Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 91 records · Page 5Linked to original sources

PubMed1997

Case-control study of leukemia and diagnostic radiation exposure.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

Adolescent↗

PubMed1997

Inhaled low-dose nitric oxide for postoperative care in patients with congenital heart defects.

Postoperative pulmonary hypertensive crisis is a major problem that may account for a substantial part of the postoperative mortality and morbidity. We, therefore, evaluated the effect of inhalation of low-dose nitric oxide (NO) on postoperative care in pediatric patients with pulmonary hypertension. We studied 10 infants and children ages 1-108 months (median age, 11 months) with congenital heart disease associated with pulmonary hypertension. The NO and N2 gas mixture was then mixed with varied quantities of air and oxygen and delivered into a respirator instead of an inspiratory tube. Patients were treated with inhaled NO for 38.6 +/- 19.6 h (range 1-200 h). All patients were eventually weaned from high level sedation and respirator. The NO concentration ranged from 2 to 5 parts per million. During NO inhalation patients demonstrated a statistically significant reduction in systolic pulmonary arterial pressure by approximately 26%; from 55 +/- 10 to 41 +/- 20 mm Hg. Inhalation of NO resulted in a significant increase of Pao2 from 110 +/- 16 to 149 +/- 29 mm Hg. A-aDo2 significantly decreased from 284 +/- 27 to 247 +/- 31 mm Hg. In conclusion, we have shown that a low-dose NO inhalation acted as pulmonary vasodilator in patients with preexisting pulmonary hypertension.

Administration, Inhalation↗

PubMed1997

Comparative assessment of D-xylose absorption between small intestine and large intestine.

The present study aimed to evaluate the absorption of D-xylose, a passively absorbed five-carbon monosaccharide, from the large intestine compared with the small intestine, in order to explore the absorption potential of the large intestine. D-Xylose absorption was evaluated in the intestinal loop and everted sacs in rats and comparisons were made between small intestine (mid-gut) and large intestine (colon). The absorption of D-xylose was smaller, by an order of magnitude or more, after administration into the loop of large intestine than after administration into that of small intestine, based on appearance in plasma and disappearance from the intestinal loop. D-Xylose absorption was practically insignificant (nominal 4.9%) in 60 min in the large intestine, whereas it was moderate (57.0%) in the small intestine. Consistently, the uptake of D-xylose in everted sacs was about 20 times larger in the small intestine than in the large intestine. Thus the passive membrane permeability of D-xylose was demonstrated to be negligible in the large intestine, even though the small intestine was fairly permeable. This result helps rationalize kinetic modelling strategies assuming the small intestine as the sole absorption site for gastrointestinal absorption in-vivo. It also suggests that hydrophilic drugs with molecular size similar to or larger than D-xylose may not be good candidates for colonic drug delivery by controlled release.

Animals↗

PubMed1997

Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine.

The effect of aging on the intestinal transport of hydrophilic drugs (and probe compounds) was investigated in the rat small intestine. Passive transport was suggested to be unchanged with aging from 8 (young) to 54 (old) and further to 101 (very old) weeks old, as shown for D-xylose and urea in single-pass intestinal perfusion (under urethane anesthesia), where steady-state transport across the intestinal membrane into the blood stream was evaluated. The passive transports of cephradine, 5-fluorouracil (5-FU) and L-glucose were also unchanged, though they were compared only between the young and the old. Consistently, the passive uptake in the intestinal everted sacs, where the entry process into the membrane was evaluated for 5-FU, D-xylose, urea and polyethylene glycol (PEG) 900, was unchanged with aging from the young to the very old. The carrier-mediated transport of cephradine was also unchanged with aging from the young to the old in perfusion under anesthesia, though that of D-glucose was declined by about 50% with aging from the young to the old and thereafter remained constant in the very old. In perfusion in unanesthetized rats, age independency in passive transport (examined for cephradine, L-glucose and D-xylose) and an age-dependent decline in D-glucose transport were also observed, suggesting that the findings under anesthesia are not qualitatively distorted. These results suggest that, although carrier-mediated transport may moderately decline with aging, the barrier function of the intestinal membrane to passive permeation of hydrophilic drugs (with molecular weight below 1000) may be unaffected by aging, supporting the suggestion from our previous in vivo studies that age-dependent increases in the orally absorbed fraction may be predicted for incompletely absorbed drugs because of delayed intestinal transit rather than increased intestinal transport (membrane permeability).

