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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 91 records · Page 5Linked to original sources

Secondary treatment failure without anti-human chorionic gonadotropin antibody in a patient with Kallmann syndrome.

A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.

Adult↗

Significance of bladder neck involvement on progression in superficial bladder cancer.

OBJECTIVES: To determine the significance of bladder neck involvement in predicting disease progression in superficial (stage Ta and T1) transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: A series of 277 patients with newly diagnosed superficial TCCs of the bladder was reviewed, and disease progression (to T2 or worse) was considered. The significance of several risk factors including bladder neck involvement was assessed in univariate and multivariate analysis. RESULTS: Progression occurred in 28 (10.1%) of 277 patients during a median follow-up period of 7.7 years. Nineteen died of bladder cancer. The following variables were found to be statistically significant at the univariate analysis (p < 0.05): irritative symptoms, urine cytology, tumor stage, involvement of the bladder neck, and tumor grade. Indeed, only involvement of the bladder neck, tumor stage, and grade retained their value as independent factors for progression at multivariate analysis. Patients were divided into three groups according to the number of independent risk factors they had. Groups having none, one, and two or three risk factors included 129, 99, and 49 patients with 5-year progression rates of 0.8, 4.6 and 27.5%, and 15-year rates of 4.0, 20.1 and 42.7%, respectively. CONCLUSION: Involvement of the bladder neck is a significant and independent risk factor for progression of superficial TCCs in addition to the histologic grade and stage. The combination of these three risk factors offers better prediction of progression in an individual patient.

Adolescent↗

Cosmetic orchiectomy using pedicled fibro-fatty tissue graft for prostate cancer: a new approach.

OBJECTIVE: To preserve the appearance of a normal scrotum at orchiectomy, a pedicled fibro-fatty tissue graft was inserted in the lumen of the tunica vaginalis. METHODS: 42 testes of 21 patients with metastatic prostate cancer were treated. A pedicled fibro-fatty tissue graft prepared from the region between the spermatic cord and the scrotal septum was inserted in the lumen of the tunica vaginalis following epididymis-sparing orchiectomy under local or spinal anesthesia. RESULTS: A pedicled fibro-fatty tissue graft which reached the epididymal tail was prepared in all instances. The average postoperative volume of the scrotal content was 18 ml (range 5-30 ml). Postoperative complications were scrotal edema, sensation of traction at the inguinal region and epididymitis. All but 1 patient were satisfied with the appearance of the scrotum and achieved sufficient androgen ablation. Mean follow-up was 8 (3-11) months. CONCLUSION: This cosmetic orchiectomy is a safe, simple and economical procedure to preserve the appearance of a normal scrotum; it also achieves the reliable result of androgen deprivation.

Aged↗

Preservation of ejaculatory function by reconstruction of the canine hypogastric nerve.

OBJECT: The hypogastric nerve (HGN) plays a crucial role in the primary functions of ejaculation: sperm transport through the vas deferens, secretion of prostatic fluid, and bladder neck closure. This study was undertaken to explore the possibility of restoring HGN function to the seminal tract and preserving its cross-innervation mechanism to the seminal tract after HGN-HGN reattachment. METHODS: Responses of the vas deferens/epididymis, prostate, and bladder neck to electrical stimulation of the lumbar splanchnic nerve (LSN) or the HGN and occurrence of antegrade ejaculation as a result of manual penile stimulation were examined in dogs that had undergone HGN-HGN reattachment. Eighteen months after the procedure had been performed bilaterally, 23 LSNs were electrically stimulated. In 17 LSNs this stimulation elicited elevation of vasal pressure (12 nerves bilaterally); in 18 LNs, bladder neck pressure; and in 15 LSNs, prostate contraction. After retransection of the right HGN in the dogs that had undergone HGN-HGN reattachment, 11 right-sided LSNs were stimulated; in seven LSNs, the stimulation elicited elevation of vasal pressure (five bilaterally), in seven bladder neck pressure, and in six prostate contraction. Twelve left-sided LSNs were stimulated; in seven LSNs, the stimulation elicited elevation of vasal pressure (four bilaterally), in six bladder neck pressure, and in six prostate contracton. Each of the 12 HGN stimulations made proximal to the site that had been sutured in dogs that had HGN-HGN reattachment caused responses of the three organs specified above that were comparable to those in control dogs. Manual penile stimulation elicited antegrade ejaculation in all three dogs examined. CONCLUSIONS: The results of this study show that the function of the HGN in the seminal tract can be preserved after HGN-HGN reattachment and that restoration of its cross-innervation mechanism is possible.

Anatomy, Artistic↗

[Management of invasive carcinoma of bladder and abdominal aortic aneurysm (AAA); technique of radical total cystectomy and simultaneous AAA repair].

