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Biomedical subjects

N Takagi

Publications and source records attributed to N Takagi.

At least 217 records · Page 12Linked to original sources
PubMed1989

[The pharmacokinetics of cisplatin and its influence on renal function according to different infusion methods (report II)--alleviation of renal impairment by bismuth subnitrate combined with ginseng and tang-koui ten].

In the previous report, we discussed in vivo dynamics and renal impairment resulting from the difference in cisplatin CDDP administration. In the present study, we investigated in vivo dynamics and renal impairment under 1 h of continuous drip infusion of CDDP. The free-type Pt concentration ratio, which is considered to indicate antitumor activity in the overall plasma Pt concentration at the end of the administration, was noted to be approximately 64%. This was significantly higher than other administration methods, making this an effective administration procedure. However, NAG, which is considered to be an index of renal impairment along with the amount of beta 2-microglobulin urine excretion, showed higher values than those by other administration methods. Thus, using the 1-hr continuous CDDP drip infusion, we attempted to alleviate the renal impairment, combining bismuth subnitrate with ginseng and Tang-koui ten. As a result, the amount of beta 2-microglobulin excretion in the urine was diminished as well as NAG, and a reduction of the renal impairment was noted. These alleviational effects of the renal impairment were attributed to the method of consistent oral administration by which alleviation could take place with little load on the patient.

Acetylglucosaminidase↗
PubMed1989

High-performance liquid-chromatographic analysis for serotonin and tryptamine excreted in urine after oral loading with L-tryptophan.

We describe a method used for determining serotonin and tryptamine in urine after oral loading with their precursor amino acid. Several factors affecting prepurification and chromatographic separation of both indoleamines were optimized, including sample extraction and mobile-phase composition. Under optimal conditions, serotonin and tryptamine are extracted from urine samples together with an internal standard, and then they are separated by reversed-phase chromatography followed by native fluorescence detection. The analytical procedure is simple enough to apply to routine analysis and performable at low cost. Sensitivity and selectivity of the method are satisfactory enough to determine urinary serotonin and tryptamine. By pursuing urinary excretion of serotonin and tryptamine after oral loading with L-tryptophan (30 mg per kilogram body weight), our method proves that urinary excretion of both indoleamines increases immediately after loading and reaches a maximum in about 45 min.

Adult↗
PubMed1988

Requirement of mitoses for the reversal of X-inactivation in cell hybrids between murine embryonal carcinoma cells and normal female thymocytes.

By means of a 5-bromodeoxyuridine (BrdU) incorporation and acridine orange fluorescence staining method we studied reactivation of the inactivated X chromosome (Xi) in newly formed cell hybrids between the near-diploid HPRT-deficient OTF9-63 murine embryonal carcinoma cell (ECC) with an XO sex chromosome constitution and the normal female mouse thymocyte. As reported earlier, most near-tetraploid hybrid cells were ECC in morphology and retained all chromosomes from both parents including three X chromosomes. Synchronization of the late replicating X chromosome in such hybrid cells, indicative of reactivation, was found for the first time on Day 3, and the frequency of reactivation was attained 90% on Day 5. Inhibition of cell cycle progression either by methylglyoxal bis(guanylhydrazone) dihydrochloride, an inhibitor of polyamine metabolism, or by isoleucine-deficient medium after cell fusion delayed reactivation of the Xi, which implied that the number of cell division cycles traversed by individual cells rather than the length of time after cell fusion is critical for the reactivation. Double-labeling experiments using [3H]thymidine and BrdU indicated that hybrid cells had undergone three or four mitoses before reactivation of the Xi. Most probably reactivation of the Xi is consequent to reversion of the thymocyte genome to an undifferentiated state under the influence of OTF9 genome. DNA demethylation or dilution of Xi-specific factors by mitoses may be involved in this process.

Animals↗
PubMed1988

Nonhistone nuclear proteins specific to certain mouse embryonal carcinoma clones having an inactive X chromosome.

By means of one-dimensional polyacrylamide slab gel electrophoresis nonhistone nuclear proteins were compared in murine embryonal carcinoma cell clones with two X chromosomes; both are active in some clones and one of them is inactive in others and in a population of cells having only one X chromosome. Under our experimental conditions, we succeeded in finding two extra bands at approximately 46,000 Da in cells having an inactive X chromosome. Furthermore, a band at approximately 71,000 Da was significantly heavier in cells having an inactive X chromosome than in those having two active X or those having only one X chromosome.

Animals↗
PubMed1988

Antihypertensive effects and pharmacokinetics of single and consecutive doses of cilazapril in hypertensive patients with normal and impaired renal function.

