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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 73 records · Page 4Linked to original sources

Detection of disseminated urothelial cancer cells in peripheral venous blood by a cytokeratin 20-specific nested reverse transcriptase-polymerase chain reaction.

More than half of all patients with invasive urothelial cancer subsequently develop metastatic disease even after radical resection of the primary cancer. In these patients, neoplastic cells may be disseminated prior to or during the operation. A nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) assay which amplifies cytokeratin (CK) 20 transcripts was used to detect cancer cells in the peripheral blood of urothelial patients. This assay was able to detect 10 bladder cancer cell line cells in a sample of ten million peripheral-blood mononuclear (PBMN) cells. CK 20-specific signals were detected in 9 (22.5%) of 40 PBMN cell samples prepared from 40 urothelial cancer patients in relation to the tumor stage, including 0/13 patients with a superficial tumor, 4/21 (19%) with a regionally invasive tumor and 5/6 (83%) with a metastatic tumor (P = 0.0002 in chi 2 test). No signals were detected in any of 25 healthy donor PBMN cell samples. The present results indicate that the CK 20 RT-PCR assay is applicable for detection of urothelial cancer cells in the peripheral blood. The assay also confirms that hematogenic dissemination occurs in invasive urothelial cancers but rarely in superficial ones.

Biomarkers, Tumor↗

Late recurrence and progression after a long tumor-free period in primary Ta and T1 bladder cancer.

OBJECTIVE: To determine the probability and risk factors of recurrence and progression (to T2 or worse) after a long tumor-free period in patients with superficial (stage Ta and T1) bladder cancer. PATIENTS AND METHODS: A consecutive series of 100 patients with superficial bladder cancer who remained tumor-free for longer than 4 years after initial treatment were reviewed. The rates of recurrence and progression were statistically assessed and the significance of risk factors was determined. RESULTS: Of the 100 patients, 24 (24. 0%) recurred within 15 years after the initial treatment. The 10- and 15-year recurrence-free rates were 76.0 and 59.6%, respectively. Among the clinicopathological variables examined, intravesical chemotherapy was determined by a log-rank test to be a significant unfavorable risk factor for late recurrence (p < 0.001). Progression of the tumor occurred in 5 patients. Four variables including presence of multiple tumors, involvement of the bladder neck, positive urine cytology, and intravesical chemotherapy were found by a univariate analysis to be significant risk factors for late progression (p < 0.05). Among these factors, initial presence of multiple tumors (3 or more) was determined by a multivariate analysis to be an independent risk factor for late progression. CONCLUSION: Recurrence and progression continue to occur in patients with superficial bladder cancer even after long periods of dormancy. Regular follow-up urological assessments should be continued until at least 15 years of tumor-free existence, especially in patients treated by intravesical chemotherapy or those initially having multiple tumors.

Administration, Intravesical↗

True hermaphroditism associated with microphthalmia.

A 4-year-old boy with an undescending left testis, penoscrotal hypospadia and bilateral microphthalmia was admitted to our hospital. Chromosome analysis revealed a karyotype of 46, XX del(x)(p2 2,31) and the sex-determining region of the Y chromosome (SRY) was negative. The right testis was located in the scrotum and a left cystic ovary-like gonad, a salpinx and a unicorn uterus were found in the left inguinal canal. Histologically the gonad was an ovotestis in which primordial follicles covered infantile seminiferous tubules. Microphthalmia is observed in some congenital syndromes caused by interstitial deletion of the X chromosome. This case suggested that the short arm of the X chromosome was involved in the differentiation of the gonad. Very closely located follicles and infantile seminiferous tubules indicated that induction of meiosis in the fetus was controlled by the local microenvironment in follicles and seminiferous tubules, and not by the systemic hormonal condition.

Child↗

[A case of retroperitoneal hemangiopericytoma].