BACKGROUND: There is no consensus on the optimal surgical treatment for patients with concomitant invasive carcinoma of bladder and abdominal aortic aneurysm (AAA). We experienced two patients who were treated successfully with simultaneous radical cystectomy and AAA repair. The techniques required for the combined procedure and case reports are discussed. PROCEDURE: The goal of the one-stage operation was to minimize the risk of graft infection without compromising postoperative morbidity and mortality secondary to carcinoma of bladder. Initially pelvic lymph node dissection and radical cystectomy were performed. We preferred retrograde cyctoprostatectomy because most of the cystectomy procedure can be performed without opening the peritoneal cavity and the extent of the retroperitoneal dissection can be minimal. A single-stoma ureterocutaneostomy was preferable urinary diversion. Urinary diversions which utilize intestine such as ileal conduit or ileal urinary reservoir may cause contamination of a graft with bowel content and should be avoided. Before or after urinary diversion, aneurysmal resection and a bifurcated graft replacement were performed. The replaced graft was wrapped with the aneurysmal wall. The major omentum was mobilized and fixed in front of the graft, thereby serving as a protective barrier of the graft. A Dacron graft which was sealed with rifampicin-bonding gelatin was used to further reduce the risk of graft infection. RESULT: Two male patients were treated with the one stage radical cystectomy and AAA repair. Single-stoma ureterocutaneostomy and bilateral ureterocutaneostomy were selected as a urinary diversion. No major postoperative complications, except for paralytic ileus in one case, were observed. CONCLUSION: Our experience and reports of others indicate that radical cystectomy and simultaneous AAA repair can be safely performed with less morbidity than staged operations for the management of concomitant invasive carcinoma of bladder and AAA.

Aged↗

[High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer].

Five patients with metastatic testicular cancer of advanced extent according to the Indiana University criteria were enrolled into this study. All tumors were non-pretreated non-seminomas. Initially all patients were treated with standard dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the five patients showed a good response to VIP and subsequently achieved a pathological complete response (pCR) following surgical resection of residual masses after 3 or 5 courses of VIP. However, they suffered from severe myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT) following the final course of VIP. The remaining three patients unlikely to be cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10 g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400 mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial response (PR) with marker-negative and two PR with marker-positive. Residual masses were removed in all three patients and viable tumor cells were found in two. Of the five patients enrolled, four patients (80%) remain disease-free with minimal follow-up of 20 months, and the remaining one died of cancer 10 months after PBSCT. No serious side effects or complications were encountered. This study shows that standard dose induction therapy of VIP followed by early salvage chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the treatment of advanced poor-risk testicular cancer.

Adult↗

Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice.

Mutations in the human adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed Apc gene knockout mice that contained a truncation mutation at codon 716 (Apc(delta716)). The heterozygous mice developed numerous intestinal polyps. All microadenomas dissected from nascent polyps had already lost the wild-type allele, indicating the loss of heterozygosity (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). We also demonstrated that cyclooxygenase 2 is induced in the polyps at an early stage and plays a key role in polyp development (M. Oshima et al., Cell 87: 803-809, 1996). We have analyzed the process of polyp development in these mice both at morphological and molecular levels. A small intestinal microadenoma is initiated as an outpocketing pouch in a single crypt and develops into the inner (lacteal) side of a neighboring villus forming a double-layer nascent polyp. The microadenoma then enlarges and gets folded inside the villus. When it fills the intravillous space, it expands downward and extends into adjoining villi, rather than rupturing into the intestinal lumen. During this course of development, the basement membrane remains intact, and the labeling index of the microadenoma cells is similar to that of the normal crypt epithelium. As in the crypt cells, neither transforming growth factor beta1 nor its receptor type II is expressed in the microadenoma cells. No hot spot mutations in the K-ras gene are found in the microadenoma tissue during these early stages of polyp development. Essentially, the same results have been obtained for the colonic polyps as well. These results suggest that early adenomas in the Apc(delta716) polyps are very similar to the normal proliferating cells of the crypt except for the lack of directed migration along the crypt-villus axis.

Activin Receptors, Type I↗

Nuclear ADP-ribosylation factor (ARF)- and oleate-dependent phospholipase D (PLD) in rat liver cells. Increases of ARF-dependent PLD activity in regenerating liver cells.

