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T Yokoyama

Publications and source records attributed to T Yokoyama.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.

A series of 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)- pyrimidinedione derivatives were synthesized and studied for their class III electrophysiological activity and class II (beta-blocking) effects in in vitro and in vivo models. Structure-activity relationships are discussed for a series of compounds. Several members of this series prolonged the action potential duration at 75% repolarization of isolated canine Purkinje fibers and were 10-30-fold more potent than d-sotalol. 1,3-Dimethyl-6-[[2-[N-[3-(4-nitrophenyl)propyl]-N- (hydroxyethyl)amino]ethyl]amino]-2,4-(1H,3H)-pyrimidinedione (40), is one of the most potent compounds in this series.

Animals↗
PubMed1992

Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways.

To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (RL) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For comparison, responses after 1 microgram/kg substance P were also examined. After measurement of RL, microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30 micrograms/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.

Aging↗
PubMed1992

Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a significant rise in arterial PO2 from 84 to 99 Torr. The findings are highly compatible with the idea that HPV is distinctly attenuated in diseases areas induced by oleic acid probably due to a local accumulation of vasodilator prostanoids. Inhibiting prostanoid biosynthesis may selectively enhance the vascular reactivity to O2 in shunt vessels and may redistribute the perfusion from shunt to relatively normal areas, thereby improving gas exchange at alveolar region without altering the total amount of extravascular lung water.

Animals↗
PubMed1992

Effects of lobenzarit on murine acute viral myocarditis.

Lobenzarit (CCA) is a newly developed immunomodulating drug that has been demonstrated to enhance suppressor T-cell number and function. In this study we investigated the effect of CCA on murine myocarditis induced by the encephalomyocarditis (EMC) virus. Mice were first inoculated with the EMC virus. CCA (100 mg/kg) was administered daily for 14 days, starting on the day the mice were inoculated. The concentrations of Lyt2+ (suppressor/cytotoxic T) cells in the peripheral blood and heart were examined by laser flow cytometry and in situ staining. The concentration of Lyt2+ cells increased significantly in the peripheral blood and heart of CCA-treated mice when compared with untreated mice (blood: 23.0 +/- 2.6% vs. 18.8 +/- 2.8%, p less than 0.05; heart: 30.1 +/- 4.6% vs. 15.8 +/- 4.3%, p less than 0.05, respectively). Surprisingly, however, the severity of myocardial inflammation in CCA-treated mice was significantly greater than in untreated mice (area of inflammation: 33.1 +/- 10.5% vs. 18.8 +/- 19.5%, respectively, p less than 0.05). Thus, these findings suggest that CCA may aggravate EMC-induced acute myocarditis by enhancing the number of Lyt2+ cells.

Adjuvants, Immunologic↗
PubMed1992

Rectal bioavailability of 6-mercaptopurine in children with acute lymphoblastic leukaemia: partial avoidance of "first-pass" metabolism.

Plasma levels and the area under the plasma concentration-time curve (AUC) values of 6-mercaptopurine (6-MP) were determined in a balanced crossover study of oral (powder) and rectal (macrogol suppository) administration to 5 children with acute lymphoblastic leukaemia (ALL). The AUC (538.6 ng.h.ml-1) after the rectal dose of 30 mg/m2 was approximately 1.5-times of that (365.5 ng.h.ml-1) after the oral dose of 87.5 mg/m2. The coefficients of variation of interindividual variability of the AUCs were 21.5% and 32.3%, respectively. The relative bioavailability of the macrogol suppository compared to the powder was approximately 4.39. These findings indicate that rectal administration of 6-MP could avoid the first-pass effect of this drug in the alimentary canal and/or liver, resulting in a large AUC of 6-MP, and so could reduce interindividual variability in plasma 6-MP concentrations. Rectal administration of 6-MP may be more effective than empirical oral dosing for the treatment of children with ALL, especially for patients with nausea and/or vomiting.

