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Biomedical subjects

T Yokoyama

Publications and source records attributed to T Yokoyama.

At least 19 recordsLinked to original sources
PubMed1995

Antithrombotic effects of orally active synthetic antagonist of activated factor X in nonhuman primates.

BACKGROUND: Since activated factor X (FXa) has a central role in hemostasis and thrombosis, it is an attractive target for antithrombotic strategies. Accordingly, we evaluated the relative antihemostatic and antithrombotic effects of an orally active amidinoaryl propanoic acid inhibitor of FXa, APAP, in baboons. METHODS AND RESULTS: With a two-component thrombogenic device that induced the concurrent formation of both arterial-type platelet-rich and venous-type fibrin-rich thrombus when interposed in chronic exteriorized arteriovenous (AV) femoral shunts flowing at 40 mL/min, thrombus formation was compared for oral versus parenteral APAP by measurement of 111In-platelet deposition, 125I-fibrin accumulation, thrombotic obstruction of flow, and circulating levels of blood biochemical markers of thrombosis. The direct infusion of APAP (120 micrograms/min) into AV shunts proximal to thrombogenic devices for 1 hour achieved local drug levels of 4.3 +/- 0.4 mg/L and substantially reduced the accumulation of platelets and fibrin in the formation of venous-type fibrin-rich thrombus (P < .01) but not in the formation of platelet-rich arterial-type thrombus (P > .1). APAP was subsequently removed from plasma with plasma clearance rates of T50 alpha of 6.3 minutes and T50 beta of 99 minutes. The oral administration of APAP (50 mg/kg) produced peak plasma levels of 3.7 +/- 1.4 micrograms/mL at 30 minutes and gradually declining plasma levels over about 6 to 8 hours, with bioavailability estimated to be approximately 5% to 12%. Oral APAP decreased platelet deposition (P < .01) and fibrin accumulation (P < .05) in venous-type thrombus but failed to decrease platelet or fibrin accumulation in arterial-type thrombus (P > .1 in both cases). Oral and infused APAP prolonged the activated partial thromboplastin time and prevented thrombus-dependent elevations in plasma fibrinopeptide A, thrombin-antithrombin III complex, beta-thromboglobulin, and platelet factor 4 levels. Additionally, APAP produced dose-dependent inhibition of FXa bound to thrombus on segments of vascular graft interposed in exteriorized AV shunts for 15 minutes. CONCLUSIONS: An oral synthetic antagonist of FXa, APAP, inhibits the formation of venous-type fibrin-rich thrombus by inactivating bound and soluble FXa without impairing platelet hemostatic function.

Administration, Oral↗
PubMed1995

Telomerase activity in gastric cancer.

Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.

Base Sequence↗
PubMed1995

Cutaneous oxalate deposition in a hemodialysis patient.

We describe calcium oxalate and amyloid arthropathy with cutaneous calcinosis without vitamin C supplement. A 34-year-old woman developed glomerulonephritis requiring chronic hemodialysis. Seven years after beginning hemodialysis, multiple crystal deposits appeared in her skin; she also presented with arthralgia and gait disturbance. A skin biopsy was performed, which disclosed calcium oxalate deposition. In addition, a right femoral neck prosthetic replacement was performed. Pathologic examination of the hip synovia revealed diffuse calcium oxalate, amyloid, and iron deposition. Calcium oxalate and amyloid arthropathy with synovial hemosiderosis was diagnosed, and therapy with desferal and high-flux membrane dialysis was started. Clinical improvement occurred after 6 months.

Adult↗
PubMed1995

Effect of green tea rich in gamma-aminobutyric acid on blood pressure of Dahl salt-sensitive rats.