The antihypertensive effects and pharmacokinetic properties of cilazapril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF; n = 5) and those with impaired renal function (IRF; n = 7). A 1.25-mg dose of cilazapril was administered orally once a day for 5 or 8 days. Measurement of blood pressure and sampling of blood specimens were done on the first and last days of treatment. Cilazapril induced significant falls in systolic and diastolic blood pressures as early as 1 h after administration. The antihypertensive effects were still present at 24 h postdose. Serum ACE activity was markedly suppressed over 24 h, with the enzyme inhibition greater in the IRF group. Plasma levels of the active diacid in the IRF group were higher than those in the NRF group, with significant differences in the peak levels and areas under the curve (AUC). A significant inverse correlation was found between the creatinine clearance and the AUC for the diacid. Cilazapril was well tolerated by all the patients, and no adverse reactions were observed. These results suggest that cilazapril has a long-lasting action and that it is a useful antihypertensive agent for controlling blood pressure in patients with either NRF or IRF.

Administration, Oral↗
PubMed1987

Absence of the hybrid bcr-abl mRNA in Ph1-positive B lymphoblastoid cell lines established from a patient with chronic myelogenous leukemia.

The expression of c-abl, c-sis, c-myc and N-ras oncogenes was examined in 2 lymphoblastoid cell lines, one with Ph1 (PB-1049) and the other without Ph1 (LN-1049), both established from a patient with chronic myelogenous leukemia (CML), and in a Ph1-positive cell line (PB-1049-T) derived from a tumor formed after transplantation of PB-1049 cells in a nude mouse with reference to their tumorigenic potential in nude mice. The normal transcripts of c-abl were detected in all 3 lymphoblastoid cell lines. Although in situ hybridization of v-abl proved, and restriction endonuclease analyses of the bcr region strongly indicated the occurrence of bcr-abl rearrangement in PB-1049 and PB-1049-T, we could not obtain any evidence for the expression of the hybrid bcr-abl mRNA. These results indicate that the Ph1 translocation does not ensure the production of the hybrid bcr-abl mRNA, and that the expression of hybrid bcr-abl gene is not essential for the maintenance of tumorigenicity of these cell lines. Expression of c-sis was not detected in any of the cell lines examined, whereas the expression of c-myc was uniformly higher in the 3 cell lines than in normal control cells. The levels of N-ras expression varied considerably, probably in parallel with the changes in tumorigenicity of the cell lines. N-ras expression in the PB-1049 and PB-1049-T cell lines was higher than that in the LN-1049 line when they retained tumorigenic potential, but it fell to the level of LN-1049 with loss or decline of tumorigenicity.

Fusion Proteins, bcr-abl↗
PubMed1987

Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation.

DNA sequences have previously been identified in the first intron of the mouse Hprt gene that are methylated on the inactive but not the active X chromosome. The temporal relationship between methylation of these sequences and X-inactivation was studied in teratocarcinoma cells and postimplantation mouse embryos: the sequences are unmethylated prior to X-inactivation and do not become methylated on the inactive X in most fetal cells until several days postinactivation. Such inactive X-specific methylation occurs in a significantly smaller proportion of the cells in the extra-embryonic tissues, yolk sac mesoderm and endoderm, than in the fetus. These data suggest that the inactive X-specific methylation of sequences such as those in the first intron of the Hprt gene does not play any role in the primary events of X-inactivation, but may function as part of a secondary, tissue-specific mechanism for maintaining the inactive state.

Animals↗
PubMed1987

Determination of catecholamines in rat tissues by high-performance liquid chromatography using a precolumn fluorescence labeling method.

A high-performance liquid chromatographic method using solid-phase dansylation on alumina for precolumn fluorescence label has been developed for the determination of catecholamines (norepinephrine, epinephrine, and dopamine) in various rat tissues. After alumina treatment of the tissue homogenate, catecholamines adsorbed on the alumina were dansylated by solid-phase reaction. Both the excess reagent and fluorescent degradation products produced during dansylation were washed out from the alumina. Dansylated catecholamines were eluted from the alumina and separated by reversed-phase high-performance liquid chromatography. The four catecholamine derivatives, including the internal standard, were separated within 17 min, and no major interfering peak could be detected on any chromatograms. The calibration graph showed a good linearity in a range of 10 to 500 pmol for each catecholamine per sample. This method was applied to different rat tissues, and both the recovery and the reproducibility for all samples proved to be satisfactory. The present study provides a simple, sensitive, and selective method useful for routine pharmacological experiments of the determination of catecholamines.

Animals↗
PubMed1987

Facial reconstruction with latissimus dorsi myocutaneous island flap following total maxillectomy.

