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Biomedical subjects

Y Sawada

Publications and source records attributed to Y Sawada.

At least 253 records · Page 14Linked to original sources
PubMed1996

Lack of potentiation with felbinac patch on the convulsive toxicity of enoxacin in rats.

We investigated the possible potentiation of the convulsive toxicity of enoxacin (ENX) by the concomitant topical application of a felbinac (FLB) patch in rats. A felbinac patch (Seltouch; 0.5%, 3 cm x 4 cm) was attached on the back of rats where their hair has been removed. ENX was infused from the left jugular vein at 8 h after the application of FLB patch under an unanesthetized and unstrained condition. Blood, CSF and brain samples were collected at the occurrence of convulsion, and ENX concentrations of each part were determined. As a result, no significant potentiation by FLB patch was found in the onset time of convulsion or in the ENX concentration of each part. Moreover, based on the assumption that there are no inter-species differences in ENX concentration in the brain at the occurrence of a convulsion (Cbr), the predicted plasma ENX concentration required to elicit convulsions in humans, which was estimated from the Cbr and Kp value of ENX in the brain of rats, was 20 times higher than the therapeutic plasma level.

Administration, Cutaneous↗
PubMed1996

[Surgical treatment of active infective endocarditis].

Between August 1980 and December 1995, 29 patients have undergone valve replacement for active infective endocarditis (IE) at our institute. Twenty five patients had native valve endocarditis (NVE) and 4 had prosthetic valve endocarditis (PVE). The indication for surgery in 29 patients was congestive heart failure, septicemia or systemic embolization. Twenty six patients had vegetation. Eleven patients had AVRs, including one modified Bentall operation, 10 had MVRs and four had DVRs with mechanical prosthetic valve. There were eleven early death (38%) and one late death. Operative mortality rate has reduced to 24% after 1991. We conclude that early surgical intervention should be taken according to the hemodynamic state of the patients irrespective of the presence of septicemia.

Adolescent↗
PubMed1996

[Comparative study on serological diagnosis of entamoebiasis histolytica].

The practicability of four diagnostic methods for entamoebiasis histolytica including micro-gel diffusion precipitin test (MGDP), indirect immunofluorescent antibody test (IFA), indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA) was evaluated. The serological test methods were compared by using sera obtained from 30 entamoebiasis histolytica patients and 130 normal health individuals. The highest sensitivity was obtained with the method of ELISA, followed by IFA and IHA : the lowest was obtained with MGDP. On the contrary, the high specificity was obtained with IHA, IFA, MGDP : the lowest was obtained with ELISA. Intensity of the antibody titers in IHA was correlated well with that of IFA. In addition, we studied antibodies nonspecifically reactive to Entamoeba histolytica in sera from E. histolytica-negative individuals with high CRP patients with regard to the sensitivity and specificity. Among 101 sera examined, six showed false positive results of which five were the sera with extremely high CRP.

Animals↗
PubMed1996

[Two cases of total arch replacement after coronary artery bypass surgery with internal mammary artery graft].

We report two successful cases of total arch replacement after coronary artery bypass surgery (CABG) using internal mammary artery graft (ITA). Case 1 had a true aneurysm of the distal aortic arch occurring 7 years after CABG using left ITA, and case 2 had a dissecting aneurysm of DeBakey II occurring 10 months after CABG using right ITA. This patient was also complicated by a preexisting true aneurysm of the proximal descending aorta. Both cases were managed by repeat midsternal incision, selective cerebral perfusion (SCP) and retrograde cardioplegia. In both cases, functioning ITAs were dissected out easily without injury, and an operative filed for total arch replacement was well obtained under the cardioplegia and brain protection mentioned above.

Aged↗
PubMed1996

[Surgical treatment of aortic stenosis with polycythemia vera: a case report].

We report a case of 67-year-old woman with severe aortic stenosis complicated by polycythemia vera (PV). She has been treated for PV with busulfan over the past three years. On admission, she had increase in white blood cell, red blood cell and platelet count. The pressure gradient between left ventricle and aorta was 170 mmHg. Aortic valve was bicuspid and replaced with a 21 mm Carpentier-Edwards pericardial xenoprosthesis. Ascending aorta with a diameter 6.0 cm was replaced simultaneously with a 30 mm Dacron graft (Hemashield). Post-CPB course was uneventful except for a tendency to the prolongation of activated clotting time. She was discharged from the hospital in good condition.

