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Biomedical subjects

S Ohtake

Publications and source records attributed to S Ohtake.

At least 91 records · Page 5Linked to original sources

Primary prostatic lymphoma of mucosa-associated lymphoid tissue.

We present a case of primary prostatic lymphoma referring to a 57-year-old man, who was admitted with the symptom of bladder outlet obstruction, and had a history of urination difficulty for two years. The symptoms and signs were compatible with a diagnosis of benign prostatic hypertrophy (BPH). The pathology of the specimen obtained from transurethral prostatectomy showed B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The patient has been asymptomatic and under complete remission after completion of chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine and prednisone for 6 cycles.

Antineoplastic Combined Chemotherapy Protocols↗

Experimental replacement of the thoracic inferior vena cava with a high-porosity expanded polytetrafluoroethylene graft wrapped in an omental pedicle flap.

We examined the patency and healing of a high-porosity expanded polytetrafluoroethylene (ePTFE) graft implanted as an interposition graft in the thoracic inferior vena cava (IVC) and wrapped in an omental pedicle flap. High-porosity ePTFE grafts of 60 microns fibril length, with an internal diameter of 10 mm and a length of 4 cm, were implanted in 12 mongrel dogs. In 6 dogs, the grafts were wrapped in omental pedicle flap, and in the remaining 6 the grafts were unwrapped. The animals were killed 4 weeks after the replacement and the grafts were removed for examination. Patency of the graft in both groups was 100%; however, the thrombus-free area in the omentum-wrapped group was significantly larger (P < 0.05) than that in the unwrapped group. Light microscopy revealed the marked infiltration of cells and capillaries within the graft interstices in the omentum-wrapped group. These findings suggest that encapsulation of the high-porosity ePTFE graft is promoted by an omental pedicle flap.

Anastomosis, Surgical↗

Expanded polytetrafluoroethylene grafts for portal vein replacement: use of omentum wrap to promote graft healing.

This study was designed to reexamine the healing process of expanded polytetrafluoroethylene (EPTFE) grafts with standard porosity (30 microm) and high porosity (60 microm) in portal vein replacement, and to evaluate the effect of an omentum wrap, which has certain functions that promote healing, on graft healing. These grafts, either wrapped by the omentum or not, were placed as portal vein replacements in 24 mongrel dogs. After 1 month, the grafts were retrieved and examined for patency, thrombus-free areas, thickness of the pseudointima, and the total number of cells growing into the graft wall. There were no statistical differences in the patency rates. The high-porosity grafts had a significantly larger thrombus-free area, a thicker pseudointima, and a larger growth of cells than the standard-porosity grafts. The omentum wrap significantly increased the thrombus-free area and stimulated a larger growth of cells in both grafts. The high-porosity grafts plus omentum demonstrated a thrombus-free area of 82.2% vs 27.3% in the standard-porosity grafts. In addition, the migration of fibroblasts and macrophages was most evident in the high-porosity grafts wrapped by the omentum. In conclusion, graft healing enhancement was observed in the high-porosity EPTFE grafts wrapped by the omentum. It is thus suggested that transmural cellular migration plays an important role in the process of graft healing.

Animals↗

Purification and characterization of a 39,000-Da serine proteinase from the hemolymph of a solitary ascidian, Halocynthia roretzi.

A new endogenous serine proteinase from the cell-free hemolymph of a solitary ascidian, Halocythia roretzi, was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography on TSKgel Toyopearl HW 65 F, ion exchange chromatography on TSKgel DEAE-Toyopearl 650 M, affinity chromatography on Arginine-Sepharose 4B, gel filtration on TSKgel Toyopearl HW 65F and hydroxyapatite chromatography on Bio-Gel HT. The serine proteinase is a single polypeptide chain whose molecular weight and isoelectric point are 39 kDa and about 7.6 pI, respectively. The most susceptible substrate was Boc-Leu-Gly-Arg-4-methyl-coumaryl-7-amide (MCA), and activity was optimal at pH 8. The enzyme was relatively stable at high temperatures; about 50% activity was retained even at 60 degrees C for 30 min in 50 mM Tris-HCl, pH 8.0, containing 0.5 M NaCl, and 0.05% Brij-35. The enzyme was characterized by the inhibitory effects of synthetic or natural inhibitors, substrate specificity toward 26 peptidyl-MCAs, proteinase activity toward natural proteins and complex formation with a serine proteinase inhibitor (58 kDa) previously found in H. roretzi hemolymph, indicating that the enzyme was a member of serine proteinases and strongly inhibited by the 58 kDa serine proteinase inhibitor as well as human antithrombin III. We also demonstrated the clotting enzyme activity of the purified serine proteinase toward bovine fibrinogen and Limulus coagulogen, a fibrinogen-like clottable protein of horseshoe crabs.

