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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 199 records · Page 11Linked to original sources

Intratumoral tumor necrosis factor induction in tumor-bearing mice by exogenous/endogenous tumor necrosis factor therapy as compared with systemic administration of various biologic response modifiers.

The relationship between the induction of tumor necrosis factor (TNF) (as an indicator of inflammatory reaction) in tumor tissues and its antitumor effect was investigated in tumor-bearing mice by using nine biologic response modifiers (BRMs) and by exogenous/endogenous TNF therapy following a previously reported protocol. Close correlation between the induction of TNF-rich inflammation in tumor tissues and the antitumor effect of BRM were observed. The results of this study suggest that the conditions necessary for exerting antitumor effects of biologic response modifiers may be the induction of TNF (50 to 200 U/g) at the tumor lesions at an early stage after BRM administration and maintenance of the detectable amount of TNF (approximately 10 U/g) for more than 6 hours. Tumor necrosis factor should also be induced in the liver and spleen so that its activity can be maintained in the tumor lesions.

Animals↗

Glucocorticoid receptors in normal leukocytes: effects of age, gender, season, and plasma cortisol concentrations.

We measured glucocorticoid receptors (GR) in mononuclear leukocytes (MNL) isolated from peripheral blood of 145 apparently healthy volunteers (86 men and 59 women). An age-related decrease in the number of GR was suggested between subjects younger than 20 years and elderly subjects; there was no apparent seasonal variation in GR. Gender difference in the number of GR was not significant, although women showed slightly fewer GR. Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of GR in MNL could be down-regulated by their cognate ligands. The number of GR in MNL from these patients was significantly decreased one month after the initiation of prednisolone therapy. However, in normal subjects, the GR in MNL did not demonstrate circadian variation, in contrast to concentrations of plasma cortisol.

Adult↗

[A case of infantile Sertoli cell tumor].

A case of infantile Sertoli cell tumor of the testis is presented. A 2-year-old child visited our hospital with the complaint of painless swelling of the left scrotal content. A solid tumor was demonstrated in the left testis by scrotal echography. Physical and laboratory examinations were within normal limits and alpha-fetoprotein and beta-HCG were not elevated. The left testis was removed. The tumor sized 3.0 x 3.0 x 2.2 cm and weighted 14.5 g. Pathohistological diagnosis was benign Sertoli cell tumor. Tumor cells were vimentin positive and TM-1 reactive antigen positive and revealed electronmicroscopically some features of Sertoli cells such as intermediated microfilament, rich lysosomes and interdigitation between adjacent cells. The patient was well with no evidence of diseases one and a half years after the operation.

Age Factors↗

[Treatment methods as a prognostic factor in eight patients with urachal carcinoma].

Between 1960 and 1982, 8 patients with urachal carcinoma underwent segmental resection of the bladder or en bloc resection, and their five-year survival rate was 50%. One patient each with well, moderate and poorly differentiated adenocarcinoma and one patient with transitional cell carcinoma, died of cancer from 6 months to 2 years and 2 months after operation (mean duration: 1 year and 3 months). The patient with well differentiated adenocarcinoma underwent en bloc resection and was recognized to have peritoneal involvement of the tumor at the operation. The remaining three patients were diagnosed to have tumors confined to their bladder and urachal remnant and were treated with segmental resection of the bladder. Two patients each, with well and moderately differentiated carcinoma confined to their bladder and urachal remnant, were treated with en bloc resection and have been surviving from 8 years and 5 months to 24 years and 10 months (mean duration: 13 years and 7 months) postoperatively as of Dec. 1987. Therefore, patients with well and moderately differentiated adenocarcinomas confined to the bladder and the urachal remnant could be expected to survive longer by en bloc resection.

Adenocarcinoma↗

[Two cases of urachal cyst].

Case 1: A lower abdominal large painful mass was recognized by palpation, CT scan and ultrasonography in a 64-year-old house wife. Urine cytology was negative. The mass at the dome of bladder was covered with normal epithelium cystoscopically. Aspiration cytology of the lower abdominal mass demonstrated no malignancy and total excision of urachal remnant with a portion of bladder wall was carried out. Histologically, the mass was an urachal cyst with granulomatous change infected with C group beta-streptococcus. Case 2: A 46 year-old male engineer complained of asymptomatic hematuria. Cystoscopic examination revealed a small bleeding lesion at the dome of bladder. Urine cytology was negative. CT scan and ultrasonography revealed a tiny cystic mass lesion with irregular density. Biopsy or aspiration cytology appeared difficult because of the size and localization of the mass. En bloc segmental resection of urachal remnant was carried out. Since intraoperative rapid histological examination of the specimen confirmed no malignancies, dissection of pelvic lymph node was not performed. Urachal cysts presented above were suspicious of malignant degeneration from findings of imaging examination. Either preoperative or intraoperative histological examination in such cases appears to be indispensable to avoid unnecessary extensive operation as well as to perform radical operation required for malignant lesions.

