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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 163 records · Page 9Linked to original sources
PubMed1993

[Effects of endothelin-1 on the smooth muscle contractility of human urinary bladder, spermatic cord and prostatic adenoma].

Effects of endothelin-1 (ET-1) on the smooth muscle contractility of human detrusor, spermatic cord and hypertrophied prostatic adenoma were examined in muscle bath studies. ET-1 increased the contractile forces of all above smooth muscle strips in concentration dependent manner. The contractile force induced by 10(-6) M ET-1 was approximately 30% of that induced by 3 x 10(-5) M carbachol in detrusor muscle strips, approximately 40% of that induced by 10(-4) M norepinephrine in spermatic cord muscle strips and almost equal to that induced by 10(-5) M phenylephrine in prostatic adenoma muscle strips. The contractions induced by ET-1 in those muscle strips were not inhibited by any of tetrodoxine, atropine, phentolamine, propranolol and indomethacine. These results suggest that ET-1 may act as a constrictor on lower urinary tract and genital smooth muscles and especially on prostatic adenoma and that ET-1 may affect those smooth muscles directly not through autonomic receptors or prostaglandins.

Aged↗
PubMed1993

[Intra-arterial CDDP and CDDP plus THP-ADM therapy for bladder cancer].

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Clinical evaluation of flutamide, a pure antiandrogen, in prostatic cancer phase II dose-finding study].

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1,125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1,125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

Administration, Oral↗
PubMed1992

Expression of transcripts of complement components and their receptors during differentiation of embryonal carcinoma cell lines.

Based on our previous finding that TNF-alpha and TNF-beta can be expressed constitutively during early embryonal development [1], we extended our work to identify factors which are generally known to take part in inducing inflammation in adults. They can be regarded as candidate molecules involved in ontogenic inflammation during embryonal development. In this study, we chose the factors which are constituents of either a classical or an alternative pathway of a complement system and found that mRNAs corresponding to those of C2, C3, C4, C5 and to those of receptors CR1 and CR2 were expressed. Among them, mRNA expression of C3, C4, and CR1 was especially constitutive. Contrary to these observations, expression of two kinds of scavenger receptors (SR-I, SR-II) proved to be negative. In this report, the framework of ontogenic inflammation as a regulatory mechanism in embryonal development at the molecular level is discussed.

Animals↗
PubMed1992

Induction of Ca2+/calmodulin-dependent NO synthase in various organs of rats by Propionibacterium acnes and lipopolysaccharide treatment.

Ca2+/calmodulin-dependent nitric oxide synthase was found to be induced during rat liver necrosis caused by administration of Propionibacterium acnes and E. coli lipopolysaccharide to rats. Examination of the specific induction of Ca2+/calmodulin-dependent NO synthase showed that the enzyme was induced in the lung, spleen and colon as well as the liver. Northern blot analysis revealed that the induction occurred at the transcriptional level.

Amino Acid Oxidoreductases↗
PubMed1992

BRM activities of low-toxic Bordetella pertussis lipopolysaccharides.

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.

Animals↗
PubMed1992

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response.

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.

Administration, Intravesical↗
PubMed1992

Sling operation for male stress incontinence by utilizing modified Stamey technique.

A modified Stamey operative technique was applied to 3 men with stress incontinence due to transurethral prostatectomy or transurethral resection of bladder neck. Two pieces of polytetrafluoroethylene grafts (Gore-Tex) were positioned at the membranous and bulbous urethra as sling loops, and hung up by nylon sutures that were brought to the abdominal wall along each side of the urethra by means of a modified Stamey needle and tied over the rectus fascia. Postoperatively, maximum urethral closure pressure and functional urethral length were increased, and urinary continence was achieved in all 3 patients, however, urinary retention developed in 1 patient with bladder arefrexia.

Adult↗
PubMed1992

Modulation of the agonist activity of antisteroids by a novel cis-acting element.

The amount of agonist activity displayed by the antiglucocorticoid dexamethasone mesylate (Dex-Mes) for the induction of tyrosine aminotransferase (TAT) in rat hepatoma cells is greater than for glutamine synthetase and varies over a period of weeks. This variation, which has been reproduced over a period of 40 h by changing the density of the cells, suggests the involvement of a trans-acting factor. The target of this proposed trans-acting factor has now been localized to the region between -3.9 to -2.9 of the rat TAT gene from experiments with cells that were stably transfected with hybrid TAT/CAT constructs. Deletion experiments with transiently transfected TAT/tk promoter/CAT constructs revealed that this entire activity could be conveyed by a 21 bp sequence of the TAT gene. Gel shift experiments support the binding of a factor(s) to this 21 bp sequence. Thus the activity of the antagonist Dex-Mes is relatively independent of steroid structure and is largely determined by the further interactions of a trans-acting factor with the cis-acting sequence. We call this novel sequence a glucocorticoid modulatory element. A model is advanced which accounts for almost all of the results concerning TAT induction by glucocorticoids. This same model may also be useful in explaining why the amount of agonist activity of most antisteroids varies, even for different genes within the same cell.

