Search PubMed⌕ Search

Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS susceptibility gene. In the study presented here, we detected two novel mutations of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese patients. Early protection of the skin from the sunlight is important to the prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH gene is essential for the early, definitive diagnosis of NBCCS, especially before the expression of clinical manifestations is complete.

Adult↗
PubMed2001

Pattern of chromosome 16q loss differs between an atypical proliferative lesion and an intraductal or invasive ductal carcinoma occurring subsequently in the same area of the breast.

Atypical proliferative lesions of the breast, such as atypical ductal hyperplasia and atypical papilloma, are considered to be precursors of breast carcinomas and have frequently been shown to have loss of heterozygosity (LOH) on chromosome 16q at the DNA level. We evaluated whether an atypical proliferative lesion and a carcinoma that subsequently occurred in the same area of the ipsilateral breast were of identical clonal origin in seven patients. Using DNA isolated from microdissected archival tissue of epithelial components of both the biopsy specimen of the atypical proliferative lesion and the mastectomy specimen of the carcinoma, the pattern of LOH on 16q was compared between these two lesions using polymerase chain reaction -microsatellite LOH analysis. As a control, LOH on 16q was examined in 13 cases of usual ductal hyperplasia, 10 usual papillomas, and 6 atypical ductal hyperplasias. In the seven cases, LOH on 16q was detected in three of the six atypical proliferative lesions and in five of the seven carcinomas, but the allele with LOH or a deleted region always differed between the two. LOH was detected in both atypical proliferative lesions and carcinomas in one case, only in the atypical proliferative lesion in two cases, and only in carcinomas in three cases. In the controls, LOH on 16q was absent in usual ductal hyperplasias or usual papillomas but was detected in two of six atypical ductal hyperplasias. Although atypical proliferative lesions were frequently confirmed to be of clonal nature with LOH on 16q, these lesions and carcinomas were considered to be clones, probably originated from a field with these clones.

Adult↗
PubMed2001

A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy.

It has been demonstrated that pregnancy induces the immunomodulation of cytokine responses away from the Th1 paradigm and towards the Th2 paradigm. In this study, we examined the expression of CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2) on decidual CD4+ and CD8+ T cells during the early stages of pregnancy. Examination of the cytokine profile revealed that CRTH2 was expressed on CD4+-type-2 T helper (Th2-type) and CD8+-type 2 T cytotoxic (Tc2-type) cells. The percentages of CRTH2+ cells in CD3+/CD4+ T cells and CD3+/CD8+ T cells were significantly higher in the decidua than in the peripheral blood. These results indicate the significance of Th2- and Tc2-type cells of the decidua in the maternal immune system, presumably through their production of cytokines which may contribute to the maintenance of pregnancy.

Adult↗
PubMed2001

Quantitative immunohistochemical evaluation of HER2/neu expression with HercepTestTM in breast carcinoma by image analysis.

HercepTestTM (DAKO A/S, Glostrup, Denmark) is an immunohistochemical assay that detects HER2/neu gene products, and evaluates the overexpression status of the HER2/neu protein in determining eligibility for the Trastuzumab (HerceptinR, Genentech, San Francisco, CA, USA) therapy. However, practically, interobserver variability of the HER2/neu interpretation of the immunostained results has caused marked disagreement with regard to the intensity of tumor staining. In this study, we quantitated HER2/neu expression by image analysis, and applied this analyzing system to help to minimize interobserver variability of the interpretation of the HercepTestTM. All the immunostained results were scored semiquantitatively on a range of 0 to 3+ in accordance with the criteria described as per the manufacturer's instructions, and quantitatively evaluated using an image analyzing system with image processing software. Among the 92 cases, 15 were scored as 3+, six were 2+, and 32 were 1+ under intraobservers agreement. When the cases were quantitated, a high correlation was shown between the signal area extracted by image analysis and the corresponding score of staining intensity with the HercepTestTM. By converting the quantitatively extracted data into a scoring system based upon the criteria, the outcome demonstrated a strong concordance with the scoring data obtained from immunostaining. The results indicated that a quantitative scoring system performed by simple image analysis may provide to improve interobserver agreement of the interpretation of the HercepTest TM in clinical practice.