Cytodiagnosis↗

In vitro inhibition by ketoconazole of human testicular steroid oxidoreductases.

An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome P-450-dependent monooxygenases. To investigate its effect on steroid oxidoreductases, in vitro studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3 beta-hydroxy-5-ene-steroid oxidoreductase/isomerase and NADH-linked 20 alpha-hydroxysteroid oxidoreductase for steroid substrate and the Ki values were 2.9 and 0.9 microM, respectively. In contrast, ketoconazole inhibited neither 17 beta-hydroxysteroid oxidoreductase nor NADPH-linked 20 alpha-hydroxysteroid oxidoreductase, indicating that the two 20 alpha-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome P-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides.

20-Hydroxysteroid Dehydrogenases↗

Inhibitory effect of testosterone on gap junctional intercellular communication of human transitional cell carcinoma cell lines.

A dye transfer method was applied to investigate the effect of testosterone on gap junctional intercellular communication (IC) of two kinds of human transitional cell carcinoma cell lines, JTC-30 and JTC-32. When JTC-30 cells were cultured with testosterone at nontoxic concentrations (17-69 microM), a dose and time dependent inhibition of dye transfer was observed. More than 90% inhibition occurred after exposure to 69 microM testosterone for 96 h. The inhibition was reversed rapidly after testosterone deprivation. Similar results were obtained with JTC-32 cells. 17 beta-Estradiol showed no inhibitory effect on IC of both transitional cell carcinoma cell lines even at toxic levels. Testosterone exhibited no inhibitory effect on IC of human fibroblasts. The inhibitory effect of 5 alpha-dihydrotestosterone was almost similar to that of testosterone. At concentrations examined, cyproterone acetate influenced neither dye transfer nor the inhibitory effect of testosterone, suggesting a mechanism of testosterone action different from that of the known receptor system. Since blockage of IC has been indicated as one reliable evidence for tumor promotion, current results suggest that testosterone is a possible endogenous promoter of the bladder carcinoma and may therefore possibly play a role on the sexually different incidence of bladder carcinoma.

Carcinoma, Transitional Cell↗

Age-related decrease in the number of hemopoietic stem cells and progenitors in senescence accelerated mice.

Senescence accelerated mice (SAM-P) were used for the study of the possible aging of hemopoiesis. The number of peripheral leukocytes decreased significantly with age, whereas hematocrit showed only a slight decrease. Although the number of total nucleated cells in the bone marrow increased, the number of hemopoietic stem cells (CFU-S) as well as that of granulocyte-macrophage colony forming cells (GM-CFC) showed a decrease in old mice. A significant decrease in the number of GM-CFC was observed in the spleen of old SAM-P mice, whereas no decrease was found in the number of CFU-S. Such a profound reduction of the recruitment of GM-CFC from CFU-S in the spleen together with a reduction of bone marrow hemopoiesis may be responsible for the decrease in the number of peripheral leukocytes in the old mice. SAM-P mice could provide a good model for the study of the aging of hemopoietic system.

Aging↗

Intratumoral induction of tumour necrosis factor by systemic administration of Bordetella pertussis vaccine.

Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect.

Animals↗

Effects of castration on luteinizing hormone and follicle-stimulating hormone secretion by pituitary cells from male rats.