Aged↗
PubMed1996

Solitary malignant schwannoma of the lower extremity-a case report.

A case of solitary malignant schwannoma, appearing as a painless mass near the right ankle of a 46-year-old female, is presented. Solitary malignant schwannoma without neurofibromatosis is considered to be quite rare. However, this disorder has a better prognosis than neurofibromatosis. Previous reports indicate that the treatment usually chosen is wide local excision without lymph node dissection, unless clinically involved nodes are present.

Female↗
PubMed1995

Development of electrical activity in regenerating aggregates of hydra cells.

The development of electrical activity in aggregates of dissociated hydra cells was investigated. Both the number of events and the distribution of amplitude of electrical pulses during the process of regeneration were determined. Correlations between electrical pulses at two separate positions on an aggregate were also examined as regeneration progressed. The main results were as follows: From the measured frequency and amplitude of pulses, together with the correlations between pulses at two different sites, we could observe the way in which contraction pulses developed in regenerating aggregates. The percentage of the electrical pulses of large amplitude increased about 20 hr after the start of regeneration. The correlation between electrical pulses measured at two sites separated by 0.3 mm also increased at about 20 hr, reaching about 80% at 40 hr. The results suggest the possible details of the reorganization of the conduction system for contraction pulses among cells in a regenerating aggregate of hydra cells.

Animals↗
PubMed1995

Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and their relation to p53 and proliferating cell nuclear antigen expression.

BACKGROUND: The etiology of oral squamous cell carcinoma (SCC) is still obscure. Since human papillomavirus (HPV) DNAs are associated with carcinoma of the uterine cervix, carcinomas of the oral cavity were investigated to ascertain if these viruses are present in squamous carcinomas of this anatomic site. METHODS: Seventy-seven oral mucosal SCCs were examined for the presence of HPV DNAs by polymerase chain reaction and dot blot hybridization. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and p53 was performed and single strand conformation polymorphism analysis for p53 was undertaken. In situ hybridization detection of HPV-16 DNA also was performed. RESULTS: Human papillomavirus-16 DNA was detected in 23 cases of oral SCC and both HPV-16 and HPV-18 DNA were detected in one case of tongue SCC. Human papillomavirus DNAs were detected of 11 of 33 tongue, 4 of 15 gingival, 2 of 4 palate, 2 of 5 buccal mucosa, 3 of 7 maxillary sinus, and 2 of 11 the floor of the mouth SCCs. None were detected in SCCs of the retromolar region (0/2). Immunohistochemical examination for p53 was performed in 26 cases of oral SCC and the accumulation of p53 protein was observed in 6 cases (i.e., in 4 of 17 HPV DNA-negative cases and in 2 of 9 HPV DNA-positive cases). Single strand conformation polymorphism analysis confirmed gene mutations in all 6 cases. Human papillomavirus-16 DNA was predominantly identified in cancer cells that showed a morphologic resemblance to basal cells and its hybridized signal in keratinized cells was reduced by in situ hybridization detection. Immunohistochemical detection of PCNA revealed its cooccurrence with HPV-16 DNA in cancer cells. CONCLUSIONS: These results suggest that HPV-16 DNA sequences may have the capability to maintain the proliferative state of epithelial cells, and may contribute to the production of malignant phenotypes.

Adult↗
PubMed1995

70-kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb. Identification of a novel region of pRb-mediating protein interaction.

