PPAR-gamma is induced on collecting ducts, interstitial cells, and endothelial cells in a rat model having renal ischemia-reperfusion injury.

Animals↗

Little effects of low dosage of levomepromazine on plasma risperidone levels.

In the present study, we investigated the effects of levomepromazine on plasma risperidone concentrations in a steady state. Twenty patients taking risperidone at a stable dose for more than 2 weeks who were considered to require levomepromazine coadministration were selected. The scores of excitement in BPRS significantly decreased 2 weeks after the coadministration of levomepromazine. Plasma risperidone concentrations and the ratio of risperidone and 9-hydroxyrisperidone (risperidone/9-hydroxyrisperidone) did not change between before and 2 weeks after the coadministration of levomepromazine. The extrapyramidal symptoms were not worsened by the coadministration of levomepromazine. These results suggest that a low dosage of levomepromazine, use as a sedative adjuvant to risperidone treatment, have no statistically significant effect on the trough plasma concentrations of risperidone.

Adolescent↗

The risk of radiation-induced cancer in patients with squamous cell carcinoma of the head and neck and its results of treatment.

The purpose of this study was to determine the incidence and the results of treatment of cancer induced by radiotherapy for early stage (stage I and II) squamous cell carcinoma of the head and neck (SCH). The clinical records of 355 patients with early stage malignant lymphoma of the head and neck region treated by radiotherapy were reviewed, and then the records of 1358 patients with early stage SCH (oral cavity, 956; larynx, 154; oropharynx, 110; maxillary sinus, 86; lip, 20; epipharynx, 17; hypopharynx, 15) who underwent radiotherapy were reviewed. The disease-specific 10-year survival rate of the patients with 355 malignant lymphoma was 61%, and 5 cases of radiation-induced cancer occurred more than 8 years after irradiation. The crude incidence of radiation-induced cancer in the malignant lymphoma patients was 1.4%, and the 10-year probability by the actuarial life table method was 0.8%. The 10-year survival rate of the early stage SCH patients was 71%. The crude incidence of a second cancer in a previously irradiated field after an 8-year latent period (SCI) in the SCH patients was 1.8% (25/1358), and the 10-year probability was 1.6%. 12 SCIs were treated by surgery and 8 of those 12 patients (67%) resulted in success, whereas treatment by radiation resulted in failure in every other case. The risk of SCIs in the SCH group was higher than in the early stage malignant lymphoma group, although the difference was not statistically significant. The possibility of radiation-induced cancer in SCH is small, and the advantage of radiation therapy compares favourably with the risks of other treatments.

Adolescent↗

A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic effects in human brain: findings from neuroendocrine challenge tests.

RATIONALE: Perospirone is a new antipsychotic drug in which dopamine D(2) antagonist and serotonin 5-HT(2) antagonist effects have been found in animal studies. It was developed by a Japanese pharmaceutical company and launched in 2001. Perospirone's receptor binding profile may resemble that of atypical antipsychotic drugs, but to date there has been no evidence relating to its receptor binding affinity in the human brain. OBJECTIVE: The purpose of this study was to investigate the receptor binding profile of perospirone via neuroendocrine challenge tests. METHODS: Twenty subjects (ten females and ten males) were tested on four occasions in a double-blind, cross-over design receiving: (a) placebo, (b) perospirone 4 mg, (c) paroxetine 20 mg, and (d) paroxetine 20 mg plus perospirone 4 mg, administered orally at 8.00 a.m. Plasma cortisol and prolactin levels were measured prior to administration and every hour for 6 h thereafter. In addition, psychological responses rated by visual analog scales and vital signs such as body temperature, pulse, and blood pressure were assessed in combination with blood sampling. RESULTS: Perospirone 4 mg increased prolactin levels significantly higher than placebo, whereas paroxetine 20 mg plus perospirone 4 mg significantly attenuated cortisol responses induced by paroxetine 20 mg. CONCLUSIONS: The present findings suggest that perospirone has the characteristics of both D(2) and 5-HT(2) antagonist in the human brain. Further PET studies in the human brain are required in order to directly investigate these effects.

Adult↗

Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils, the action mechanism of inflammatory cytokines. However, few reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of the rat. Male Lewis rats were used. The right kidney was harvested and the left renal artery and vein were clamped at 90 minutes of ischemic time. Rats were killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was studied by immunohistostaining. PPAR-gamma expression was observed only on mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after reperfusion, PPAR-gamma expression gradually became stronger on mesangial and endothelial cells. PPAR-gamma expression was most intense on mesangial cells and endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma was expressed in the rat model having renal I/R injury. Several hours after maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These results may indicate a relationship between PPAR-gamma expression and renal I/R injury.

Animals↗

The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils as well as the actions of inflammatory cytokines. However, few reports address cyclooxygenases (COXs) and lipoxygenases (LOXs). We researched the expression of COXs (COX-1 and COX-2) and LOXs (5-LOX and 12-LOX) in rat renal I/R injury. The right kidney of male Lewis rats was excised, and the left renal artery and vein clamped for a 90-minute ischemia time. Rats were humanely killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. COX and LOX expressions were studied using immunohistostaining. COX-2 and LOX expressions were observed only on endothelial cells of normal kidney. From 1.5 to 5 hours after reperfusion, COX-2 and LOXs expressions gradually intensified on endothelial cells. COX-2 and LOXs expression were most intense on endothelial cells at 5 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed. Thus, at 12 hours after reperfusion, COX-2 and LOXs expressions on endothelial cells became weaker. However, COX-1 expression was not different at every time after reperfusion. COX-2 and LOXs were expressed in a rat model showing renal I/R injury. Several hours after the maximum of COX-2 and LOXs expressions, the maximal renal I/R injury was observed. These results suggest a relationship between COX-2 and LOXs expressions and renal I/R injury.