Because the role of the pituitary in the testicular control of gonadotropin secretion remains controversial, we examined the effects of castration on the release of LH and FSH under basal conditions and in response to GnRH stimulation by dispersed pituitary cells in monolayer culture as well as by cells perifused with pulses of GnRH. These effects were compared to changes in LH beta, FHS beta, and alpha-subunit mRNA levels determined by Northern blot analysis. Pituitary cells were prepared from 7-week-old intact rats and rats orchidectomized 2 weeks previously. Castration increased basal FSH secretion from monolayer cultures, interpulse FSH release from perifused pituitary cells, FSH beta mRNA concentrations and serum FSH levels each approximately 2-fold, whereas pituitary FSH contents were similar in cells from intact and castrated rats. Pituitary LH content rose 3-fold, LH beta mRNA rose 5.6-fold, and basal LH secretion increased 6-fold, but serum LH levels increased 22-fold. Thus, the change in FSH synthesis inferred from the increase in FSH beta mRNA was proportional to the increase in FSH secretion both in vitro and in vivo. Whereas the basal release of LH in vitro was also proportional to the change in LH beta mRNA, secretion of LH in vivo exceeded these changes, underscoring the importance of increased GnRH to the serum LH castration response. Castration resulted in an increase in the sum of FSH content and secretion during 10 days in culture in the absence of GnRH, indicating ongoing FSH synthesis. Total LH declined in cells from intact rats, and this decline was prevented by castration; this effect may be due to a castration-related decrease in intracellular LH degradation or increased LH synthesis in the absence of GnRH. Castration also augmented the GnRH-stimulated release of LH and FSH from monolayer cultures 4.5- and 1.8-fold, respectively, and increased the amplitude of GnRH-stimulated LH and FSH pulses 5- and 2-fold in experiments with perifused pituitary cells. The EC50 for GnRH was unaffected by castration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Autoantibody to growth hormone in a patient with myasthenia gravis.

An autoantibody to GH was detected in the serum from a patient with myasthenia gravis (MG) who had never been prescribed GH. Using an immunoprecipitation technique, this autoantibody was found to belong to the IgG class and had a kappa chain. The dissociation constant of the antibody was 56.8 nmol/l and the binding capacity was 37 nmol/l. Serum samples from another 130 patients, including 37 with MG, were examined, but the GH autoantibody could not be detected. To our knowledge, this is the first report demonstrating the presence of a GH autoantibody.

Adult↗

[Multiple urothelial cancers accompanied by acquired cystic disease of the kidney in a long-term hemodialysis patient].

A 41-year-old miller undergoing hemodialysis for 9 years presented with recurrent episodes of asymptomatic gross hematuria of a 7 years' duration and left flank pain with slight fever of a four months' duration. CT scans revealed bilateral acquired cystic disease of the kidney (ACDK) and a mass (phi 4 cm) in the medial portion of the left kidney, which was angiographically a hypovascular tumor. Cystoscopic examination revealed multiple papillary tumors arising from the entire bladder wall. These findings suggested that the renal mass was a renal pelvic tumor. Bilateral nephroureterectomy with left paraaortic lymph nodes dissection and radical cystectomy were carried out, followed by urethrectomy two weeks later. Histologically, multiple papillary transitional cell carcinomas with G2 greater than G3 anaplasia were found in the left renal pelvis, the lower portion of the left ureter and the bladder. The tumors were predominantly superficial, although the renal pelvic one focally invaded into the muscular layer. Lymph node metastasis and renal cell carcinoma were not recognized. Postoperative course was uneventful with normal blood pressure, though anemia was slightly progressive. He has been free of disease for six months.

Adult↗

[Neurogenic bladder in patients with lumbar vertebral disorders].

Bladder and urethral functions were evaluated urodynamically in 114 patients with lumbar disorders including prolapsed lumbar intervertebral disc (66 patients), lumbar canal stenosis (19 patients), lumbar spondylolysis and/or spondylolisthesis (21 patients), lumbar spondylosis deformans (5 patients) and ossification of the yellow ligament of the lumbar spine (3 patients). The patients consisted of 88 males and 26 females with an average age of 47 years (range 17 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination. Cystometry revealed preoperative neurogenic bladder in 23 patients (20%); normal detrusor with overactive sphincter in 2 (9%), underactive in 8 (36%), overactive in 5 (23%) and equivocal in 7 (32%). One patient not receiving cystometry revealed abnormal uroflowmetry with 140 ml residual urine. Twenty of them underwent electromyographic examination of the external sphincter and 15 (75%) had an overactive sphincter. Nine (39%) of them complained no urological symptoms. Neurogenic bladder seemed to highly associate in those having abnormal tendon reflex in the lower extremities, decreased bulbocavernosus reflex and sensory disturbance in the perineal area, but there was no statistical significance. Of twenty-three neurogenic bladder patients, eighteen underwent a lumbar vertebral operation and fifteen received postoperative urodynamic evaluation. Uroflowmetry was improved in more than half of the patients within 3 months after the operation and cystometry was normalized in 4 of 7 patients who underwent cystometry over 6 months after the operation. Preoperative overactive detrusor remained unchanged in two of three patients who underwent cystometry over 6 months after the operation.

