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Biomedical subjects

T Ohtsu

Publications and source records attributed to T Ohtsu.

At least 55 records · Page 3Linked to original sources

Remote subarachnoid haemorrhage in the posterior fossa following supratentorial surgery. Clinical observation of 6 cases.

Haemorrhage in regions remote from the site of following intracranial operations is rare, but they do occur. We performed supratentorial craniotomy on 639 patients between the time of introduction of computed tomography (CT) for clinical use in 1983 and June 1992; subarachnoid haemorrhage (SAH) in the posterior fossa occurred postoperatively in six of these cases. These included four patients with tumours in the sellar region, one with an arteriovenous malformation (AVM) and one who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis. The ages of the six patients ranged from 17-72 years. Haemorrhage occurred on the day of operation in one case and was detected on CT examination on the day following surgery in the remaining five cases. Of three patients with disturbance of consciousness, two underwent suboccipital craniectomy for reduction of intracranial pressure, while one received barbiturate therapy and later underwent cerebrospinal fluid (CSF) shunt surgery. No special treatment was necessary for the remaining three patients with less serious lesions. Five of the six patients ultimately recovered their pre-operative neurological status apart from the primary diseases. Factors inducing such haemorrhages seem likely to include displacement of the cerebellum by reduced CSF pressure during and after operations, and stretching and tearing of the veins and venules in the sulci of the tentorial surface of the cerebellum. Consideration should therefore be given to the maintenance of an appropriate CSF pressure during operation; this is particularly important in elderly patients and those with an atrophied cerebral cortex.

Adolescent↗

Development of pseudolymphoma of liver following interferon-alpha therapy for chronic hepatitis B.

A 42-year-old woman with biopsy-proven chronic hepatitis B, who had been treated with human leukocyte-derived interferon-alpha (huLe-IFN alpha) therapy for two months was found to have liver tumors on routine abdominal ultrasonography examination. She underwent laparotomy, and partial hepatectomy was performed under the clinical diagnosis of hepatocellular carcinoma. The lesions were diagnosed histologically as pseudolymphoma based on the massive infiltration of small mature lymphocytes and the presence of hyperplastic lymph follicles with germinal centers. Immunohistochemistry revealed polyclonal origin of the involved lymphocytes. The possible association between IFN alpha treatment and chronic hepatitis B with the development of pseudolymphoma is discussed.

Adult↗

Cold adaptations in Drosophila. Qualitative changes of triacylglycerols with relation to overwintering.

Triacylglycerols are the major fuel for basal metabolism during the winter in temperate species of the Drosophila melanogaster species group. Differential scanning calorimetry analysis revealed that the transition temperatures of triacylglycerols were lower in diapausing adults than in reproducing ones, and also lower in species or strains adapted to cooler climates than those adapted to warmer climates. These phenomena were correlated to the fatty acid compositions of the triacylglycerols; the proportion of unsaturated fatty acids in the triacylglycerols was higher in the diapausing individuals, and in the species or strains adapted to cooler climates. Furthermore, in the temperate species of the montium species subgroup (D. subauraria, D. biauraria, D. triauraria, and D. rufa), the amount of saturated triacylglycerols was smaller than the value expected on the assumption that fatty acids are randomly distributed in the triacylglycerols, suggesting the nonrandom distribution of unsaturated fatty acids among triacylglycerols. This may facilitate the lowering of the transition temperature of triacylglycerols, and hence may be related to the ability of Drosophila to cope with temperate climates.

Adaptation, Physiological↗

[Pharmacodynamics of anticancer agents].

Studies of anticancer pharmacodynamics were reviewed. Pharmacodynamics deals with the relationship between therapeutic or toxic response and pharmacological measurements. It is suggested that the lack of pharmacodynamic information is currently limiting the application of pharmacokinetic information to cancer therapy. The studies contain pharmacodynamics of hematologic and non-hematologic toxicities, tumor response and cellular pharmacodynamics. It would be desirable to develop pharmacodynamic models using a limited sampling model during phase II trials, when all patients are treated with the same recommended dose, to relate pharmacokinetic parameters to tumor responses. The return knowledge of pharmacodynamics to cancer chemotherapy makes the concept of individualized therapy, adaptive control strategy with feedback (ACF) and targeted systemic exposure strategy (TSES). St. Jude Children's Research Hospital is now performing a randomized prospective trial to evaluate the efficacy and toxicity of conventional dosages versus individualized therapy using TSES with ACF in Acute lymphocytic leukemia pulse therapy with high-dose methotrexate, teniposide, and cytarabine. It would be a good model for the establishment of oncological pharmacology-based optimal administration of anticancer drugs.

Antineoplastic Agents↗

Energy storage during reproductive diapause in the Drosophila melanogaster species group.