Amino Acid Sequence↗

Treatment of acute myeloid leukemia and myelodysplastic syndrome with orally administered cytarabine ocfosfate and granulocyte colony-stimulating factor.

Cytarabine ocfosfate (SPAC) was administered orally to 19 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). SPAC was administered at doses of 200-300 mg/day for more than 14 days with granulocyte colony-stimulating factor (G-CSF). Four of the 12 patients with AML and 1 of the 7 patients with MDS achieved complete remission (CR) after one cycle of SPAC treatment. Especially, 3 of the 6 patients with newly diagnosed AML achieved CR. Major side effects of SPAC were myelosuppression and tolerable gastrointestinal disorders. The treatment with SPAC is a therapeutic option in elderly patients or patients with organ failure.

Administration, Oral↗

Prognostic significance of immunoglobulin heavy chain gene rearrangement in patients with acute myelogenous leukemia.

Recently the immunoglobulin heavy chain (IgH) gene rearrangement in B cell malignancies has been analyzed. Clonality can be determined using the polymerase chain reaction (PCR). Little attention, however, has been given to the relationship between prognosis and IgH gene rearrangement in patients with acute myelogenous leukemia (AML). In this study, we examined IgH gene rearrangement in 35 untreated AML patients by PCR. PCR was performed using consensus heavy chain complimentarity-determining region (CDR)-3 primers. Clonal IgH gene rearrangement was detected in 14 patients (40%). Four of five patients (80%) who were positive for B cell markers had clonal IgH gene rearrangement. Ten of 30 B cell antigen-negative patients (33%) also showed IgH rearrangement. All patients were treated with a daunorubicin-based regimen, resulting in complete remission for 29 patients (83%). Sixty-four percent of those with IgH rearrangement and 95% of those without rearrangement had complete remission. Overall survival of IgH-PCR positive and negative patients at 25 months was 29 and 88%, respectively. IgH-PCR positivity may be a poor prognostic factor in AML.

Adolescent↗

Thyroid tumor as initial presentation of Hodgkin's disease: a case report including an immunophenotypic characterization.

A rare case of Hodgkin's disease which initially presented with a thyroid tumor in an 18-year-old-man is reported. The tumor involved most of the thyroid gland but was well demarcated, and the border between the tumor and the remnants of the thyroid gland was relatively clear, suggesting secondary Hodgkin's disease involving the thyroid gland. Histologic examination of the tumor revealed nodular sclerosing Hodgkin's disease composed of many peculiar osteoclast--like giant cells and a few typical Reed--Sternberg cells in the background of dominant eosinophils. With an immunophenotypic study it was shown that these giant cells were positive for the monoclonal antibodies LeuM1 and BerH2, but negative for LCA. Thus the histological diagnosis was clearly confirmed.

Adolescent↗

[Antithrombotic property of new growing endothelial cells on the prosthetic vascular grafts--experimental study of portal vein replacement].

On experimental portal vein replacement of mongrel dogs with high porosity EPTFE grafts (fibril length: 60 microns) wrapped in omental pedicle flap, it has been reported that healing process is promoted. But it is not clear on the antithrombotic properties of the newly growing endothelial cells on prosthetic vascular grafts. PGI2 and NO are known as antithrombotic factors that restrain the agglutination of platelets. We evaluated PGI2 and NO production from the newly growing endothelial cells on prosthetic vascular grafts. High porosity EPTFE grafts were implanted at the portal veins of mongrel dogs. After 3 months we removed the grafts and tried to procure the new growing endothelial cells by trypsinization and culture them. We confirmed by using Dil-Ac-LDL that endothelial-like cells on prosthetic vascular grafts were as same as the endothelial cells. As control cells, we used the endothelial cells of canine portal vein and infra vena cava. The basal PGI2 production from each cells and the thrombin-stimulated production of PGI2 were measured by radioimmuno assay. Thrombin concentration was established at 2 unit/ml. On the basal PGI2 production there was no significant difference between the grafts and the portal veins, and between the grafts and the infra vena cava. The PGI2 production of the grafts increased significantly by stimulating with thrombin. On the thrombin-stimulated production, there was no significant difference between the grafts and the portal veins, and between the grafts and the infra vena cava. NO production of the grafts was measured by the griess reaction. On NO production there was no significant difference between the grafts and the portal veins. But the grafts produced significantly more NO than the infra vena cava (P < 0.05). This study suggests that the newly growing endothelial cells on the prosthetic vascular grafts may have the antithrombotic properties equal to the endothelial cells on the portal vein and the infra vena cava.