Administration, Oral↗
PubMed1992

Verbal versus non-verbal visual evoked potentials: Kanji versus line drawings.

Cortical areas related to perception of verbal and non-verbal stimuli were studied using VEPs. Kanji characters, line drawings (LD), or a blank were displayed. Verbal VEPs were obtained by subtracting the blank-VEPs from the Kanji-VEPs, and non-verbal VEPs by subtracting the blank-VEPs from the LD-VEPs. Both the verbal and non-verbal VEPs showed a negative peak (100-300 msec) focally over bilateral occipital, posterior temporal and parietal areas, and a positive peak diffusely over frontal halves. Differences between the non-verbal from the verbal VEPs showed an initial peak (100-200 msec) focally over bilateral occipital and posterior temporal areas, followed by a peak (200-300 msec) focally over bilateral posterior temporal areas. The frontal areas diffusely showed peaks at 100-200, 200-300 and 300-400 msec. Left-right asymmetries of both the verbal and non-verbal VEPs showed peaks between 100 and 300 msec over posterior temporal, parietal, and occipital areas. Left-right asymmetries of the subtraction to the non-verbal from the verbal VEPs showed a peak (100 msec) over occipital and parietal areas, and a broader peak over posterior temporal area (100-200 msec). Bilateral occipital, posterior temporal, and parietal areas are focally activated by the two perceptions (100-300 msec), while frontal areas are activated diffusely. Further, different processes may be focally involved between the hemispheres over occipital (100-200 msec) and posterior temporal (100-200 and 200-300 msec) regions. Initial left-right asymmetries of the subtracted VEP between the two perception would occur over occipital and parietal areas (100 msec) and last for 200 msec over posterior temporal area.

Acoustic Stimulation↗
PubMed1992

Fructose and glucagon loading in siblings with fructose-1,6-diphosphatase deficiency in fed state.

Hypoglycaemia induced by fructose administration is one of the diagnostic clues to fructose-1,6-diphosphatase (FDPase) deficiency (McKusick 229700). However, the pathological mechanism of this reactive hypoglycaemia is not fully known. This paper describes two siblings with FDPase deficiency, diagnosed enzymatically in leukocytes, who failed to correct reactive hypoglycaemia after glucagon administration even in the fed state, supporting a possibility that disturbed hepatic phosphorylase activity may be a main cause of reactive hypoglycaemia.

Blood Glucose↗
PubMed1992

Photoreceptor-specific activity of the human interphotoreceptor retinoid-binding protein (IRBP) promoter in transgenic mice.

In order to define the cellular specificity of the interphotoreceptor retinoid-binding protein (IRBP) promoter in the retina, we linked the human IRBP promoter to the beta-galactosidase (lacZ) gene and made five lines of transgenic mice. In three of the five transgenic mouse lines, retinas showed positive staining upon incubation with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal). Mice from one line (OVE278B) showed positive X-gal staining throughout the retina except for the most peripheral regions. Interestingly, the staining was heterogeneous throughout the retina. Heavily stained regions were interspersed with lightly stained areas. Mice in two other lines showed highly mosaic X-gal staining patterns. Histological examination demonstrated that staining was confined to photoreceptor cells in all three expressing families. Furthermore, electron microscopy showed that the promoter is active in both rod and cone cells. Our results demonstrate that the human IRBP promoter can be used to obtain photoreceptor-specific gene expression in transgenic mice.

Animals↗
PubMed1992

Effects of NZ-105, a new calcium antagonist, on renal function in anesthetized spontaneously hypertensive rats.