We report a case of a huge retroperitoneal tumor in a 67-year-old woman. When the patient was taken to another hospital by ambulance, she had lost consciousness because of hypertension and hypoglycemia and abdominal CT revealed a huge retroperitoneal tumor with deviation of the right kidney and inferior vena cava. After further examinations including ultrasonography, MRI and angiography in our hospital, the tumor was extirpated. The tumor, 22 x 17 x 10 cm in size and 2,580 g in weight was diagnosed as hemangiopericytoma histologically. She has remained well with no evidence of recurrence for 9 months since the operation.

Aged↗

[Primary progressive limb-kinetic apraxia: a case report with an electrophysiological study].

We report a 53-year-old right handed woman with a 5-year history of slowly progressive clumsiness of her right hand. Neurologic symptoms was otherwise unremarkable except for mild dysarthria. Brain CT and MRI revealed a focal atrophic change in the left precentral gyrus. She was thought to have the primary progressive limb-kinetic apraxia. Electrophysiological studies were performed to explore physiologic mechanism of her apraxia. Surface EMG revealed co-contraction of antagonistic muscles in her right upper extremity with rhythmic myoclonic discharges. C-reflex was positive after median nerve stimulation only on the affected side. SEPs elicited by the median nerve stimulation were not enlarged and the SEP recovery curves showed no abnormal facilitation or inhibition. In addition, the premyoclonus spike was demonstrated by Jerk-locked averaging. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition on the motor cortex in the affected side. Median nerve stimulation given prior to the transcortical magnetic stimulation on the size of the magnetic evoked potential (MEP) revealed abnormal facilitations on the affected side, especially at conditioning-test interval of 60-80 ms. Therefore, our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.

Apraxias↗

Sympathetic efferent pathways projecting to the vas deferens.

The abdominal and pelvic sympathetic nervous system controlling the vas deferens has elaborate mechanisms to preserve its function against various injuries. The main sympathetic signals to the vas deferens proceed the common pathway in mammalians, which consists of the lumbar splanchnic nerve, caudal mesenteric plexus, hypogastric nerve, pelvic plexus and its branches. On the way of this common pathway, some signals cross to the other side of the body at the level of the caudal mesenteric plexus and/or the pelvic plexus. The preganglionic axons passing through the hypogastric nerve very likely provide a bilateral innervation to postganglionic neurons in the pelvic plexuses, which also exhibit crossing to the bilateral vasa deferentia. The sympathetic nerves originating from the thoracic spinal cord are of minor importance in contraction of the vas deferens but possibly influence it by the hormonal system consisting of the major splanchnic nerve and the adrenal medulla. When the common pathway is interrupted, various compensatory mechanisms are generated: enhancement of the remaining sympathetic pathways or reorganization of synaptic connection in the pelvic plexus. Surgical reconstruction of the transected hypogastric nerve is possible and cross-innervation mechanism via the hypogastric nerve can also be preserved. Elevation of intraluminal pressure at the cauda epididymis/proximal vas deferens induced by nerve impulse pushes the spermatozoa out to the ampulla and distention of the wall of the ampulla triggers its contraction to emit the content into the urethra. After seminal emission, a portion of the seminal fluid remaining in the vas deferens moves in a retrograde direction to the cauda epididymis for the next emission. It remains to be seen whether similar mechanisms in animals are at work in humans.

Adrenal Medulla↗

Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7.

The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in eliciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815). CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-12. The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD8+ T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4+ T cells and endogenous B7. These results indicated a potent antitumor effect of CD40L that is mediated by potentiation of host Ag-presenting cell functions, and introduction of CD40L will be useful as a new strategy of immuno-gene therapy against tumors.

Animals↗

Cloning and characterization of a novel binding factor (GMEB-2) of the glucocorticoid modulatory element.