gamma-Aminobutyric acid (GABA) is known to be involved in the regulation of blood pressure by modulating the neurotransmitter release in the central and peripheral sympathetic nervous systems. This study investigated the antihypertensive effect of green tea rich in GABA (GABA-rich tea) in young and old Dahl salt-sensitive (S) rats. GABA-rich tea was made by fermenting fresh green tea leaves under nitrogen gas. In experiment 1, 21 11-month-old rats, fed a 4% NaCl diet for 3 weeks, were given water (group W), an ordinary tea solution (group T), or a GABA-rich tea solution (group G) for 4 weeks. The average GABA intake was 4.0 mg/rat per day. After 4 weeks of the treatment, blood pressure was significantly decreased in group G (176 +/- 4; P < .01) compared with group W (207 +/- 9) or group T (193 +/- 5 mm Hg). Plasma GABA levels were more elevated in group G (111 +/- 54) than in group W (not detectable) or group T (14 +/- 8 ng/mL; P < .01 v G). In experiment 2, 21 5-week-old rats, fed a 4% NaCl diet, were divided into groups W, T, and G. The average GABA intake was 1.8 mg/rat per day. Body weight or chow and beverage consumption did not differ significantly among the three groups. After 4 weeks of the treatment, although blood pressure was comparable in groups W and T (165 +/- 3 v 164 +/- 5 mm Hg, mean +/- SE), it was significantly lower in group G (142 +/- 3 mm Hg) than in the other groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.

Animals↗
PubMed1995

Correlating telomerase activity levels with human neuroblastoma outcomes.

Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase activity was not detected in normal adrenal tissues or benign ganglioneuromas, almost all neuroblastomas (94%) did express it, suggesting an important role for telomerase in neuroblastoma development. Neuroblastomas with high telomerase activity had other genetic changes (for example, N-myc amplification) and an unfavourable prognosis, whereas tumours with low telomerase activity were devoid of such genetic alterations and were associated with a favourable prognosis. Three neuroblastomas lacking telomerase activity regressed (stage IVS). Thus telomerase expression may be required as a critical step in the multigenetic process of tumorigenesis, and two different pathways may exist for the development of neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1995

Transient dilatation of the abdominal aorta in an infant with Kawasaki disease associated with thrombocytopenia.

We report on an 8 month old infant with Kawasaki disease associated with giant coronary aneurysms and transient thrombocytopenia. The patient's platelet count decreased to 24,000/mm3 on the 31st day of illness and fibrin degradation product was 5 micrograms/mL. Platelet count increased to the normal level (357,000/mm3) on the 35th day of illness. On the 27th day of illness, dilatation of the distal abdominal aorta adjacent to the bifurcation of the iliac arteries was observed by B-mode and color Doppler ultrasonography. It gradually returned to a normal size by the 45th day of illness. Aspirin administered from the 3rd to the 26th day of illness was replaced with flubioprophen because of liver dysfunction. Although we can not eliminate aspirin allergy as the cause of the transient thrombocytopenia, we think that the thrombocytopenia may have been related to the regression of the abdominal aorta.

Aortic Aneurysm, Abdominal↗
PubMed1995

Effect of Kil769, a novel K(+)-channel opener, on sensitivity to Ca2+ of contractile elements and inositol phosphate formation in porcine coronary artery.

To determine whether Kil769, a novel K(+)-channel opener, acts intracellularly in vasorelaxation, we compared the effects of Kil769 on force of contraction, intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP1) formation with those of Ca(2+)-channel blockers in isolated porcine coronary artery. Kil769 (10 microM) and verapamil (1 microM), which produced submaximal relaxation, reduced the increase in [Ca2+]i and force of contraction induced by 25 mM KCl. Verapamil reduced [Ca2+]i and the force of contraction to a similar extent but Kil769 reduced force of contraction more strongly than it did [Ca2+]i. Kil769 also inhibited U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha)-induced IP1 formation and glibenclamide blocked its inhibitory effect. These results suggest that the opening of K+ channels induced by Kil769 reduces the Ca2+ sensitivity of contractile elements and inositol phospholipid hydrolysis which is related to the Ca2+ release from intracellular storage.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Preparation and characterization of antibodies against mouse prion protein (PrP) peptides.

Antisera were raised in rabbits against three peptides, representing amino acid sequences 150 to 159, 165 to 174, and 213 to 226 of mouse prion (PrP), which were synthesized by using a multiple antigenic peptide (MAP) system. The reactivities of these sera to PrP were examined by an enzyme-linked immunosorbent assay (ELISA), Western immunoblotting (WB), and immunohistochemical procedures. The results of both ELISA and WB showed that antisera to peptide sequence 150 to 159 (Ab150-159) did not react with purified mouse PrP. On the other hand, sera to the sequence 165 to 174 (Ab165-174) reacted weakly with purified mouse PrP, as detected by WB but not by ELISA. However, antiserum to peptide sequence 213 to 226 (Ab213-226) reacted strongly with mouse, Syrian hamster, and sheep PrP by WB and with mouse PrP as shown by the results of ELISA. Moreover, Ab213-226 clearly detected PrP immunohistochemically in mouse, Syrian hamster, and sheep brains affected with scrapie as well as in the brain of a cow with bovine spongiform encephalopathy. From these data, we conclude that rabbit antiserum against the MAP representing amino acid sequence 213 to 226 of mouse PrP is useful as a diagnostic tool for prion disease of animals.