Animals↗
PubMed1992

A mechanism of retrograde ejaculation after bilateral hypogastric nerve transections in the dog.

To pursue the mechanism of retrograde ejaculation after bilateral hypogastric nerve transections, the disability of the lumbosacral sympathetic trunk and the spermatic nerve to compensate bladder neck closure was investigated while both act as compensatory pathways for seminal emission. Five mongrel dogs were used for each experiment. By manual penis-stimulation, all dogs showed only retrograde ejaculation one month and six months after transection of bilateral hypogastric nerves. Bladder neck closure did not occur by electrical stimulation of either the lumbosacral sympathetic trunk or the spermatic nerve before and one month after transection of bilateral hypogastric nerves in all dogs examined and persistent relaxation of bladder neck was observed one and six months after transection of bilateral hypogastric nerves. The present results and our previous data indicate that retrograde ejaculation after bilateral hypogastric nerve transections is attributable to the absence of effective compensatory sympathetic pathways for bladder neck closure under the recovery of seminal emission by compensatory pathways.

Animals↗
PubMed1992

Ability of each lumbar splanchnic nerve and disability of thoracic ones to generate seminal emission in the dog.

Control of seminal emission by canine thoracolumbar splanchnic nerves which constitute the caudal mesenteric plexus (inferior mesenteric and superior hypogastric plexuses in human) was investigated. Electrical stimulation of a splanchnic nerve group which branched from sympathetic trunks at thoracic and L1 ganglia and descended on the ventral wall of the aorta between bilateral spermatic arteries via the intermesenteric plexus did not cause seminal emission in all 13 dogs examined. In contrast, electrical stimulation of the other splanchnic nerve group which branched from lumbar sympathetic trunks at ganglia L1-L5 and descended behind bilateral spermatic arteries induced seminal emission regardless of branching levels or sides. The results indicate that efferent signals via the intermesenteric plexus do not generate seminal emission, while those via each lumbar splanchnic nerve have ability to generate seminal emission in the dog.

Animals↗
PubMed1992

A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia.

1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues were investigated for beta- and alpha 1-adrenoceptors by radioligand binding and in vitro isometric tension experiments. 2. Hyperplastic and control prostatic tissues had a similar number (per mg protein) of prazosin binding sites with similar affinities. Noradrenaline (NA) induced dose-dependent contraction in both tissues. Contraction induced by either exogenous NA or transmural stimulation was inhibited by prazosin in both tissues, indicating that the same contractile mechanisms mediated by alpha 1-adrenoceptors exist in hyperplastic and control tissues. 3. The number of dihydroalprenolol (DHA) binding sites (per mg protein) was less in hyperplastic tissues than in controls, whereas the affinity to the ligand was identical in both tissues. Isoprenaline caused a marked relaxation of the tonic contraction induced by KCl in control tissues, but not in hyperplastic tissues. Propranolol enhanced exogenous NA- or transmural stimulation-induced contraction more in control tissues than in hyperplastic tissues. Both tissues, however, similarly responded to forskolin by relaxation. 4. These results indicate that decreased beta-adrenoceptor-mediated relaxation in hyperplastic prostatic tissues, which is attributable at least in part to the decreased number of beta-adrenoceptors, may play a role in the urinary obstruction of BPH in addition to mechanical compression of the urethra by the enlarged prostate.

Adult↗
PubMed1992

Effect of gonadotropin-releasing hormone pulse frequency on gonadotropin secretion and subunit messenger ribonucleic acids in perifused pituitary cells.