Adult↗
PubMed2001

Concordance in judgments among c-erbB-2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma.

We compared the c-erbB-2 protein overexpression status detected by the HercepTestTM (DAKO A/S, Grostrup, Denmark) with another conventional immunohistochemistry system using an anti-c-erbB-2 rabbit polyclonal antibody (Nichirei Co., Tokyo, Japan) and with the c-erbB-2 gene amplification status detected by Southern blot hybridization in 101 surgically resected breast carcinomas. According to the criteria for overexpression, recommended by the manufacturer, c-erbB-2 overexpression by HercepTestTM was detected in 24 cancers (24%), comprising six score-2 tumors and 18 score-3 tumors. The level of agreement in judgment of the HercepTestTM, among three independent observers, was excellent (kappa = 0.845). C-erbB-2 overexpression by Nichirei's antibody and c-erbB-2 gene amplification were detected in 21% and 16% of cases, respectively, and their concordance with HercepTestTM scores of 2-3 was 89% and 90%, respectively. In the score-3 cases by Hercep TestTM only, the concordance rates with overexpression by Nichirei's immunohistochemistry and with gene amplification were slightly higher, 94% and 93%, respectively. Score-2 cases by HercepTestTM were mostly judged as negative overexpression by Nichirei's antibody and as no amplification by Southern blot hybridization. The present results showed that HercepTestTM score-3 detected c-erbB-2 overexpression almost optimally as well as the conventional methods and the score-3 breast carcinomas had clinical and biological implications. Further examination would be necessary to decide the significance of breast cancers of HercepTestTM score 2.

Blotting, Southern↗
PubMed2001

Establishment and characterization of three new rat renal cell carcinoma cell lines from N-ethyl-N-hydroxyethylnitrosamine-induced basophilic cell tumors.

Three new rat cell lines (designated as BP13, BP30 and BP36B), derived from rat basophilic-type renal cell carcinomas induced with N-ethyl-N-hydroxyethylnitrosamine, were established and characterized. Passaged up to 100 times in vitro for 3 years, each cell line forms epithelial monolayers with cell cycles for BP13, BP30 and BP36B of 29, 21 and 17 h, respectively. Positive glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltransferase (gamma-GT) activity in their cytoplasm, but negative succinate dehydrogenase (SD) and slightly positive carbonic anhydrase type II (CA) localization indicates an origin from proximal tubules. Ultrastructural examination showed the presence of variable numbers of mitochondria and many microvilli and intracellular junctions on the plasma membrane. BP13 and BP30 were found to be tetraploid and BP36B diploid. BP13 has one marker chromosome 15p+, and BP36B an isochromosome of 1q. Anchorage-independent growth and tumorigenicity in immunosuppressed nude mice of BP13 and BP36B, but not BP30, proved their neoplastic nature. These three cell lines should provide useful tools for studying the biological characteristics of renal cell tumors.

Animals↗
PubMed2001

Detection of numerical alterations of chromosome 1 in cytopathological specimens of breast tumors by chromogen in situ hybridization.

To investigate the effectiveness of chromogen in situ hybridization (CISH) in the diagnosis of breast tumors, numerical alterations of chromosome 1 were examined by CISH and fluorescence in situ hybridization (FISH) methods, and the presence of der(16)t(1;16) was also examined by FISH in imprinted cytology specimens from resected tissues of 14 carcinomas and five non-malignant lesions. The modal signal counts of chromosome 1 were compared between the specimens processed by CISH and FISH for each case. Aneusomies of the long arm of chromosome 1 were detected in 10 (71%) carcinomas as the major clones by both methods. In addition, one atypical papilloma demonstrated tetrasomy of 1q12 as a major clone by CISH, but such a clone was at first overlooked by FISH. Four other benign lesions showed disomic 1q12 signals as a major clone by both CISH and FISH. As additional information from FISH, eight cancers showed structural or numerical alterations of chromosome 16, and four showed der(16)t(1;16). In total, 10 carcinomas showed chromosome 16 alterations, and all of these overlapped with the carcinomas with 1q12 aneusomies. The CISH method provided almost the same results as the FISH method, and both methods were considered applicable in supportive diagnosis of cytological specimens of breast tumors. In addition, the CISH method was superior in the detection of numerical alterations in carcinoma cells by referring to the morphology of cells and in the detection of significant clones which might be missed under dark-field microscopy.