The 21-base pair glucocorticoid modulatory element (GME) of the rat tyrosine aminotransferase gene is the only cis-acting element known to modulate the transcriptional activity of receptors bound to glucocorticoid response elements. Specifically, the GME increases the activity of complexes bound both by physiological concentrations of glucocorticoids, due to a left shift in the dose-response curve, and by saturating concentrations of anti-glucocorticoids. For this reason, the nuclear protein(s) that has been demonstrated to bind to the GME is of major interest as a possible transcription factor with hitherto undescribed properties. Subsequent studies indicated that not one but two proteins of 88 and 67 kDa (= GMEB-1 and -2, respectively) formed a heteromeric complex with double-stranded GME oligonucleotides in gel shift assays and participated in the expression of GME activity (Oshima, H., Szapary, D., and Simons, S. S., Jr. (1995) J. Biol. Chem. 270, 21893-21910). Here, we report the use of polymerase chain reaction of degenerate oligonucleotides and 5'- and 3'-rapid amplification of cDNA ends to clone two cDNAs of 2. 0 and 1.9 kilobase pairs that probably result from alternative splicing. Both cDNAs encoded open reading frames containing all four previously sequenced peptides. The longer 2.0-kilobase pair cDNA encoded an open reading frame for an acidic, 529-amino acid protein and afforded a major 67-kDa and a minor 58-kDa protein after in vitro transcription/translation. Both proteins were recognized by a mono-epitopic antibody raised against a peptide of GMEB-2. The in vitro translated protein bound to GME DNA in gel shift assays. However, the binding to GME DNA increased markedly after mixing with authentic GMEB-1 to give a gel-shifted complex that was similar to that derived from HTC cell cytosol. GMEB-2 shares a unique domain (KDWKR) with proteins derived from diverse organisms as follows: Drosophila (DEAF-I), rat (Suppressin), and Caenorhabditis elegans (three unknown open reading frames). Collectively, these data suggest that the 67-kDa GMEB-2 not only is an important factor for the modulation of glucocorticoid receptor bound to glucocorticoid response elements but also may belong to a novel family of transcription factors.

Amino Acid Sequence↗

International Society of Andrology and International Union of Pure and Applied Chemistry, Clinical Chemistry Section, Commission on Nomenclature, and International Federation of Clinical Chemistry Scientific Division. Properties and units in the clinical laboratory sciences XIII. Properties and units in reproduction and fertility (IUPAC-IFCC technical report 1998).

This document is the first recommendation on the presentation of properties in reproduction and fertility and their values in clinical laboratory sciences from The International Society of Andrology, IFCC and IUPAC. It forms part of the ongoing effort to standardise requests and reporting of laboratory data for transmission across cultural and linguistic domains, without attempting to standardise the language used by clinicians and laboratory practitioners. The document is accessible on Internet from C-NPU home page address: http://inet.uni-c.dk/ home/ifcc_iupac_cnpu.

Chemistry, Clinical↗

Evaluation of clinical indexes to predict fate of pelvic nerve dysfunction.

This study was designed to evaluate posterior urethral sensation and sacral reflex evoked by posterior urethral stimulation to predict fate of pelvic nerve dysfunction. Enrolled were 24 male patients sequentially receiving the following examinations 1-3 months (postoperative) and more then 6 months (follow-up) after surgery for rectal cancer: sensory thresholds of the penile skin (SS) and the posterior urethra (SU), sacral reflex evoked by penile stimulation (BCR) and posterior urethral stimulation (UUR), and urodynamic study. Controls included 25 patients with normal voiding function before pelvic surgery. SS, SU and latencies of BCR and UUR averaged 1.9+/-0.6 mA, 5.6+/-1.8 mA, 33.3+/-4.2 ms and 65.0+/-9.3 ms in controls, respectively, and unchanged postoperatively in 13 patients with normal voiding function. Of 11 patients with voiding dysfunction whose SS and latency of BCR remained unchanged, SU increased in 7, voiding function remained unrecovered in 6 patients during the follow-up period and recovered in the remaining 5. None of four patients with nonevocable UUR recovered voiding function. Thus, unchanged SU and disappearance of UUR were useful to predict recovery and nonrecovery of postoperative voiding dysfunction, respectively.

