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Biomedical subjects

R Sakai

Publications and source records attributed to R Sakai.

At least 109 records · Page 6Linked to original sources
PubMed1994

Liver function tests of recipients with hepatitis C virus infection after bone marrow transplantation.

We used the polymerase chain reaction (PCR) to determine the presence of hepatitis C virus (HCV)-RNA in serum samples obtained from 19 patients with leukaemia or severe aplastic anaemia and investigated the correlation between HCV status and the results of liver function tests after bone marrow transplantation. PCR analysis of serum samples obtained before transplant showed that 10 of 18 patients were HCV-RNA-positive; 5 of these patients had developed acute post-transfusion hepatitis 1-11 months before transplant. An additional patient was HCV-RNA-positive on post-transplant day 62. Eight HCV-RNA-positive patients had pre-transplant GPT levels above the upper limit of normal. In these patients the GPT decreased significantly from a median of 104 IU/l (54-822 IU/l) pre-transplant to 23 IU/l (15-56 IU/l) on post-transplant days 8-12. In 9 of 11 HCV-RNA-positive patients, the GPT increased transiently from days 40 to 50 and again increased after day 100. Two of these patients died from hepatic failure; the GPT levels normalised in 3 patients after day 300 but continued to fluctuate in 4 patients. In the remaining 2 HCV-RNA-positive patients, the GPT remained close to the normal range throughout the follow-up period. Three HCV-RNA-positive patients became HCV-RNA-negative after 1-3 years. In these patients, the GPT remained normal for > 3 years after day 300.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Auer-rod-like bodies in plasma cells in patient with plasma cell dyscrasia].

Auer-rod-like bodies were found in plasma cells from a 74-year-old man with plasma cell dyscrasia. These bodies exhibited red purple staining by May-Giemsa staining and were indistinguishable from Auer bodies often found in acute myeloid leukemia. These bodies, however, failed to stain with peroxidase and showed acid phosphatase positivity. Bone marrow examinations were performed three times at the sternum or iliac crest. The proportions of plasma cells were 4.4%, 3.4% and 3.8%. The Auer-rod-like bodies were found in 0.05% (2/3824), 0.07% (4/6883) and 0.08% (2/2656) of the plasma cells.

Aged↗
PubMed1994

The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells.

We have isolated the mouse c-crk cDNA from a mouse liver cDNA library. It encodes 304 amino acids and consists mainly of SH2/SH3 regions. In Northern blot analysis, the mouse c-crk mRNA is expressed ubiquitously in every tissue and organ, suggesting that the c-Crk protein may be a common signal transducing molecule among tissues. In contrast to the v-Crk protein, which has a single SH3 domain, the c-Crk protein contains two, the more N-terminal SH3(1) domain and the C-terminal SH3(2) domain. To elucidate functions of these SH3 domains, we have constructed two c-crk mutants, B-crk and D-crk, which lack the SH3(2) and the SH3(1) domain, respectively. These mutants were expressed in rat 3Y1 cells, and examined for their transforming ability in terms of morphological phenotypes and for tyrosine phosphorylation profiles of cells expressing the mutant proteins. Morphological alteration and increased tyrosine phosphorylation of 130-140 kDa proteins, the major component of which is the Crk-associated p130, were observed in cells expressing B-Crk as well as those expressing v-Crk, but little in cells expressing c-Crk even at a similar level of expression. Although a highly tyrosine-phosphorylated form of the p130 was coimmunoprecipitated with c-Crk as well as B-Crk, the relative level of tyrosine phosphorylation of the p130, which is normalized to the amount of Crk protein immunoprecipitated, was 10 to 20 times higher in B-Crk-expressing cells than in c-Crk- or D-Crk-expressing cells. The present results indicate that the SH3(2) domain of mouse c-Crk protein negatively regulates tyrosine phosphorylation of the p130, and that lack of the SH3(2) domain in B-Crk and v-Crk may contribute, at least partly, to their morphological alteration or transforming ability through increasing tyrosine phosphorylation of the p130.

Amino Acid Sequence↗
PubMed1993

Activin enhances osteoclast-like cell formation in vitro.

The effect of activin (activin A/EDF) on osteoclast formation was investigated. In mouse bone marrow cell cultures, activin enhanced the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells (MNC) in a dose-dependent manner, either in the presence or absence of 1,25-(OH)2D3 or PTH. In organ cultures of neonatal mouse calvaria, activin also enhanced the generation of TRACP-positive giant cells in the endosteal periosteum and increased the TRACP staining of whole calvaria, but did not exhibit bone resorbing activity. These results indicate that activin stimulates the formation of osteoclasts, but not osteoclast activation. Activin is produced by bone marrow cells and might be involved in the local process of osteoclast differentiation.