Breast Neoplasms↗
PubMed2001

Current topics on cytapheresis technologies.

Cytapheresis has been investigated recently for the treatment of autoimmune related diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, and so on. A large number of physicians have indicated that patients with autoimmune diseases respond to cytapheresis treatment. The effective mechanism of cytapheresis for immune disorders is still controversial. However, the removal of the leukocyte including granulocyte, lymphocyte, and monocyte may play a crucial role in correcting imbalance of the immune system. A session of cytapheresis including leukocytapheresis (LCAP) and granulocytapheresis (GCAP) may not create a sufficient amount of cell removal for the human body. However, the cell removal can be a trigger of the immunomodulation as the treatment for immune disorder. Furthermore, not only cell removal but also reaction by blood contacting with medical device materials may play a role as an immunomodulation for immune disorders. This review introduces current cytapheresis technologies and attempts to elucidate the effective mechanism of cytapheresis for immune disorders, focused on LCAP and/or GCAP for RA or IBD.

Arthritis, Rheumatoid↗
PubMed2001

Combined analysis of p53 and RB pathways in epithelial ovarian cancer.

Disruptions of the p16-CDK4/cyclin D1-pRb pathway (RB pathway) and the p14ARF-MDM2-p53 pathway (p53 pathway) are important mechanisms in the development of human malignancies. In this study, we investigated RB and p53 pathways in 46 epithelial ovarian cancers (EOCs). In the RB pathway, 16 (34.8%) of 46 cases had p16 gene alterations or loss of expression. The deletion of the p16 gene was a rare event. In 7 cases, we observed methylation in the 5'CpG island in the promoter region of the p16 gene. Abnormal expressions of pRb and CDK4/cyclin D1 were 10.9% and 30.4%, respectively. In the p53 pathway, 10 (21.7%) of 46 cases had p14ARF gene alterations or abnormal expression. In 4 cases, methylation in the 5'CpG island in the promoter region of the p14ARF gene was present. MDM2 overexpression was a rare event. Thirty-six (78.3%) of 46 patients had p53 gene alterations or expression. In our studied cases, p14ARF abnormalities were independent of p16 abnormalities. Abnormal RB and p53 pathways were present in 60.9% and 80.4% of cases, respectively. In conclusion, disruptions of p53 and RB pathways are frequent events and the inverse correlations were present between the abnormality of p16 and p14ARF in EOCs.

Carcinoma↗
PubMed2001

Management of the axilla in breast cancer: a comparative study between sentinel lymph node biopsy and four-node sampling procedure.

BACKGROUND: The aim of this study was to compare the efficacy of sentinel lymph node biopsy and that of four-node sampling for predicting other nodal status in breast cancer. METHODS: 206 patients with operable breast cancer were enrolled. The identification of sentinel lymph nodes (SLNs) was carried out in 110 patients using a gamma probe after injection of radioactive tin colloids. Four palpable lymph nodes (FNs) were removed from the lower axilla at the first step of axillary dissection in 98 patients. The predictive value of nodal status was compared between SLNs and FNs, based on the pathological findings of all dissected lymph nodes. To examine the relationship between SLNs and FNs, we chose the FNs retrospectively (defined as rFNs) from among all nodes in SLNs. RESULTS: SLNs were identified in 108 (98%) of 110 patients. With one patient having skip metastasis, the accuracy and sensitivity were 99 and 98%, respectively. In the four-node sampling (FNS) group, two in 98 patients had skip metastasis and the accuracy and sensitivity were 98 and 96%, respectively. Findings on the relationship between these methods of biopsy were as follows: (i) rFNs included SLNs in 79 patients (73%); (ii) rFNs partially included SLNs in 24 patients (22%); and (iii) no relationship was evident in five patients (5%). CONCLUSIONS: The accuracy/sensitivity of FNs was comparable to that of SLNs. FNS can be considered to represent a highly promising approach and may be used as an alternative procedure that can be performed safely and easily in any institute.