Retinoblastoma protein (pRb) functions as a tumor suppressor, and certain proteins are known to bind to pRb in the C-terminal region. Although the N-terminal region of pRb may also mediate interaction with some proteins, no such protein has been identified yet. We demonstrated previously the in vivo protein association between pRb and 73-kDa heat shock cognate protein (hsc73) in certain human tumor cell lines. In this report we analyzed the interaction between these two proteins in vitro. Our data showed that hsc73 interacts with the novel N-terminal region of pRb; that is, pRb binds directly to hsc73 and dissociates from hsc73 in an ATP-dependent manner. By using deletion mutants of cDNA encoding pRb, the hsc73 binding site of pRb was determined to be located in the region (residues 301-372) outside the so-called A pocket (residues 373-579) of this tumor suppressor protein. This finding was compatible with the fact that the adenovirus E1A oncoprotein, which is known to bind to the E2F binding pocket region of pRb, could not compete with hsc73 for the binding. Furthermore, phosphorylation of pRb by cyclin-dependent kinase inhibited the binding of pRb to hsc73. These data suggest that hsc73 may act exclusively as the molecular chaperone for nonphosphorylated pRb. As a result, hsc73 may function as a molecular stabilizer of nonphosphorylated pRb.

Adenosine Triphosphate↗
PubMed1995

The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis.

The pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half-life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7-7.6 h and 6.2-40.1 h, and the total body clearance (CLtot) in the range of 2.8-23.2 mL h-1 kg-1 and 1.4-12.9 mL h-1 kg-1, respectively. The t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtot values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtot and hepatic function (aspartate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtot for glycyrrhizin increased from 2.8 ml h-1 kg-1 to 11.4 mL h-1 kg-1, and the t1/2 shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the extent of the liver function.

Adult↗
PubMed1995

Antibronchospasmic, tachycardiac, and hypokalaemic effects of L-isoproterenol in guinea-pigs.

The relationship between antibronchospasmic, tachycardiac, or hypokalaemic effects and plasma concentration of L-isoproterenol (ISP) hydrochloride was investigated in guinea-pigs in vivo. ISP was infused at the rate of 10, 30, 50, 100, and 300 ng kg-1 min-1. The antibronchospasmic effect was expressed as the attenuation of methacholine-induced bronchospasm. The EC50 values of ISP for antibronchospasmic and tachycardiac effects were 5.12 nM and 3.95 nM, respectively. Although they were comparable to the values reported in vitro (7.23-0.358 nM, 1.77 nM), the concentration response relationship of ISP for antibronchospasmic effect was quite steep with a slope factor of more than six. Moreover, a decrease in plasma potassium level was not clearly detected. The experimental procedure in our present study was useful for evaluating antibronchospasmic and tachycardiac effects of beta-agonists.

Adrenergic beta-Agonists↗
PubMed1995

Plasma concentrations and coronary vasodilation after sublingual and intracoronary administration of isosorbide dinitrate.

To investigate the relationship between plasma levels and coronary vasodilation after administration of isosorbide dinitrate (ISDN), the plasma concentration and diameters of six segments of the left coronary artery were measured before and after sublingual (SL) ISDN (5 mg) and left intracoronary (IC) administration of ISDN (3 mg) in 12 patients. After SL-ISDN, the systolic aortic pressure decreased with no significant concomitant changes in heart rate or diastolic aortic pressure. After IC-ISDN, all hemodynamic parameters showed significant changes, and these were greater after IC-ISDN than those after SL-ISDN. The individual mean vasodilation of six segments induced by SL- and IC-ISDN, were 23 +/- 9 and 35 +/- 11% (p < 0.01), respectively. Before SL-ISDN, ISDN was not detected in plasma. After SL- and IC-ISDN, however, the plasma values of the ISDN were 36.1 +/- 53.3 and 101.5 +/- 90.0 ng/ml (p < 0.01), respectively. Thus, both coronary vasodilative responses and plasma ISDN levels after IC-ISDN were significantly greater than those after SL-ISDN. However, neither the individual mean coronary vasodilation nor the hemodynamic changes correlated significantly with plasma ISDN levels. Consequently, with administration of the same dose, the coronary vasodilative response to ISDN did not correlate with plasma levels. Furthermore, IC-ISDN dilutes coronary arteries more effectively than SL-ISDN.

Administration, Sublingual↗
PubMed1995

Effects of fibroblasts of different origin on long term maintenance of xenotransplanted human epidermal keratinocytes in immunodeficient mice.