Aging↗

PubMed1997

Kinetic characterization of binding and internalization of fractionated [3H]heparin in rat liver parenchymal cells in primary culture.

The binding and internalization of fractionated [3H]heparin (FH) was kinetically analyzed in rat liver parenchymal cells to clarify its cellular uptake mechanism. The binding of FH to the cell surface was saturable with the dissociation constant (Kd) of 53.5 nM and a maximum binding capacity (Bmax) of 19.9 pmol/mg protein. The binding of FH to the cell surface was competitively inhibited not only by heparan sulfate, a polyanion analogous to heparin, but also by rose bengal, an organic anion, suggesting the binding is based on an electric interaction requiring an anionic charge for substrates and consistent with the earlier suggestion of the involvement of the scavenger-like receptor. According to kinetic model analysis, the rate constants of association (K(on)), dissociation (k(off)), and internalization (k(int).app) were estimated to be 0.0005 nM-1 min-1, 0.0112 min-1, and 0.0056 min-1, respectively. Although both Kd and Bmax were larger than those reported in Kupffer cells, suggesting lower affinity and higher capacity in liver parenchymal cells, the apparent internalization rate constant was similar to that in Kupffer cells. We thus provided additional evidence suggesting that a scavenger-like receptor exists in rat liver parenchymal cells, and then kinetically characterized the surface binding and internalization of fractionated heparin by this receptor.

Animals↗

PubMed1997

Erythropoietin in pediatric cardiac surgery: clinical efficacy and effective dose.

We assessed the clinical efficacy and determined the effective dose of erythropoietin (EPO) in 48 children scheduled for open heart surgery without blood transfusion. The children were divided into three groups: group 1 (n=21) was treated with 300 U/kg of EPO; group 2 (n=11) was treated with 150 U/kg of EPO; and group 3 (n=16) was not treated with EPO. EPO was administered on the day of hospital admission (6 to 7 days prior to surgery), on the following day, immediately after surgery, and on the following day. Immediately after surgery, the hemoglobin concentration in groups 1 and 2 was significantly higher than that in group 3. The reticulocyte count in groups 1 and 2 was significantly higher than that in group 3. Open heart surgery was completed without transfusion in all 21 patients in group 1 (100%), 10 of 11 in group 2 (90.9%), and 11 of 16 in group 3 (68.8%). EPO caused no adverse reactions. In conclusion, EPO was effective as an adjuvant therapy for open heart surgery without blood transfusion in children. Administration of a relatively high dose of EPO (300 U/kg) seems to be effective for pediatric patients.

Adolescent↗

PubMed1997

Effect of sex hormones on the tissue localization of nuclear estrogen receptor positively stained cells in the seminal vesicle of immature castrated rats.

We studied the changes in the tissue localization of nuclear estrogen receptor (ER) positively stained cells in the seminal vesicle of immature castrated rats under various environmental conditions of sex hormones by immunohistochemical methods. In castrated rats of 6 weeks of age, the percentage of nuclear ER positively stained cells showed remarkable increase in the periglandular stroma region, but not in the epithelium and the peripheral stroma region. Estrogen administration to castrated rats dramatically increased the percentage of nuclear ER positively stained cells in both the epithelium and the peripheral stroma region, whereas cessation of estrogen treatment caused a significant percentile decrease. These results suggest that the nuclear ER expression in both the epithelial cells and the peripheral stromal cells seems to respond to estrogen. The concomitant treatment of estradiol-17 beta (E2) with 5 alpha-dihydrotestosterone (DHT) completely inhibited these E2 mediated ER expression in the epithelium and the stroma. This result suggests that ER works only when E2 is given in the absence of DHT in the seminal vesicle of immature castrated rats.