Adult↗
PubMed2001

Phase I-II study of neoadjuvant chemoradiotherapy followed by radical surgery in locally advanced cervical cancer.

The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.

Adenocarcinoma↗
PubMed2001

A ferulic acid derivative, ethyl 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate, as a new candidate chemopreventive agent for colon carcinogenesis in the rat.

The inhibitory influence of ferulic acid (FA), a rice germ component, and its geranylated derivative 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate (EGMP) on the post-initiation stage of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats given two s.c. injections of AOM (15 mg / kg body weight) during week 1. Diets containing EGMP or FA at doses of 0.1 or 0.2% were then fed for 3 weeks from week 2 to 5, when the animals were sacrificed. The numbers of aberrant crypt foci (ACF) and aberrant crypts (AC) per rat in the group given 0.2% FA were significantly decreased (P < 0.001) as compared to the AOM alone group. Furthermore, the numbers of ACF and AC per rat fed the 0.2% and 0.1% EGMP were significantly reduced (P < 0.001 and P < 0.01, respectively). Colonic epithelial cells in S-phase, as measured by bromodeoxyuridine (BrdU) labeling, in rats fed EGMP were significantly decreased in the 0.2 and 0.1% EGMP groups as compared to the AOM alone group (P < 0.05). BrdU labeling indices in rats fed FA and EGMP assessed by a test using a coefficient for linear contrast were also significantly decreased as compared to the AOM alone value (P < 0.05, P < 0.01, respectively). The results indicate that FA and EGMP have inhibitory effects on ACF and AC development, EGMP being more potent, possibly due to stronger suppressive effects on cell proliferation. No toxic effects were observed in rats given either compound in terms of body and organ weights, and liver or kidney histology. The findings thus suggest that EGMP and FA, especially the former, might have potential as chemopreventive agents against colon tumor development.

Animals↗
PubMed2001

Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat multi-organ carcinogenesis model.

Organotropic chemopreventive effects of n-3 unsaturated fatty acids were studied using a multi-organ carcinogenesis model in male rats. Rats were treated with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-4-hydroxybutylnitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and dihydroxy-di-n-propylnitrosamine (DHPN) during the first 7 weeks, and then given unsaturated fatty acid (UFAs), docosahexaenoic acid (n-3, C(22:6)) (DHA), eicosapentaenoic acid (n-3, C(20:5)) (EPA), linoleic acid (n-6, C(18:2)) (LA) or oleic acid (n-9, C(18:1)) (OA) at a dose of 1.0 ml/rat, 3 times a week by gavage for the consecutive 30 weeks. All rats were fed a low LA basal diet throughout the experiment and a calorie-restricted basal diet during the period of UFAs feeding administration. DHA significantly reduced tumor size and numbers in the large intestine as compared to OA treatment. Furthermore, DHA showed a tendency to inhibit carcinogenesis in the small intestine and lung. EPA also showed a tendency to inhibit intestinal carcinogenesis. On the other hand, LA showed a tendency to inhibit lung carcinogenesis, but to promote large intestinal carcinogenesis. However these UFAs did not influence preneoplastic and neoplastic lesion development in the liver, kidney, and urinary bladder. Levels of the administered fatty acids were clearly increased in the serum and organs. In contrast, arachidonic acid (AA) levels in the large and small intestines and liver were markedly decreased by treatment with DHA and EPA. Decreased levels of AA in the large intestine correlated well with tumor incidence, although the number of glutathione S-transferase-positive (GST-P(+)) foci showed an inverse correlation with AA levels. The data thus provide evidence that an organotropism exists with regard to the influence of UFAs on carcinogenesis, which correlates with reduction of tissue AA levels in the target organs.

