Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 109 records · Page 6Linked to original sources

PubMed1997

Telomere length and telomerase activity in bladder and prostate cancer cell lines.

BACKGROUND: Specific repeats of oligonucleotides at the ends of chromosomes (telomeres) are shortened by cell division in somatic cells and are thought to be related to aging. Immortal cells such as germ-line cells or cancer cells have demonstrated increased activity of the telomere-elongating enzyme (telomerase). The length of the telomeres of these cells is stable regardless of cell division. We examined the telomere length and telomerase activity in 3 bladder (JTC30, JTC32, and T24) and 2 prostate cancer (LNCaP and DU145) cell lines. METHODS: Telomere lengths were evaluated by Southern blot analysis with a oligonucleotide probe, (TTAGGG)5, and telomerase activities were detected with a polymerase chain reaction-based assay method. RESULTS: Telomerase activity was detected in all of the cell lines. Each cell line had a specific telomere length. In 2 bladder cancer cell lines (JTC30 and JTC32), the telomere length decreased with increased passage of the cells. CONCLUSION: The presence of telomerase may be a biological character of bladder and prostate cancers as well as other malignancies, although it does not always compensate telomere shortening.

Biomarkers, Tumor↗

PubMed1997

The 72nd codon change of p53 in primary renal cell carcinoma was confirmed as a polymorphism among Japanese.

OBJECTIVE: The role of p53 mutation in renal cell carcinoma (RCC) is not fully understood particularly among Japanese, although frequent loss of heterozygosity (LOH) has been demonstrated at polymorphic exon 4. METHODS: We examined the p53 gene in 43 primary RCC samples by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for exons 4-9 and restriction fragment length polymorphism (RFLP) analysis. RESULTS: In PCR-SSCP analysis, no apparent mobility shift was observed regardless of the clinical stage of the disease, histological subtype or malignancy grade of the tumor. In RFLP analysis, none of 13 informative cases showed gross alteration of the gene. CONCLUSION: We conclude that mutations of the p53 gene are not major events in the development and progression of RCC among Japanese.

Adult↗

PubMed1997

Stronger suppression of serum testosterone and FSH levels by a synthetic estrogen than by castration or an LH-RH agonist.

Serum levels of LH, FSH and testosterone (T) were measured by radioimmunoassays in 36 patients with advanced prostate cancer before and during androgen ablation therapies. Both leuprolide acetate (LH-RH agonist: LHRH-A) and diethylstilbestrol diphosphate (DES-DP) administration decreased serum LH significantly to an undetectable level (LHRH-A: P < 0.01, DES-DP: P < 0.05). LHRH-A and DES-DP diminished serum FSH to 20% of the pre-treatment level (P < 0.005) and to an undetectable level (P < 0.001), respectively. LHRH-A and DES-DP decreased serum T to the castration level and an undetectable level, respectively (P < 0.001). Serum levels of the same 3 hormones before and after DES-DP administration were measured in 8 patients who received DES-DP after LHRH-A treatment or castration because of relapse of the disease. DES-DP lowered serum FSH further than LHRH-A to an undetectable level (P < 0.005) and diminished T further than previous treatments to an undetectable level (P < 0.05 vs. LHRH-A, P < 0.01 vs. castration). These results suggest that 1) DES-DP is able to reduce T production from extra-testicular site(s), and achieve the minimal serum T level, and 2) this DES-DP action appears to be one of the mechanisms of the effectiveness of the estrogen on refractory prostate cancer after castration or LHRH-A. In addition, basal (independent of LH-RH) FSH secretion in elderly men is about 20% of total FSH secretion and DES-DP inhibits the basal FSH secretion at the level of the pituitary.

Aged↗

PubMed1997

[Metastatic tumor of spermatic cord and tunica vaginalis testis from gastric cancer: a case report].

A 62-year-old man with advanced gastric cancer was admitted with a swelling of the left scrotum. He had undergone subtotal and total gastrectomies 10 and 5 years earlier, respectively. A hard mass was palpated along the left spermatic cord associated with hydrocele testis. A left high orhiectomy was performed. Multiple small nodules were noted on the surface of the tunica vaginalis. Also, a tumor in the spermatic cord was present at the level of the internal inguinal ring, protruding into the peritoneal cavity and adherent to the colon. Peritonitis carcinomatosa was recognized. Histopathological diagnosis was tubular adenocarcinoma showing extensive vascular invasion, consistent with a metastasis from gastric cancer.