Animals↗

PubMed1997

[Repeated dose toxicity studies of taltirelin tetrahydrate (TA-0910) with oral administration to dogs].

Taltirelin tetrahydrate (TA-0910), novel thyrotropin-releasing hormone (TRH) analogue, was orally administered to dogs as dose levels 0.5, 5, and 50 mg/kg for 13 weeks and 0.15, 1.5 and 15 mg/kg for 52 weeks. Blood concentrations of test substance measured in 52-week study revealed that absorption of TA-0910 was with dose-dependent manner and not changed through the treatment period. These toxicokinetics suggested that there were no alterations on metabolism of TA-0910 with repeated treatment. The animals receiving 5 or 50 mg/kg showed decrease in body weight or suppression of body weight gain, and decrease in food intake (13-week study). As an abnormality in general conditions, vomiting and salivation (5 mg/kg or more, both in 13- and 52-week studies), increase in behavior as water intake (5 mg/kg or more, 13-week study), and hyperlocomotion (50 mg/kg) were observed. Elevating GPT values were noted temporally in the animals treated with 5 mg/kg or more (both in 13- and 52-week studies) without abnormal findings in histopathology. The thyroid weights were increased in treated animals receiving 5 or 50 mg/kg in 13-week study, but no histopathological changes were noted. Electron microscopy revealed dilatation of granular endoplasmic reticulums in follicular cells of thyroid from 50 mg/kg group in 13-week study. It was concluded that no-effect levels of 13- and 52-week studies were 0.5 mg/kg and 1.5 mg/kg, respectively.

Administration, Oral↗

PubMed1997

Lhermitte-Duclos disease associated with Cowden's disease--case report.

A 49-year-old Japanese male with Lhermitte-Duclos disease subsequently developed a very rare association with Cowden's disease. Partial tumor removal established the diagnosis of Lhermitte-Duclos disease. Follow-up examinations discovered the presence of Cowden's disease. Long-term follow-up of patients with Lhermitte-Duclos disease is essential to identify signs of Cowden's disease, which carries the risk of developing malignancy.

Cerebellar Neoplasms↗

PubMed1997

[Treatments for T4 advanced lung cancer with invasion to the superior vena cava].

We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.

Adult↗

PubMed1997

[A nonparametric estimation of survival curve with interval censored data].

Although survival analysis dealing with right-censored data has enjoyed wide use, analysis of data with left-censored and interval censored cases is available only to a very limited number of clinical researchers because of the difficulty in understanding the concepts and performing the calculations. This paper applies Turnbull's self-consistency algorithm, which he applied in his paper on survival data with only left-censored cases, for nonparametric estimation of survival curve including both left and interval censored data. A difference in the estimates of survival rate among different modes of calculation was demonstrated using the data from the Hematopoietic Cell Transplantation Registry of the Japan Society for Hematopoietic Cell Transplantation, which illustrated the necessity of a correct analysis.

Algorithms↗

PubMed1996

Convergent evolution. The gene structure of Sulculus 41 kDa myoglobin is homologous with that of human indoleamine dioxygenase.

The abalone Sulculus diversicolor contains abundant myoglobin in its buccal mass. The myoglobin consists of 377 amino acid residues and has a molecular mass of 41 000 Da, 2.5 times larger than that of other myoglobins. Sulculus myoglobin can bind oxygen reversibly, and the P50 was determined to be 3.8 mmHg at 20 degrees C and pH 7.4, showing that the oxygen affinity of Sulculus myoglobin is lower than those of vertebrate and invertebrate myoglobins. The cDNA-derived amino acid sequence showed no significant homology with those of any other invertebrate myoglobins and hemoglobins, but surprisingly showed 35% homology with a vertebrate tryptophan-degrading enzyme, indoleamine dioxygenase (IDO). The structure of the Sulculus myoglobin gene has been determined to consist of 14 exons and 13 introns (15.3 kbp). Compared with the gene of human IDO (10 exon-9 intron structure), the splice junctions of 7 introns were exactly conserved between the two genes, suggesting that these introns have been conserved for at least 600 million years. The Sulculus gene has 5 additional introns, one of which is located outside the coding region. From these results we conclude that Sulculus myoglobin evolved from an IDO gene and represents a typical case of functional convergence. Comparison of the amino acid sequence of each exon of Sulculus myoglobin with those of usual globin sequences showed that there is no significant evolutionary relationship between them. The IDO-like myoglobin is unexpectedly widely distributed among gastropodic molluscs, such as Sulculus, Nordotis, Battilus, Omphalius and Chlorostoma.