Adult↗

Modulation of TAT gene induction by glucocorticoids involves a neutralizing sequence.

Recent studies have indicated that two elements in addition to the glucocorticoid response element (GRE) are involved in the induction of the endogenous TAT gene in FuS-5 rat hepatoma cells. The first is the 21 bp glucocorticoid modulatory element (GME) at -3648 bp, which causes reporter constructs to display both a left shift in the dose-response curve for glucocorticoids and increased percentages of agonist activity for antiglucocorticoids. The second is a negative element at -3340 to -3050 that blocks the action of the GME. This last observation raised the question of how GME activity can be expressed in Fu5-5 cells in the intact TAT gene that contains both the GME and the negative element. The present study identifies a third element, a "neutralizing" sequence, that restores the activity of the GME even when otherwise inactivated by the negative element. This neutralizing sequence was located within the region surrounding the GREs of the TAT gene but is separate from the GREs. The activity of the individual GME and negative elements was found to depend upon spacing. However, in combination with the natural GRE, the native TAT gene spacing of the GME and negative elements was able to reproduce the activity of the intact gene. Thus, a total of three additional elements (an activator, a negative element, and a neutralizer) appear to cooperate with the GREs in glucocorticoid induction of the TAT gene in Fu5-5 cells. While such a grouping of elements may be novel among steroid regulated genes, it is a not uncommon occurrence for the transcriptional control of other genes.

Animals↗

Differences between proximal and distal portions of the male rabbit posterior urethra in the physiological role of muscarinic cholinergic receptors.

1. The aim of the present study was to elucidate functional differences between embryologically different portions of the posterior urethra of male rabbits in response to muscarinic acetylcholine receptor (mAChR) stimulation using in vitro isometric tension experiments and radioligand binding studies. 2. In the in vitro isometric tension experiments, carbachol, produced a dose-dependent contraction of the proximal portion under the resting state, but did not change the basal tone of the distal portion. Contraction of the proximal portion by 10(-5) M noradrenaline (NA) was dose-dependently enhanced by carbachol either in the presence or absence of NG-nitro-L-arginine (NOARG). In contrast, carbachol induced relaxation of the distal portion contracted by 10(-5) M NA, which was reversed to dose-dependent contraction in the presence of NOARG. 3. Both portions of the urethra had a similar number of [3H]-quinuclidinyl benzilate ([3H]-QNB) binding sites (195.3+/-74.1 fmols mg(-1) protein for the proximal portion and 146.5+/-8.5 fmols mg(-1) protein for the distal portion) with similar affinities (115.0+/-45.4 pM for the proximal portion and 79.9+ 2.9 pM for the distal portion). 4. The concentration-response curves to carbachol in both portions were shifted to the right in a parallel manner in the presence of pirenzepine (an M1 antagonist), 11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-2,3-b)-(1,4)-benzodiazepin-6-one (AFDX-116, an M2 antagonist) and 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP, an M1/M3 antagonist). The pA2 values for pirenzepine, AFDX-116 and 4-DAMP were 7.5+/-0.1, 7.2+/-0.02 and 9.3+/-0.1 respectively for the contraction of the proximal portion, and 7.2+/-0.1, 7.1+/-0.2 and 9.1+/-0.2, respectively for the relaxation of the distal portion. 5. In conclusion mAChR subtypes distribute in a similar fashion throughout the length of the male rabbit posterior urethra with the discrepant responses to carbachol attributable to the differential involvement of the NO pathway in mAChR-generated reactions.

Animals↗

Localization of rat FGF-5 protein in skin macrophage-like cells and FGF-5S protein in hair follicle: possible involvement of two Fgf-5 gene products in hair growth cycle regulation.

