Biomedical subjects

T Tsunoda

Publications and source records attributed to T Tsunoda.

At least 73 records · Page 4Linked to original sources

PubMed2000

Improvement of growth of Plasmodium falciparum fresh clinical isolates by using an established serum-free medium, GIT.

In the present study, we have tried to establish continuous cultures of fresh clinical isolates of P. falciparum by using a serum-free medium, GIT. To examine the ability of GIT to support the parasite growth, the growth of various P. falciparum isolates including two laboratory strains of P. falciparum, FCR3 and K1 was compared in both of GIT and RPMI 1640 medium supplemented by 10% human serum (RPMI-HS). Growth rates of various P. falciparum expressed as fold increases were compared in GIT and RPMI-HS, and the maximum growth rates of P. falciparum were 72 in GIT and 35 in RPMI-HS during the culture for 8 days. Growth rate of the clinical isolates varied individually in both culture media, with average growth rates of parasites being 15.9 in GIT and 8.8 in RPMI-HS, respectively (not significant). Growth rates of FCR3 and K1 strains were 28.0 and 6.6 in GIT, and 10 and 7.5 in RPMI-HS. After 30 days culture of P. falciparum in GIT, 9 of 12 clinical isolates still continuously propagated but other three isolates disappeared. Despite variation of the P. falciparum isolates in their abilities to multiply in GIT, our experiments suggested that GIT is useful for culture of fresh clinical isolates of P. falciparum that are derived from geographically distinct areas as well as laboratory strains used commonly in laboratory research.

Animals↗

PubMed2000

Environmental factor dependent maximum likelihood method for association study targeted to personalized medicine.

The most challenging strategy for analyzing genome-wide polymorphisms and/or expression profiles is to solve multi-factor causal-relationship simultaneously. As the first step, we propose a framework of association study using maximum likelihood method that simultaneously handles genetic polymorphisms and epi-genetic information, e.g. environmental factors. We evaluate the theory by applying it to genotyped data of myocardial infarction (MI) patients.

Algorithms↗

PubMed2000

Inferring genetic networks from DNA microarray data by multiple regression analysis.

Inferring gene regulatory networks by differential equations from the time series data of a DNA microarray is one of the most challenging tasks in the post-genomic era. However, there have been no studies actually inferring gene regulatory networks by differential equations from genome-level data. The reason for this is that the number of parameters in the equations exceeds the number of measured time points. We here succeeded in executing the inference, not by directly determining parameters but by applying multiple regression analysis to our equations. We derived our differential equations and steady state equations from the rate equations of transcriptional reactions in an organism. Verification with a number of genes related to respiration indicated the validity and effectiveness of our method. Moreover, the steady state equations were more appropriate than the differential equations for the microarray data used.

Computational Biology↗

PubMed1999

The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection.

To investigate the prognostic factors of pancreatic cancer, a retrospective analysis of 193 patients who underwent curative resection was conducted. Of the 193 patients, 38 (20%) survived for more than 5 years, the 5-year survival rates for stages I, II, II, and IV disease being 41%, 17%, 11%, and 6%, respectively. According to a multivariate analysis, lymph node metastasis, intrapancreatic perineural invasion, and portal vein invasion were significant prognostic factors. Subsequently, a subgroup analysis concerning nodal metastasis and intrapancreatic perineural invasion was performed in 126 patients with records of these histological findings. In the group of patients without nodal metastasis, the 5-year survival rate for those without perineural invasion was 75%, whereas that for those with perineural invasion was 29%, the difference in survival of these subgroups being significant (P < 0.02). In the group of patients with nodal metastasis, the 5-year survival rate for those without perineural invasion was 17%, while that for those with perineural invasion was 10%. The most favorable 5-year survival of 89% was observed in the subgroup of patients with stage I disease without perineural invasion. Thus, pancreatic adenocarcinoma categorized by the combination of these independent types of biological behavior showed 5-year survival rates ranging from very high to low, indicating that these two factors play an important role in the prognosis of this disease.

Adenocarcinoma↗

PubMed1999

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Primary hepatic carcinoid tumor.

A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 x 12 x 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.

Antineoplastic Agents↗

PubMed1999

Malignant mesothelioma of the tunica vaginalis testis: report of a case.

We describe herein the case of a 68-year-old man with malignant mesothelioma of the tunica vaginalis testis. The pathological diagnosis was based upon the clinical findings, gross and microscopic morphology, and special stains. Malignant mesothelioma is a rare tumor associated with asbestos exposure that can be effectively treated with orchidectomy via an inguinal approach.