Acid Phosphatase↗
PubMed1993

Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position.

Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2'-ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3-propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute to the bronchodilator action of 1- and 7-substituted xanthines. This study indicates that the substitutions with none or low polar functional groups at the 1-position could improve the selectivity and duration of the bronchodilator effects of xanthines.

Administration, Oral↗
PubMed1993

Profile of subjective complaints and activities of daily living among current patients with Minamata disease after 3 decades.

We surveyed 1144 current patients with Minamata disease (MD) aged 40 or over in the Minamata area and the same number of neighbor controls matched with age and sex by questionnaire interview with regard to subjective complaints and activities of daily living (ADL). From analysis of subjective complaints, it was found that MD patients had significantly higher rates of all complaints than controls (P < 0.05). Multivariate analysis showed that subjective complaints in controls were clearly separated into the following two categories: sensory disturbances and movement nerve disturbances, but all complaints in MD patients formed one cluster. Such variation seemed to be due to methylmercury exposure to the central nervous system. ADL analysis revealed that the difference in the ADL disability between MD patients and controls significantly increased with age (P < 0.05) and that ADL disability in MD patients was aggravated by aging.

Activities of Daily Living↗
PubMed1993

Electrophysiological effects of flecainide acetate on stretched guinea pig left atrial muscle fibers.

The electrophysiological effects of flecainide acetate (3 x 10(-6) M) on stretched atrial tissue were investigated using guinea-pig left atrial muscle fibers. Before stretching, the resting membrane potential was not affected by flecainide at 1 Hz, although the overshoot potential (Eov) and the action potential duration at 50% repolarization (APD50) were slightly but significantly decreased by 2 +/- 1 mV and 2 +/- 1 msec, respectively. The effective refractory period (ERP) was increased by 3 +/- 1 msec. The reduction of Vmax was 20.6 +/- 1.2%. The half-maximum potential (Vh) of the relationship between Vmax and the resting potential was shifted to become more negative by flecainide (from -60.6 +/- 2.1 mV to -63.2 +/- 1.7 mV). After 90-120 min of washout with drug-free Tyrode's solution, the tissue was mechanically stretched to 150% of its slack length. Stretching significantly decreased the Vmax by 16.9 +/- 3.1%, along with a slight but significant increase in ERP (3 +/- 1 msec) and shifted Vh to become more negative (from -60.6 +/- 2.1 to -63.1 +/- 1.8 mV). In the presence of flecainide, Vmax further decreased by 20.2 +/- 2.6%, and Vh shifted from -63.1 +/- 1.8 to -65.0 +/- 1.5 mV. Comparison with the control unstretched fibers showed that flecainide significantly decreased Vmax by 34.0 +/- 2.7%, reduced the resting membrane potential by 3 +/- 1 mV, decreased Eov by 4 +/- 1 mV, and shifted Vh from -60.6 +/- 2.1 to -65.0 +/- 1.5 mV, while the APD50 and ERP did not change. In conclusion, the reduction of Vmax in the presence of flecainide was much greater in the stretched atrial muscle fibers than in the unstretched fibers, because the Vmax-resting potential relationship was shifted towards more negative potentials by both flecainide and stretching. These results suggest that flecainide exerts a stronger antiarrhythmic action on stretched atrial muscle fibers than on normal fibers.

Animals↗
PubMed1993

Presence and possible function of activin-like substance in human follicular fluid.

We assessed the presence of an activin-like substance in human follicular fluid that was obtained from women undergoing in-vitro fertilization using a bioassay for activin A. Activin activity was not detected in crude follicular fluids; the bioactivity of standard activin A was inhibited by the addition of follicular fluid. After the follistatin (binding protein of activin A) was removed from follicular fluid using a purification procedure, activin activity was detected in the follicular fluids (mean concentration: 131 +/- 40 ng/ml). Activin activity was inhibited by the addition of follistatin to fluid. The concentration of activin activity was substantially higher (approximately 100-fold) than that reported in serum. The concentration negatively and significantly correlated with the number of developed follicles in the ovary (r = 0.501, P < 0.01). These results suggest that activin A and its binding protein are present in follicular fluid in large amounts and that they may have a role in local ovarian regulation.

Activins↗
PubMed1993

Pharmacokinetic evaluation of (glycolato-O,O')diammine platinum(II) in lung lymph in sheep.