We examined effects of fibroblasts of different origin on long-term maintenance of xenotransplanted human epidermal keratinocytes. A suspension of cultured epidermal cells, originating from adult human trunk skin, was injected into double mutant immunodeficient (BALB/c nu/scid) mice subcutaneously, with or without cultured fibroblastic cells of different origin. At one week after transplantation, the epidermal cells generated epidermoid cysts consisting of human epidermis-like tissue. When the epidermal cells were injected alone or together with fibroblastic cells derived from human bone marrow, muscle fascia, or murine dermis, organized epidermoid cysts regressed within 6 weeks. In contrast, when the epidermal cells were injected together with human dermal fibroblasts, generated epidermoid cysts were maintained in vivo for more than 24 weeks. Histological examination showed that the reorganized epidermis, after injection of both epidermal keratinocytes and dermal fibroblasts, retained normal structures of the original epidermis during 6 to 24 weeks after transplantation. The results indicate that human dermal fibroblasts facilitate the long-term maintenance of the reorganized epidermis after xenotransplantation of cultured human epidermal keratinocytes by supporting self renewal of the human epidermal tissue in vivo.

Animals↗
PubMed1995

Risk assessment of adverse pulmonary effects induced by adrenaline beta-receptor antagonists and rational drug dosage regimen based on receptor occupancy.

To clarify the beta-1 selectivity of beta-adrenergic receptor blocking agents (beta-blocking agents) after typical oral doses, the relationships between the effects on exercise heart rate or FEV1 and beta-1 or beta-2 receptor occupancies (phi 1, phi 2) of seven beta-blocking agents, acebutolol, atenolol, metoprolol, oxprenolol, timolol, propranolol, and pindolol were analyzed retrospectively. Nonlinear relationships between the pharmacologic effect and phi 1 and between the pulmonary adverse effect and phi 2 were obtained. Based on these findings, a new index of cardiovascular selectivity is proposed, given by the ratio of beta-1 receptor occupancy to beta-2 receptor occupancy (phi 1/phi 2). Using this new index, there was a little difference in beta-1 selectivity between acebutolol and pindolol (3.1:1.0), in contrast to a marked difference in beta-1 selectivity (320:1) as a conventional index between these two drugs. This finding indicates that even beta-1 selective drugs must be administered carefully to patients with pulmonary disease. Furthermore, the relationship between the pharmacologic or pulmonary effects and phi 1 or phi 2 has been analyzed quantitatively with a ternary complex model and used to develop rational dosage regimens for beta-1 selective beta-blocking agents, such as atenolol, to obtain the desired pharmacologic effects with minimum adverse pulmonary effects.

Adrenergic beta-Antagonists↗
PubMed1995

Prediction of sleep disorders induced by beta-adrenergic receptor blocking agents based on receptor occupancy.

beta-adrenergic receptor blocking agents (beta-blocking agents) have been widely used clinically for the treatment of various cardiovascular conditions. However, beta-blocking agents are liable to cause sleep disturbance, such as vivid dreams, nightmares, increased waking, and insomnia. The mechanisms of the sleep disorders are not known, but several may conceivably be responsible for these CNS-related side effects. In the present study, we hypothesized that the sleep disorders are induced by the blockade of central or peripheral beta 2 receptors and/or central serotonin (5-HT) receptors. To verify the hypothesis, we retrospectively analyzed the relationships between the extent of the sleep disorders and the beta 1, beta 2, or 5-HT receptor occupancies for four beta-blocking agents (atenolol, metoprolol, pindolol, and propranolol). No significant correlations were observed among pharmacokinetic/physicochemical parameters (therapeutic dose, plasma concentration, plasma unbound concentration, cerebrospinal fluid concentration, and lipid solubility) and pharmacodynamic parameters (the scores of the sleep disorders such as the number of dreams). Furthermore, no significant relationship (correlation coefficient: r < 0.3) was observed between beta 1 receptor occupancies of the drugs and the number of dreams. On the other hand, good relationships (r > 0.95) were observed between central and peripheral beta 2 or central 5-HT receptor occupancies and the number of dreams. These findings suggest that beta 2 and/or 5-HT receptor occupancy is superior to beta 1 receptor occupancy as an index for the sleep disorders.

Adrenergic beta-Antagonists↗