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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 109 records · Page 6Linked to original sources

Adhesive explant culture of allergic nasal mucosa: effect of emedastine difumarate, an anti-allergic drug.

Allergic reaction of the nose comprises of an immediate and a late reaction. To evaluate nasal allergic reactions, many experiments have been performed by investigators. In this study, we performed a new tissue culture technique (adhesive explant culture) to analyze the migration of cells into the culture medium from the cultured allergic nasal mucosa in response to an allergen. Basophilic cells (mast cells and basophils) and eosinophils, which were released into the culture medium after the allergen challenge, were evaluated by the analysis of histamine and eosinophil cationic protein (ECP) content in the culture medium. Histamine and basophilic cells in the culture medium were more abundant in the immediate phase (within 30 min) after challenge than in the late phase (from 30 min to 10 hr). On the other hand, ECP and eosinophils in the culture medium were more abundant in the late phase than in the immediate phase. The increase of histamine content in both phases were not inhibited by pre-treatment of emedastine difumarate (EME), an anti-allergic drug. However, the increase of ECP in the late phase was inhibited by pre-treatment with EME. Moreover, the number of EG2-positive cells was also decreased by pre-treatment with EME. These results suggest that EME might lower the activation of eosinophils in the late phase of the allergic reaction. The present study also indicates that this adhesive explant culture system is useful model for studying the cellular allergic responses to drugs ex vivo.

Anti-Allergic Agents↗

[Role of angiotensin-converting enzyme on bradykinin nasal provocation: comparison of normal volunteers and allergic subjects].

Nasal allergy is the most common type I allergic disease. During allergic reaction, chemical mediators may be released from residual cell, and thus, attract additional inflammatory cells. One mediator implicated in this response is bradykinin (BK), a potent proinflammatory nonapeptide. This study was designed to investigate the effects of BK on nasal mucosa, and to determine the role of angiotensin-converting enzyme (ACE) in BK-induced nasal responses. BK nasal provocation (100 micrograms) was studied in 7 normal volunteers and 7 patients with perennial allergic rhinitis. After provoking of BK response, nasal secretions and saline lavage fluids were collected for analysis of total protein (a protein secretion marker), albumin (a vascular permeability marker), and lysozyme (a serous cell marker). In addition, after administering of Captopril 50 mg, a specific ACE inhibitor, the same protocol was performed. In both groups, BK induced plasma exudation and serous gland secretion. Premedication with captopril did not alter BK-induced responses in normal individuals. In allergic patients, captopril enhanced BK-induced vascular permeability, but not glandular secretion. These results indicate that allergic subjects have nasal hyperresponsiveness to BK, and that ACE predominantly modulates the vascular permeability of allergic nasal mucosa. It seems likely that BK may contribute to the expression of nasal allergic symptoms, and that inhibition of ACE may lead to increased nasal responsiveness.

Adult↗

[Clinical study of retroperitoneal lymph node dissection for patients with advanced germ cell tumors].

We performed retroperitoneal lymph node dissection (RPLND) on 14 patients (IIA: 1, IIB: 4, IIIA: 3, IIIB2: 2, IIIC: 4) with testicular and one with retroperitoneal germ cell tumor at the Nagoya University Hospital between 1986 and 1997. According to the international germ cell consensus classification, 4 patients were classified as "good-prognosis", three as "intermediate-prognosis" and eight as "poor-prognosis". RPLND was performed on 12 patients with the tumor marker levels normalized preoperatively and on three without the marker normalization. The mean surgical time was 510 (195-1, 125) minutes and the mean bleeding volume was 3,806 (100-12,598) g. The surgical time and bleeding volume were correlated with the size of the tumor in the body axis. Intraoperative complications occurred in 5 (33%) out of 15 patients: injury of renal artery (2), renal vein (1), ureter (1) and common iliac artery (2). Postoperative complications occurred in 2 patients: ileus (2) and lower extremity edema resulting from resection of the inferior vena cava (1) and would dehiscence (1). Of the 8 patients whose completely resected retroperitoneal tumors were necrosis/fibrosis or teratoma (psCR), 6 achieved survival with no evidence of disease (NED). Among 4 patients, whose tumor was not completely resected but pathologically diagnosed as necrosis/fibrosis or teratoma (pCR), NED without recurrence was achieved in 2 and also in one with resection of relapsed teratoma 2.5 years after RPLND. All three patients with cancer tissues pathologically retained in the resected tumors (sCR or psIR), consequently died of the disease. In six patients with relapse, the initial sign was elevation of the tumor marker levels, which was noted more than 30 days postoperatively in 2 patients with psCR and 7 to 15 days in 4 patients without psCR. We believe that RPLND is needed to examine the pathology and to predict the prognosis of the poor-risk patients with NSGCT. Careful dissection of vessels is needed to reduce vascular complications.

