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Biomedical subjects

R Yoshimura

Publications and source records attributed to R Yoshimura.

At least 73 records · Page 4Linked to original sources

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement.

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.

Adolescent↗

Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine.

The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and found that the low dosage of levomepromazine was effective in counteracting the fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels. These results suggest that the inhibition of CYP2D6 by levomepromazine has little effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine, used as a hypnotic agent, appears to be effective and safe when coadministered with fluvoxamine. Since this was a pilot study without a placebo control, a double-blind placebo-controlled study is needed to confirm our preliminary findings.

Adult↗

p53 status in multiple human urothelial cancers: assessment for clonality by the yeast p53 functional assay in combination with p53 immunohistochemistry.

Multifocal synchronous or metachronous tumor development is a common observation in human urothelial cancer cases. However, the underlying mechanism has remained obscure. We have employed a new tool to investigate the p53 gene status, the yeast p53 functional assay, in combination with immunohistochemistry in a total of 50 tumor samples from 32 cases with urothelial cancers, including 8 with multiple synchronous tumor development and 2 demonstrating metachronous tumors. p53 mutations were found in 13 cases (9 with missense mutations, 3 with deletion, 1 with splicing mutation) by the yeast p53 functional assay. p53 protein overexpression was seen in all 9 cases with missense mutations, but in only one of the 4 cases with nonsense mutations. Two tumors without p53 mutation also showed positive p53 immunoreactivity. Overall, p53 abnormalities including mutations and/or protein overexpression were found in 15 (47%) cases. p53 abnormalities were significantly more frequent in non-papillary and in high grade tumors. Loss of the wild type allele in addition to a p53 mutation was suggested in 8 of the 15 (53%) cases. All 4 cases with mutations in multiple synchronous tumors had identical p53 mutations in the separate urothelial cancers, strongly suggestive of monoclonality. The one case with multiple metachronous tumors, in contrast, was characterized by variation in the p53 status, indicative of different clonal origins. In conclusion, combined assessment for p53 status as used here (yeast p53 functional assay plus immunohistochemistry) may provide insights into the molecular mechanisms of urothelial carcinogenesis.

Adult↗

A novel servo-control system that imposes desired aortic input impedance on in situ rat heart.

To clarify the pathophysiological role of dynamic arterial properties in cardiovascular diseases, we attempted to develop a new control system that imposes desired aortic impedance on in situ rat left ventricle. In 38 anesthetized open-chest rats, ascending aortic pressure and flow waveforms were continuously sampled (1,000 Hz). Desired flow waveforms were calculated from measured aortic pressure waveforms and target impedance. To minimize the difference between measured and desired aortic flow waveforms, the computer generated commands to the servo-pump, connected to a side branch of the aorta. By iterating the process, we could successfully control aortic impedance in such a way as to manipulate compliance and characteristic impedance between 60 and 160% of their respective native values. The error between desired and measured aortic flow waveforms was 70 +/- 34 microl/s (root mean square; 4.4 +/- 1.4% of peak flow), indicating reasonable accuracy in controlling aortic impedance. This system enables us to examine the importance of dynamic arterial properties independently of other hemodynamic and neurohumoral factors in physiological and clinical settings.

Algorithms↗

Can quinolones cause hemorrhagic colitis of late onset? Report of three cases.

PURPOSE: This study was undertaken to demonstrate that quinolones may cause acute colitis resembling penicillin-induced hemorrhagic colitis. METHODS: We reviewed the medical records of patients with acute colitis in our institutes. Twenty-eight patients with acute hemorrhagic colitis in which no pathogenic microorganisms were identified were the subjects of this study. Pseudomembranous colitis caused by Clostridium difficile was excluded. Ulcerative colitis, Crohn's disease, and radiation proctocolitis were also excluded. RESULTS: Among these patients, 25 had a history of recent administration of penicillin derivatives. The remaining three patients had never been given any penicillin derivatives, but had ingested quinolones approximately four weeks before the developing colitis had been identified. Klebsiella oxytoca was also isolated in these three patients. CONCLUSIONS: Quinolones may cause acute hemorrhagic colitis. The time interval from antibiotic ingestion to onset of the condition may be much longer in quinolones than in penicillin derivatives.