Slow frequency GnRH pulses have been proposed to preferentially increase circulating FSH levels by increasing FSH synthesis and pulsatile release. Examination of this proposal using various in vivo models, however, has produced conflicting results. To examine directly the effects of GnRH pulse frequency on the pituitary, we compared the effects of 2.5-nM GnRH pulses administered every 1 h or every 4 h vs. no GnRH, using perifused rat pituitary cells. FSH secretion (total area under the response curve) was 2-fold greater (P less than 0.01) with every hour than with every 4 h GnRH pulses. This difference resulted from the increased number of GnRH pulses and increased (P less than 0.05) interpulse FSH secretion, whereas FSH pulse amplitude was unchanged. FSH beta mRNA levels at the completion of the 11-h perifusion were increased 4.5-fold by GnRH every h (P less than 0.01) and 3.3-fold by GnRH every 4 h (P less than 0.05) above levels in untreated cells. FSH beta mRNA levels were greater (P less than 0.05) at the faster GnRH pulse frequency. Because more frequent stimulation delivered more GnRH during the study, cells were next stimulated with 2.5 nM GnRH every 1 h for nine pulses, 7.5 nM GnRH every 4 h for three pulses to equalize the GnRH dose, or 2.5 nM GnRH every 4 h for three pulses. Interpulse FSH secretion and FSH beta mRNA levels were again greater (P less than 0.05) with every hour than every 4 h GnRH pulses. Interpulse LH secretion, FSH and LH pulse amplitude, and LH beta and alpha-subunit mRNA levels were not different between the groups. GnRH doses of 0.1-10 nM every hour increased FSH and LH pulsatile secretion dose-dependently, but FSH beta, LH beta, and alpha-subunit mRNA levels were similar. In conclusion, our data reveal that reducing the frequency of GnRH pulses from every hour to every 4 h reduces both FSH beta mRNA levels and FSH interpulse secretion, but does not change GnRH-stimulated FSH pulsatile release. We suggest that the finding by others that slow frequency GnRH pulses increase circulating FSH levels under certain experimental conditions in vivo may instead be explained by complex hormonal interactions or changes in FSH clearance.

Animals↗
PubMed1992

Modulation of glucocorticoid induction of tyrosine aminotransferase gene expression by variations in cell density.

Glucocorticoids induce tyrosine aminotransferase (TAT) in hepatoma cells. We have previously shown that both the concentration of the agonist dexamethasone (Dex) required for half-maximal induction (EC50) and the amount of agonist activity produced by the antagonist dexamethasone 21-mesylate (Dex-Mes), expressed as a percentage of maximum induction achieved by Dex, are different in Fu5-5 and HTC cells. Furthermore, both activities vary over several weeks in each cell line in an apparently random manner, but, nevertheless, are correlated by a linear semilog plot. We now find that this long term and previously unpredictable variation in both the Dex EC50 and the amount of Dex-Mes agonist activity for the induction of TAT enzyme activity can be made to occur reproducibly in 40 h or less by changing the cell density and/or amount of medium in the tissue culture plates. Thus, a higher cell density and/or a lower volume of medium produced both higher amounts of Dex-Mes agonist activity and lower EC50 values for Dex. Experiments with cells at different densities but exposed to the same medium indicated that cell density was the dominant determinant. A qualitatively identical modulation was seen at the level of TAT mRNA, but not mouse mammary tumor virus RNA. We are not aware of any previous report of cell growth conditions altering either the level of agonist activity of an antisteroid or the EC50 of a full agonist. These results further indicate that extrachromosomal parameters, such as cell-cell contact and/or a diffusable factor(s), can modulate the basic features of glucocorticoid induction of some, but not all, glucocorticoid-inducible genes.

Animals↗
PubMed1992

Modulation of glucocorticoid induction of stably transfected tyrosine aminotransferase gene constructs involves elements up-stream of the glucocorticoid-responsive element.

Previous studies have documented that the amount of agonist activity expressed by the antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) for tyrosine aminotransferase (TAT) induction in two rat hepatoma cell lines (Fu5-5 and HTC) is greater in Fu5-5 cells and could be varied in each cell line with changes in cell density. We have proposed that both phenomena are mediated by the binding of a trans-acting factor, the concentration or activity of which is lower in HTC cells. We have now used DNase-I hypersensitivity studies to identify a possible binding site for this factor at around -3.6 kilobases (kb) of the TAT gene. Fu5-5 and HTC cells were then stably transfected with hybrid constructs either with (3.9TATCAT) or without (2.9TATCAT) this region of the TAT gene fused up-stream of a chloramphenicol acetyltransferase (CAT) reporter gene. High levels of Dex-Mes agonist activity for the induction of CAT activity in Fu5-5 cells were seen only with the 3.9TATCAT construct, indicating that the 0.97-kb region unique to this construct controlled the high levels of Dex-Mes agonist activity. Furthermore, variations in Fu5-5 cell density caused major quantitative changes in the amount of Dex-Mes agonist activity only in cells containing the 3.9TATCAT construct, consistent with the same 0.97-kb sequences also controlling the variations in Dex-Mes agonist activity. Additional studies at high and low cell densities revealed that the modulation of Dex-Mes agonist activity for both the endogenous TAT gene and the transfected TAT/CAT gene was not due to changes in the start site of gene transcription. These studies both support our previous hypothesis that modulation of Dex-Mes agonist activity results from changes in a trans-acting factor and localize a necessary cis-acting element to sequences between -3.9 and -2.9 kb of the TAT gene. These studies, thus, define a potentially new element for glucocorticoid regulation of TAT gene transcription.

Animals↗