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Biomedical subjects

T Nishida

Publications and source records attributed to T Nishida.

At least 199 records · Page 11Linked to original sources
PubMed1999

The No-React anticalcification treatment: a comparison of Biocor No-React II and Toronto SPV stentless bioprostheses implanted in sheep.

Calcification of stentless aortic heterografts still limits the use of these bioprostheses in young patients despite their superior hemodynamic profile. The No-React treatment is described as an anticalcification treatment for biomaterials. We compared the Biocor No-React treated stentless bioprosthesis with the routine glutaraldehyde-fixed Toronto SPV bioprosthesis in a juvenile sheep model. Toronto SPV or Biocor No-React valves were implanted in pulmonary position in juvenile sheep (n = 6). The valves were explanted after 3 months and analyzed by gross inspection, x-ray studies, histological examination, and transmission electron microscopy. The Toronto SPV valve showed calcification of the aortic wall portion at both the inflow and outflow sides of the valve. No significant calcification of the cusps was found by gross inspection or by radiographic or histological examinations. Calcification was visible with electron microscopy in cell remnants and between collagen fibers in the cusps. The Biocor No-React valve showed extensive calcification of the residual aortic wall portion that is contained in the valve. With x-ray and histological examinations, clear calcification of the pericardial wrap, largely replacing the aortic wall tissue, was seen. Calcification scattered throughout the cusp was seen by electron microscopy. We conclude that the Biocor No-React process did not prevent calcification of glutaraldehyde-fixed stentless bioprostheses in a juvenile sheep experimental model. Furthermore, replacement of a large part of the aortic wall by a pericardial wrap did not prevent calcification of the stentless valve "wall."

Animals↗
PubMed1999

Induction of human gamma delta T cells in myasthenia gravis thymus transplanted SCID mice.

BACKGROUND: TCR-gamma delta cells develop by extrathymic differentiation and might play an important role in thymectomy-resistant myasthenia gravis (MG) patients. In this study, we show development of human TCR-gamma delta cells in periphery of SCID mice by transplantation of human MG thymus or thymoma. METHODS: Three pieces of thymoma tissue and four of non-thymoma thymic tissues were obtained from MG patients by thymectomy. Each tissue was transplanted into 5-6 weeks old female SCID mice by intraperitoneal injection or surgical implantation. Rate of human TCR-positive cell development and its subtypes (TCR-alpha beta, TCR-gamma delta) were measured in the mice blood at one, three, and six weeks after the transplantation. RESULTS: Human TCR-positive cells were detected three weeks after transplantation. Rate of TCR-gamma delta T cell development got higher in thymoma transplanted group than in non-thymoma transplanted group. CONCLUSIONS: We could successfully develop human mature T cells in SCID mice by transplantation of human MG thymus or thymoma.

Aged↗
PubMed1999

Prognostic Factors in Breast Cancer and their Limitations.

Evaluation of the prognosis of patients with breast cancer is criticai in determining post-surgical adjuvant therapy because of great heterogeneity in response to the therapy, At present, the decision-making for adjuvant therapy largely depends on histologic nodal status, but a significant number of patients without nodal involvement undergo relapse. Although great efforts have been made for more accurate and potent factors, significant indicators have not yet been found. One of the promising candidates, however, is histologic angiogenesis in tumors, which we and others have indicated as an independent prognostic factor in node-negative subset by the multivariate analysis. Here we will evaluate several prognostic factors in clinical use.

Journal Article↗
PubMed1999

Differential distribution of subchains of the basement membrane components type IV collagen and laminin among the amniotic membrane, cornea, and conjunctiva.

PURPOSE: Amniotic membrane transplantation has been reported to be an effective surgical procedure for the reconstruction of the anterior segment of the eye. To understand better the function of transplanted amniotic membrane, we compared the distributions of subchains of type IV collagen and laminin in the amniotic membrane to those in the cornea and conjunctiva. METHODS: Five human corneas with conjunctivas and three human amniotic membranes were frozen in OCT compound. Cryosections were cut with a cryostat and stained by an indirect immunofluorescent microscopy. We used antibodies of the collagen alpha2(IV) and alpha5(IV) subchains, laminin-1, laminin-5, fibronectin, and type VII collagen. RESULTS: In the conjunctival basement membrane and the amniotic membrane, fluorescence was evident for collagen alpha2(IV) but not for collagen alpha5(IV). By contrast, in the corneal basement membrane, fluorescence was apparent for the collagen alpha5(IV) subchain but not for the collagen alpha2(IV) subchain. Laminin-1, laminin-5, fibronectin, and type VII collagen were present in all the basement membranes examined. CONCLUSION: The distribution of alpha subchains of type IV collagen in the amniotic membrane was identical to that in the conjunctiva but different from that in the cornea. No difference in the distribution pattern of other basement membrane components was observed. These results demonstrate that the basement membrane of the amniotic membrane and the conjunctiva might share the same components; therefore, the amniotic membrane might be useful as a replacement for the basement membrane of the conjunctiva.