Acute Disease↗

A polydiagnostic study of depressive disorders according to DSM-IV and 23 classical diagnostic systems.

The classification of mood disorders is one of the most highly debated topics in modern psychiatry. The introduction of DSM-III (and its followers) has set a new standard in this controversy but little empirical evidence is available as to how the various classical diagnostic categories of mood disorders by Kraepelin, Schneider, Leonhard, Hamilton, Kielholz, Winokur and others compare with this new standard. The Intensive Prospective Study arm of the Group for Longitudinal Affective Disorders Study has studied a broad spectrum of mood disorders in 23 participating centres from all over Japan with a polydiagnostic semistructured interview called Comprehensive Assessment List of Affective disorders. In this paper we examined how the various classical diagnostic systems of depressive disorders correspond to the DSM-IV diagnoses, and found the following: (1) The classical 'neurotic' or 'psychogenic' depressions are diagnosed as major depression and not as dysthymia in DSM-IV; although dysthymia was dubbed as 'depressive neurosis' in DSM-III, its criteria were not true to the traditional usage of the term. Viewed from the other side of the coin, DSM-IV can be said to stand in the unitary tradition. (2) Some of the classical diagnostic categories such as Schneider's depressive psychopathy and Klein's acute dysphoria as well as modern ones such as Akiskal's subaffective dysthymia and Angst's recurrent brief depression were rarely seen in traditional psychiatric treatment settings. (3) Comparisons of the unique diagnostic systems such as those by Leonhard, Winokur and Berner warrant further studies on their validity.

Adult↗

Why the flexible cystoscope has not yet been widely introduced?: A questionnaire to Japanese urologists.

BACKGROUND: The flexible cystoscope has not been as widely accepted in the field of urology as in other fields. The results of this investigation provided implications for determining the reasons for the under-use of flexible cystoscopy as well as for the drawbacks of the flexible cystoscope. METHODS: We performed an investigation by sending a questionnaire to urologists asking them to compare the flexible cystoscope with the rigid cystoscope in order to determine why use of the former lags behind that of the latter. RESULTS: We received answers from 420 urologists. We classified the urologist into four groups according to their years of experience. We also classified patients, for whom flexible cystoscopy was carried out, into four groups. The majority of the urologists in all groups thought that the flexible cystoscope provided a small field of vision and rough images. Urologists thought that the flexible cystoscope was inferior to the rigid cystoscope in terms of manipulability in biopsy. However, doctors who examined many patients using flexible cystoscopy believed that it was advantageous in terms of decreasing the patients' pain and they have experienced no problem in clinical practice. CONCLUSIONS: Lack of experience in using the flexible cystoscope appears to be the main reason for the negative impression it generates. The flexible cystoscope can be routinely used in place of the rigid counterpart for urological investigations and it is recommended that it be used more widely for the benefit of the patients.

Cystoscopes↗

A simpler and more accurate equation to predict daily lithium dose.

Recently, the authors suggested that the lithium dose prediction equation created by Zetin and associates cannot always accurately predict a required lithium dose and that the inclusion of renal function data may improve the accuracy of the equation. The charts of 70 patients were reviewed to obtain data regarding factors thought to affect serum lithium concentrations, including renal function, and an equation to estimate the dose intended to achieve an expected concentration was derived by stepwise multiple linear regression. The equation was also applied to 30 other patients to evaluate its accuracy. The authors obtained the following equation: daily lithium carbonate dose (in milligrams) = 100.5 + 752.7 x (expected lithium concentration in millimoles per liter) - 3.6 x (age in years) + 7.2 x (weight in kilograms) - 13.7 x (blood urea nitrogen [BUN] in milligrams per deciliter). When the equation was applied to 30 patients, the mean +/- SD of deviations from the expected concentration was 0.15 +/- 0.30 mmol/L, and 19 patients (63%) had deviations of less than 0.20 mmol/L. On the other hand, when the equation set forth by Zetin and associates was applied to the same patients, the mean +/- SD of deviations from the expected concentration was 0.52 +/- 0.42 mmol/L, and only 6 patients (20%) had deviations of less than 0.20 mmol/L. Although it is necessary to measure BUN levels before starting lithium, this equation may be simpler and more accurate than that offered by Zetin and associates.