Adenocarcinoma↗

PubMed1997

[Small cell carcinoma of the urinary bladder: a case report and review of the Japanese literature].

A 50-year-old man presented with asymptomatic gross hematuria which he had first noticed 3 months earlier. Clinical examinations revealed a non-papillary, broad-based tumor on the left lateral wall of the urinary bladder with a clinical stage of T3N0M0. The pathological diagnosis of a transurethral biopsy tissue specimen was small cell carcinoma. Neoadjuvant intraarterial infusion chemotherapy using cisplatin and adriamycin was initially administered but proved to be ineffective. Thus, we performed a radical cystectomy. The tumor tissue was apparently homogenous and composed of small cells arranged in sheets and solid patterns, and was staged to be pT3bR1L2V0N0. An electron microscopic study confirmed small cell carcinoma with neurosecretory granules. Postoperatively, 4 courses of adjuvant chemotherapy consisting of cisplatin, etoposide and ifosfamide were administered. The patient is alive without any evidence of tumor recurrence 26 months after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[Organization and regulation of spermatogenesis].

We briefly overview the process as well as hormonal and paracrine regulation of spermatogenesis. Initiation of sperm production occurs under stimulation by FSH and LH. Spermatogenesis can be maintained by testosterone alone at least qualitatively. Stimulatory function of gonadotropic hormones can be modified or modulated on the basis of the local environment present in the testis. Sertoli cells create the blood-testis barrier modulating the entry of substances into the seminiferous tubules. Sertoli cells play the main role in paracrine regulation of spermatogenesis by providing factors required for the development of germ cells. Substances regulating spermatogenesis as paracrine factors in the testis are summarized.

Animals↗

PubMed1996

Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2).

Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H2: constitutive COX-1 and inducible COX-2. To assess the role of COX-2 in colorectal tumorigenisis, we determined the effects of COX-2 gene (Ptgs2) knockouts and a novel COX-2 inhibitor on Apc delta716 knockout mice, a model of human familial adenomatous polyposis. A Ptgs2 null mutation reduced the number and size of the intestinal polyps dramatically. Furthermore, treating Apc delta716 mice with a novel COX-2 inhibitor reduced the polyp number more significantly than with sulindac, which inhibits both isoenzymes. These results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis and indicate that COX-2-selective inhibitors can be a novel class of therapeutic agents for colorectal polyposis and cancer.

Adenomatous Polyposis Coli↗

PubMed1996

TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis.

TGF-beta signaling is mediated through two types of serine/threonin kinase-containing receptors, type I (TGF-betaRI) and type II (TGF-betaRII), which form a heteromeric complex. In this signaling complex, ligand binding TGF-betaRII phosphorylates and thereby activates the TGF-betaRI to signal downstream pathways. To determine the role of TGF-betaRII in embryogenesis, we have generated a TGF-betaRII gene (Tgfbr2) knockout mouse line. The heterozygous Tgfbr2 knockout mice are developmentally normal. The homozygous Tgfbr2 mutation causes defects in the yolk sac hematopoiesis and vasculogenesis, resulting in an embryonic lethality around 10.5 days of gestation. This phenotype is indistinguishable from the previously reported embryonic lethality by the homozygous TGF-beta1 gene (Tgfb1) null mutation. In addition, we have generated chimeric mice using a Tgfbr2 (-/-) embryonic stem cell line. Some chimeric mice showed several types of congenital anomalies, suggesting that TGF-beta II is important for normal development in a variety of organs.

Animals↗

PubMed1996

Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene.

Thioredoxins belong to a widely distributed group of small proteins with strong reducing activities mediated by a consensus redox-active dithiol (Cys-Gly-Pro-Cys). Thioredoxin was first isolated as a hydrogen donor for enzymatic synthesis of deoxyribonucleotides by ribonucleotide reductase in Escherichia coli. Recent studies have revealed a variety of roles that thioredoxin plays in transcription, growth control, and immune function. In this report, we describe the phenotype of mice carrying a targeted disruption of the thioredoxin gene (Txn). Heterozygotes are viable, fertile, and appear normal. In contrast, homozygous mutants die shortly after implantation, and the concepti were resorbed prior to gastrulation. When preimplantation embryos were placed in culture, the inner cell mass cells of the homozygous embryos failed to proliferate. These results indicate that Txn expression is essential for early differentiation and morphogenesis of the mouse embryo.