Amino Acid Sequence↗

PubMed1996

Synthesis of 1',6'-disubstituted sucroses and their behavior as glucosyl donors for a microbial alpha-glucosyltransferase.

Versatile 6'-chloro-6'-deoxy-1'-substituted sucrose derivatives were synthesized in search of an optimum donor substrate for the intermolecular transglucosylation with the alpha-glucosyltransferase from Protaminobacter rubrum. Two substituents at the C-1' and C-6' positions of sucrose were introduced utilizing the distinct reactivity of the corresponding sulfonates. Methyl beta-D-arabinofuranoside was most efficiently glucosylated with the 1'-deoxy derivative 5. Hydroxyl and fluoro groups at C-1' show a tendency to enhance the intramolecular transglucosylations, giving 3-O-(alpha-D-glucopyranosyl)-D-fructose derivatives.

Bacteria↗

PubMed1996

Effects of fibrin and alpha2-antiplasmin on plasminogen activation by staphylokinase.

Staphylokinase obtains plasminogen activating activity by forming a complex with plasminogen. Although the enzymatic activity of staphylokinase is enhanced by fibrin, how fibrin enhances enzymatic activity has not been determined yet. The effects of fibrin, or fibrinogen fragments, on the activation of plasminogen by staphylokinase was investigated using CNBr-digested fibrinogen fragments (FCB-2 and FCB-5) and plasmin-degraded cross-linked fibrin fragments ((DD)E complex, DD fragments and E fragments). Kinetic analysis of the activity of staphylokinase revealed that its plasminogen activating activity, which was expressed as kcat/Km, was enhanced by FCB-2 (10-fold) and FCB-5 (5-fold). These fibrin fragments caused 38-, 30-, and 8.5-fold increases in activity for the DD fragment, (DD)E complex and E fragment, respectively. Although alpha2-antiplasmin inhibited the activation of plasminogen by staphylokinase, FCB-2 abolished its inhibitory effects, and the plasminogen activating activity of staphylokinase was restored. The inhibitory effects of alpha2-antiplasmin on the activation of mini-plasminogen by staphylokinase were less than for Glu- or Lys-plasminogen, and the inhibitory effect of alpha2-antiplasmin was not altered by fibrin or EACA. These findings indicate that the staphylokinase/plasmin(ogen) complex reacts with fibrin even in the presence of alpha2-antiplasmin, and efficient plasminogen activation takes place on the surface of fibrin.

Aminocaproic Acid↗

PubMed1996

[Invasive amebiasis at an institution for the mentally retarded in Shizuoka Prefecture].

Amebiasis caused by Entamoeba histolytica at an institution for mentally retarded in Shizuoka Prefecture is reported. Five of the 50 patients showed E. histolytica cysts in their stools and 4 were positive serologically. The polymerase chain reaction and restriction fragment length polymorphism revealed that the isolates were pathogenic-type E. histolytica. Epidemiological analysis revealed that the amebic infection was caused by the abnormal behavior of mentally retarded patients. Administration of diloxanide furoate and metronidazole for cyst-carriers eliminated cysts from the stool and lowered the antibody titer.

Adult↗

PubMed1996

Concentrations of trichloroethylene and its metabolites in blood and urine after acute poisoning by ingestion.

