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Biomedical subjects

Y Takagi

Publications and source records attributed to Y Takagi.

At least 523 records · Page 29Linked to original sources

Multihormonal regulation of transcription of the tryptophan 2,3-dioxygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the action of glucocorticoids.

For study of hormonal regulation of gene expression of tryptophan 2,3-dioxygenase (EC 1. 13. 11. 11, TO), a DNA clone containing a sequence complementary to TO mRNA was prepared with TO mRNA from rat liver enriched 62-fold by immunoadsorption. Primary cultures of adult rat hepatocytes were treated with dexamethasone, and the amount of TO mRNA was measured by RNA dot-blot hybridization with this TO cDNA. Dexamethasone induced this TO mRNA 7-fold, while their treatments with dexamethasone plus glucagon induced the TO mRNA 18-fold. This induction of TO mRNA by dexamethasone plus glucagon was inhibited by insulin or epinephrine. Studies on transcription in isolated nuclei showed that these hormonal changes in the level of TO mRNA were caused by changes in the rate of transcription of the TO gene. Thus, expression of TO in the liver is regulated multihormonally at the transcriptional step. There was a long lag period before stimulation of transcription of the TO gene by dexamethasone in hepatocytes cultured for 20 h: the maximal rate was attained after 6-8 h. The lag time depended on the culture time without dexamethasone and was shorter after shorter culture of the cells. This finding suggested that a transcriptional factor that was lost during culture mediated the action of glucocorticoids. Consistent with this idea, cycloheximide or puromycin almost completely blocked enhanced transcription of the TO gene by dexamethasone after a 20-h culture, but not after a 2-h culture. These findings indicate that a short-lived transcriptional protein, which is also regulated by glucocorticoids, mediates their effect on expression of the TO gene.

Animals↗

Ethyl alcohol-induced cardiovascular malformations in the chick embryo.

Chick embryos incubated for 72-80 hours were exposed to various volumes (0.20-0.40 m1/egg) of 50% ethyl alcohol. Examination of embryos at day 14 of incubation showed that higher doses of ethanol decreased the survival rate of embryos compared with control embryos. Three major categories of cardiovascular malformations were observed in this study: intracardiac anomalies characterized primarily by isolated ventricular septal defect, ventricular septal defect with overriding aorta, double outlet right ventricle or common aorticopulmonary trunk; aortic arch anomalies; and subclavian artery anomalies. Frequencies of embryos with intracardiac anomalies were equal to or greater than 64.8% in the six groups exposed to ethanol. Administration of ethanol also induced high frequencies of embryos with subclavian artery anomalies (11.2-89.1%). Absence or hypoplasia of the right and/or left secondary subclavian artery was commonly associated with persistence of the corresponding primary subclavian artery. Bilateral absence and/or hypoplasia of the secondary subclavian arteries was more common than unilateral anomalies, whereas absence of the left secondary subclavian artery was more commonly observed than an absent right secondary subclavian artery. No embryos in the two control groups combined (n = 94) demonstrated aortic arch or subclavian artery anomalies.

Abnormalities, Drug-Induced↗

Intravascular survival of leukemic cells labeled with indium-111-oxine.

A method for labeling leukemic cells in vitro with 111In-oxine is described. Intravascular survival data and organ distribution of 111In-oxine-labeled leukemic cells in patients with acute leukemia are presented. No evidence of diminished cell viability or significant elution of the label could be found by the in vitro studies. Disappearance curves of 111In-labeled leukemic cell radioactivity in the circulation were a single exponential with average T1/2 value of 15.3 +/- 2.5 hr (mean +/- SEM), which was found to be prolonged when compared with the results of 4 hematologically normal subjects (7.0 +/- 0.8) and those of previously reported DF32P studies. Migratory patterns of the labeled leukemic cells, obtained by a scintillation camera, demonstrated sequestration in the lungs 5 min after the infusion, and thereafter, the uptake into the spleen and liver gradually increased. We believe that the properties of 111In-oxine might overcome many of the difficulties of studying leukemic cell kinetics with cells labeled with tritiated thymidine.

Acute Disease↗

New mechanism for foam cell generation in atherosclerotic lesions.

Because of a close association between platelets and macrophages in early fatty streak lesions, the hypothesis was tested that platelets contribute to lesion progression by directly enhancing macrophage cholesteryl ester (CE) accumulation. Both the rate of cholesterol esterification and the accumulation of CE were increased within 24 h of the co-culture of adherent macrophages with platelets. Maximum increases in esterification and CE accumulation were observed within 3 to 4 d of culture and were greater than 10-fold over controls. Optimum accumulation of CE by 5 X 10(5) was obtained with 5 X 10(8) autologous platelets. When similar amounts of free cholesterol were supplied with platelets, red blood cells (RBC), RBC ghosts, or sonicated RBC, only platelets enhanced macrophage CE accumulation, which indicates specificity for platelets. Products released from platelets 30 min after thrombin stimulation were active as well. The results suggest that platelets and/or substances shed by activated platelets are potent mediators of macrophage CE accumulation.

Apolipoproteins E↗

Clonal lifespan of Paramecium tetraurelia: effect of selection on its extension and use of fissions for its determination.