Adolescent↗

[Three cases of urinary retention caused by uterine leiomyoma].

Three females with urinary retention caused by uterine leiomyoma are reported. The patients were 35, 48 and 50 years old. In each patient, transabdominal ultrasonography showed a large and homogeneous mass located in the retrovesical space, compressing the bladder. Pre-operative computed tomographic (CT) scan and magnetic resonance (MR) imaging revealed uterine leiomyoma which severely compressed the bladder from the posterior wall to the urethra. The urinary symptoms completely resolved in all patients following total hysterectomy, and postoperative uroflowmetry demonstrated normal voiding.

Adult↗

[A case of gastric carcinoma treated effectively with 5'-DFUR].

A 79-year-old male was admitted to our hospital for further examination on gastric carcinoma (1' type) in the cardia. The histology of biopsied tissue was moderately differentiated adenocarcinoma (tub2). The patient refused a gastrectomy and received three cycles of local injection therapy with OK-432 + Beriplast into the tumor. However, the tumor showed no decrease in size. Considering the quality of life, the patient was given out patient treatment with 5'-DFUR (Furtulon, 800 mg/day). Three months later, the patient showed a partial response (PR) on the basis of gastric X-ray and endoscopic findings. No adverse reactions to the drug were seen. The patient has been receiving the same drug since then, and has continued to show PR for 15 months. Biopsied tissues were checked immunohistochemically for expression of thymidine phosphorylase (TdRPase), and changes in tissue TdRPase level were examined by ELISA. The TdRPase level decreased with shrinking of the tumor. These results suggest that the shrinking of tumor following 5'-DFUR therapy is closely related to TdRPase.

Adenocarcinoma↗

Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778.

TAK-778 [(2R,4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4, 5-tetrahydro-4-methyl-7, 8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; mw 505.53], a novel osteoblast differentiation promoting compound, was characterized in vitro and in vivo models. TAK-778 at doses of 10(-6) M and higher promoted potently bone-like nodule formation in the presence of dexamethasone in rat bone marrow stromal cell culture. This was accompanied by increases in cellular alkaline phosphatase activity, soluble collagen release, and osteocalcin secretion. Under the culture conditions, TAK-778 also stimulated the secretion of transforming growth factor-beta and insulin-like growth factor-I, indicating that TAK-778 may exert regulatory effects on osteoblast differentiation via autocrine/paracrine mechanisms. Furthermore, the in vivo osteogenic potential of TAK-778 was studied in bony defect and osteotomy animal models, using sustained release microcapsules consisted of a biodegradable polymer, poly (dl-lactic/glycolic) acid (PLGA). Single local injection of TAK-778/PLGA-microcapsules (PLGA-MC) (0.2-5 mg/site) to rat skull defects resulted in a dose-dependent increase in new bone area within the defects after 4 weeks. When the pellet containing TAK-778/PLGA-MC (4 mg/pellet) was packed into place to fill the tibial segmental defect in rabbit, this pellet induced osseous union within 2 months, whereas the placebo pellet did not. In addition, single local application of TAK-778/PLGA-MC (10 mg/site) to rabbit tibial osteotomy site enhanced callus formation accompanied by an increase in breaking force after 30 days. These results reveal for the first time that a nonendogenous chemical compound promotes potently osteogenesis in vitro and enhances new bone formation during skeletal regeneration and bone repair in vivo and should be useful for the stimulation of fracture healing.