Aged↗

PubMed1999

Isolation and chromosomal mapping of a novel human gene showing homology to Na+/PO4 cotransporter.

We isolated a cDNA clone which shows a significant similarity with the renal Na+/phosphate cotransporter (NPT) from a human intestine mucosa cDNA library. The cDNA is 2626 bases long, with one open reading frame encoding a protein of 497 amino acids. The deduced amino acids sequence shows an overall homology of 48% with the human renal NPT1 protein. This gene is expressed in intestine, colon, liver, and pancreas. Thus, this gene may code for intestinal type NPT or closely related proteins. The chromosomal location of the gene was determined on the chromosome 6p21.3-p22 region by polymerase chain reaction-based analysis with both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid mapping panel.

Amino Acid Sequence↗

PubMed1999

Cloning, expression analysis, and chromosomal localization of a novel butyrophilin-like receptor.

We isolated a cDNA clone which shows a similarity with human butyrophilin from a human colon mucosa cDNA library. The cDNA is 1964 bases long, with one open reading frame encoding a protein of 433 amino acids. The deduced amino acid sequence shows an overall homology of 36.5% with the human butyrophilin protein. This gene is mainly expressed in small intestine, colon, testis, and leukocytes. The chromosomal location of the gene was determined on the chromosome 5q35 region by polymerase chain reaction-based analysis with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel.

Amino Acid Sequence↗

PubMed1999

Differential expression of Ca(2+)-binding proteins on follicular dendritic cells in non-neoplastic and neoplastic lymphoid follicles.

We studied the Ca(2+)-capture ability of follicular dendritic cells (FDCs) in tonsillar secondary lymphoid follicles (LFs) and the expression of six Ca(2+)-binding proteins (CBPs), caldesmon, S-100 protein, calcineurin, calbindin-D, calmodulin, and annexin VI in LFs of various lymphoid tissues and caldesmon and S-100 protein in neoplastic follicles of follicular lymphomas. First, Ca(2+)-capture cytochemistry revealed extensive Ca(2+) capture in the nuclei and cytoplasm of FDCs, but little or none in follicular lymphocytes. All six CBPs were localized immunohistochemically in the LFs and were always present in the basal light zone. Immunoelectron microscopic staining of FDCs was classified into two patterns: caldesmon was distributed in the peripheral cytoplasm like a belt; S-100 protein, calcineurin, calbindin-D, and calmodulin were distributed diffusely in the cytosol. Annexin VI was, however, negative on FDCs. Immunocytochemistry also demonstrated CBP-positive FDCs within FDC-associated clusters isolated from germinal centers. In situ hybridization revealed diffuse calmodulin mRNA expression throughout the secondary LFs. These data indicate that the CBPs examined may regulate Ca(2+) in the different subcellular sites of FDCs, and the roles of CBPs may be heterogeneous. We also investigated the distribution of caldesmon and S-100 protein in follicular lymphomas on paraffin-embedded tissue sections. FDCs within grades I and II neoplastic follicles clearly expressed caldesmon, but not S-100 protein, except a part of grade II neoplastic follicles. FDCs within grade III follicles showed no caldesmon, but frequently expressed S-100 protein. These results demonstrate that the caldesmon and S-100 protein staining patterns of grade I follicular lymphomas are different from those of grade III follicular lymphomas and suggest that FDC networks in grade I neoplastic follicles may be similar to those in the light zone within non-neoplastic follicles, FDC networks in grade III neoplastic follicles may be similar to those in dark and basal light zones within non-neoplastic follicles, and grade II follicles may be intermediate between grade I and grade III follicles.

Annexin A6↗

PubMed1999

Resolution of bullous pemphigoid and improvement of vitiligo after successful treatment of squamous cell carcinoma of the skin.

The significance of the association of malignant diseases with bullous pemphigoid is still unknown. We report a case of squamous cell carcinoma of the skin associated with both bullous pemphigoid and vitiligo. It is possible that there is a common underlying pathogenic mechanism involved in the co-existence of these three skin diseases as successful treatment of the carcinoma was accompanied by resolution of the bullous pemphigoid and improvement of the vitiligo.

Aged↗

PubMed1999

Solid-pseudopapillary carcinoma of the pancreas.