Amnion↗
PubMed1998

Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7,12-dimethylbenz[a]anthracene-coated suture: common epithelial tumors of the ovary in rats?

BACKGROUND: The surface epithelium of the human ovary simulates the mullerian form in tumor formation. In experimental animals, however, such a phenomenon has not previously been observed. METHODS: A chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was heated, and the central portion of a 3-0 silk suture was immersed in the melted carcinogen. After vaginal cytology, the DMBA-coated silk was inserted into the ovaries of 40 Wistar strain rats age 7 weeks. The animals were sacrificed when a tumor mass became large enough to extend the abdominal wall. The experimental period lasted for 60 weeks. The tumor histology was compared with that in human counterparts and the mullerian derivatives in rats. RESULTS: In 19 rats, including 4 animals with cornified vaginal smears at the time of DMBA treatment, an ovarian carcinoma developed within 36 weeks. In 17 epithelial tumors, the neoplastic cells proliferated to form papillary or glandular structures, and the lining epithelium consisted of flattened or cuboidal cells and columnar cells, often with pseudostratified nuclei. Adenocarcinoma components transformed into squamous cells in two cases. The remaining two neoplasms were pure mesenchymal tumors with histology of a fibrosarcomatous tumor, and one of them contained heterologous malignant osteoid components. In the remaining 21 rats, including 5 with cornified smears, no tumors developed during the experimental period. CONCLUSIONS: The histologies of DMBA-induced rat ovarian carcinoma simulated the epithelia of rat ovarian surface, fallopian tube, endometrium, and uterine cervix. The results of this study suggest that the surface epithelium of rat ovary also simulates the mullerian form in tumor formation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Demonstration of receptors specific for connective tissue growth factor on a human chondrocytic cell line (HCS-2/8).

The presence of receptors specific for connective tissue growth factor (CTGF) was demonstrated on a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8. The binding of 125I-labeled recombinant CTGF to HCS-2/8 cells was inhibited by unlabeled CTGF but not by PDGF-BB or bFGF. Scatchard analysis revealed the presence of two classes of binding sites with Kd values of 18.6 and 259 nM on cells. A cross-linking study revealed the formation of 125I-CTGF-receptor complex with an apparent molecular weight of 280 kDa. The 125I-CTGF-receptor complex disappeared almost completely on the addition of unlabeled CTGF but not PDGF-BB or bFGF. In addition, the 125I-CTGF-receptor complex was immunoprecipitated with anti-CTGF antiserum but not with anti-PDGF receptor antiserum. These findings suggest that CTGF directly binds to specific receptor molecules on HCS-2/8 cells.

Binding Sites↗
PubMed1998

Irinotecan (CPT-11) combined with cisplatin in patients with refractory or recurrent ovarian cancer.

Irinotecan hydrochloride (CPT-11) is reportedly effective for the treatment of refractory or recurrent ovarian cancer. We investigated the antitumor efficacy and toxicity of combination therapy with CPT-11 and cisplatin in 25 patients (mean age 55 years, range 35-73 years) with refractory or recurrent ovarian cancer who had previously undergone platinum-based combination chemotherapy. Patients received two or more courses of treatment consisting of 50 or 60 mg/m2 of CPT-11 on days 1, 8 and 15 and 50 or 60 mg/m2 of cisplatin on day 1 administered intravenously. All patients were evaluable for the response and the toxicity profile. Complete responses were obtained in two (8.0%) patients and partial responses were obtained in eight (32.0%) patients, giving an overall response rate of 40% (10 of 25 patients) (95% CI 23.0-59.0%). The median duration of response was 5.5 months (range 2-27 months), the median time to tumor progression was 6 months (range 3-28 months) and the median overall survival was 12 months (range 3-39+ months). Grade 3 or 4 neutropenia, which was the most frequent and severe toxic effect, occurred in 36 (54.5%) of the 66 treatment courses and in 16 (64.0%) of 25 patients. The nadir of the leukocyte count occurred on days 18-19. Neutropenia was reversed by short-term administration of granulocyte colony-stimulating factor for 2-10 days. Less serious hematologic effects and non-hematologic effects, such as diarrhea, were also observed. This preliminary study showed that this regimen of CPT-11 and cisplatin was effective in patients with recurrent ovarian cancer.

