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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 271 records · Page 15Linked to original sources

The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on ethanol-induced sleep time and ethanol elimination in inbred strains of mice with different alcohol preference.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases. Male C57BL/6J and DBA/2J mice were given 6R-BH4 (0, 12.5, 25.0 and 50.0 mg/kg of body weight, i.v.) or saline, and then 4 h later, all animals were injected with ethanol (EtOH) (4.0 g/kg, i.p.), which causes them to lose the righting reflex, to investigate the differences in EtOH-induced sleeping time. 6R-BH4 pretreatment reduced EtOH-induced sleep time in DBA/2J mice with lower alcohol preference (p < 0.05), which showed no changes in the pharmacokinetics of blood EtOH. No changes in EtOH-induced sleep time were observed in C57BL/6J mice with higher alcohol preference. These results indicate that the sensitivity to EtOH in mice with lower alcohol preference was associated with 6R-BH4 activity in the CNS.

Alcohol Drinking↗

Antiviral substance from silkworm faeces: purification and its chemical characterization.

In a previous paper, we reported that an extract of silkworm faeces has a marked antiviral activity on enveloped viruses, but not on a non-enveloped virus, and we showed that it inhibits the synthesis of a viral specific gene of HVJ (Sendai virus) without affecting the viral adsorption and entry into the host cell. In this paper, we accomplished the purification of an antiviral active substance by extraction of a hydrophobic substance and thin layer chromatography. The active substance was found to be a chlorophyll-like substance with a molecular mass of about 530. This substance shows clear antiviral activity against HVJ, HSV (herpes simplex virus type-1), and HIV (human immunodeficiency virus type-1). Its antiviral activity was dependent on light irradiation and temperature. Furthermore, it also possesses a strong hemolytic activity under light.

Animals↗

Cyclooxygenase metabolites possibly produced by endothelial cells mediate the lung injury caused by mechanically stimulated leukocytes.

To determine whether mechanically stimulated leukocytes increase pulmonary vascular permeability and resistance and, if so, whether cyclooxygenase metabolites mediate the increase, we assessed the effects of stimulated and unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular permeability and resistance in isolated perfused lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentle agitation in a glass container for 10 seconds. After baseline measurements were made, stimulated or unstimulated leukocytes were added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and pulmonary vascular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of leukocytes to the pulmonary vascular endothelium. These findings suggest that mechanically stimulated leukocytes increase pulmonary vascular permeability and that cyclooxygenase metabolites produced by endothelial cells may injure the cells.

Animals↗

Fosinopril. Clinical pharmacokinetics and clinical potential.

Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.

Absorption↗

Measurement of cell kinetic parameters in meningiomas.

Cell kinetic parameters were measured in four cases of meningioma showing regrowth. The cell cycle time (Tc) and tumor doubling time (Td) were established by histological evaluation of the biopsy specimens and calculation of the growth curve based on computed tomography (CT)/magnetic resonance (MR) images. MIB-1 mouse monoclonal antibody, which recognizes an epitope of the Ki-67 antigen, was used to establish the MIB-1 staining index (SI) (MIB-1-positive nuclei/5000 tumor cells) for each tumor. The changes in tumor volume were calculated from CT/MR images, and the Td was estimated from the growth curve. The Tc was calculated using Steel's formula from the MIB-1 SI and tumor volume. MIB-1 SI varied from 0.0055 to 0.0468, Td from 270 to 1429 days, and Tc from 10.4 to 15.9 days. Furthermore, the potential doubling time (Tp) was calculated using the corresponding Tc and MIB-1 SI (growth fraction) for the four cases; these values varied from 197 to 1645 days and were very close to the Td values. This method of evaluation of tumor Tc and calculation of Tp may be useful for predicting the postoperative course in meningiomas.

Adult↗

Preoperative detection of the composition of atherosclerotic plaque in the carotid artery using ultrasonography and magnetic resonance imaging.

Preoperative identification of the components of atherosclerotic plaque was attempted using ultrasonography in five patients and magnetic resonance (MR) imaging in three patients before carotid endarterectomy. The correlation between surgical and histological findings, and preoperative ultrasonography and MR imaging was evaluated. Plaque consisting predominantly of calcification appeared as bright echo on ultrasonography and was tough. Plaque consisting predominantly of hemorrhage was echolucent, appeared as low intensity on T2-weighted MR images and was fragile. Such preoperative assessment of plaque composition using ultrasonography and MR imaging is useful for manipulation of atherosclerotic plaque during carotid endarterectomy.

Aged↗

[Lipoprotein(a) as a risk factor for cardiovascular disease in elderly patients with diabetes].

Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases in non-diabetic people, but few studies have been done in diabetic patients. To investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly people with diabetes, we examined the association of Lp(a) and serum lipid levels (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein cholesterol: HDL-c) with the incidence of coronary artery disease and cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97 years of age) with non-insulin-dependent diabetes mellitus. The mean concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The Lp(a) concentration did not correlate significantly with age or with sex, but it did correlate significantly with TC (r = 0.152, p < 0.05) and with the level of apoprotein B (r = 0.168, p < 0.05). The incidence of cerebrovascular disease was significantly higher in patients with high concentrations of Lp(a) (> or = 30 mg/ dl) than in those with low concentrations (< 30 mg/ dl). Multivariate logistic regression analysis revealed that male sex, hypertension, a high level of HbA1c, a low level of HDL, and a high level of Lp(a) were independent risk factors for cerebrovascular disease. The incidence of coronary artery disease tended to the higher in those with high concentrations of Lp(a) (> or = 30 mg/dl). However, multivariate logistic regression analysis revealed no significant correlation between Lp(a) concentration and the incidence of coronary artery disease. We conclude that a high concentration of Lp(a) is an independent risk factor for cerebrovascular disease in elderly patients with diabetes.

Aged↗

Normal-mode ruby laser for treating congenital nevi.

BACKGROUND: Q-switched laser therapy is known to be highly effective in treating dermal melanocytosis and pigmented epidermal lesions. However, to our knowledge, there are no reports on the effectiveness of laser therapy for congenital nevi. We evaluated the clinical efficacy and side effects of normal-mode ruby laser therapy for congenital pigmented lesions containing abundant melanin. OBSERVATIONS: A normal-mode ruby laser (pulse duration, 0.3-1.0 x 10(-3) seconds; energy fluence, 10-30 J/cm2; and spot size, 10 x 10 or 15 x 15 mm) (Toshiba Corp, Tokyo, Japan) was used to treat 3 patients with congenital nevi at intervals of 1 to 4 months. In all 3 cases, the pigmented lesions were significantly reduced almost to the level of the surrounding normal skin after 4 laser treatments. The treated areas were virtually free of scarring, and the skin texture resembled that of the surrounding normal skin. Unsightly hair growth was also reduced. CONCLUSIONS: The normal-mode ruby laser was effective in treating congenital nevi and produced good cosmetic results. The risk of recurrence is unknown, but the 3 patients in our study did not have any recurrences during the 18- to 39-month study period.

Child↗

Necrotizing alveolar capillaritis in autopsy cases of microscopic polyangiitis. Incidence, histopathogenesis, and relationship with systemic vasculitis.

OBJECTIVES: To determine the incidence of necrotizing alveolar capillaritis, to elucidate its histopathogenesis and the most reliable histopathologic features for its detection, and to explore its relationship with systemic vasculitis in microscopic polyangiitis. METHODS: Twenty-five autopsy cases of microscopic polyangiitis were examined. Double staining with periodic acid-silver methenamine and trichrome was used. RESULTS: Periodic acid-silver methenamine and trichrome staining proved to be a useful and convenient method for the detection of necrotizing alveolar capillaritis. Capillaritis was detected in 10 (40%) of the 25 cases studied. Of 18 cases that exhibited the early degenerative stage of systemic vasculitis, capillaritis was seen in 10 (56%). Fibrinoid necrosis of the alveolar wall was the most reliable histopathologic feature for detecting necrotizing alveolar capillaritis in microscopic polyangiitis. The early stage of capillaritis displayed very little neutrophil exudation, and conspicuous accumulation of neutrophils developed after fibrinoid necrosis. Statistical analysis revealed that alveolar capillaritis had a statistically significant correlation (P < .05) with necrotizing vasculitis of the pulmonary circulatory system. Capillaritis tended to occur when systemic vasculitis of microscopic polyangiitis was in its early degenerative stage. CONCLUSION: Necrotizing alveolar capillaritis was detected in about half of the microscopic polyangiitis autopsy cases that exhibited the early degenerative stage of systemic vasculitis, and results based on earlier reports of clinical observations may have been too conservative.

Adult↗

[Management and long-term follow-up results in patients with carotid artery dissection].

The recognized incidence of extra- and intracranial carotid artery dissection has increased concomitantly with the progress and development of diagnostic methods. However, management for this condition is still controversial. We report in the present study the management and long-term follow-up results of 15 patients with carotid artery dissection. Mean age of the patients at onset was 47.8 years old, and male/female ratio was 12:3. Two patients were considered to be traumatic dissections and the other 13 patients were spontaneous dissections. Dissection occurred in 10 patients at the extracranial carotid artery, in 4 at the intracranial carotid artery and in 1 at the middle cerebral artery. Nine of 15 patients demonstrated hemiparesis and 5 complained of headache or facial pain. However, it was not possible to identify a characteristic symptom of dissection. Final diagnosis of dissection was made by cerebral angiography in all patients. Serial angiography was carried out in 10 of those, and 5 of the 10 patients showed some improvements of dissection in the cerebral angiogram. Treatment for those patients was selected according to the neurological and angiographical changes. Five patients were managed conservatively and 10 patients underwent surgical revascularization. During the follow-up period (mean 77.6 months), none of them showed any symptoms of reattack, and all but one, who died of heart failure 193 months after revascularization surgery, have lived independently. Although diagnosis of dissection was difficult because of the lack of characteristic symptom, serial angiography was a useful method for diagnosis and adequate management has led to a good clinical outcome.

Adolescent↗

Effects of ethanol on the levels of brain 6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin in the inbred strains of mice. DBA/2J, C3H/HeJ and C57BL/6J with different alcohol preferences.