Following total maxillectomy for maxillary cancer, facial reconstruction was performed using a latissimus dorsi myocutaneous island flap. Postreconstructive deformity was studied in 10 patients. In 5 patients, after simple total maxillectomy the inner raw surface of the facial skin and orbito was covered by the flap, and the other extended total maxillectomy patients where the orbital contents and facial skin were involved, reconstruction was by means of the folded flap. In the patients with simple total maxillectomy, cicatricial contracture of the facial skin and cicatricial ectropion of the lower eyelid were quite small, and in the patients with extended total maxillectomy, reconstructed facial skin did not give rise to cicatricial contracture.

Cicatrix↗
PubMed1987

Antihypertensive effects and pharmacokinetics of single and consecutive administration of doxazosin in patients with mild to moderate essential hypertension.

A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once daily (o.d.) for evaluation of its consecutive dosing effect. The antihypertensive effect, pharmacokinetics, and effects on the plasma renin activity (PRA) of doxazosin were investigated. Following a 2-mg single dose of doxazosin, the systolic blood pressure (SBP) decreased significantly up to 12 h, whereas consecutive dosing produced a significant decrease in the SBP up to 24 h and a significant decrease in the mean blood pressure up to 24 h as compared with placebo. The pharmacokinetic parameters of doxazosin in both single- and consecutive-dose study were 18.9 and 25.8 ng/ml in Cmax, 11.1 and 12.9 h in half life (t1/2), and 182.0 and 273.0 ng h/ml in area under the curve (AUC)24(0), respectively. No significant changes were observed in PRA and plasma concentration of catecholamines. Neither were there any observable changes in endogenous creatinine clearance and in the urinary excretion rates of Na, K, and Cl. Doxazosin was well tolerated by all patients, and no untoward effects were observed. Doxazosin effectively reduces blood pressure and, because of its long t1/2 and minimal effects on PRA catecholamines, and electrolytes, seems to be a useful antihypertensive agent in patients with essential hypertension.

Adult↗
PubMed1987

Renal haemodynamics and comparative effects of captopril in patients with benign- or malignant-essential hypertension, or with chronic renal failure.

Effects of captopril on arterial pressure (AP) and renal function were investigated in patients with non-malignant "benign" or malignant phase essential hypertension (EH group), or with chronic renal failure (CRF group). After captopril administration, AP and renal vascular resistance (RVR) decreased significantly, and renal blood flow (RBF) and plasma renin activity (PRA) increased in both groups. Glomerular filtration rate (GFR) increased in the EH group, but was unchanged in CRF. Filtration fraction decreased in the malignant hypertension and CRF groups. Significant correlations were found between baseline PRA and baseline RVR, and the captopril-induced decrease in mean AP, decrease in RVR, increase in RBF, and increase in GFR in the EH group, while these associations were not observed in CRF. These results indicate that the high AP, RVR, suppressed RBF and GFR in the EH group were closely related to activity of the renin-angiotensin system, but not so the low RBF and GFR in CRF. Small doses of captopril may improve impaired renal function in EH, and may not cause deterioration in the CRF group.

Captopril↗
PubMed1987

[The pharmacokinetics of cisplatin and its influence on renal functions based on different infusion methods].

The pharmacokinetics of cisplatin, together with its renal toxicity in relation to different infusion methods were examined. The subjects were 21 in-patients suffering from pulmonary carcinoma treated by anti-neoplastic agents including cisplatin. The patients included 12 given a 5-division dosage, 5 cases given 24-hour continuous infusion, 6 given 12-hour continuous infusion, and 7 given 6-hour continuous infusion. Cisplatin was determined as the concentrations of Pt in plasma and non-protein-bound Pt. Also, as indices of renal function, NAG in urine together with beta 2-microglobulin were examined. No substantial difference could be found in Pt concentration in plasma upon completion of the respective infusion methods. A dual-phase attenuation curve was obtained after the completion of infusion and the half-life period of the beta-phase was around 200 hours. With respect to non-protein-bound Pt concentrations, the 5-division dosage showed the highest value, which was considered to be a temporary phenomenon, while with continuous infusion, the shorter the infusion period, the higher the value became. With respect to the amount of NAG excreted in urine, 12-and 6-hour continuous infusion showed the higher value in comparison with the others in terms of the maximum value and the total amount. With regard to beta 2-microglobulin, 6-hour continuous infusion showed the highest value. The above results therefore suggest that in continuous infusion, the shorter the infusion period the greater the degree of renal tubule injury, and that particularly, 6-hour continuous infusion will possibly cause dysfunction of the renal tubules.

Acetylglucosaminidase↗