Animals↗

A randomized comparative study of the Bandloop versus the standard loop for transurethral resection of the prostate.

PURPOSE: The Bandloop is a new electroresection loop that is broader than the standard loop and thickens from front to back. We compared the safety and efficacy of the Bandloop to the conventional loop electrode for transurethral prostatectomy. MATERIALS AND METHODS: A randomized prospective study was performed on 53 patients with lower urinary tract symptoms and estimated prostatic volume greater than 30 ml. on transrectal ultrasonography. The Bandloop was used in 25 cases (Bandloop group) and standard loop was used in 28 (standard group). Surgical outcomes, including International Prostate Symptom Score, resected prostatic weight, operative time, uroflowmetry, post-void residual urine, postoperative catheterization period, time to disappearance of macrohematuria, and serial changes of hemoglobin and urinalysis, between the 2 groups were compared. RESULTS: A total of 23 Bandloop and 28 standard loop cases were evaluable. There was no difference in preoperative estimated prostatic volume (mean 44.7 versus 47.8 ml.), resected prostatic weight (36.5 versus 29.4 gm.) or operative time (61 versus 60 minutes) between the 2 groups. The ratio of resected weight-to-estimated prostatic volume was significantly greater in the standard group (81.4% versus 61.9%). There was no difference in postoperative catheterization period (3.3 versus 3.4 days) or time to disappearance of macroscopic hematuria (5.0 versus 5.0 days). Postoperative changes in symptom score (-15.1 versus -15.9), maximum flow rate (11.8 versus 16.3 ml. per second at 12 weeks) and residual volume (-31.6 versus -48.6 ml. at 12 weeks) demonstrated no significant difference between the 2 groups. There was no difference in intraoperative and postoperative bleeding estimated by serial changes in serum hemoglobin and urinalysis after surgery. No patient had major complications or required transfusion. CONCLUSIONS: Transurethral prostatectomy using the Bandloop is as safe and effective in achieving subjective and objective improvements as standard transurethral prostatectomy. However, our randomized study indicates that the Bandloop offers no advantage compared to the standard loop electrode for transurethral prostatectomy.

Aged↗

[Congenital arteriovenous malformation of the scalp with a drainage to the transverse sinus: a case report].

Arteriovenous malformation (AVM) of the scalp is uncommon, and a subtype which has connection with the intracranial dural sinus is extremely rare. Only 3 cases have been reported. We present a case of congenital AVM of the scalp which was connected with the intracranial venous sinus. A 27-year-old woman had been noted as having a pulsatile soft mass in the midline of the occipital region since her birth. She visited our hospital because of pain and enlargement of the mass. The patient had had no history of trauma. Physical examination revealed a pulsatile scalp mass in the midline of the occipital region, measuring 3.5 x 3.5 x 1 cm. A loud bruit was ausculated. Tenderness was noted. The skin over the mass was slightly reddish. No focal neurological deficits were noted. Plain skull films demonstrated a round defect in the midline of the occipital bone. Magnetic resonance imaging (MRI) demonstrated a subcutaneous mass with low signal intensity and an infratentorial mass with flow void. 3D CT angiograms demonstrated a subcutaneous vascular mass with a single large vein draining into the right transverse sinus. External carotid angiograms revealed a vascular lesion within the scalp with supply from the branches of the bilateral occipital arteries and the meningeal arteries. The nidus penetrated the skull and connected to a dilated varix, which had a draining vein shunting into the right transverse sinus. After embolization of the right meningeal feeding arteries, surgery was performed. The vascular lesion penetrated the skull and the dura. The infratentorial mass was in the epiarachnoid space and was fed by a small pial artery. The mass was excised completely after interruption of the pial artery and the draining vein. Postoperative course was uneventful. Histologically, the subcutaneous mass and infratentorial vascular mass were shown to be AVM and varix, respectively.