It has been reported that the gene for murine fibroblast growth factor-5 (Fgf-5) is expressed in the rat hair follicle and that this expression may be associated with catagen induction (Hebert et al, 1994). In this study, we analyzed the Fgf-5 gene product in skin because the gene generates two mRNA that translate into the FGF-5 protein and a short form of the FGF-5 protein (FGF-5S) as a result of an alternative splicing (Hattori et al, 1996; Ozawa et al, 1996). Indeed, we detected both types of FGF-5 mRNA in rat skin samples. Two monoclonal anti-FGF-5 antibodies, one (E723) being specific for FGF-5 long-form protein and the other (B2B6) being reactive with both FGF-5 and FGF-5S proteins, were used to locate these proteins by immunohistochemistry. Staining of the rat skin revealed that only the B2B6 antibody reacted with hair follicles and that both antibodies reacted with macrophage-like round cells, suggesting that the product of the Fgf-5 gene in the hair follicle is FGF-5S. The immunoreactivity of the FGF-5S protein increased during early anagen VI and decreased rapidly during catagen. The density of FGF-5-positive macrophage-like cells in the dermis increased during anagen and decreased during catagen and telogen, whereas the density of these cells in the panniculus adiposus did not change during anagen and increased during catagen and telogen. There was no apparent association between the density of FGF-5-positive macrophage-like cells and that of FGF-5-negative, dendritic macrophage-like cells. Thus, the results suggest the possible involvement of FGF-5S in the hair follicle in anagen VI and catagen development and that the density of FGF-5-positive macrophage-like cells may also be associated with the hair growth cycle.

Animals↗

Characterization of murine CD70 by molecular cloning and mAb.

CD27, a member of the tumor necrosis factor (TNF) receptor family, has been implicated in T cell activation, T cell development and T-dependent antibody production by B cells. Its ligand CD70 has been identified only in humans, and, thus, physiological and pathological roles of the CD70-CD27 interaction remain to be determined in an experimental animal system. In the present study, we identified murine (m) CD70 by molecular cloning, and characterized its expression and function by generating an anti-mCD70 mAb. The mCD70 cDNA encoded a type II transmembrane glycoprotein of the TNF family, having 56.5% identity to the human CD70 amino acid sequence. The mCd70 gene was assigned in the central region of chromosome 17. To explore the expression and function of mCD70, we generated cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein (mCD27-Ig) to mCD70 transfectants. FR70, as well as mCD27-Ig, immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70 far more efficiently than mCD27-Ig. FR70 also abrogated the CD28-independent co-stimulatory activity of A20 cells. The expression of mCD70 was detected on splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti-IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced mCD70 expression on splenic B cells. These results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system. FR70 will be useful for further investigating the physiological and pathological roles of the CD70-CD27 interaction in T cell development, T-dependent antibody production and various disease models in the murine system.

Amino Acid Sequence↗

Advanced testicular germ cell tumor in a hemophilic patient with human immunodeficiency virus infection.

A stage IIIB anaplastic seminoma which occurred in an HIV-infected hemophilia is reported. The patient with hemophilia A was 36 years old and had been seropositive for HIV antibody for 3 years. Inguinal orchiectomy and subsequent chemoradiotherapy for retroperitoneal lymphadenopathy were performed and a marker negative partial response was obtained. In spite of a low initial CD4+ lymphocyte count (90/microliter), the patient tolerated the treatment well without life-threatening opportunistic infection. Although factor VIII supplement was performed, continuous bleeding from the operative wound made postoperative care difficult.

Acquired Immunodeficiency Syndrome↗

Chromophobe cell renal carcinoma in childhood.

We report the first case of chromophobe cell renal carcinoma in childhood. A 12-year-old boy presented gross hematuria following minor trauma. He was diagnosed as having a left renal tumor 45-mm in diameter. Radical nephrectomy was performed. One year later the boy was well.

Carcinoma, Renal Cell↗