Animals↗

Paroxetine as a 5-HT neuroendocrine probe.

RATIONALE: Acute administration of 40 mg paroxetine (a selective serotonin reuptake inhibitor) reportedly increases plasma cortisol in human subjects. This suggests that paroxetine may be a useful tool to probe brain serotonin function. OBJECTIVE: To investigate a dose-response relationship for paroxetine administration, and to determine whether a lower dose of paroxetine is sufficient to increase plasma ACTH and cortisol. METHODS: Twenty subjects were tested on three occasions in a double-blind, cross-over design receiving: (a) placebo, (b) paroxetine 20 mg and (c) paroxetine 40 mg administered orally at 8.00 a.m. In addition, five of the 20 subjects received paroxetine 20 mg plus cyproheptadine (a 5-HT(2) receptor antagonist) 4 mg and four subjects were given paroxetine 40 mg plus cyproheptadine 4 mg in an open manner. Plasma ACTH and cortisol levels were measured prior to administration and every hour for 6 h thereafter. RESULTS: Paroxetine, particularly 20 mg rather than 40 mg, significantly increased plasma ACTH and cortisol. Paroxetine 40 mg but not 20 mg caused significantly more nausea than the placebo. Cyproheptadine attenuated ACTH and cortisol responses to 20 mg but not to 40 mg paroxetine. CONCLUSIONS: Low-dose (20 mg) paroxetine has greater potential utility than larger doses as a neuroendocrine challenge test. The endocrine responses to paroxetine are probably mediated at least partially by 5-HT(2A/2C) receptors.

Adrenocorticotropic Hormone↗

Cyclooxygenase-1 and -2 in human testicular tumours.

In this study, we investigated the expression of cyclooxygenase (COX)-1 and -2 in human testicular cancer (TC) and normal testis (NT) tissues, as well as the effects of COX ligands on viability and proliferation. Tumour specimens were obtained from 72 patients with TC and 20 patients with NT. RT-PCR and immunohistochemical methods were used to determine COX expression. While COX expression was not noted in any of the NT tissues, a marked expression was observed in the TC samples. The extent and intensity of immunoreactive COX-1 and -2 polypeptides in the TC tissues was statistically greater than the expression in the NT tissues. The synthetic COX inhibitors inhibited the growth of the TC cells. Both COX-1 and COX-2 are induced in testicular cancer, and these results indicate that both COX-1 and COX-2 are essential for the growth of TC cells.

Adult↗

Time to recurrence after recovery from major depressive episodes and its predictors.

BACKGROUND: Depression is a remitting but recurring disease. However, there is a paucity of prospectively recorded data on the course of depression after recovery. METHOD: A multi-centre prospective serial follow-up study of an inception cohort of hitherto untreated unipolar major depression (N = 95) for 6 years. We report the time to recurrence after recovery from the index depressive episode and their predictors. RESULTS: The cumulative probability of remaining well without subthreshold symptoms was 57% (95% CI, 46 to 68%) at 1 year, 47% (95% CI, 36 to 58%) at 2 years and 35% (95% CI, 23 to 47%) at 5 years. The same without full relapse was 79% (95% CI, 70 to 88%) at 1 year, 70% (95% CI, 60 to 80%) at 2 years and 58% (95% CI, 46 to 70%) at 5 years. The median duration of well-interval from the end of the index episode to the beginning of the subthreshold episode was 19-0 months (95% CI, 2-4 to 35-7), and that to the end of the full episode was over 6 years. Residual symptoms at time of recovery predicted earlier recurrence. CONCLUSIONS: The median length of the well-interval was much longer than previously reported in studies employing similar definitions but dealing with a more severe spectrum of patients. However, the sobering fact remains that less than half of the patients can expect to remain virtually symptom-free for 2 years or more after recovery from the depressive episode.

Adolescent↗

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↗

MR detection of iliac bone marrow involvement by malignant lymphoma with various MR sequences including diffusion-weighted echo-planar imaging.

OBJECTIVE: To assess the diagnostic accuracy of MR imaging for detecting bone marrow infiltration by malignant lymphoma. PATIENTS AND DESIGN: Fifty-three patients with malignant lymphoma underwent MR imaging and bone marrow biopsy. In 80 iliac crests of the 53 patients (13 positive specimens in 9 patients and 67 negative specimens in 44 patients), biopsy results and the signal intensity characteristics were compared. MR sequences included T1-weighted SE, T2-weighted FSE with fat suppression, FSE STIR, and diffusion-weighted EPI with fat suppression at 1.5 T. RESULTS AND CONCLUSIONS: To detect lymphoma infiltration, T1-weighted SE had the highest sensitivity (92%) and diffusion-weighted EPI with fat suppression and FSE STIR had the highest specificity (92.5% and 92%, respectively). A combination of T1-weighted SE and FSE STIR yielded the highest sensitivity and specificity (85% and 97%, respectively). A combination of T1-weighted SE and FSE STIR sequences seems to be the current choice of imaging protocol for detecting bone marrow infiltration by malignant lymphoma.

Biopsy↗