Adolescent↗

New simple methods for isolating baroreceptor regions of carotid sinus and aortic depressor nerves in rats.

We developed new methods for isolating in situ baroreceptor regions of carotid sinus and aortic depressor nerves in halothane-anesthetized rats. After ligation of the root of the external carotid artery, the internal carotid and pterygopalatine arteries were embolized with two ball bearings of 0.8 mm in diameter. Bilateral carotid sinus pressures were changed between 60 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between aortic and carotid sinus pressures in 11 rats indicated the maximum gain of the carotid sinus baroreflex to be -2. 99 +/- 0.75 at 120 +/- 5 mmHg. An in situ isolation of the baroreceptor area of the right aortic depressor nerve could be made by ligation of the innominate, common carotid, and subclavian arteries in 9 rats. Pressure imposed on the subclavian baroreceptor was altered between 40 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between the aortic depressor nerve activity and imposed pressure showed that the baroreceptor gain peaked at 118 +/- 4 mmHg. We established an easy approach to the rat baroreflex and baroreceptor research.

Animals↗

Simultaneous identification of static and dynamic vagosympathetic interactions in regulating heart rate.

We earlier reported that stimulation of either one of the sympathetic and vagal nerves augments the dynamic heart rate (HR) response to concurrent stimulation of its counterpart. We explained this phenomenon by assuming a sigmoidal static relationship between nerve activity and HR. To confirm this assumption, we stimulated the sympathetic and/or vagal nerve in anesthetized rabbits using large-amplitude Gaussian white noise and determined the static and dynamic characteristics of HR regulation by a neural network analysis. The static characteristics approximated a sigmoidal relationship between the linearly predicted and the measured HRs (response range: 212.4 +/- 46.3 beats/min, minimum HR: 96.0 +/- 28.4 beats/min, midpoint of operation: 196.7 +/- 31.3 beats/min, maximum slope: 1.65 +/- 0.51). The maximum step responses determined from the dynamic characteristics were 7.9 +/- 2.9 and -14.0 +/- 4.9 beats. min-1. Hz-1 for the sympathetic and the vagal system, respectively. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic HR response to stimulation of the other nerve.

Acoustic Stimulation↗

Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation.

Recently, studies in our laboratory involving the use of a Gaussian white noise technique demonstrated that the transfer function from sympathetic stimulation frequency to heart rate (HR) response showed dynamic characteristics of a second-order low-pass filter. However, determinants for the characteristics remain to be established. We examined the effect of an increase in mean sympathetic stimulation frequency and that of a blockade of the neuronal uptake mechanism on the transfer function in anesthetized rabbits. We found that increasing mean sympathetic stimulation frequency from 1 to 4 Hz significantly (P < 0.01) decreased the dynamic gain of the transfer function without affecting other parameters, such as the natural frequency, lag time, or damping coefficient. In contrast, the administration of desipramine (0.3 mg/kg iv), a neuronal uptake blocking agent, significantly (P < 0.01) decreased both the dynamic gain and the natural frequency and prolonged the lag time. These results suggest that the removal rate of norepinephrine at the neuroeffector junction, rather than the amount of available norepinephrine, plays an important role in determining the low-pass filter characteristics of the HR response to sympathetic stimulation.

Adrenergic Uptake Inhibitors↗

The effect of immunosuppressive agents (FK-506, rapamycin) on renal P450 systems in rat models.