A 58-year-old man fell into a trichloroethylene reservoir bath head first, during a maintenance degreasing bath and accidentally ingested the solvent. Although he showed deep coma, chemical burns and pneumonia on admission, these symptoms gradually subsided. The concentrations of trichloroethylene (TRI) and its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were measured during hospitalization. Eight hours after the accident, the concentrations of TRI and its metabolites in serum were 31.4 micrograms/ml TRI, 16.5 micrograms/ml TCE and 79.5 micrograms/ml TCA. The serum TRI concentration decreased to 4.3 micrograms/ml on the following day. Elimination of TCE and TCA from serum occurred biphasically, the estimated half-lives of each metabolites being about 52.6 and 50.4 h in an initial fast phase and 268.3 and 277.2 h in a subsequent slow phase, respectively. Urinary TRI excretion persisted for the first 2 days. The urinary TCE and TCA excretions were longer than that of TRI with a biphasic decrease and the total amount of TCE excreted during the first 2 days was about two times that of TCA. The half-life of urinary TCE excretion (t1/2 25.7 h) was shorter than that of TCA (t1/2 52.1 h) in the fast phase but did no difference during the slow phase, with each half-time being about 166.3 h. The kinetics of TRI metabolites in blood and urine in this case were in slight agreement with the results following inhalation exposure previously reported in the literature.

Accidents, Home↗

PubMed1996

Macromolecule-macromolecule interaction in drug distribution. V. Effects of plasma proteins on uptake of fractionated [3H]heparin in isolated rat Kupffer cells.

Effects of plasma proteins such as alpha-globulin on the uptake of high molecular weight (HMWFH: 23000 Da) and low molecular weight fractionated [3H]heparin (LMWFH: 10000 Da) were examined in isolated rat Kupffer cells. alpha-Globulin (8 mg/ml) affected neither surface binding nor internalization of LMWFH by Kupffer cells, while it reduced both surface binding and internalization of HMWFH without affecting the fraction internalized, which was a ratio of internalized amount to the total association. The total associations of HMWFH were about four times larger than that predicted assuming only the unbound fraction is available for uptake, suggesting the participation of protein-mediated transport in the uptake of HMWFH in Kupffer cells. Based on the same assumption, the saturable initial uptake of HMWFH versus concentration profile in the presence of alpha-globulin (8 mg/ml) was also analyzed to further examine the suggested protein-mediated transport. The estimated dissociation constant of 487 nM was three times larger than that in in vitro binding experiments (168 nM) and the binding capacity of 0.155 was one third of the value in vitro (0.5), suggesting apparent reductions in both binding affinity and capacity. Thus, we demonstrated the involvement of protein-mediated transport in the uptake of fractionated heparin in Kupffer cells and kinetically characterized it as the apparent enhancement of dissociation.

Alpha-Globulins↗

PubMed1996

Dose-dependent gastrointestinal absorption of 5-fluorouracil in rats in vivo.

Dose-dependent gastrointestinal absorption of 5-fluorouracil (5-FU) was kinetically evaluated in rats in vivo by analyzing gastrointestinal disposition after oral administration, where a linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (Ka). With an increase in dose from 1.5 nmol/rat (low dow) to 15 mumol/rat (high dose), the Ka decreased from 5.95 to 0.55 min-1, suggesting the involvement of carrier-mediated transport. This study is the first to demonstrate the dose-dependent gastrointestinal absorption of 5-FU in vivo, though it has long been suggested in situ and in vitro. Meanwhile, at both the low and high doses, the Kg values, which were unaffected by dose (0.069 and 0.082 min-1, respectively, for the low and high doses), were smaller than the Ka values by an order of magnitude or more and the recovery of 5-FU was negligible, compared with that of inulin (a nonabsorbable marker), in the most distal segment of ileum. These results suggest that, regardless of dose, 5-FU is highly absorbable in a gastric emptying-limited manner. Thus, well-publicized bioavailability problems (low and erratic) of 5-FU may be attributable to extensive and variable first-pass metabolism rather than poor and variable gastrointestinal absorption.

Animals↗