Animals↗

PubMed1996

TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor.

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for several members of the TNF receptor superfamily. We have identified a novel member of the TRAF family by degenerate oligonucleotide polymerase chain reaction amplification that contains a zinc RING finger and zinc finger motifs, a coiled-coil region, and a C-terminal "TRAF" homology domain. In vitro translated TRAF5 binds to the cytoplasmic region of the lymphotoxin-beta receptor (LT-betaR) but not to several other related receptors including CD40, both TNF receptors, Fas, and nerve growth factor receptor. TRAF5 and LT-betaR coimmunoprecipitate when overexpressed in COS7 cells. TRAF5 mRNA expression is found in all visceral organs and overlaps with LT-betaR. These features distinguish TRAF5 from the other members of the TRAF family. The transcription factor NF-kappaB is activated in HEK293 cells by overexpression of full-length TRAF5 but not a truncated form lacking the zinc binding region. Furthermore, overexpression of LT-betaR in HEK293 cells also results in activation of NF-kappaB, which is partially inhibited by the truncated TRAF5 mutant. These results show TRAF5 is functionally similar to TRAF2 in that both mediate activation NF-kappaB and implicate TRAF5 as a signal transducer for LT-betaR.

Amino Acid Sequence↗

PubMed1996

Effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on intestinal polyp development in Apc delta 716 knockout mice.

Damage to the human adenomatous polyposis coli (APC) gene is responsible for not only familial adenomatous polyposis but also many sporadic cancers of the entire digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed gene knockout mice with a truncation mutation in the Apc gene. These heterozygous mice developed intestinal polyps. We found that all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating loss of heterozygosity (LOH) (Oshima et al., Proc. Natl. Acad. Sci. USA 92:4482-4486, 1995). Using these knockout mice, we investigated the effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), one of the most abundant heterocyclic amines found in cooked meat and fish. When PhIP was fed to these mice at 400 ppm for 8 wk, the polyp distribution shifted to a larger size range, although the total polyp number did not change significantly. Similar, but weaker, effects were observed with the other heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. On the other hand, intraperitoneal injections of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhlP) at a higher dose (50 mg/kg) for five consecutive days increased the polyp number significantly. This increment was not associated with mutations in the Apc gene; however, most polyps showed loss of the full-length Apc allele (LOH). These results suggest that PhIP affects intestinal polyp development by accelerating the growth rate of microadenomas. It is also possible that high doses of N-OH-PhIP increase the frequency of Apc gene LOH.

Age Factors↗

PubMed1996

The influence of skin flap ischemia on serum nitric oxide concentrations.

Nitric oxide (NO), identified as a mediator of endothelium-dependent relaxation of vascular smooth muscle, is known to cause a number of inflammatory diseases, especially ischemia-reperfusion injury. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia followed by reperfusion influences serum NO concentrations. In addition, the author investigated the effects of NO synthase inhibitors and heparin on skin flap ischemia. Serum NO concentrations after 15, 30, 45, and 60 minutes of ischemia followed by reperfusion were significantly increased compared with non-ischemic controls and elevated flaps. On the other hand, serum NO concentrations were suppressed in nitro-amino-methyl-L-arginine- and aminoguanidine-treated animals. Furthermore, administration of heparin increased serum NO concentrations in controls and animals with elevated flaps, but decreased serum NO concentrations in ischemic flaps with subsequent reperfusion. These results suggest that NO is one of the factors responsible for ischemia-reperfusion injury and that NO synthase inhibitors and heparin may protect against such injury.

Animals↗

PubMed1996

Significant telomere reduction in human superficial transitional cell carcinoma.