Animals↗

Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies.

It is now evident that the cell cycle machinery has a variety of elements negatively regulating cell cycle progression. However, among these negative regulators in cell cycle control, only 4 have been shown to be consistently involved in the development of human cancers as tumor suppressors: Rb (Retinoblastoma susceptibility protein), p53, and two recently identified cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in human cancers, including leukemias/lymphomas. To address this point, we examined inactivations of these four genes in primary lymphoid malignancies by Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. We also analyzed Rb protein expression by Western blot analysis. The p16INK4A and p15INK4B genes were homozygously deleted in 45 and 42 of 230 lymphoid tumor specimens, respectively. Inactivations of the Rb and p53 genes were 27 of 91 and 9 of 173 specimens, respectively. Forty-one (45.1%) of 91 samples examined for inactivations of all four tumor suppressors had one or more abnormalities of these four tumor-suppressor genes, indicating that dysregulation of cell cycle control is important for tumor development. Statistical analysis of interrelations among impairments of these four genes indicated that inactivations of the individual tumor-suppressor genes might occur almost independently. In some patients, disruptions of multiple tumor-suppressor genes occurred; 4 cases with p16INK4A, p15INK4B, and Rb inactivations; 2 cases with p16INK4A, p15INK4B, and p53 inactivations; and 1 case with Rb and p53 inactivations. It is suggested that disruptions of multiple tumor suppressors in a tumor cell confer an additional growth advantage on the tumor.

Adolescent↗

Medullary thyroid carcinoma experienced at Kanazawa University Hospital.

Eleven cases of medullary thyroid carcinoma (MTC), which were experienced at Kanazawa University Hospital between 1975 and 1993, were examined to correlate the clinical, histologic, and immunohistochemical findings. Seven patients were women and four men, and the mean age was 46.6 years. The mean follow-up was 88.3 months. Three patients had familial non-multiple endocrine neoplasia (MEN) MTC (familial MTC unassociated with other endocrinopathies) and the remaining eight had sporadic disease. At the end of the observation period, six patients were alive without disease and four were alive with metastatic disease. One patient died of MTC 8.3 years after surgery. Thus, the 10-year survival and disease-free survival rates were 67% and 53%, respectively. Histologically MTCs from the 10 surviving patients showed a classic type, while the one patient who died had a tubular variant MTC. Immunohistochemically, there were no significant correlations between the outcome of the patients and the expression of calcitonin (CT), carcinoembryonic antigen (CEA), calcitonin gene-related peptide (CGRP), or chromogranin A (CgA) in the primary tumors, and there were no differences in expression of these antigens between the primary and the recurrent tumors. Although only a small number of patients with MTC were studied here, it was suggested that the prognosis of MTC is worse than that of papillary and follicular thyroid carcinoma. The patients with lymph node involvement at the time of primary surgery showed a high risk of persistent or recurrent disease. The expressional level for the antigens did not influence the prognosis of MTC.

Adult↗

Purification and characterization of a 58,000-Da proteinase inhibitor from the hemolymph of a solitary ascidian, Halocynthia roretzi.

A new endogenous proteinase inhibitor from the cell-free hemolymph of a solitary ascidian, Halocynthia roretzi, was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography on Ether-Toyopearl and affinity chromatography on Heparin-Sepharose. The purity of the inhibitor was examined by SDS-PAGE, gel-permeation chromatography, reversed-phase chromatography, isoelectric focusing, immunological analysis and amino-terminal amino acid sequence analysis. The inhibitor is a single polypeptide chain whose molecular weight, isoelectric point and the first 10 amino-terminal amino acid sequences are 58 kDa, pI 9.2 and NH2-Thr-Lys-Lys-Asp-Gly-Glu-Glu-Lys-Val-Ala, respectively. The purified protein inhibits plasma enzyme(s) of H. roretzi, and the rate of inhibition to the plasma enzyme(s) activity was accelerated by incubation with dextran sulfate, but the effect was neutralized by further incubation with polycation, such as polybrene or protamine sulfate. The inhibitory activity was not affected appreciably by pH 7-10 but ceased completely below pH 5 or by heating at 50 degrees C for 30 min.

Amino Acid Sequence↗

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗

Hematopoietic clone with karyotypic abnormalities of host origin after bone marrow transplantation: two case reports.