The effects of a new dihydropyridine derivative, NZ-105, on renal function were investigated in anesthetized spontaneously hypertensive rats. Intravenous injection of NZ-105 (0.01 and 0.03 mg/kg of body weight) significantly increased the urine flow rate (UV) and renal absolute excretion of sodium and chloride. Potassium excretion also increased significantly, but it was relatively slight in comparison with sodium or chloride excretion. There was a decrease in mean blood pressure (-14.5 +/- 2.3 and -22.3 +/- 3.4 mm Hg, 20 min after the administration of 0.01 and 0.03 mg/kg of body weight, respectively). The glomerular filtration rate (GFR) was not changed; however, the renal plasma flow (RPF) was significantly increased. The tubular site of action of NZ-105 was investigated by the lithium clearance technique. Intravenous injection of NZ-105 inhibited sodium reabsorption beyond the proximal tubules about four to five times more effectively than at the proximal tubules. In conclusion, intravenous administration of NZ-105 in anesthetized spontaneously hypertensive rats caused diuretic and natriuretic action. The possible site of diuretic action may be mainly at the nephron segments beyond the proximal tubules.

Anesthesia↗
PubMed1992

Direct injection analysis of melphalan in plasma using column-switching high-performance liquid chromatography.

An automated column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection is described for a simple and rapid determination of melphalan, an alkylating agent, in human plasma following direct sample injection. The system consists of a pretreatment column and an analytical column connected in series via a switching valve. Plasma samples are loaded onto a pretreatment column with an aqueous mobile phase, with which the sample to be analyzed is retained and the solubilized plasma proteins are flushed to be discarded. The retained compound is eluted from the pretreatment column onto the analytical column by using the chromatographic mobile phase with a higher elution capacity. The column-switching technique can be used to achieve an automated assay. Analytical recovery of the compound was 99.1%, and the coefficients of both intra- and interday variations did not exceed 3.5%. The detection limit was 10 ng/ml for the compound. Recovery of melphalan in plasma was only 2.1% after 4 weeks at 25 degrees C, as compared to 24.5% at 5 degrees C and 100.1% at -20 degrees C.

Adolescent↗
PubMed1992

Maintenance of liver graft viability in the state of brain death. Synergistic effects of vasopressin and epinephrine on hepatic energy metabolism in brain-dead dogs.

The influence of vasopressin and epinephrine on hepatic energy metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) and hepatic energy charge (EC) in brain-dead dogs. Mean arterial blood pressure (MABP) was significantly decreased from 125.5 +/- 5.5 to 53.4 +/- 1.7 mmHg after complete brain death (P less than 0.01). In the control group AKBR and EC were maintained at near the normal values thereafter, despite marked hypotension. Combined administration of vasopressin and epinephrine sustained AKBR normally and improved MABP above 90 mmHg (P less than 0.01). EC was also maintained within the normal range at 5 hr after initiation of administration of the drugs. By contrast, vasopressin or epinephrine alone maintained AKBR and EC at near the normal values, but improved MABP just slightly to around 60 mmHg (P less than 0.01). As for the volume control, the urinary output was significantly smaller in the vasopressin and epinephrine-treated group than in the control group (P less than 0.05). It is suggested that combined administration of vasopressin and epinephrine has a synergistic effect in improving the hemodynamics and maintenance of the energy status of the liver. This regimen is recommended as a good one for maintaining potential liver donors in the state of brain death.

Adenine Nucleotides↗
PubMed1992

Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death.

The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.

Animals↗
PubMed1992

Length of telomeric repeats in neuroblastoma: correlation with prognosis and other biological characteristics.

Telomeres are the physical ends of eukaryotic chromosomes. In view of reports of the reduction of telomeric repeats in human malignant tumors, we measured the lengths of telomeric repeats in 55 primary neuroblastomas. The average lengths of telomeric repeats in these tumors fell in a wide range (from 1.1 kb to more than 23 kb) relative to those in ganglioneuromas and normal peripheral mononuclear cells. The reduction of telomeric repeats was significantly correlated with advanced stages of tumor development, poor prognosis, and increased S-phase fractions in tumor cells. On the other hand, three cases of Stage IV-S tumors showed the reduction of telomeric repeats and low percentage of S-phase fractions. These Stage IV-S patients had a good prognosis with spontaneous regression of metastatic tumors.