Animals↗
PubMed2001

Characterization of NKT cells in human peripheral blood and decidual lymphocytes.

PROBLEM: To examine whether natural killer (NKT) cells are present in human pregnancy decidua. METHOD OF STUDY: We calculated the percentage of CD3+CD161+Valpha 24+-NKT cells in peripheral blood and early pregnancy decidua, and analyzed intracellular cytokines, interleukin (IL)-4 and interferon (IFN)gamma in NKT cells using flow cytometry. RESULTS: A distinct subset of CD3+ CD161+ lymphocytes expressing an invariant antigen receptor encoded by the Valpha24 and Vbeta11 segment was accumulated in the decidua. In pregnant subjects the percentages of NKT cells were significantly increased in the decidua compared with peripheral blood. Both NKT cells in the decidua and the peripheral blood had an ability to rapidly produce cytokine associated with Th1 (IFNgamma) and Th2 (IL-4). Interestingly, the percentages of IL-4 and IFNgamma producing NKT cells were significantly higher in the decidua compared with the peripheral blood. CONCLUSIONS: These findings suggest that NKT cells might control the Th1/Th2 balance by producing IL-4 and IFNgamma at the feto-maternal interface.

Adult↗
PubMed2001

Basic science and epilepsy: experimental epilepsy surgery.

Epilepsy surgery, as is employed for the management of intractable seizures, was performed in animals harboring a seizure focus induced by a local application of kainic acid (KA). Amygdalo-hippocampectomy failed to stop spontaneous seizures in the contralateral hippocampus. Callosotomy inhibited seizure propagation to the contralateral sensori-motor cortex. However, epileptic activity ipsilateral to the focus, including subcortical structures, persisted even after the callosotomy. Multiple subpial transection (MST) around the epileptic cortical focus suppressed the seizure activity of the cortex. However, seizure propagations in subcortical structures remained, even after MST. Nefiracetam (a new nootropic agent) was tested in these models, and its promising effect on the intractable extratemporal epilepsy is reported.

Amygdala↗
PubMed2001

Hodgkin's disease preceded by unique neurological symptoms.

This is the first case report of Hodgkin's disease (HD) which showed both remission and exacerbation of neurological signs before a confirmed diagnosis of HD. The episodes occurred three times and multiple lesions were involved. Immunoabsorption plasmapheresis and double filtration plasmapheresis were effective for the first episode, whereas, corticosteroids partly improved the second and third episodes. Fever and lymph node swelling were apparent afterward and she was diagnosed as having HD from a supraclavicular lymph node biopsy. The remaining neurologic deficits responded to chemotherapy and radiotherapy. The neurological symptoms were considered as a paraneoplastic syndrome of HD.

Adult↗
PubMed2001

Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS.

OBJECTIVE: B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) has been increasingly reported in Asia and is regarded as a variant of intravascular lymphomatosis (IVL). Recently CD5 was reported to be expressed in some cases of diffuse large cell lymphoma and IVL. We therefore examined the expression of CD5 on lymphoma cells in B-LAHS and compared the clinical and laboratory data between CD5+ and CD5- B-LAHS. METHODS: The expression of CD5 on lymphoma cells was examined using flow cytometry and immunohistochemical analysis of paraffin sections. The clinical records were reviewed to characterize clinical features. PATIENTS: Twelve patients with B-LAHS; ten men and two women, age ranging from 41 to 82 years (median, 63.5 years) were included in this study. RESULTS: B-LAHS is characterized by fever and hepatosplenomegaly without lymphadenopathy at the initial presentation. Histological examination showed hemophagocytosis and infiltration of lymphoma cells in the bone marrow, and in some cases intravascular proliferation of lymphoid cells characteristic of IVL. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. In eight of the twelve patients, lymphoma cells were positive for CD5. But no differences were observed in the clinical or laboratory findings between CD5+ B-LAHS and CD5- B-LAHS. CONCLUSION: No clinical differences were observed between CD5+ B-LAHS and CD5- B-LAHS. Further studies are required to elucidate the differences in pathogenesis between these two subgroups of B-LAHS.

Adult↗