Paramecia cells, like human diploid cells cultured in vitro, provide a useful model system for understanding the mechanism that limits division potential. The reported maxima of the clonal lifespan of Paramecium tetraurelia fall into two ranges: from 220 to 258 fissions and from 310 to 325 fissions. We found that neither the selection of vigorous lines nor the cryptic occurrence of autogamy offers a plausible explanation for the much longer lifespans in the latter range. We found the sporadic occurrence of very long clonal lifespans, such as 330 fissions, without selection and autogamy. Selection, which was evaluated by using different methods to maintain lines, had little effect on the extension of the maximal clonal lifespan, whereas it did have a marked effect on the extension of the mean clonal lifespan. Autogamy, which was checked with two closely linked marker genes, was frequent, but only during the period when lines were terminating. Statistical analysis on the mean clonal lifespans of two groups of subclones cultured at 25 and 20 degrees C or with rich and poor nutrition showed that the clonal lifespan that was fission-related under favourable conditions tended to dissociate from fissions under less favourable conditions. We discuss mechanisms that determine the clonal lifespan, programmed events contributing to the maximum clonal lifespan and random events contributing to the mean clonal lifespan.

Animals↗

[Uroflowmetry of males over 50 years old--analysis of the mass examination of the prostate].

The uroflowmetry of a total of 533 males over 50 years old, who had undergone a mass examination of the prostate in Tanno Town, Hokkaido Prefecture in 1982, and 1985, was studied. These subjects were divided into 4 groups, i.e., those 50 to 69 years old and those over 70 years old and those with and without prostatic hypertrophy by rectal palpation, the relationship between voided volume and flow rate was examined. Subjects without prostatic hypertrophy by rectal palpation in the older group showed markedly lower flow rate rate than the younger group and subjects with prostatic hypertrophy in the younger group had a lower flow rate than the older group. Thus, urinary disturbance in elderly men was supposed to occur due to aging changes such as benign prostatic hypertrophy and bladder neck contracture.

Age Factors↗

[Clinical efficacy of oxendolene (antiandrogen) and bunazosin hydrochloride (alpha-adrenergic blocker) in the treatment of prostatism--comparative study of oxendolone, bunazocin hydrochloride and their combination].

Antiandrogen and alpha-adrenergic blockers have recently been tried in the medical treatment for benign prostatic hypertrophy and bladder neck contracture. We herein report our results of a randomized comparative study on the clinical efficacy of oxendolone, bunazosin hydrochloride (bunazosin) and their combination for the treatment of benign prostatic hypertrophy and bladder neck contracture. The attending doctors evaluated at twelve weeks the improvement rate for three treatment regimens, 400 mg/day oxendolone, 3 mg/day bunazosin and a combination of both. Oxendolone + bunazosin showed the highest improvement rate in the evaluation of each subjective symptom and objective finding and of both. Oxendolone + bunazosin tended to show a better clinical efficacy than the other of these regimens, when the improvement was defined as that with more than one degree in the severity of retarded voiding, prolonged voiding, urinary stream condition, abdominal pressure on voiding and residual urine sensation. The improvement of such subjective symptoms seemed to occur earlier with oxendolone + bunazosin or bunazosin than with oxendolone. A significant difference was shown among the three treatment regimens in the general improvement rate on four subjective symptoms, with oxendolone + bunazosin being the highest followed by bunazosin and oxendolone in this order. The improvement rates of maximum and mean flow rate which are most important parameters to evaluate the voiding condition, at twelve weeks were significantly higher with oxendolone + bunazosin. No serious side effects were observed in this study, although treatment regimens containing bunazosin caused some minor side effects. These side effects could be prevented by the use of initial low doses of bunazosin with a subsequent gradual increment up to 3 mg/day. Taking the differences in the mechanism of oxendolone and bunazosin and the results of our study into consideration, we believe that the combination of oxendolone and bunazosin would be more useful in a clinical situation.

Adrenergic alpha-Antagonists↗

[Bilateral renal cell carcinoma: report of two cases].

Two cases of bilateral renal cell carcinoma are reported. The first case is of a 54-year-old male who visited our hospital on March 7, 1984 complaining of colicky pain in his left flank. Intravenous urography showed a large mass in the upper pole of the left kidney causing deformity and dislocation of the upper calyces. There were no remarkable findings in the right kidney. Abdominal CT-scan and arteriography revealed a round and hypervascular tumor with soft tissue mass density in the upper pole of both kidneys. Nephrectomy of the left and segmental resection of the upper pole of the right kidney were performed on April 11, 1984. The second case is a 47-year-old male who visited our hospital complaining of total gross hematuria. Intravenous urography showed a large soft tissue mass at the lower pole of the left kidney. Abdominal CT-scan revealed a large tumor mass associated with central necrosis in the left kidney and also a small tumor lesion at the center of the contralateral kidney. Bilateral nephrectomy was performed on December 19, 1984, and the patient was referred to hemodialysis treatment. The cut section of the nephrectomized right kidney specimen revealed multiple minor accessory tumors. Both patients have been doing well without any evidence of recurrence or metastasis.

Carcinoma, Renal Cell↗

[A clinical study of testicular tumors].

Fifty-eight of the 44,698 patients seen at our Department, between 1972 and 1984 had a testicular tumor. The incidence rate was 0.13%. The mean age of these 58 cases was 28.6 years and two peak distributions, one in the 0 to 5 year and another in 26 to 30 year age group were observed. Among them, 54 patients (93.1%) had chief complaints of painless testicular swelling at initial examination. The vast majority of them had unilateral tumors; 28 in the right and 29 in the left. Only one patient had bilateral seminomas. Histologically, 30 of them (51.7%) were seminoma, 8 were embryonal carcinoma (13.8%), 2 were teratoma (3.5%) and the remaining 18 had tumors of double or multiple histological type. Most of the seminomas were treated by a combination of high orchiectomy and radiotherapy, and chemotherapy was done mainly for non-seminomatous cases. The 5-year survival rate calculated by the Kaplan-Meier method was 100% for patients with low stage (I, II) seminomas and 62% for those with non-seminomatous tumors.

Adolescent↗

A delta-globin gene derived from patients with homozygous delta zero-thalassemia functions normally on transient expression in heterologous cells.

Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T-C) 77 base pairs 5' to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.

Animals↗