OBJECTIVE: To investigate telomere reduction and telomerase activity in human transitional cell carcinomas (TCCs) of the bladder, using primary tissue preparations, and their relationship to the clinicopathological properties of the TCC. MATERIALS AND METHODS: Tumour tissues were obtained from 21 patients together with apparently normal urothelia as controls. The mean telomere length of each sample was determined using southern blot analysis with an oligonucleotide probe (TTAGGG)4 and telomerase activity was semi-quantified using a polymerase chain reaction based assay. RESULTS: The mean (SE) telomere length was 6.6 (0.7) kb in tumour tissues and 11.5 (0.4) kb in apparently normal urothelia adjacent to the tumour (P < 0.001). Furthermore, it was 8.9 (1.4) kb and 3.4 (0.9) kb in superficial and invasive tumours (P = 0.002), respectively. Telomerase activity was detected in all 13 of the tumour tissues examined, with no relationship to telomere reduction, while it was undetectable in any of the control tissues. CONCLUSIONS: In human TCCs, telomere length was reduced in tumour tissue, more so in superficial than in invasive tumours. Telomerase was detectable only in tumour tissues and its activity was unrelated to telomere reduction.

Adult↗

PubMed1996

A negative tyrosine aminotransferase gene element that blocks glucocorticoid modulatory element-regulated modulation of glucocorticoid-induced gene expression.

Tyrosine aminotransferase (TAT) is the prototypic steroid-inducible gene. Recently, we have found that the modulation of TAT induction properties is reproduced by a novel cis-acting TAT gene element, the glucocorticoid modulatory element (GME). This GME lies about 1 kb upstream of the glucocorticoid response elements (GREs) of the TAT gene and binds a heterooligomer of two recently defined proteins. We now report the existence of an additional TAT gene element between the GME and the GREs that blocks the action of the GME and thus prevents the left shift in the glucocorticoid dose-response curve caused by the GME. This negative element has the properties of a silencer because its activity is relatively position- and orientation-independent. The interaction appears to be stoichiometric in that the effects of a single negative element can be overcome by a second GME. This negative element also has an intrinsic inhibitory activity in the absence of the GME. The majority of the negative element activity could be elicited by a 56-bp sequence between -3105 and -3050 bp of the TAT gene. Multiple, clustered mutations of this sequence reduced, but did not eliminate, the negative activity. Further efforts to restrict the negative element were unsuccessful, suggesting that multiple sequences are required for full activity. High affinity, sequence-specific binding of a trans-acting factor(s) was observed in gel shift assays. This binding was half-maximally competed by a 4.4-fold excess of nonradioactive probe and was very stable once formed (delta H [symbol: see text] dissoc. = 32 kcal/mol), suggesting that low concentrations of a high affinity binding protein(s) exist in nuclear extracts. Further support for this conclusion came from the observation that cotransfection of a plasmid containing multiple copies of the 56-bp negative element was able to relieve the negation of GME activity in a GME-56-bp-GRE reporter construct. These data directly support the role of a trans-acting factor(s) in binding to the 56-bp negative element and blocking GME activity. Collectively, these data suggest that glucocorticoid induction of TAT gene expression is subject to multiple levels of control by several new cis-acting elements and thus is much more complex than previously appreciated.

Base Sequence↗

PubMed1996

[A case of renal cell carcinoma with hyperglycemia].

A 71-year-old male with hyperglycemia was incidentally found to have a right renal tumor. Hyperglycemia had been controlled by administration of 34 units of insulin. Immediately after radical nephrectomy, hyperglycemia was improved to be able to stop insulin. His fasting blood glucose level remained within normal limits without any treatment. Laboratory studies, however, failed to reveal any endocrinopathy derived from renal cell carcinoma responsible for the diabetic state.

Aged↗

PubMed1996

[Results of genitoplasty for virilized genitalia of 41 females with congenital adrenal hyperplasia].