Adult↗
PubMed1998

Up-regulation of integrin alpha 5 expression by combination of substance P and insulin-like growth factor-1 in rabbit corneal epithelial cells.

To clarify the mechanisms by which substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial wound healing, we tested the hypothesis that the combination promotes cell attachment to a fibronectin matrix through up-regulation of expression of integrin alpha 5 beta 1, the major cell surface fibronectin receptor in rabbit corneal epithelial cells. Cultured rabbit corneal epithelial cells were treated with SP and/or IGF-1 and then plated on wells coated with fibronectin and bovine serum albumin. After incubation, the number of cells attached to the wells was counted. In a second experiment, reverse transcription-polymerase chain reaction was used to determine the expression of integrin alpha 5 and beta 1 by cells pretreated with SP and/or IGF-1. The combination of SP and IGF-1 significantly increased the number of cells attached to the fibronectin matrix and the expression of integrin alpha 5. However, attachment to the fibronectin matrix was inhibited by the addition of GRGDSP, a synthetic peptide that mimics fibronectin. Thus, the synergistic enhancing effect of SP and IGF-1 on the attachment of corneal epithelial cells to the fibronectin matrix and on corneal epithelial migration is partly due to the up-regulation of integrin alpha 5 expression in corneal epithelial cells.

Animals↗
PubMed1998

Selective expression of beta 7 integrin on lymphocytes undergoing apoptosis in lymphoid tissues.

It has been previously shown that the beta 7 chain of integrin forms heterodimers with the alpha 4 or alpha E chain, which plays essential roles in lymphocyte homing to mucosal lymphoid tissues. The aim of this study was to re-evaluate the possible role of the beta 7 integrin other than lymphocyte homing. We prepared spleen and lymph node lymphocytes from biopsied specimens from macaque monkeys and examined for the reactivity with a monoclonal antibody specific for the beta 7 chain. As a result, a minor population of the lymphocytes with a smaller size, which were in the early stage of apoptosis, was found to express a higher level of the beta 7 integrin than a majority of the lymphocytes with a normal size. Interestingly, the apoptotic lymphocytes expressed neither alpha 4 nor alpha E chains, suggesting that the beta 7 chain on these cells may be associated with an undefined alpha chain. These findings indicate that in the lymphoid tissues the shrunken lymphocytes undergoing apoptosis selectively express a unique beta 7 integrin.

Animals↗
PubMed1998

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.

Amino Acid Sequence↗
PubMed1998

Functional involvement of serum response factor in the transcriptional regulation of caldesmon gene.

A 22-bp fragment including the CArG element (CArG1) is essential for the transcription of the caldesmon gene. In this study, we investigated the effects of serum response factor (SRF) on the functional regulation of caldesmon promoter in smooth muscle cells. Gel supershift assay revealed that SRF was one component of the CArG1-protein complex. Dominant-negative mutants of SRF suppressed the promoter activity of caldesmon, whereas wild-type SRF overcame this suppression. These results suggest that SRF functions as a core activating factor of the caldesmon promoter. Furthermore, fractionation of smooth muscle cells' nuclear extracts using DNA affinity paramagnetic particles suggests that SRF transactivates the caldesmon promoter in concert with additional factors in the flow-through fraction recruited to the CArG element.

Animals↗
PubMed1998

Up-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells.

We previously reported that substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vitro and in vivo. We wanted to determine whether proteins responsible for cellular attachment are activated in corneal epithelial cells. To do this, we examined changes in tyrosine phosphorylation in focal adhesion kinase (FAK) and paxillin in cultured SV-40 transformed human corneal epithelial cells (HCE cells). HCE cells were cultured in the absence or presence of either SP (2 x 10(-5) M) or IGF-1 (10 ng/ml) or both SP and IGF-1. Treatment of HCE cells by either SP or IGF-1 alone did not alter tyrosine phosphorylation in either FAK or paxillin. However, the combination of SP and IGF-1 significantly increased tyrosine phosphorylation in both FAK and paxillin. In contrast, the combination of SP and IGF-1 was not observed to produce synergistic effects on the activation of mitogen-activated protein kinase in HCE. These results show that the synergistic effects of SP and IGF-1 on corneal epithelial wound healing were expressed through activation of the integrin, FAK, and paxillin system.

Biological Transport↗
PubMed1998

Langerhans cell histiocytosis localized to the eyelid.