Temperate species of the Drosophila melanogaster group enter reproductive diapause for overwintering in response to short daylength. During the prediapause period they accumulate triacylglycerols, but not glycogen, as energy resources. The capacity for storing triacylglycerols differs between species, and appears to be closely correlated with diapause and cold-hardiness; cool-temperate species, such as those of the auraria species complex, which enter a deep diapause and are highly cold-hardy, accumulate larger quantities of triacylglycerols than warm-temperate species, such as D. rufa and D. lutescens, which enter a weak diapause and are less cold-hardy. Among the cool-temperate species, D. subauraria occurs at a higher latitude and has the greatest capacity for accumulating triacylglycerols. A subtropical species, D. takahashii, which has no diapause in nature and is not cold-hardy, is unable to store the same quantities of triacylglycerols as temperate species.

Adaptation, Physiological↗

Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma.

A Japanese patient with adult T-cell leukemia-lymphoma (ATL) showed a disease progression from the smoldering type to the chronic type and finally to the acute type. The patient was variously treated, including 2'-deoxycoformycin, with some beneficial effects. During the chronic type he developed a composite lymphoma consisting of T-cell lymphoma (ATL) of medium-sized cells and B-cell lymphoma of diffuse large cell type. At that time, he also suffered from miliary tuberculosis and adenovirus type 11-induced hemorrhagic cystitis, indicating that he was in a marked immunodeficient state. Southern-blot analysis revealed that the two malignancies have distinct clonal origin on the basis of the following results: (1) clonally rearranged T-cell receptor beta-chain gene (TcR-beta gene) and germline configuration of immunoglobulin heavy chain gene (IgH gene) in ATL leukemic cells, (2) clonal rearrangement of IgH gene in lymphoma cells, indicating a monoclonal B-cell lymphoma, (3) monoclonal integration of HTLV-I provirus in ATL leukemic cells, (4) definite presence and monoclonal origin of EBV genome in lymphoma cells. This is the first report of secondary EBV genome carrying monoclonal B-cell lymphoma in an ATL patient. It is suggested that the immunodeficient state in the patient with ATL allows the emergence of EBV-related B-cell lymphoma.

Adult↗

Activation of hepatitis B virus infection by chemotherapy containing glucocorticoid in hepatitis B virus carriers with hematologic malignancies.

Among 262 inpatients with hematologic diseases who were referred for chemotherapy or immunosuppressive therapy between January, 1985, and December, 1989, nine (3.4%) patients, including two with Hodgkin's disease (HD), three with acute myeloblastic leukemia, one with chronic myelogenous leukemia, two with multiple myeloma and one with aplastic anemia, were found to be hepatitis B virus (HBV) carriers before their chemotherapy began. All six HBV carriers who received chemotherapy containing glucocorticoid showed mild-to-moderate elevations in serum transaminase levels after the chemotherapy. Five showed a rise in titer of the hepatitis B surface antigen, HBsAg. In contrast, three HBV carriers not receiving glucocorticoid showed no change in serum transaminase after chemotherapy. One HBV carrier with HD suffered from severe icteric hepatitis after the withdrawal of multiagent chemotherapy containing glucocorticoid. The HBV-DNA polymerase rose markedly and was accompanied by a marked rise in titer of HBsAg. The results warn us to keep in mind the possibility of glucocorticoid inducing an activation of HBV infection, which may result in severe hepatitis in some HBV carriers. Although further investigation is required, it is recommended that HBsAg-positive patients with hematologic malignancies should, if possible, be treated without glucocorticoid.

Adult↗

Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16.

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20.

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.

Antibiotics, Antineoplastic↗

[Detection of multidrug resistant cells in human malignant diseases by monoclonal antibodies and strategy to eradicate resistant malignant cells].

Two monoclonal antibodies of F (ab')2 form, MRK 16 and MRK 20 that recognize P-glycoprotein and P85 kD protein respectively, were useful to detect multidrug resistant cells in human lymphoma, leukemia and gastrointestinal cancer cell lines. They were classified into 4 groups: Group I (4 cell lines) was insensitive to vinca alkaloids, anthracyclines, etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK 16 and MRL 20. Group II (2 cell lines) was insensitive to vincristine (VCR), but not reactive to both antibodies. Group III (3 cell lines) was insensitive to anthracyclines and VP-16, but sensitive to vinca alkaloids and ACT-D, and reactive to MRK 20 but not to MRK 16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. MRK 16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK 20 detects P 85kd-associated novel MDR. These monoclonal antibodies were useful for detection of MDR cells in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Cross and non-cross resistant anticancer agents to multidrug-resistant cultured cells from hematologic malignancies].