Two forms of phospholipase D (PLD) have been found to be present in nuclei isolated from rat hepatocytes by measuring phosphatidylbutanol produced from exogenous radiolabeled phosphatidylcholine in the presence of butanol. In nuclear lysates from either rat liver or ascites hepatoma AH 7974 cells, the PLD activity was markedly stimulated by a recombinant ADP-ribosylation factor (rARF) in the presence of the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and phosphatidylinositol 4, 5-bisphosphate. ATP and phorbol-12-myristate 13-acetate had no synergistic effect on this PLD activity. On the other hand, the nuclear PLD was stimulated by unsaturated fatty acids, especially by oleic acid. The ARF-dependent nuclear PLD activity was increased in the S-phase of the regenerating rat liver after partial hepatectomy and also was much higher in AH 7974 cells than in the resting rat liver. In contrast, the levels of the oleate-dependent PLD activity remained constant throughout the cell cycle in liver regeneration. The intranuclear levels of the stimulating proteins of the nuclear PLD activity, e.g. ARF, RhoA, and protein kinase Cdelta increased in the S-phase of the regenerating liver. These results suggested that the nuclear ARF-dependent PLD activity may be associated with cell proliferation.

ADP-Ribosylation Factors↗

Intraoperative monitoring of jugular bulb oxygen saturation in patients with moyamoya disease.

The jugular bulb oxygen saturation (SjO2) and end-tidal carbon dioxide (ETCO2) were monitored continuously during surgery in six cases of Moyamoya disease who had demonstrated multiple episodes of transient ischemic attacks (TIAs) and/or fluctuating neurological deficits preoperatively. The arterial carbon dioxide tension (PaCO2) levels were also measured repeatedly at predetermined interval. In two cases (group H), the ETCO2 was controlled at hypercapnic levels during surgery (45.5 +/- 1.5 mmHg) and the remaining four (group N) were operated on in a normocapnic state (39.0 +/- 2.0 mmHg). The group H patients demonstrated high levels of SjO2 ranging from 72 to 85%, indicative of excessive hyperemia. One of the group H patients demonstrated mild and transient motor weakness postoperatively. The group N patients demonstrated normal levels of SjO2 ranging from 66 to 78%. All the patients in both groups demonstrated fluctuations in SjO2 levels in clear positive correlation with spontaneous changes in PaCO2 levels. The present findings indicated that: (1) Global carbon dioxide reactivity of cerebral perfusion is well preserved in patients with Moyamoya disease; and (2) hypercapnia in these patients often causes excessive hyperemia. The occurrence of postoperative neurological deficits in association with such an excessive hyperemia suggests that hyperapnia during surgery is not always beneficial. Intraoperative monitoring of SjO2 is useful for maintaining cerebral perfusion within the optimum range.

Adolescent↗

A possibility for new evaluating method of cytotoxicity by using heat shock protein assay.

To determine whether heat shock proteins can be utilized as a biomarker for cytotoxicity of dental materials the induction of synthesis of heat shock proteins by mercuric chloride was examined. To analyse the synthesis of heat shock proteins, HeLa cells were labelled with [35S] methionine, and the labelled proteins were separated by SDS-PAGE and autoradiographed. Incubation of the cells in a medium containing 1.25 to 40 microM mercuric chloride markedly increased the synthesis of HSP70. At 20 or 40 microM mercuric chloride in medium, HeLa cells synthesized HSP70 at 2 h after exposure, maximally at 4-7 h, and gradually diminished thereafter. Examination of the cytotoxicity of mercuric chloride by the conventional neutral red uptake assay revealed a reduction of uptake of the dye in the presence of mercuric chloride at 40 microM and above. These findings suggest that the induction of synthesis of HSP70 is one of the most sensitive cellular responses caused by mercury ion, and the heat shock protein assay can be utilized for evaluation of the cytotoxicity of dental materials.

Journal Article↗

Involvement of the adrenal medulla in ejaculatory reactions in the dog.

To explore the peripheral signal controlling ejaculatory reactions, contraction of the seminal tract and seminal emission were monitored in the dog during electrical stimulation of the lumbar and greater splanchinc nerves in the presence or absence of sympathetic pathways connecting the lumbar sympathetic trunk to the seminal tract including the vas deferens, prostate and bladder neck. Electrical stimulation of the lumbar splanchnic nerve caused seminal emission, elevation of intraluminal pressure of the vas deferens and bladder neck, and contraction of the prostate without elevation of blood pressure. Transection of all peripheral sympathetic nerve pathways to the seminal tract completely blocked these responses. Electrical stimulation of the greater splanchnic nerve caused a marked elevation of blood pressure as well as the responses described above in both the presence and absence of peripheral sympathetic nerve pathways to the seminal tract. However, clamping the adrenal veins bilaterally blocked all of the above responses and declamping immediately reversed the block. Serum levels of epinephrine, norepinephrine and dopamine were significantly increased by electrical stimulation of the greater splanchnic nerve, while cortisol levels remained unchanged. Furthermore, intravenous administration of epinephrine (5 micrograms/kg) caused responses similar to those elicited by stimulating the greater splanchnic nerve. Dogs in which all sympathetic pathways to the seminal tract had been transected chronically showed retrograde ejaculation during manual penile stimulation. The above results indicate possible involvement of the greater splanchnic nerve and adrenal medulla in ejaculatory reactions in the dog.