A case of solid-pseudopapillary carcinoma (SPC) of the pancreas in a 34-year-old Japanese woman is presented. An abdominal ultrasonography revealed a mass, which measured 10 cm in diameter, in the body and tail of the pancreas. The tumor was resected and it was originally diagnosed as a non-functioning islet cell tumor. One year and five months later, the patient was re-admitted to hospital, and liver metastasis was confirmed by ultrasonography. The patient died 6 days after the second transcatheter arterial embolization (TAE) required for the metastasis. The autopsy showed small foci of liver metastasis. A retrospective examination of the tumor suggested the diagnosis of SPC because of its characteristic solid and pseudopapillary structures, immunohistochemical findings, and liver metastasis. This case suggests that capsular invasion, specifically found at the surgical margin of the peritoneal side, may be an important pathological finding that is suggestive of malignant potential in solid-pseudopapillary tumor. If there is such a finding in a surgical specimen, an intensive follow up should be advised to the clinician.

Adult↗

PubMed1999

An analysis of risk factors for upper urinary tract deterioration in patients with myelodysplasia.

OBJECTIVE: To identify the risk factors for upper urinary tract deterioration in a retrospective study of patients with myelodysplasia. PATIENTS AND METHODS: The medical history, radiographic studies and urodynamic results from 39 children with myelodysplasia who were treated at our hospital were reviewed retrospectively to obtain more accurate data in the prognosis of such patients. The upper urinary tracts were assessed by cysto-urethrography and excretory urography to determine the incidence of vesico-ureteric reflux (VUR) and hydronephrosis. The relationships between the urodynamic variables, including vesical compliance, detrusor hyper-reflexia, detrusor-sphincter dyssynergia (DSD) and the maximum urethral closing pressure (MUCP) to such upper tract deterioration were evaluated using both univariate and multiple logistic regression analysis. RESULTS: The univariate analysis showed low vesical compliance, a high level of MUCP and the presence of DSD to be significant factors for the incidence of VUR. Low vesical compliance and a high level of MUCP also correlated with the incidence of hydronephrosis. The multivariate analysis showed a significant relationship between urodynamic values and upper urinary tract deterioration. The incidence of VUR was strongly correlated with a high MUCP and the presence of DSD. A high MUCP was also a significant factor in the incidence of hydronephrosis. CONCLUSION: Urodynamic results associated directly with the abnormal function of urethral control are significantly correlated with the cause of upper tract deterioration in patients with myelodysplasia.

Adolescent↗

PubMed1999

Expression of matrix metalloproteinase 2 (MMP-2), membrane-type 1 MMP and tissue inhibitor of metalloproteinase 2 and activation of proMMP-2 in pancreatic duct adenocarcinomas in hamsters treated with N-nitrosobis(2-oxopropyl)amine.

In order to assess the significance of changes in metalloproteinase activity in pancreatic carcinogenesis, the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively), tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and membrane-type 1 MMP (MT1-MMP) and MT2-MMP in ductal lesions in a rapid-production model for pancreatic duct carcinomas (PCs) in hamsters initiated with N-nitrosobis(2-oxopropyl)amine (BOP) and in subcutaneous transplantable tumors of hamster pancreatic duct carcinoma (HPDs) was investigated. Northern analysis revealed MMP-2, MMP-9, TIMP-2 and MT1-MMP mRNAs to be overexpressed in PCs. Immunohistochemically, elevated levels of MMP-2 were apparent in early duct epithelial hyperplasias and staining increased from atypical hyperplasias to carcinomas. Gelatin zymography demonstrated clear activation of proMMP-2 but not proMMP-9 in both of primary and HPD tumors, the MT1-MMP mRNA level and proMMP-2 activation being significantly correlated (r = 0.893, P < 0.001). In our rapid production model, 0.1 and 0.2% OPB-3206, an inhibitor of MMPs, given in the diet after two cycles of augmentation pressures for 48 days decreased the incidence and number of carcinomas. Gelatin zymography demonstrated that OPB-3206 inhibited activation of proMMP-2 in pancreatic cancer tissues. These results indicate that overexpression of MMP-2, TIMP-2 and MT1-MMP, and cell surface activation of proMMP-2 by MT1-MMP, are involved in the development of PCs, and that MMP-2 expression at the protein level appears in the early phase of pancreatic duct carcinogenesis. OPB-3206 may be a candidate chemopreventive agent for pancreatic ductal adenocarcinomas.

Adenocarcinoma↗

PubMed1999

Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model.

