Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 127 records · Page 7Linked to original sources

PubMed1996

Water channel protein subtype suggests the origin of renal cell carcinoma.

PURPOSE: Several subtypes of water selective channel protein have been cloned. In normal kidneys, CHIP-28 (channel forming integral protein of 28 kd) is expressed solely in the proximal tubules and descending thin limbs, and aquaporin-CD (AQP-CD) expression is restricted to collecting ducts. We assessed expression of these 2 distinct types of water channels in renal cancer tissues. MATERIALS AND METHODS: Expression of CHIP-28 and AQP-CD was examined in 12 samples of primary renal cell carcinoma by Northern blot, reverse transcriptase-polymerase chain reaction and immunohistochemistry. We also evaluated expression of these 2 molecules immunohistochemically in 4 samples of Bellini duct tumor, which has been thought to arise from renal collecting ducts. RESULTS: Expression of CHIP-28 was detected in all of the samples of primary renal cell carcinoma, whereas none of them expressed AQP-CD. None of 4 samples of Bellini duct tumor expressed CHIP-28, although expression of AQP-CD was recognized in 2. CONCLUSIONS: Our current observation confirms the idea of the proximal or descending tubule origin of renal cell carcinoma.

Aged↗

PubMed1996

[Combined hormone-chemotherapy for stage D2 prostatic cancer: starting time of chemotherapy in relation to hormone therapy].

We retrospectively analyzed 29 patients with stage D2 prostatic cancer who had been treated with chemotherapy at the urological clinic of Tokyo Medical and Dental University Hospital between 1983 and 1992 to evaluate the efficacy of chemotherapy for advanced prostatic cancer. The patients were divided into three groups according to the starting time of chemotherapy in relation to hormone therapy; 9 patients who received chemotherapy more than four weeks after the initial hormone therapy (group H), 9 patients who received chemotherapy only or in combination with the hormone therapy more than four weeks previously (group C), and 11 patients in whom both therapies were started within four weeks (group HC). Follow-up period ranged from four to 108 months averaging 35. Combination chemotherapy including cisplatin was administered one to 17 times with the median of five. The five-year survival rates estimated by Kaplan-Meier method were 18% in group H, 28% in group C, and 78% in group HC, respectively (HC vs. C: p < 0.05, HC vs. H: p = 0.059). These findings indicate that a combination chemotherapy including cisplatin may improve the prognosis of patients with advanced prostatic cancer when it is started with the initial hormone therapy simultaneously.

Aged↗

PubMed1996

[Rapidly deteriorating adult hydronephrosis due to an aberrant vessel: a case report].

Hydronephrosis due to ureteropelvic junction (UPJ) obstruction generally progresses gradually. We experienced a case of hydronephrosis due to UPJ obstruction deteriorating rapidly in an adult woman. In spite of percutaneous nephrostomy, 99mTc-DTPA renogram showed a non-functional pattern. A nephrectomy was done. Peri-operatively, the aberrant lower pole vessel was found to be obstructing the UPJ. The hydronephrosis deteriorated rapidly because the extrarenal pelvis dilated in the shape of box, became suspended from the aberrant vessel. Therefore, we believe that the box pelvis is one of the most important factors deteriorating hydronephrosis.

Arteries↗

PubMed1995

The factor binding to the glucocorticoid modulatory element of the tyrosine aminotransferase gene is a novel and ubiquitous heteromeric complex.

Glucocorticoid induction of the tyrosine aminotransferase gene deviates from that of many glucocorticoid-responsive genes by having a lower EC50 and displaying more agonist activity with a given antiglucocorticoid. A cis-acting element, located 3646 base pairs upstream of the start of tyrosine aminotransferase gene transcription, has been found to be sufficient to reproduce these variations with heterologous genes and promoters (Oshima, H., and Simons, S.S., Jr. (1992) Mol. Endocrinol. 6, 416-428). This element has been called a glucocorticoid modulatory element, or GME. Others have called this sequence a cyclic AMP-responsive element (CRE) due to the binding of the cyclic AMP response element binding protein (CREB). We now report the partial purification and characterization of two new proteins (GMEB1 and -2) of 88 and 67 kDa that bind to the GME/CRE as a heteromeric complex. This purification was followed by the formation of a previously characterized, biologically relevant band in gel shift assays. By several biochemical criteria, the GMEBs differed from many of the previously described CREB/CREM/ATF family members. Partial peptide sequencing revealed that the sequences of these two proteins have not yet been described. Size exclusion chromatography and molecular weight measurements of the gel-shifted band demonstrated that the GMEBs bound to the GME as a macromolecular complex of about 550 kDa that could be dissociated by deoxycholate. Similar experiments showed that CREB bound to the GME as heteromeric complexes of about 310 and 360 kDa. As determined from gel shift assays, GMEB1 and -2 are not restricted to rat liver cells but appear to be ubiquitous. Thus, these novel GMEBs may participate in a similar modulation of other glucocorticoid-inducible genes in a variety of cells.