Adolescent↗

[Relation of tumor number to clinical course of superficial papillary bladder tumors].

Clinical courses of 293 patients with superficial papillary bladder tumors were analysed on the basis of tumor number at the first presentation. The follow-up period ranged from 6 to 266 months with a median of 59 months. 171 patients (58%) had a single tumor, while 122 (42%) had multiple tumors. Those older than 60 years occupied 68% in the latter group and 51% in the former (p less than 0.01). High grade tumors were more frequent in the latter than the former (p less than 0.05). The five-year recurrence rate was 68% for the latter and 39% for the former single tumor group (p less than 0.01). Malignant progression was observed in 3.6% of patients with a single tumor and 13.4% of those with multiple tumors (p less than 0.01). The results would offer a theoretical background to the finding of a poor ten-year actuarial survival rate of 54% for multiple tumor group compared with 76% for the single tumor group (p less than 0.05). However, the rate of primary cancer death was similar in both groups.

Adult↗

[A study of cytokeratin in human normal bladder epithelium and bladder carcinoma cell lines].

Normal epithelial and carcinoma cells of human bladder were investigated for the cytokeratin which is one of the intermediate filaments and comprises cytoskeleton using the immunofluorescence method. Carcinoma cell lines used were JTC-30, JTC-32, HUB-41 and T-24. In normal urothelium, keratin fibers were fine and straight with unchanged diameter and distributed regularly in the cytoplasm. By contrast, keratin fibers in bladder carcinoma cells were kinked and changed in diameter and were distributed irregularly in the cytoplasm. The above findings were most obvious in T-24 which formed undifferentiated carcinoma when transplanted to nude mice, and keratin fibers were dominantly located in the perinuclear area. The changes of keratin fibers appeared to be parallel to the grade of histological anaplasia of the tumor formed by implantation of bladder carcinoma cell line cells to nude mice. These observations suggest that the morphology of cytokeratin is a useful indicator for evaluating the grade of malignancy in transitional cell carcinoma.

Animals↗

Priming effect of orally administered muramyl dipeptide on induction of endogenous tumor necrosis factor.

Orally administered muramyl dipeptide (MDP) was found to prime induction of endogenous tumor necrosis factor (TNF) in mice. This priming effect was observed after oral administration of MDP of more than 100 micrograms/mouse; the maximal time interval between oral administration of MDP and i.v. injection of OK-432, a triggering agent for induction of endogenous TNF, was extended over 3-10 h and then decreased after 24 h. Antitumor effect against Meth-A, MH134, and MM46 tumor cells in mice was observed after oral administration of MDP followed by i.v. injection of OK-432. These findings suggest that orally administered MDP can be used as a priming agent for inducing endogenous TNF in cancer patients, and that MDP, a component of enteric bacteria, must have an important role in maintaining homeostasis through activation of macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Cytotoxic effects of restorative materials on early passage cultured cells derived from human gingiva (in vitro)].

This study evaluated the cytotoxic effects of three common restorative materials on early passage cultured cells derived from human gingiva (HG cells). Other early passage cultured cells derived from human dental pulp tissues (HP cells) and L cells established obtained from mouse subcutaneous tissues, were also examined. Cytotoxicity was assessed according to the uptake of neutral red and dye exclusion with nigrosin. The cytotoxicity was in the order of glass ionomer cement (highest), light cured composite resin and dental amalgam. HG cells were the least sensitive to the materials tested. Both filtration of extracts and addition of serum into the extract affected the cytotoxicity. Glass ionomer cement increased the acidity of the extract, but the two other materials did not. Dissolution of metal ions, aluminium, tin, copper, mercury and zinc occurred from the materials. The extract of the composite resin had a different absorbance. This study disclosed differences in the cellular reaction to the restorative materials. Thus, utilization of early passage cultured cells is necessary for biological evaluation of the dental materials in vitro.

Animals↗

[Clinical studies on endocrine therapy of prostatic carcinoma (2): Prognosis of patients with prostatic carcinoma given endocrine therapy, and analyses of causes of death and side effects of endocrine therapy].

Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.

Cause of Death↗