A patient with non-Hodgkin's lymphoma in remission developed a myelodysplastic syndrome (MDS) 12 years after ABMT. This patient had undergone bone marrow harvesting prior to any chemoradiotherapy. He had received the autograft following conditioning with high-dose CY and TBI. Chromosomal analysis of BM cells revealed complicated abnormalities. Similar karyotypic abnormalities in host-derived BM cells were found in another patient with AML who had received allogeneic BM following conditioning with CY plus TBI 15 months previously. These findings suggest that MDS or clonal karyotypic abnormalities following ABMT may derive from endogenous hematopoietic stem cells that survive the BMT preparative regimen.

Adult↗

[Multidrug resistant P-glycoprotein expression on acute nonlymphocytic leukemia cells at diagnosis].

In performing cancer chemotherapy, it is essential to know the expression of multidrug resistant (MDR) P glycoprotein (p-gp) on cancer cells. In the present study, in order to clarify the relationship between MDR of leukemic cells and cytologic, immunological and clinical features of acute nonlymphocytic leukemia (ANLL), leukemic cells in peripheral blood and/or bone marrows obtained from 28 ANLL patients were examined. Each smear was stained with C219 monoclonal antibody against P-gp by the APAAP method, and then 1,000 ANLL cells in each smear were observed. Among the FAB subtypes, M4 showed the highest proportion of leukemic cells expressing P-gp. Concerning the response to chemotherapy, five of seven patients (71%) having 1.0% or more of P-gp positive leukemic cells and 11 of 19 patients (58%) having less than 1.0% of those cells achieved complete remission. However, there was no significant correlation between P-gp expression and clinical outcome. There was also no significant correlation between P-gp expression and CD7 or CD34. Furthermore, no significant correlation between chromosome 7 abnormality and P-gp expression was observed. From these results, if we can clarify the mechanism of MDR and the relationship between MDR and cytogenetic or clinical features of ANLL with further study, P-gp expression may become a useful marker for predicting the outcome of ANLL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in and highly specific to lymphoid tumors in primary human hematopoietic malignancies.

The cyclin-dependent kinase 4-inhibitor (CDK41; p16; or MTS1) gene has been proposed as a candidate for a tumor-suppressor gene located in chromosome 9p21, a frequently deleted region in a wide spectrum of human cancers, including leukemias. Recent studies disclosed that it was frequently deleted or mutated in a variety of primary human cancers, including acute lymphoblastic leukemia. The purpose of this study is to figure out the precise manners and frequencies of p16 gene inactivation in diverse hematopoietic tumor types and thus to clarify its significance in development of human hematopoietic malignancies. A total of 410 tumor specimens from patients with primary hematopoietic malignancies were examined for deletions of the p16 gene as well as the neighboring p15 gene and the nearby interferon alpha gene by Southern blot analysis. Tumor-specific mutations or small deletions of the p16 gene were also studied in 74 patients using single-strand conformation polymorphism analysis and direct sequencing. Loss of the p16 gene was most frequently observed among the three genes examined and was found in 59 of the 410 patients: 2 of 134 with acute myelocytic leukemia, 41 of 105 with acute lymphocytic leukemia, 2 of 15 with chronic lymphocytic leukemia, 5 of 14 with adult T-cell leukemia, 4 of 33 with non-Hodgkin's lymphoma, 3 of 8 with mixed-lineage leukemia, and 2 of 61 with chronic myelocytic leukemia. In 16 of the 59 patients, the p16 deletions occurred due to rearrangements within the small region between the p15 exon 2 and the p16 exon 2. Tumor-specific mutations or small deletions of the p16 gene were not detected in the 74 patients examined, including 12 of 14 patients with hemizygous deletions of the gene. Loss of the p16 gene is frequent in and highly specific to lymphoid malignancies (54 of 183 [30%] in lymphoid tumor v2 of 219 [1%] in myeloid tumors; P < .0001). The deletion analyses strongly suggest that the p16 gene is a tumor-suppressor gene located in chromosome 9p21 that is involved in development of human lymphoid tumors. Gene deletions but not minute mutations should be the predominant mechanism of p16 gene inactivation in these types of tumors.

Adolescent↗

Acute nonlymphocytic leukemia complicated by Garcin's syndrome.

A 15-year-old girl was diagnosed as having acute nonlymphocytic leukemia (ANLL, FAB M2) in January 1990 and achieved complete remission with chemotherapy. She was readmitted to our hospital with a hearing disturbance and hoarseness in October 1990. A suprapharyngeal tumor was found on cranial MRI, and bone marrow leukemic cells were slightly increased in number. Involvement of leukemic cells was proven by biopsy of the tumor. Therefore, we made a diagnosis of ANLL relapse with Garcin's syndrome. To our knowledge, this is the first reported case of leukemia complicated by Garcin's syndrome.

Adolescent↗