Amino Acid Sequence↗
PubMed1995

Soluble TNF binding proteins modulate the negative inotropic properties of TNF-alpha in vitro.

Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-alpha in isolated contracting cardiac myocytes. Three TNF-BPs were evaluated: two natural monomeric human TNF monomeric binding proteins, TNF-BP1 and TNF-BP2, and sTNFR:Fc, a dimer of two molecules of human TNF-BP2 linked by the Fc portion of the human immunoglobulin G1 molecule. When TNF-alpha (25 pM) was allowed to form TNF-BP-TNF-alpha complexes, the negative inotropic effects of TNF-alpha were completely prevented by "neutralizing concentrations" of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-alpha. The dimeric binding protein sTNFR:Fc was more effective on a molar basis than either of the monomeric binding proteins (TNF-BP1 or TNF-BP2) with respect to blocking the negative inotropic effects of TNF-alpha. When cardiac myocytes that had been treated with TNF-alpha (25 pM) were exposed to neutralizing concentrations of TNF-BP1, TNF-BP2, and sTNFR:Fc, the negative inotropic effects were completely reversed within 30 min. Thus these studies show for the first time that TNF-BPs are sufficient to prevent, as well as reverse, the negative inotropic properties of TNF-alpha in vitro.

Animals↗
PubMed1995

Chronological changes of arterial diameter, cGMP, and protein kinase C in the development of vasospasm.

BACKGROUND AND PURPOSE: We hypothesized that nitric oxide exerts a negative feedback control on protein kinase C (PKC) activation, and the disturbance of the feedback control after subarachnoid hemorrhage results in vasospasm due to PKC activation. This study was undertaken to verify this hypothesis. METHODS: Different dogs were prepared for three separate experiments: measurement of the angiographic diameter of the basilar artery and determination of cGMP and PKC activity in vascular smooth muscle cells. In each experiment, two models were used: the single-hemorrhage model for mild vasospasm and the two-hemorrhage model for severe vasospasm. In both models, chronological changes of these three parameters were examined from day 1 until day 7. RESULTS: In the single-hemorrhage model, mild vasospasm and a slight decrease of the cGMP level were noted on day 4, then both returned to the baseline levels on day 7. PKC activity was slightly enhanced throughout the study period. In the two-hemorrhage model, severe vasospasm and a significant decrease of the cGMP level were observed on day 5 and persisted until day 7. PKC activity was remarkably enhanced from day 5 until day 7. The differences between the two models with regard to the three parameters were statistically significant. CONCLUSIONS: The decrease of cGMP level and the enhancement of PKC activity were obviously associated with the development of severe vasospasm. We conclude that subarachnoid hemorrhage disturbed the feedback control exerted by nitric oxide on PKC activation, leading to PKC-dependent vasospasm.

Animals↗
PubMed1995

Transport mechanism of anthracycline derivatives in rat polymorphonuclear leukocytes: effect of sodium fluoride on pirarubicin uptake.

We previously revealed that pirarubicin (THP) was actively taken up by rat polymorphonuclear leukocytes via a carrier-mediated transport system. In the experiment on the effects of the metabolic inhibitors, rotenone, 2,4-dinitrophenol and sodium cyanide significantly decreased the THP transport. However, sodium fluoride (NaF) significantly increased the uptake, and this result is different from that in some reports. Therefore, we examined the action of NaF on THP uptake by the leukocytes to clarify the discrepancy in the effect of NaF on drug transport. The accelerating effect of 30 mM NaF on the THP uptake by the cells had an optimum period of action (15-20 min), and was concentration-dependent (5-30 mM). Thirty mM potassium fluoride, as well as NaF, increased the uptake amount. On the other hand, NaF (5-30 mM) dose-dependently decreased the ATP content in these cells. Additionally, the viable cells in the reaction suspension decreased by about 40% after incubation with 30 mM NaF for 15 min. Observing these leukocytes treated with NaF by optical microscopy, swelling of the cell and an alteration of the nuclei form occurred. On the basis of these results, we speculated that the increased THP transport in polymorphonuclear leukocytes by NaF, probably F-, might be due, at least in part, to an alteration of the morphological form.