OBJECTIVE: The results of genitoplasty performed at our clinic for 41 female patients with congenital adrenal hyperplasia (CAH) were reviewed. PATIENTS: Among 57 females with CAH (56 with 21-hydroxylase deficiency and 1 with 11 beta-hydroxylase deficiency) diagnosed between 1961 and 1995, 41 underwent genitoplasty. For the rest of 16 patients, 1 received already clitorectomy, 11 (19%) needed no surgical reconstruction, 2 died before surgery, and 2 are in a waiting list for surgery. RESULTS: According to Prader's classification of virilized genitalia, 41 patients who received surgery included 8 of type I, 10 of type II, 17 of type III, and 4 of type IV. There was no patients of type V, and 2 were not classified because of previous surgery. Four patients underwent genitoplasty 7 times in total before visiting us. The age receiving initial genitoplasty at our clinic ranged from one year and 9 months to 20 years (median: 4 years and 5 months). Follow-up period averaged 17 years with the range of 2 months to 33 years. For enlarged clitoris, clitorectomy (amputation of clitoris) was carried out for 22 patients before 1975 and corporal resection for 17 after 1975. Two patients manifested recurrence of clitoromegaly after the surgery because of either incomplete resection of the clitoris or patient's ignorance of taking glucocorticoid regularly. Thirty-six patients needed labiovaginoplasty. Simple midline cutback was performed for 6 patients and Y-V plasty (skin flap labiointroitoplasty) for 30. Vaginal orifice was not identified in 5 patients at the initial surgery. Two patients received successful second introitoplasty at the older age than 10. Post-operative stenosis of vaginal orifice was confirmed in 6 patients and 3 underwent second introitoplasty. Among 23 patients older than 25 years at present, 7 got married and 4 raised 6 children with assistance of Caesarian section. CONCLUSIONS: Most of female patients with CAH needed genital plastic surgery including clitoroplasty and labiovaginoplasty. Corporal resection for enlarged clitoris with sufficient hormone therapy brought a satisfactory result. Y-V plasty for labiovaginoplasty proved to be an excellent method, especially from cosmetic viewpoint, but remained some problems as one stage operation including difficult identification of vaginal orifice and post-operative stenosis of introitus in some patients.

Adrenal Hyperplasia, Congenital↗

PubMed1996

[Relationship between pretreatment serum levels of prostate specific antigen and bone metastasis in prostate cancer].

We retrospectively reviewed pretreatment levels of serum prostate specific antigen (PSA) in 138 newly diagnosed, untreated patients with prostate adenocarcinoma to evaluate the usefulness of serum PSA levels to predict results of radionuclide bone scans. All of the 24 patients with serum PSA levels above 200 ng/ml showed positive bone scans whereas those with serum PSA levels below 10 ng/ml included only three cases (3/51, 5.1%) positive for bone metastasis. All of the three had poorly differentiated adenocarcinoma of the prostate. In conclusion, bone scans may not be necessary in the cases with serum PSA levels less than 10 ng/ml except for those with poorly differentiated adenocarcinoma.

Adenocarcinoma↗

PubMed1996

[Results of transurethral resection of prostate plus incision (TUR-P+I) for benign prostatic hypertrophy].

The results of 14 patients treated by TUR-P+I and 15 patients by TUR-P between September 1991 and August 1993 were reviewed to evaluate the effects of TUR-P+I. Tur-P+I is a combined technique of channelling TUR-P and transurethral incision of the bladder neck and the prostate. After receiving modest TUR of the adenoma, the bladder neck and anatomical capsule of the prostate was incised by electroresectoscope at 6 o'clock position from the bladder neck toward to verumontanum. Before operation, the maximum floor rate, average flow rate, and residual urine volume were measured, which were respectively 9.9 +/- 5.6 ml/s (M+SEM), 4.4 +/- 2.3 ml/s, and 130 +/- 80 ml in TUR-p+I group, and 11.6 +/- 2.9 ml/s, 4.3 +/- 1.8 ml/s, and 60 +/- 60 ml (p < 0.01) in TUR-P group. The operation time and resected tissue weights were similar in both groups; 68 +/- 16 min and 11 +/- 5.2 g in TUR-P+I group, and 72 +/- 25 min and 11 +/- 6.5 g in TUR-P group. The post-operative maximum flow rate, average flow rate and residual urine volume were respectively improved to 19.0 +/- 5.7 ml/s, 9.3 +/- 3.7 ml/s, and 20 +/- 20 ml in TUR-P+I group, and 14.6 +/- 6.1 ml/s (p = 0.057), 6.6 +/- 2.6 ml/s (p < 0.05), and 30 +/- 30 ml (not significant) in the TUR-P group. Neither significant blood loss nor complications were experienced in either procedure. It is suggested that TUR-P+I could be a safe and effective alternative of TUR-P. Longer follow-up and the prospective study are required to establish the value of the current combined technique.

Aged↗