It is well known that cyclosporin, rapamycin and FK-506 (tacrolimus) are metabolized by the liver microsomal cytochrome P450 enzyme system. Although there have been reports of interaction between these drugs and the renal P450 enzyme system, differences among these immunosuppressants has not been comprehensively demonstrated. We have studied the individual capacities of these immunosuppressants to induce renal microsomal P450 enzymes similar to CYP2B4 and CYP4A2 by examining renal function in treated rats, and have correlated the results by means of biochemical, immunological and immunohistochemical assays of renal P450 enzymes. Cyclosporin caused impairment of renal function with an increase in renal-specific P450 content, but FK-506 and rapamycin did not. Laurate omega- and (omega-1)-hydroxylase activity increased in rats treated with rapamycin but decreased in those treated with FK-506. Prostaglandin A1 (PGA1) omega-hydroxylase activity increased in rats treated with FK-506 but was reduced by treatment with cyclosporin. Aminopyrine N-demethylase activity increased in rats treated with cyclosporin or FK-506, but not in those treated with rapamycin. Western-blot analysis revealed significant induction of P450, (similar to CYP2B4 of the rabbit P450 isozyme) in kidneys from rats treated with cyclosporin but not in those from rats receiving FK-506 or rapamycin. Histochemical studies clearly demonstrated a form of P450 such as CYP4A2 in the proximal tubules of rats treated with cyclosporin, but not in those of rats treated with FK-506 or rapamycin. These results show that although cyclosporin has a strong effect on renal P450 systems and induces such a system in kidney cortex (microsomal P450), FK-506 and rapamycin have no substantial effect on the induction of renal P450. These findings might clarify the nephrotoxicity induced by these immunosuppressive drugs.

Aminopyrine N-Demethylase↗

Successful interstitial treatment for bilateral tongue cancer.

We report three cases of bilateral tongue cancer who received interstitial brachytherapy successively for each tumour. Tumour control following treatment are as good as that for unilateral tongue cancer and there have been no severe complications in, or around, the tumour area after using a mandibular protective spacer and dose reduction for the second treatment.

Adult↗

The influence of chronic sympathectomy on cutaneous blood flow in the rat tail.

Tail blood flow (TBF) in the rat markedly increases during sympathetic withdrawal such as hyperthermia or lumbar sympathetic blockade. However, a long-term alteration of TBF after chronic sympathetic denervation is not well understood. In the present study, TBF following lumbar sympathectomy (LSX) was observed to ascertain whether subsequent changes in TBF occur in the absence of the sympathetic nervous activity in the rat tail. Assessed by recording tail and rectal temperature, the LSX immediately caused an increase in TBF. TBF was gradually decreased along with time and returned to the sham operated (SO) control level within 4 days. About a week after the surgery, a rapid increase in TBF in response to whole body heating was almost abolished in denervated animals. Neither hexamethonium (20 mg/kg, i.v.) for ganglion blockade nor intra-arterial infusion of alpha-receptor antagonist, phentolamine (10, 100 microg) produced vasodilation in LSX animals. Nitroprusside, a donor of nitric oxide, produced an increase in TBF in both LSX and SO animals. These results indicate that the tail vasculature after LSX constricts with capability to be vasodilated independent of sympathetic reinnervation. Quantification of the tail vascular mRNA expression by reverse transcriptase-polymerase chain reaction showed less endothelial nitric oxide synthetase in LSX group than that in SO group whereas endothelin-1 was not significantly different in both groups. It is suggested that functional changes in tail vascular endothelium takes at least a part in the reduction in TBF after LSX.

Animals↗

Immunocytochemical localization of taurine in the developing retina of the lefteye flounder Paralichthys olivaceus.

Light microscopic immunolocalization of taurine, a sulfur-containing free amino acid, was investigated in the developing retina of a lefteye flounder, Paralichthys olivaceus, which exhibits metamorphic changes with rod cell addition for 3-5 weeks after hatching. This immunocytochemical study of the developing retina revealed: 1) From 3 to 13 days after hatching, intense immunostaining was shifted from the surroundings of neural cells to the neural somata and processes in the inner retina. 2) Intense immunoreactivity appeared also in the outer and inner segments and basal processes (pedicles) of cone cells within 6 days or 13 days after hatching. 3) Lack of immunoreactivity was found in the outer segment of rod cells from their appearance during metamorphosis. These findings are discussed with the possible functional roles of taurine in the fish retina: 1) involvement in cell differentiation and/or development; 2) protection of the outer segments against light stimuli; and 3) regulation of neural transmission.

Age Factors↗

[Intrascrotal epidermoid cyst: report of two cases].

A 41-year-old man and a 47-year-old man presented with an intrascrotal mass. The routine studies and ultrasonography showed that the mass was not associated with the testis, epididymis or spermatic cord, but the magnetic resonance imaging was the most useful for making a preoperative diagnosis. Both patients received transscrotal resection of the mass, the histopathological diagnosis of which was epidermoid cyst. A total of 24 cases of epidermoid cyst have been reported in the Japanese literature.

Adult↗