Animals↗
PubMed1995

A sensitive postcolumn derivatization/UV detection system for HPLC determination of antitumor divalent and quadrivalent platinum complexes.

A sensitive postcolumn derivatization/UV detection system has been developed for HPLC analysis of antitumor divalent and quadrivalent platinum complexes. It is based on the derivatization of platinum complexes by reaction with sodium bisulfite to corresponding product(s) which has enhanced absorptivity at 280-300 nm. Platinum complexes examined in this study were cisplatin, carboplatin and oxaliplatin (divalent platinum complexes) and oxoplatin and tetraplatin (quadrivalent ones). The proposed detection system was sensitive to all these complexes. Under the detection conditions optimized for individual complexes, the HPLC gave linear relationships between the complex concentration and the peak height. Detection limits at 290 nm with 100 microliters injection were 20 nM for cisplatin, 40 nM for oxoplatin, 60 nM for carboplatin and tetraplatin and 100 nM for oxaliplatin (S/N = 3 at 0.005 AUFS). The proposed system was successfully applied for the determination of cisplatin and oxoplatin in plasma and urine. Pharmacokinetic behavior of oxoplatin and its reduced product cisplatin following a single intravenous injection of oxoplatin in rabbits has been discussed.

Animals↗
PubMed1995

Pulmonary embolism after cerebral angiography--three case reports.

Three patients developed acute pulmonary embolism after cerebral angiography. The diagnoses were based on the clinical symptoms and echocardiography, chest roentgenography, blood gas analysis, and pulmonary perfusion scans after intravenous injection of 5 mCi of technetium-99m-labeled human albumin macroaggregates. Two of the three patients achieved clinical improvement, but one patient with severe embolization and circulatory deterioration died in spite of anticoagulation therapy. Recognition of the potential risk of pulmonary embolism after angiography and active prophylaxis are most important in preventing this complication.

Adult↗
PubMed1995

Hormone receptors in pulmonary lymphangiomyomatosis.

Biochemical assays have demonstrated the existence of hormone receptors in lung tissue from patients with pulmonary lymphangiomyomatosis (LAM). This finding is the biologic corollary to the finding that LAM responds to hormonal therapy. We have examined lung tissue from two patients with LAM for estrogen and progesterone receptors by immunohistochemistry and a biochemical assay. Although specimens from both patients were negative for estrogen receptor activity by the biochemical assay, positive stain of estrogen receptors was observed in both patients with immunohistochemistry.

Adult↗
PubMed1995

[Endocrinological analysis before and after living-related renal transplantation in a patient of Bartter's syndrome].

In order to clarify endocrinological changes before and after living-related renal transplantation in a patient of Bartter's syndrome involving chronic renal failure, serial quantitative determinations of the renin-angiotensin-aldosterone system and 24-hour urinary excretion of 6-keto-prostaglandin F1 alpha and kallikrein were performed. A male patient was admitted to hospital because of a pale face and short stature at the age of 13 years. He was 126 cm in height (M-3.8SD). Blood pressure was 110/60 mmHg and edema was not observed. Laboratory findings showed that his hematocrit was 22.1%, serum potassium 2.9 mEq/1, creatinine clearance was 30.7 ml/min/1.73m2 and beta 2-microgobulin was elevated to 39.9 mg/1 in urinalysis. Plasma renin activity and aldosterone were remarkably elevated to 24.23 ng/ml/hr and 738 pg/ml, respectively. The kidney biopsy specimen showed diffuse glomerulosclerosis and hypertrophic change of the juxtaglomerular apparatus was also demonstrated. He was diagnosed as Bartter's syndrome with short stature and chronic renal failure. At the age of 18, he was introduced on hemodialysis and the living-related renal transplantation was performed the next year. Two weeks after the transplantation, plasma renin activity, angiotensin, I,II and aldosterone were markedly changed from 37.8 to 2.3 ng/ml/hr, 2400 to 220 pg/ml, 256 to 17 pg/ml and 3700 to 110 pg/ml, respectively. Urine prostaglandin F 1 alpha was improved from 860 to 321 ng/day and kallikrein was also changed from 400 to 25.2 micrograms/day. These results indicated that abnormalities of several hormones in Bartter's syndrome could be normalized by living-related renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