Amino Acid Sequence↗

PubMed1995

Evidence against dominant negative mechanisms of intestinal polyp formation by Apc gene mutations.

Mutations in the adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Most mutations found in familial adenomatous polyposis patients are of the truncation type, and the phenotype is affected by the mutation sites in the gene. Truncated APC proteins can associate with the wild-type protein. Accordingly, it has been proposed that the polyposis is caused by a dominant negative mechanism. To test this possibility, we constructed transgenic mice that contained mutant minigenes. They expressed the APC protein truncated either at codon 716 (Apc delta 716) or 1287 (Apc delta 1287) at high levels in the intestinal epithelium. Contrary to our expectation, no intestinal polyps or tumors were found in any of such mice, even after 7 months. These results rule out any dominant negative mechanisms in which the truncated APC protein is directly involved in the formation of intestinal polyps in the mouse.

Adenomatous Polyposis Coli Protein↗

PubMed1995

Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

Adenoma↗

PubMed1995

Effects of docosahexaenoic acid (DHA) on intestinal polyp development in Apc delta 716 knockout mice.

Epidemiological studies and animal experiments show an association of dietary intake of fish oils and low incidence of several types of cancers. The active ingredients of fish oils appear to be polyunsaturated fatty acids of omega-3 type such as eicosapentaenoic acid and docosahexaenoic acid (DHA). We have investigated chemopreventive effects of DHA on mouse intestinal polyposis using adenomatous polyposis coli (Apc) gene knockout mice. Damage to the human 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 containing a truncation mutation in the Apc gene at codon 716 (Apc delta 716). The heterozygous mice developed numerous intestinal polyps, and all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating the loss of heterozygosity [Oshima et al. (1995), Proc. Natl Acad. Sci. USA, 92, 4482-4486]. We fed Apc delta 716 heterozygotes with AIN-76A purified diet containing 3% DHA for 7 weeks, and scored the number and size of intestinal polyps. Average DHA intakes per day were 4.1 and 4.3 g/kg body wt for males and females, respectively. DHA-fed females had only 31% of polyps compared with the control females that developed about 220 polyps, whereas DHA-fed females showed no significant decrease in the polyp number. As for the polyp size, the proportion of larger polyps decreased more significantly in females than in males. This is the first demonstration that DHA inhibits intestinal polyposis induced by an Apc mutation at both its formation and growth.

Animals↗

PubMed1995

Antegrade and retrograde fluid transport through the vas deferens.

Intraluminal pressure of the seminal tract at seminal emission from the ejaculatory duct and the mode of transport of cauda epididymal contents were investigated to explore the mechanism of sperm transport. Direct electrical stimulation of any site of the cauda epididymis and vas deferens, which generated nerve-transmitted muscle contraction, caused elevation of the intraluminal pressure only at the cauda epididymis, whereas stimulation of the testis, caput, and corpus epididymis caused no response. The dye instilled in the cauda was emitted into the urethra during the stimulation. Shortly after discontinuation of the stimulation, retrograde movement of residual dye in the vas resulted in its ultimate reentry into the cauda epididymis. Significant decrease of the muscle tonus just after contraction was observed at the cauda. Distension of the wall of the vas generated elevation of the intraluminal pressure only at the site distended. The above results indicate the presence of rapid antegrade and retrograde movement of the sperm and the crucial role of the cauda epididymis on the sperm transport.

Animals↗

PubMed1995

Relationship of the structure of ureteral muscularis to in vitro spontaneous contractions.

We investigated the anatomical structure of the smooth muscle layers of the mid portion of the canine ureter. In transverse sections the inner muscle bundles appear to be oriented longitudinally and the outer muscle bundles appear to be oriented in a circular configuration. In sections cut parallel with the longitudinal axis of the ureter, the inner and outer bundles appear to be oblique and are oriented in a mesh-line manner. In oblique sections, cut parallel with the helically oriented ureteral muscle, bundles appear to be oriented in a lengthwise configuration. These anatomical studies show that canine ureteral smooth muscle is composed of spiral fibers in a mesh structure and that helical muscle strips which include a significant percentage of continuous bundles have a greater capacity to generate spontaneous contractions in vitro than do transverse and longitudinal muscle strips.

Animals↗

PubMed1995

Chlormadinone acetate as a possible effective agent for congenital adrenal hyperplasia to suppress elevated ACTH and antagonize masculinization.