Adrenal Medulla↗

Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice.

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber. In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significant decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calcium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract. We previously constructed a mouse strain Apc(delta716), carrying a truncation mutation at codon 716 of the Apc gene, the homolog of human APC (10). 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. Using these Apc(delta716) knockout mice, we have investigated the effect of a low-fat and high-fiber diet (LRD for 'low-risk' diet) on intestinal polyposis, and compared it with that of a high-fat and low-fiber diet (HRD for 'high-risk' diet). The mice were fed either diet for 7 weeks, and the number and size of intestinal polyps were scored. The LRD-fed mice had fewer polyps than the HRD-fed mice, by 36% in the small intestine and by 64% in the colon. As for the polyp size distribution, there was no significant difference between the HRD- and LRD-fed mice. These results indicate that LRD can suppress intestinal polyposis compared with HRD which does not, and suggest that its suppression is at the initiation of polyp formation. This is likely to be due to a decreased frequency of loss of heterozygosity, rather than a retarded growth of the polyp adenomas.

Animals↗

Favorable donor site for epidermal cultivation for the treatment of burn scars with autologous cultured epithelium.

It is very important to determine from where we select the donor skin for epidermal cultivation in the treatment of burn scar disfigurement. To prove this point, we compared the appearance and histology of grafted sites according to the different donor sites. Thirty-eight patients with skin color difference and irregular contours of matured burn scars were superficially abraded and underwent autologous cultured epithelial grafting. These patients were followed more than 2 years. The donor skin for epidermal cultivations was taken from the buttock (group 1, 8 patients), sole (group 2, 6 patients), and adjacent to the site of the scar (group 3, 24 patients). In group 3, skin elasticity was also measured after 2 years. Hypo- and hyperpigmentation were well treated with autologous cultured epithelial grafting. The most favorable results in terms of color match were obtained in group 3, where the skin color resembled surrounding normal skin. The skin tension returned to almost normal. In group 2, the histology of the grafted site resembled the sole epidermis. It was concluded that the general principle of conventional skin grafting (i.e., "closer is best") was also correct in cultured epithelial grafting. Furthermore, it was revealed that cultured epithelium has a site specificity even after grafting.

Adolescent↗

Treatment of giant congenital nevi with cryopreserved allogeneic skin and fresh autologous cultured epithelium.

Giant congenital nevi, confluent over 10% to 52% of the body surface area, were treated in 5 pediatric patients with allogeneic skin and autologous cultured epithelium (ACE). The lesions were excised to the adipose tissue and the wound was covered with cryopreserved or fresh allografted skin. Later, the skin surface was abraded and ACE was applied. The size of the cultured graft ranged from 360 to 900 cm2 (average, 630 cm2). In 3 patients the wounds healed well. Allograft cryopreservation averaged 50 days. The average interval to ACE application after skin grafting was 10 days. Histological rejection was minimal. In 2 patients the cultured grafts did not take. The wounds were covered with split-thickness skin grafts. In one such patient, a fresh allograft was used. In the other, ACE was applied 27 days after skin grafting. Vigorous rejection reaction was observed. Cryopreservation of allogeneic skin may be important in the treatment of human leukocyte antigen-mismatch patients with giant nevi, and ACE should be applied within 10 days of skin grafting.

Cells, Cultured↗

Physiological roles of endothelium-derived nitric oxide in the epigastric island flaps of rabbits.

Nitric oxide (NO), identified as the mediator of endothelium-dependent relaxation of vascular smooth muscle, is known to cause a number of inflammatory conditions, especially in ischemia/reperfusion injury. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia followed by reperfusion-influenced serum NO and c-GMP concentrations in the flap. In addition, we also investigated the premedicated effects of the NO synthase inhibitor and heparin on serum NO and c-GMP concentrations in skin flap ischemia/reperfusion. Serum NO concentration after 15, 30, 45, and 60 minutes of ischemia followed by reperfusion significantly increased compared with that in nonischemic control and elevated flaps. On the contrary, serum NO concentration was suppressed in L-NAME or aminoguanidine pretreated animals with ischemic group. Administration of heparin increased the serum NO concentration in elevated flaps, but suppressed it in ischemic flaps followed by reperfusion. The changes in serum c-GMP and NO concentrations were related in all of the experimental groups. These results suggest that NO may be derived from vascular endothelial cells and dilate peripheral vessels in compensation for ischemia.

Animals↗

Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

Cells, Cultured↗