We treated a 46-year-old Japanese man with Langerhans cell histiocytosis (LCH) localized to the eyelid alone. He was cured successfully by local and complete resection. Results of pathological examinations of the excised tumor demonstrated diffuse infiltration by atypical histiocytic cells with eosinophilic cytoplasm and convoluted nuclei, S100 immunoreactivity, and tennis-racket-shaped Birbeck granules. Based on these pathological findings, we diagnosed LCH. Clinical examination revealed no LCH involvement in other parts of the body. To our knowledge, there has been only one report of LCH occurring as an isolated tumor in the eyelid. Generally LCH has been reported in children or young people. This is an unusual case of LCH isolated to the eyelid of an older patient.

Eyelid Diseases↗
PubMed1998

Neoadjuvant intraarterial chemotherapy followed by radical hysterectomy and/or radiotherapy for locally advanced cervical cancer.

OBJECTIVES: We assessed neoadjuvant intraarterial chemotherapy (NAC) followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer. METHODS: Over 5 years, 48 consecutive women with International Federation of Gynecology and Obstetrics stage IIb-IVa cervical cancer were enrolled. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (100 mg/m2, day 1) or carboplatin (400 mg/m2, day 1) and peplomycin (20 mg/m2, day 1) for two courses separated by 3 weeks. Doxorubicin (30 mg/m2, day 1) was added for patients with adenocarcinoma. Stage III patients who responded to NAC and Stage IIb patients underwent radical hysterectomy with pelvic lymphadenectomy. Stage III patients not responding to NAC and all stage IVa patients were treated with pelvic radiotherapy. RESULTS: Complete response was achieved in 5 (10.4%) of 48 patients, while a partial response was noted in 32 (66. 7%) and stable disease in 11 (22.9%). Of 25 patients with stage IIIb disease, 16 (64.0%) were able to undergo surgery. The 4-year disease-free survival (DFS) was 80.0% in patients with stage IIb and 62.3% in patients with stage III. In stage IIIb, the 4-year DFS in patients receiving surgery (75.2%) was higher than the DFS for those receiving radiotherapy (44.4%) (P < 0.05). Grade 3 or 4 leukopenia developed in 17 (35.4%) patients. Nausea and vomiting of grade 2 or higher occurred in 34 (70.8%). Creatinine clearance transiently decreased (>/= grade 2) in 16.6%. Patients negative for serum squamous cell carcinoma-associated antigen (SCC) responded better to NAC than to SCC-positive cases, and SCC-negative survival was significantly better than SCC-positive survival (P < 0.05). CONCLUSIONS: Neoadjuvant intraarterial chemotherapy with platinum was safely performed, and a survival benefit followed radical surgery with or without radiotherapy after response to NAC.

Adult↗
PubMed1998

Two cases of endometrial adenocarcinoma arising from atypical polypoid adenomyoma.

Atypical polypoid adenomyoma (APA) most frequently presents as an endometrial polyp in premenopausal women and is believed to follow a benign course. In hysterectomy specimens from postmenopausal Japanease women, the endometrium contained an APA with an area of endometrial adenocarcinoma. A convincing transition zone between the APA and the adenocarcinoma was seen in our cases, suggesting that APA may develop into endometrial adenocarcinoma in postmenopausal women.

Adenocarcinoma↗
PubMed1998

Expression of CD44 variant 6 and lymphatic invasion: importance to lymph node metastasis in gastric cancer.

Lymph node metastasis is a critical prognostic factor for gastric cancer. In the present investigation we examined clinicopathologic factors influencing the metastatic processes to the lymph mode and their prognostic importance. A randomly selected group of 98 patients with adenocarcinomas of the stomach who underwent gastrectomy plus systematic lymph node dissection at Osaka Police Hospital from 1991 to 1996 were analyzed. Altogether 37 (38%) cancers were positive for CD44 variant 6 (v6) staining, 31 (32%) were intermediately stained, and 30 (30%) were negative. CD44-v6 expression correlated well with lymph node metastasis. Expression of CD44-v6 and lymphatic invasion were independent risk factors for metastatic lymph nodes. Among the patients with CD44-v6-positive and lymphatic invasion-positive cancers, 88% had lymph node metastasis, whereas only 13% of patients negative for both factors had lymph node metastasis. Although CD44-v6 expression and lymphatic invasion have been reported to be risk factors for recurrence and a poor prognosis, in this investigation these factors were found not to be significant for hematogenous and lymphatic recurrences or overall survival rates. Thus expression of CD44-v6 and lymphatic invasion may regulate lymph node metastases from gastric cancer.

Adenocarcinoma↗