Adult↗

[Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor].

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.

Adolescent↗

Cloning and characterization of the human beta4-integrin gene promoter and enhancers.

The cell-surface adhesion molecule alpha6beta4-integrin is a receptor for laminins and a component of hemidesmosomes. beta4-Integrin expression is restricted to proliferating basal keratinocytes in the epidermis and is suppressed when differentiation commences. Altered beta4-integrin expression levels correlate significantly with the aggressive behavior of cancers. In order to clarify the mechanisms that regulate transcription of the beta4-integrin gene, we cloned its 5'-flanking region. This 5'-flanking region was found to have a high G + C content and not to contain either TATA or CAAT boxes. Nested delimitation and reporter analyses mapped a basal promoter to nucleotides -106 to +105, surrounding the most proximal transcription initiation site. Gel retardation and mutational analyses revealed that cooperation between AP1 and Ets, interacting with other factors, mediated the promoter activity. In addition to the promoter element, enhancer activity was found in the first intron (+1905/+3933) and in a sequence upstream of the promoter region (-414/-107). These findings should facilitate our understanding of the regulation of beta4-integrin gene expression in processes such as cell growth and differentiation, apoptosis, and cancer development and metastasis.

Antigens, CD↗

A dynein light chain of sea urchin sperm flagella is a homolog of mouse Tctex 1, which is encoded by a gene of the t complex sterility locus.

The outer-arm dynein of sea urchin sperm flagella contains six light chains with molecular masses of 23.2, 20.8, 12.3, 11.5, 10.4 and 9. 3kDa. We have cloned a cDNA for the 12.3kDa polypeptide (light chain 3) and found that this protein is highly homologous to mouse Tctex1, a protein encoded by a member of the multigene family in the t complex region that is involved in male sterility and the development of the germ cells. Tctex1 has recently been shown to be homologous to a light chain of cytoplasmic dynein. Therefore, the cytoplasmic dynein light chain has been implicated in the mechanism for the transmission ratio distortion (meiotic drive) that is characteristic of t haplotypes in mice. Our present finding, however, indicates that axonemal light chain 3 must be considered equally important.

Amino Acid Sequence↗

Direct antigen presentation through binding of donor intercellular adhesion molecule-1 to recipient lymphocyte function-associated antigen-1 molecules in xenograft rejection.

Cellular interactions that lead to graft rejection were examined in a rat-to-mouse xenogeneic combination using species-specific monoclonal antibodies (mAbs) against donor and recipient intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) molecules, respectively. Although both mAbs displayed moderate blocking activity in an in vitro mixed lymphocyte response assay, strong suppression was observed when anti-donor (rat) ICAM-1 mAb was combined with anti-recipient (mouse) LFA-1 mAb. Likewise, significant prolongation of islet xenograft survival was observed with these mAbs. Thus, 0.05 mg of anti-mouse LFA-1 mAb and anti-rat ICAM-1 mAb given on days 0 and 1 produced significant prolongation of graft survival over the control (51+/-20 days vs. 10+/-3 days, P<0.0001), but not when anti-mouse ICAM-1 mAb was combined with anti-mouse LFA-1 mAb (13+/-3 days). In this species combination, mouse T cells were able to proliferate in the presence of rat antigen-presenting cells (APCs) in a cell number-dependent manner, but not in the presence of mouse APCs. The binding assay showed that LFA-1 molecules on mouse T cells can bind immobilized rat ICAM-1 molecules. These results suggest that rat ICAM-1 molecules on APCs can interact with mouse LFA-1 molecules on T cells across a species barrier and that this binding generates the consequent immune responses leading to rejection. mAb treatment against these adhesion molecules of recipient as well as donor is crucial for preventing rejection in a xenogeneic transplantation model.