Adolescent↗
PubMed1992

Circadian variation in plasma homovanillic acid level during and after alcohol withdrawal in alcoholic patients.

Alcohol withdrawal symptoms in alcoholics were objectively evaluated and classified into three groups according to the severity of their symptoms, and circadian variation in their plasma homovanillic acid (HVA) concentrations was determined at three different intervals after cessation of drinking. The subjects studied were 19 male alcoholic patients and five age-matched healthy male volunteers. Circadian variation in plasma HVA was compared between each patient group and the control group by two-way ANOVA. In the sympathetic overactivity (SO) group comprising nine patients and in the clouding of sensorium (CS) group comprising five patients, plasma HVA concentrations on the 2nd and 3rd day and on the 6th and 7th day after cessation of drinking were low but recovered almost normal levels on the 21st and 22nd postcessation day. The delirium tremens group (DT) comprising five patients, however, showed significantly higher plasma HVA than the control group except on the 6th and 7th postcessation day. The higher plasma HVA in the DT group indicates that there is some sort of preparatory state whereby dopamine metabolism is involved in the appearance of hallucinations at alcohol withdrawal and can possibly be used as a predictor of otherwise hardly predictable delirium tremens.

Adult↗
PubMed1992

[Rapid diagnosis of cytomegalovirus pneumonia and Pneumocystis carinii pneumonia by using polymerase chain reaction DNA amplification].

We attempted to detect cytomegalovirus DNA (CMV-DNA) and Pneumocystis carinii DNA (carinii-DNA) in urine, blood and sputum samples of 16 leukemia patients with pneumonia, using the polymerase chain reaction (PCR). Synthetic oligonucleotide primer pair were used to amplify DNA from the major immediately genes of CMV and genes for the large subunit of mitochondrial ribosomal RNA of P. carinii. Amplified products were detected by gel electrophoresis. In two cases, CMV-DNA was detected at about the time the pneumonia occurred, and in one of the two cases, CMV-DNA was detected in the sputum sample. This patient was treated immediately with ganciclovir. After ganciclovir treatment, clinical and biochemical signs of CMV pneumonia disappeared. In three cases, carinii-DNA was detected in their sputum samples. In their blood and urine samples, carinii-DNA were not detected. This three cases were treated with sulfamethoxazole-trimethoprim and successfully treated episodes of P. carinii pneumonia. We conclude that PCR amplification may be a valuable tool for rapid diagnosing CMV pneumonia and P. carinii pneumonia.

Base Sequence↗
PubMed1992

Granulocyte colony-stimulating factor does not enhance endotoxin-induced acute lung injury in guinea pigs.

We studied recombinant human granulocyte colony-stimulating factor (G-CSF) in terms of its hematopoietic and neutrophil-activating effects on acute lung injury induced by endotoxin. Guinea pigs were divided into four groups: (1) saline control animals, (2) endotoxin alone, (3) cyclophosphamide (CPA)+endotoxin, and (4) G-CSF+endotoxin. A G-CSF dose of 20 micrograms/kg was given subcutaneously twice a day for 5 days. Animals were observed for 4 h after intravenously administered endotoxin (0.02 and 2.0 mg/kg) with serial measurements of complete blood counts and hemodynamics. Lung extravascular water, [125I]albumin leakage in lung tissue, and histopathologic features were examined at death. The endotoxin-alone group showed peripheral leukopenia, transient hypotension, excess lung water, increased albumin leakage, PMN accumulation in lung tissue, and gross histopathologic edema. G-CSF-treated animals showed attenuated responses in peripheral leukopenia, excess lung water, and albumin leakage in comparison with the endotoxin-alone group. No augmented responses were seen in the G-CSF group. The CPA+endotoxin group also had attenuated lung injury, which was similar to that in the G-CSF group. In conclusion, pretreatment with G-CSF tended to attenuate rather than enhance neutrophil-dependent acute lung responses to endotoxin.

Animals↗