The pharmacokinetics of (glycolato-O,O')diammine platinum(II) (254-S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis-diamminedichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254-S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254-S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254-S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254-S and CDDP seemed to be caused by differences in their strength of protein binding; the association constants of 254-S for plasma and lymph protein were much less than those of CDDP. From these results, 254-S may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Anesthesia↗
PubMed1993

Effects of pilsicainide on the atrial fibrillation threshold in guinea pig atria. A comparative study with disopyramide, lidocaine and flecainide.

The effects of pilsicainide, a new class Ic antiarrhythmic agent, on the atrial fibrillation threshold (AFT), the atrial effective refractory period (ERP), and the interatrial conduction time (ACT) in Langendorff-perfused guinea pig hearts were investigated. These effects were compared with those of disopyramide, lidocaine and flecainide. Whole guinea pig heart was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Three indices were measured before and after the administration of the test drugs using right atrial extrastimulus and high frequency stimulation. Pilsicainide, disopyramide and flecainide (> or = 10(-6) M) all significantly increased the AFT. Both pilsicainide and flecainide (> or = 3 x 10(-6) M) significantly prolonged the ERP, but this prolongation was less pronounced than that observed with disopyramide. The ACT was significantly prolonged with pilsicainide (> or = 10(-6) M), and this prolongation was greater than that observed with disopyramide but less than that with flecainide. Lidocaine had no effects on any of the indices measured. In conclusion, pilsicainide had a preventive effect on the atrial fibrillation induced by a combination of acetylcholine and high frequency stimulation in guinea pig hearts, by increasing the atrial ERP and slowing the interatrial conduction. These effects may explain, in part, the clinical effectiveness of this drug on paroxysmal atrial fibrillation.

Animals↗
PubMed1993

Effects of caffeine on ischemia-reperfusion injury in isolated rat hearts.

Cardiac sarcoplasmic reticulum (SR) plays an important role in regulation of the intracellular Ca2+ concentration. It is well known that intracellular Ca2+ overload is one cause of reperfusion injury. Thus, it is predicted that reperfusion injury of myocardium can be prevented by eliminating the Ca2+ overload. This study examined the effects of caffeine, a SR blocker, on reperfusion injury in isolated perfused rat hearts. Working hearts were reperfused for 25 min after 30 or 50 min of ischemia. Caffeine (10(-4) M) was administered during the period of ischemia or the initial 5 min of reperfusion. The left ventricular pressure and the electrocardiogram were recorded. Rate-pressure products were calculated as an index of cardiac function. Adenine nucleotides were measured by high-performance liquid chromatography to assess energy charge. The administration of caffeine for a short period during the initial reperfusion significantly improved cardiac function in the hearts. Caffeine pretreatment during 50 min of ischemia, though, resulted in deterioration of both energy charge and cardiac function. Caffeine did not affect the incidence of either ventricular fibrillation or reversion to sinus rhythm. The energy charges were lower in the preparations with sustained ventricular fibrillation.

Animals↗
PubMed1993

Evidence through crossmating experiments of a species complex in Anopheles pseudopunctipennis sensu lato: a primary malaria vector of the American continent.

Crossmating experiments were conducted to determine if postmating reproductive barriers are involved in the maintenance of genetic divergence among populations of Anopheles pseudopunctipennis sensu lato, a primary malaria vector of the American continent. Reciprocal crosses were conducted between colony and wild strains from Mexico, Bolivia, and Peru. Hybridization experiments revealed unidirectional male/female hybrid sterility in crosses between Mexican females and South American males. The data presented provide the first evidence that genetic differences exist among geographic strains of An. pseudopunctipennis in neotropical America. There is a consistent pattern suggesting the presence of at least two allopatric sibling species. One species occurs in central Mexico, the other in the South American Andean Cordillera.

Animals↗
PubMed1993

[CD14-positive and nonspecific esterase-positive neutrophils in a patient with refractory anemia with excess of blasts in transformation].

A 34-year-old man was admitted with lumbago and anemia in November 1992. Hematological examination revealed an Hb 9.2g/dl, WBC count 13,500 microliters (33% blasts), and monocyte count 3,400/microliters. Bone marrow examination showed hyperplasia with dysplasia in trilineage blood cells and increased blasts (21.8%). A diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T) was made. Cytochemical examination revealed the neutrophils in the peripheral blood were 66.5% positive for alpha-naphthyl butyrate esterase inhibited by sodium fluoride, 4.0% positive for peroxidase and 75% positive for alkaline phosphatase. The results of immuno-alkaline phosphatase stainings (avidin biotin alkaline phosphatase complex method) of neutrophils were as follows; CD16 (94.5%), CD24 (91.0%), CD13 (93.0%), CD14 (52.5%), CD33 (39.0%), CD36 (16.5%), HLA-DR (17.0%). These neutrophils exhibited monocyte-specific features and failed to show characteristics of neutrophils.