6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of the catecholamines and serotonin, respectively. The present study was designed to determine the changes in concentrations of 6R-BH4 in striatum and midbrain of the inbred strains of mice, DBA/2J, C3H/HeJ and C57BL/6J, with different genetically determined alcohol preferences, following the injection of ethanol (EtOH). The intraperitoneal administration of EtOH (0, 1, 2 and 4 g/kg) significantly and dose-dependently reduced the levels of striatal and midbrain 6R-BH4 in DBA/2J mice with the lowest alcohol preference, and EtOH (4 g/kg, i.p.) reduced the level of striatal 6R-BH4 in C3H/HeJ with medium alcohol preference. Following the administration of EtOH (4 g/kg, i.p.), brain 6R-BH4 levels in C57BL/6J mice with high alcohol preference were lowered compared with the control group, but the difference did not reach statistic significance. EtOH has a tendency to reduce the brain 6R-BH4 levels in mice with lower alcohol preference or higher sensitivity to EtOH. Based on these findings, it was proposed that differences in alcohol drinking behavior in the inbred strains of mice was influenced by brain 6R-BH4.

Alcohol Drinking↗

[Increase in pulmonary vascular permeability caused by increased expression of Mac-1 on the surface of polymorphonuclear leukocytes].

We studied the expression of adhesion molecules on the surface of human polymorphonuclear leukocytes (PMNs). The effects of mechanical stimulation were measured with a flow cytometer and pulmonary vascular injury due to accumulation of PMNs in the lungs was assessed by a gravimetric method. The accumulation of PMNs in the lungs was studied by measuring the amount of myeloperoxidase. PMNs were stimulated by gentle agitation in a glass container for 10 s. Mac-1 (CD11b/CD18) was upregulated on the surface of PMNs that were mechanically stimulated. When unstimulated PMNs were exposed to isolated rat lungs, the filtration coefficient did not change from that under baseline conditions. However, when mechanically stimulated PMNs were exposed to isolated rat lungs, the filtration coefficient was about 5 times higher than that measured at baseline. When mechanically stimulated PMNs treated with anti-CD18 antibody were used, the increase in the filtration coefficient was completely blocked. The assay of myeloperoxidase revealed that PMNs stuck to isolated rat lungs only after stimulated PMNs were added. We conclude that when the adhesiveness of PMNs is increased by mechanical stimulation, these cells adhere to pulmonary vessels and increase pulmonary vascular permeability.

Animals↗

[Functional brain mapping in motor task and somatosensory stimulation using echo planar MRI].

Functional brain mapping was performed with a 1.5T clinical MRI apparatus. Single shot gradient echo echo-planar imaging (EPI) sequence was employed. Normal volunteers were studied with the task of grasping hand or opposition of fingers at the frequency of 3 Hz, median nerve electro-stimulation, pure somatosensory stimulation by roller for acupuncture. Apparent signal increase was observed at contralateral sensorimotor cortex with motor task. Signal changes delayed about 5 seconds compared with the start and the cessation of the task, which may suggest that regional changes of CBF and blood oxygen level in capillary and/or in venule lag behind electrical excitation. It was hard to detect the activated area with median nerve electro-stimulation. On the other hand, roller stimulation provoked distinct activated areas at contralateral sensorimotor cortex. The activated areas caused by the roller stimulation and the motor task coincided entirely, which suggests the possibility of the intermixed localization of primary areas of motor and somatosensory. It was also clearly demonstrated that the activated area was broader with quick (3 Hz) and complicated motor task (finger opposition) than with slow (1Hz) and simple motor task (hand grasping).

Adult↗

[Prediction of postoperative pulmonary hemodynamics for the second lobectomy after the contralateral lobectomy].

We presented 7 cases who were performed the second lobectomy for the second lung cancer after the first successful lobectomy on the contralateral lung (3 cases for right upper lobectomy + left lower lobectomy and 4 cases for right upper lobectomy + left lower lobectomy). In 6 patients, the predicted postoperative FEV1 estimated by multiplying the preoperative FEV1 by the fraction of perfusion to the contralateral lung was less than 800 ml/m2BSA, which is our first cut-off for identifying lung resection candidates. Unilateral pulmonary arterial occlusion test (UPAO) revealed that total pulmonary vascular resistance (TPVRI) in 3 of those 6 patients was lower than 700 dyne.sec.cm-5/m2BSA, our second cut-off for lung resection. More precise postlobectomy pulmonary hemodynamics in another 3 of those 6 patients were then estimated by adapting selective pulmonary occlusion test (SPAO). Since TPVRI during SPAO was lower than the cut-off value, it was suggested that second lobectomy would be feasible with low incidence of post operative cardiopulmonary complication. There was no serious complications in all 7 cases during their postoperative course. We believe that more precise prediction of postoperative pulmonary hemodynamics by adapting UPAO and SPAO could be one of the tools to minimumize postoperative cardiopulmonary complications in those patients needed second lobectomy for the second lung cancer after the first successful lobectomy on the contralateral lung even though their impaired lung fung function.

Aged↗