Animals↗

Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Actinin↗

Swimming stress that causes hyperglycemia increases in vivo release of noradrenaline, but not acetylcholine, from the hypothalamus of conscious rats.

The effects of acute swimming stress (10 min) on noradrenaline release from the medial basal hypothalamus (MBH; consisting of the ventromedial and dorsomedial hypothalamus) and acetylcholine release from the lateral hypothalamic area (LHA) were investigated in freely moving rats by using in vivo microdialysis techniques. Serum glucose, noradrenaline and adrenaline concentrations were also determined. Acute swimming stress produced significant hyperglycemia, with increases in serum noradrenaline and adrenaline concentrations. The release of noradrenaline from the MBH was significantly stimulated during the swimming stress. On the other hand, the swimming stress has no significant effect on the release of acetylcholine from the LHA. These findings support the idea that hypothalamic noradrenergic neurons play an important role in the sympathoadrenal hyperglycemic response to stressful stimuli. Moreover, it is suggested that hypothalamic cholinergic neurons are not involved in the responses of serum glucose, noradrenaline and adrenaline concentrations to swimming stress.

Acetylcholine↗

Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases.

The subacromial bursa is recognized as a site associated with the shoulder pain caused by rotator cuff disease in the middle-aged and elderly. Substance P is contained in primary afferent nerves, and its quantity increases during chronic pain. The amount of substance P in the subacromial bursa of patients with rotator cuff disease was examined. Radioimmunoassay and immunohistochemistry were employed to quantify and localize substance P. The preoperative pain level was measured with a visual analogue scale with 0 as no pain, 5 as moderate, and 10 as severe. Thirty-seven patients that had undergone operation were divided into two groups: one composed of 19 patients with subacromial bursitis and a partial-thickness tear of the rotator cuff (nonperforated cuff) and the other composed of 18 patients with a full-thickness tear (perforated cuff). Subacromial bursae obtained from seven fresh cadavers with no shoulder pain before death were used as controls. The visual analogue scale showed significantly greater pain in the group with the nonperforated rotator cuff than in the group with the perforated cuff. Consistent with these results, the amount of substance P in the subacromial bursa was significantly greater in the former group than in the latter. Nerve fibers immunoreactive to substance P were localized around the vessels, with a larger number of fibers in the group with the nonperforated rotator cuff. Therefore, an increased amount of substance P in the subacromial bursa appears to correlate with the pain caused by rotator cuff disease.

Adult↗

Protection of islet allografts transplanted together with Fas ligand expressing testicular allografts.

Fas ligand (FasL) is highly expressed in testicular tissues and thought to be responsible for protection from allograft rejection by inducing apoptosis of anti-graft activated T cells. FasL-expressing islets have been shown to induce a granulocyte-mediated inflammatory reaction. We investigated whether a graft can be protected from alloimmune responses by manipulating the Fas/FasL-system. We transplanted allogeneic islets under the kidney capsule of streptozotocin-induced diabetic mice together with testicular tissue. Significant prolongation of survival of C3H islet allograft was observed in C57BL/6 (B6) recipients transplanted with C3H testicular tissue, but not in those transplanted with C3H-gld testicular tissue expressing non-functional FasL. No significant prolongation was observed in B6-lpr recipients expressing non-functional Fas. Immunohistochemical staining of C3H testicular tissue in the composite graft showed a high expression of FasL, but not that of the C3H-gld testicular tissue. In situ terminal deoxynucleotidyl transferase-mediated dUDP-biotin catalysed DNA nick-end labelling (TUNEL) staining of a composite graft of C3H islet and testicular tissue in B6 recipients demonstrated extensive apoptosis of infiltrating mononuclear cells around the graft. The protective effect of C3H testicular tissue was abrogated when anti-FasL monoclonal antibody was administered i.p. postoperatively. Our results suggest that FasL-positive testicular allografts protect composite islet allografts and indicate that manipulation of Fas/FasL mediated apoptosis is a suitable strategy for controlling rejection of islet allografts.

Animals↗