Adult↗
PubMed1993

[Frequency dependent prolongation of inter-atrial conduction time by mexiletine in human atrium].

To investigate frequency dependent conduction slowing by mexiletine in the human atrium, we examined inter-atrial conduction time (IACT) at different stimulation frequencies (100/min to 220/min) in 13 patients with paroxysmal atrial fibrillation (Paf) and 7 patients without Paf. IACT was prolonged as the stimulation frequency was increased, and either before or after mexiletine administration IACT was longer in the Paf group (max 114 +/- 9 msec, p < 0.01, mean +/- SD) at any stimulation frequency than in the non-Paf group (max 100 +/- 8 msec). The change in IACT induced by mexiletine administration (% delta IACT) was larger in the Paf group (max 14.8 +/- 5.4%, p < 0.05) than in the non-Paf group (max 5.5 +/- 2.2%) at stimulation frequency over 140/min. Effective refractory period measured at the high right atrium was slightly decreased due to mexiletine in both the non-Paf and the Paf group. In conclusion, mexiletine showed frequency dependent suppression of conduction in the human atrial myocardium especially in patients with Paf.

Adolescent↗
PubMed1993

Molecular and crystal structures of ecteinascidins: potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinata.

Some members of marine alkaloid ecteinascidins (Et's), isolated from the Caribbean tunicate Ecteinascidia turbinata, exhibit potent anticancer activity. The three dimensional structures of the N12-formyl derivative of Et729 1a and the natural N12-oxide of Et743 2 have been determined by x-ray crystallography at 0.9 A resolution. Compounds 1a and 2 crystallize in the space groups P2(1)2(1)2(1) (a = 23.214(9) A, b = 28.541(10) A and c = 13.303(9) A) and P2(1) (a = 11.720(5) A, b = 13.230(4) A, c = 28.557(5) A, beta = 90.22(2) degrees), respectively. Their crystal structures have been solved by the Patterson search method, which located the sulfur atoms permitting the phase extension. The final crystallographic R-factors are 0.059 and 0.069 for 1a and 2, respectively. There are two independent molecules, associated as a dimer, in the asymmetric unit of crystals of both 1a and 2. The structure determination allows an unequivocal assignment of the relative configuration of all the chiral centers. Assuming that ecteinascidins and safracin C (whose absolute configuration is known) have the same absolute configuration at C1 position, then the absolute configurations of various chiral positions in Ets are C1(R), N2(R), C3(R), C4(R), C11(R), C13(S), C21(S) and C22(R), respectively. The four independent Et molecules adopt two conformations in which the position of ring C relative to rings A & B is different. The molecules have a compact shape and they are conformationally strained due to a severe van der Waals clash between the sulfur atom and the aromatic ring A. By analogy to the related saframycin, the potent biological activity of Et's may be associated with their ability to form a covalent adduct to DNA using the reactive carbinolamine group. The covalent binding interaction between the Et and the N2 of guanine in the minor groove of the DNA double helix has been studied by computer modelling which suggests that rings A and B "stack" against the DNA backbone. While the bulky drug molecule makes numerous contacts with DNA, it does not significantly distort the conformation of the DNA double helix.

Alkaloids↗
PubMed1993

[Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance, Part 1: Relation to anemia in renal failure and hematological disorders].

With a newly developed enzyme linked immunosorbent assay kit TOYOBO Co. in which 2 anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from normal adults, 168 patients with renal failure and 333 patients with hematological disorders. In the patients with renal failure, serum EPO level was normal (52.9%) or reduced (42.9%), and there was no correlation to their hematocrits. However, there was an increment in EPO concentration correlated to their severity of anemia in the most patients with hematological disorders, such as iron deficiency anemia (correlation coefficient r = -0.74), aplastic anemia (r = -0.89), leukemia (r = -0.81), and MDS (r = -0.65). On the other hand, EPO concentration in sera from all the untreated patients with polycythemia vera were significantly low level. But the concentrations of EPO from the patients successfully treated, with normal hematocrit were recovered to normal level. In the patients with secondary polycythemia, there were much varieties in EPO level. Assay of EPO in blood is important not only for diagnosis of polycythemia but also for the analysis of anemia and clinical use of EPO in vivo. The method described here is accurate and technically not complicated, and could be widely induced in most laboratories.

Adolescent↗
PubMed1993

[Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance: Part 2--:Relation to serum iron, UIBC and ferritin in renal failure and hematological disorders].

With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = -0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