We transduced the interleukin-2 (IL-2) gene into murine fibroblasts BALBCL7 or murine colon cancer CT26 using a retroviral vector. BALBCL7 transduced with IL-2 gene secreted 748 pg/ml of IL-2, whereas IL-2 gene-modified CT26 secreted 1,167 pg/ml of IL-2 (48 h incubation, 1x10(6)/ml). Then, we inoculated gene-modified BALBCL7 and/or CT26 cells into BALB/c female mice, and observed the tumor growth. The tumor growth was inhibited in mice inoculated with parental CT26 plus IL-2 gene-modified BALBCL7, compared with that in mice given parental CT26 alone (P<0.01). Moreover, we investigated the cytotoxic activity of spleen cells derived from mice treated with gene-modified cells, and performed phenotypic analysis of the effector cells. The killer cells derived from mice inoculated with IL-2 gene-modified BALBCL7 plus parental CT26 showed higher cytotoxic activity than those from mice inoculated with CT26 alone. The cytotoxic activity was almost completely blocked by anti-CD8 antibody (Ab), and partially blocked by anti-asialo GM1 Ab. Next, we inoculated CT26 tumor tissue into murine cecum orthotopically, and treated the animals with gene-modified BALBCL7 plus parental CT26. The tumor size in the cecum was significantly decreased, compared with parental CT26 alone (P<0.01).

Animals↗

PubMed1999

Time and memory efficient algorithm for extracting palindromic and repetitive subsequences in nucleic acid sequences.

Genomic science and structural biology meet in the relationship between the sequence and the structure of nucleic acids. The structure that supports each function is preserved in the process of evolution as specific sequences. Particularly, the same sequence which appears in a different place such as a palindromic or repetitive sequence has biophysical meaning: recognition site of dimers, forming stem-loops, and contributions to global structure of nucleic acids. Also, the genetic network, transduction pathway, and tissue specificity largely depend on these. Although the relationship between them can be found experimentally, there is increasing demand for automated analysis. Especially, it is desirable to extract the same character sequences of arbitrary length (especially, very long ones) which co-occur at an arbitrary separation. We propose an algorithm to identify the maximum match sequence at each position with a calculation cost of O(N log N) and memory space of O(N). Applying it to some sequences, we found unexpectedly large palindromes and repeats in DNA.

Algorithms↗

PubMed1999

Tumor specific CTL therapy for advanced cancer and development for cancer vaccine.

BACKGROUND/AIMS: Advanced gastrointestinal (GI) cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of tumor specific cytotoxic T Lymphocyte (CTL) therapy as multidisciplinary treatment for patients with advanced cancer. METHODOLOGY: The enrolled advanced cancer patients had distant metastases derived from gastric cancer, colon cancer and bilio-pancreatic cancer. The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by various kinds of the activated killer cells. RESULTS: There was no severe toxicity, except fever and mild myelo-suppression. Six patients had complete response, and 18 patients had partial response out of 38 enrolled patients. The performance status was improved in responders (p<0.01); however, it was not changed in non-responders. Furthermore, the ratio of discharge of the responders was higher than that of non-responders. CONCLUSIONS: It was clarified that tumor-specific CTL therapy as multidisciplinary treatment is clinically valuable, especially in terms of quality of life. For developing the new strategy against cancer, CEA specific cancer vaccine trials have just started.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Tumor necrosis factor-alpha-induced release of plasminogen activator inhibitor-1 from human umbilical vein endothelial cells: involvement of intracellular ceramide signaling event.

We have investigated the biochemical mechanism of tumor necrosis factor (TNF)-alpha-induced release of plasminogen activator inhibitor-1 (PAI-1) from human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with TNF-alpha for 3 h resulted in a 2. 8-fold increase in the PAI-1 release compared with control. The increase in PAI-1 release was accompanied by a 133% increase in the intracellular acidic sphingomyelinase (SMase) activity. High-performance liquid chromatographic (HPLC) analysis revealed that the intracellular ceramide levels increased to 126% of the control (P<0.05), but the contents of membranous ceramide remained unaltered. We have previously shown that a cell-permeable ceramide analog, N-acetylsphingosine (C2-ceramide) enhances the PAI-1 release from HUVEC. Here, N-acetylsphinganine (C2-dihydroceramide) was found to specifically suppress both C2-ceramide- and TNF-alpha-induced increase in PAI-1 release from HUVEC without affecting the control PAI-1 release. Treatment of HUVEC with staphylococcal SMase that may mimic the activation of the membranous neutral SMase also increased the PAI-1 release. The increase in PAI-1 release by this mechanism was suppressed by a cyclooxygenase inhibitor, aspirin, whereas the inhibitor did not affect TNF-alpha-induced increase in PAI-1 release. Taken together, these findings suggest that TNF-alpha prominently utilizes the lysosomal acidic SMase-ceramide signaling pathway in the induction of PAI-1 release from HUVEC.

Ceramides↗