We report here that typical and atypical multidrug resistant (MDR) cells can be identified by monoclonal antibodies, MRK16 and MRK20, respectively. Typical MDR cells were cross-resistant to vinca alkaloids, anthracyclines, mitoxantrone (MXT), etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK16. Atypical MDR cells were cross-resistant to anthracyclines, MXT, VP-16, and bleomycin but sensitive to vinca alkaloids and ACT-D. They were reactive to MRK20, but not to MRK16. Among anthracyclines, aclacinomycin A was not cross-resistant to either typical or atypical MDR cells. Methotrexate was not cross-resistant to doxorubicin, vincristine, Ara-C and cisplatin. Cisplatin was not cross resistant to 5-FU, either. Identification of cross and non-cross resistant anticancer agents may be useful to plan a cure-oriented combination chemotherapy for hematologic malignancies.

Antibodies, Monoclonal↗

[Long-term results of intra-arterial infusion therapy using cis-DDP (CDDP) in thoracic esophageal cancer].

The effects of intra arterial infusion therapy using CDDP for patients with thoracic esophageal cancer were investigated. From June 1984 to December 1988, 25 of 146 resected patients with thoracic esophageal cancer underwent preoperative therapy in our institute. All of these patients it was suspected preoperatively that their chief lesion had invaded to the aorta, trachea or main bronchi. Preoperative radio-chemotherapy with intra arterial infusion therapy was given to 10 of 25 patients (A group), and without intra arterial infusion therapy to 15 of 25 patients (B group). CDDP 75 mg was infused into the proper esophageal artery. In A group, 7 of 10 (70%) showed moderately or marked effects in histologic study, although in B group, only 4 of 15 (27%) did so. As for long-term results, the 2-year survival rates were 50% in A group and 13% in B group (Kaplan-Meier method. Preoperative intra arterial infusion therapy using CDDP with radio-chemotherapy showed markedly better effects in histologic study and survival rates than preoperative radio-chemotherapy without intra arterial infusion therapy. We consider that this therapy is very useful for controlling the local lesion in advanced esophageal cancer.

Cisplatin↗

Concurrent adult T-cell leukemia and acute myeloblastic leukemia.

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.

Antibodies, Viral↗

Plastic-coated guide wire for hepatic arteriography.

A guide wire made of a superelastic alloy coated with hydrophilic polymer has been developed for superselective catheterization in hepatic arteriography. In this study, the new wire was tested in 15 patients and a conventional spring wire was used in 25. Catheterization of the proper or more peripheral hepatic arteries was successful in 93.3% of cases in which the new wire was used versus 76.0% in which the conventional spring wire was used. Moreover, the frequency of complications, such as spasm and subintimal injury, was reduced from 28.0% to 6.7%.

Adult↗

[Detection of multidrug resistant phenotype in leukemia and lymphoma by monoclonal antibodies].

Two monoclonal antibodies, MRK16 and MRK20 that recognize P-glycoprotein and P-85 kd protein on the surface of adriamycin (ADM) resistant cells, respectively, were tested for the reactivity with 40 cultured leukemia/lymphoma cell lines. F(ab')2 form is essential to avoid false reaction through Fc gamma-R. Drug sensitivity of 19 representative cell lines were also examined in vitro. From this study, it was found that these cell lines were classified into 4 groups. Group 1 (4 cell lines) was insensitive to ADM, mitoxantron (MXT), etoposide (VP-16) and vincristine (VCR), and reactive to MRK16 and MRL20. Group II (1 cell line) was insensitive to the 4 drugs, but not reactive to both antibodies. Group III (3 cell lines) was insensitive to ADM, MXT and VP-16, but sensitive to VCR, and reactive to MRK20, but not to MRK16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. From these results, MRK16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK20 does P 85-kd-associated another type MDR (cross resistance to ADM, MXT and VP-16, but not to VCR). MRK20 reacted with monocytes, but MRK16 did not with any WBC type. One hundred and ninety eight clinical samples obtained from blood cancer were tested for the reactivity with MRK16. MRK16 did not react with any of 98 samples obtained before treatment, but did with 9 of 100 obtained at relapse or refractory stage after chemotherapy. The results indicate that MRK16 is useful to detect drug resistance phenotype of leukemia and lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Clinicopathologic, immunophenotypic, and immunogenotypic analyses of immunoblastic lymphadenopathy-like T-cell lymphoma.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.

Adult↗

Molecular genetic and immunohistochemical analyses of a case of multicentric Castleman's disease.

Whether Castleman's disease is primarily hyperplastic or neoplastic in nature is a matter of controversy; however, the classical localized form has been thought clinically benign in itself, because it can be cured by local therapy. Recently, a multicentric form of the disease has been reported and has received attention because of its aggressive clinical course and high incidence of developing malignant lymphoma. Here, we describe a case of multicentric Castleman's disease which occurred in a 24-year-old Japanese man. To ascertain whether a monoclonal population was present or not, we performed a molecular genetic analysis of the genes encoding the T-cell receptor and the immunoglobulin, as well as a conventional immunohistochemical analysis. Using these sensitive methods, no monoclonal population could be found. The findings suggest that our case represents a reactive rather than a neoplastic disorder.

Adult↗