We report two cases of congenital adrenal hyperplasia (CAH) in which administration of chlormadinone acetate (CMA), a substituted progestational agent for prostatic disease, suppressed ACTH hypersecretion and lowered plasma testosterone levels. Case 1 was 83-year-old male with advanced prostatic carcinoma and CAH due to 21-hydroxylase deficiency. His plasma testosterone did not decrease in spite of a bilateral orchiectomy. Case 2 was 40-year-old female with CAH due to 21-hydroxylase deficiency suffering from virilization after the cessation of cortisol supplement therapy because of her breast carcinoma. In these two cases, oral administration of CMA at a daily dose of 75-100 mg suppressed ACTH and cortisol to subnormal levels and reduced testosterone levels. With the suppressive effect on ACTH excess and antiandrogenic action, CMA may be suitable for patients with CAH suffering from symptoms due to overproduced ACTH or adrenal androgen.

Administration, Oral↗

PubMed1995

Effects of clenbuterol on rabbit vesicourethral muscle contractility.

Clenbuterol (10(-10)-10(-7) M), a selective beta 2-adrenoceptor agonist, reduced spontaneous contractile force of isolated rabbit bladder dome, bladder base and proximal urethra. Clenbuterol inhibited both acetylcholine (Ach)-and electrical field stimulation (EFS)-induced contractions of rabbit bladder dome, but was more potent in inhibiting EFS-than Ach-induced contractions. Acetylcholine-but not EFS-induced contractions in the bladder dome were completely inhibited by pretreatment with 10(-6) M atropine. The atropine resistant component of the EFS-induced contractions was completely inhibited by tetrodotoxin, 10(-6) M. Clenbuterol and a non-selective beta-adrenoceptor agonist, isoproterenol, potentiated the EFS-induced contractions of isolated striated muscle preparations from the external urethral sphincter and from the extensor digitorum longus in the rabbit. Clenbuterol was more potent than isoproterenol in increasing EFS-induced contractile force in the external urethral sphincter, whereas isoproterenol was more potent than clenbuterol in increasing EFS-induced contractile force in the extensor digitorum longus. These data suggest that clenbuterol may have a role in the treatment of urinary incontinence by inhibiting the detrusor contraction and fascilitating the external urethral sphincter selectively.

Acetylcholine↗

PubMed1995

Ectopic pituitary adenoma occurring in the interpeduncular cistern. Case report.

Intracranial ectopic pituitary adenoma occurs most frequently in the suprasellar cistern, usually in continuity with the pituitary stalk. Such tumors probably originate from cells of the pars tuberalis located above the diaphragma sellae or from aberrant anterior pituitary cells of the pituitary stalk. The authors report the case of a 37-year-old woman with Cushing's syndrome caused by an ectopic pituitary adenoma of unique location: the tumor was separate form the pituitary stalk and confined within the interpeduncular cistern. After surgical removal of the tumor, continued improvement in the patient's laboratory results and disappearance of her endocrine symptoms strongly indicated the absence of adenoma cells in the pituitary gland or stalk. The tumor in the present case appears to have arisen from aberrant pituitary cells that were present in the leptomeninges of the basal surface of the hypothalamus.

Adenoma↗

PubMed1995

[The experimental evaluation of the difference in closing dynamics of internal urethral ostium on the urinary continence and on the ejaculation induced by an administration of phenylephrine].

BACKGROUND: The internal urethral ostium is usually closed both on the ejaculation and on the urine collection, although the difference of the closing characteristics have not been known. METHODS: The difference in closing style of bladder neck (internal urethral ostium) between on the phenylephrine administration corresponding state to the ejaculation and on the filling of urinary bladder corresponding state to the urinary continence was evaluated by Stereo-UPP method using mongrel dogs. RESULTS: On phenylephrine administration, the length between verumontanum and bladder neck was lengthened, and a remarkable pressure increase was observed in the area. On the urinary continence filling physiological saline in the bladder, the length of the urethra on the UPP curve of the anterior wall of urethra was lengthened (10%) and the base of bladder was gradually become flat. The pressure in the bladder neck was not relatively increased. CONCLUSIONS: The internal urethral ostium was closed both on the phenylephrine administration and on the urine collection, although the closing characteristics of each was very different. It was demonstrated that on the phenylephrine administration the area between the verumontanum and the bladder neck was lengthened, together with the rise of pressure in the area, whereas on the urine collection bladder neck was closed in low pressure by flattening the base of bladder.

Adrenergic alpha-Agonists↗

PubMed1995

Infrequent mutations of the WT1 gene in primary cancers of the adult urinary tract.

Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of all of the ten exons of the WT1 gene and restriction fragment length polymorphism (RFLP) analysis of the WT1 locus were performed on primary urinary tract cancers: seven renal pelvic cancers, one ureteral cancer, 11 bladder cancers, and 22 renal cell cancers. Four human bladder cancer cell lines (T24, JTC30, JTC32, and HUB41) and three human prostate cancer cell lines (PC-3, DU145, and LNCaP) were also examined. None of the primary cancers showed any apparent mutations of the gene, whereas one base substitution of exon 5 was found in DU 145 and gross alteration of the gene was recognized in HUB41. Heterozygosity of polymorphic exon 7 was retained in all of the 12 informative cases, and none of 10 informative cases showed loss of heterozygosity at the WT1 locus in RFLP analysis. It is concluded that mutations of the WT1 gene may not be involved in the formation of malignant tumors of the adult urinary tract.

Adult↗

PubMed1995

[A case of pineal germinoma presenting with severe amnesia].

Patients who have a pineal germinoma usually present with symptoms of intracranial hypertension or disturbances in vertical ocular motion but rarely present with amnesia. We recently encountered a case of pineal germinoma accompanied by severe amnesia, but not by hydrocephalus. A 32-year-old, right-handed man was admitted with severe memory disturbance which had gradually worsened in the preceding three months. On admission, he was alert and cooperative. His speech was well preserved and not fabricated. He had neither symptoms of intracranial hypertension or visual disturbance. There was no manifestation of interhemispheric disconnection symptoms. His immediate and semantic memory was preserved, however, his recent and antegrade episodic memory was severely impaired. The amnesia involved both verbal and visual modalities. He could recall only 1 out of 5 objects in 5 minutes. He was orientated to people, but not to time and place. And his motivation was severely affected. Magnetic resonance imaging (MRI) showed a heterogeneously enhanced tumor in the splenium and pineal body that extended into the bilateral ventricular trigon through major forceps and was accompanied by edema in the retrosplenial region. The bilateral crura of the fornix was obscured by the tumor. The enlarged pineal body was slightly compressing the upper colliculus but hydrocephalus was not observed. The tumor, which was partially excised through a right parietal corticotomy, had features typical of a germinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[The regulation of testicular function by paracrine mechanism].

It is well accepted that testicular function is controlled by gonadotropins. Androgen secretion is regulated by LH, whereas spermatogenesis is controlled by FSH and locally produced androgens. However, evidence has accumulated to indicate that this extratesticular control system is modulated by equally important intratesticular cell-cell interactions. The study of this local control system has received major impetus from the development techniques which have allowed isolation and culture of purified testicular cells and has revealed that testicular cells respond to previously unexpected variable humoral factors which are produced by testicular cells themselves, namely testicular paracrinology. Numerous reviews with regard to cell-cell interactions have been published. In this paper, we attempted to summarize recent topics of para and autocrinology of testicular androgen biosynthesis and spermatogenesis.

Androgens↗

PubMed1994

Function and distribution of autonomic receptors in canine ureteral smooth muscle.

There have been only a few reports of the measurement of autonomic receptors in ureteral smooth muscle. Furthermore, it is so difficult to maintain stable spontaneous contractions in the ureter, that either electrical field stimulation or KCl at high concentrations are utilized to induce ureteral contractions in many in vitro ureteral pharmacologic examinations. We used the spiral ureteral strips which generate spontaneous contractions in the ureter in present experiments. Norepinephrine, phenylephrine, clonidine, carbachol, and prostaglandin F2 alpha enhanced the spontaneous contractile force and/or increased the contractile frequency of spontaneous rhythmic contractions in spirally-incised muscle strips from isolated canine ureters. In contrast, isoproterenol, terbutaline, a beta 2-adrenergic agonist, and prostaglandin E2 reduced the spontaneous contractile force and/or decreased the contractile frequency of spontaneous rhythmic contractions. Dobutamine, a beta 1-adrenergic agonist, did not affect significantly the spontaneous rhythmic contractions. The effects of the prostaglandins were not influenced by autonomic antagonists or tetrodotoxin. The existence of alpha 1-, alpha 2-, and beta-adrenoceptors and muscarinic cholinergic receptors were demonstrated in the canine ureter using radioligand techniques. The density of alpha 1-receptors binding sites was significantly greater than that of the other receptors examined. Our data show that the sympathetic nervous system is more involved than the para-sympathetic nervous system in canine ureteral contractile activities, and that alpha- and beta-receptors contained in canine ureteral smooth muscle are comprised mainly of the alpha 1- and beta 2-subtypes. It is also suggested that prostaglandins directly affect canine ureteral contraction.

Animals↗

PubMed1994

Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis.

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.

Animals↗