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Biomedical subjects

Y Kohgo

Publications and source records attributed to Y Kohgo.

At least 181 records · Page 10Linked to original sources

[IBL like T cell lymphoma associated with hemolytic anemia and polyploidy chromosomal abnormality--a case report].

A 56-year-old man was admitted to Sapporo Kitano Hospital on May 30, 1987 because of fever, retention of ascites and pleural effusion, generalized lymphnode swelling and hepatosplenomegaly. Laboratory findings showed Coombs' positive hemolytic anemia, leukocytosis and polyclonal hypergammaglobulinemia. Serological test included positive RA factor, anti-DNA 16 U/ml, thyroglobulin Ab 1600 x and microsome Ab 3200 x. A cervical lymphnode specimen exhibited typical histologic picture of IBL like T cell lymphoma. The surface markers of lymphoma cells were CD2(+), CD8(+) and CD4(-). Chromosomal analysis of these cells revealed polyploidy abnormality for all chromosomes except for No. 14's which are disomy. All lymphoma cells have XXY sex chromosome and mar1, mar2, mar3. Gene rearrangement for beta-chain of T cell receptor was proved in these lymphoma cells. He was treated with prednisolone, vincristine, cyclophosphamide, adriamycin etc, but died of respiratory failure 171 days after admission. We reported a rare case of IBL like T cell lymphoma with polyploidy chromosomal abnormality accompanied with hemolytic anemia.

Anemia, Hemolytic↗

[Acute megakaryoblastic leukemia with complex chromosomal aberrations].

A case of acute megakaryoblastic leukemia with complex chromosomal aberrations is reported. A 63-year-old man was admitted to our hospital because of pancytopenia. Bone marrow aspiration resulted in a dry tap and biopsy showed hypoplastic marrow with fibrosis. Blast cells in the peripheral blood were identified as megakaryoblasts because they were positive for electron microscopic platelet peroxidase (PPO). In addition, monoclonal antibody, TP80, to platelet glycoprotein II b-III a reacted with in about 26% of the blast cells. Chromosomal analysis of the peripheral blood revealed a mosaic pattern of a normal karyotype and abnormal ones, including 44, XY, -5, -7, -18, 10q-, +marker.

Chromosome Aberrations↗

Serum glutathione-S-transferase-pi as a tumor marker for gastrointestinal malignancies.

A glutathione-S-transferase-pi (GST-pi) immunoradiometric assay was devised as a potential marker for serodiagnosis of malignant disease. Elevated serum GST-pi levels were observed in patients with various gastrointestinal malignancies including gastric, esophageal, colonic, pancreatic, hepatocellular, and biliary tract cancers. Patients with benign gastrointestinal diseases had normal GST-pi, but some patients with chronic hepatitis and cirrhosis had slightly elevated levels. Over 80% of patients with Stage III or IV gastric cancer and even about 50% of those with Stage I and II had elevated serum GST-pi. After surgery serum GST-pi levels returned to normal. Resected stomach cancers were immunohistochemically positive for GST-pi. During chemotherapy of colonic, gastric, and hepatocellular cancers with a series of different drugs, GST-pi changed in a biphasic manner; increases during initial phases of therapy may reflect acquisition of drug resistance by the tumor. In general, serum GST-pi assays provide a sensitive and reliable marker for gastrointestinal malignancies.

Biomarkers, Tumor↗

[A case of cutaneous T cell lymphoma improved with local administration of tumor necrosis factor].

A 63-aged woman with cutaneous T cell lymphoma successfully treated with local administration of tumor necrosis factor (TNF) was reported. She was admitted to our hospital because of tumors and subcutaneous nodules on her bilateral inner thigh. A pathological study of her skin of right inner thigh showed mononuclear atypical cells with hyperlobulated nuclei. In peripheral blood the same lymphoid cells were found. Immunohistochemical staining of these cells was positive for OKT-3 and OKT-4, but negative for OKT-8. No lymph node swelling and no visceral involvement were detected by a CT scan and a Echography of the chest and the abdomen. A diagnosis of cutaneous T cell lymphoma was made (stage IIb TNM classification). Although the chemotherapy of VEPA and CHOP was done, about 70% (PR) of the bilateral inner thigh tumors were retracted. Owing to the interstitial pneumonia aroused in the period of bone marrow suppression and cardiomyopathy after chemotherapy, we gave up further systemic chemotherapy. And then the local administration of TNF was done and the disappearance of the bilateral inner thigh tumors was obtained. Our therapy with local administration of TNF for CTCL in the first report.

Antineoplastic Combined Chemotherapy Protocols↗

Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach.

Human gastric carcinomas were tested for their immunohistochemical reactivity with anti-type I procollagen antiserum. In all specimens of scirrhous carcinomas, staining of the tumour cells was strongly positive, while in medullary carcinomas staining of the tumour cells was generally poor. These results suggest that the tumour cells in scirrhous carcinomas produce collagen in their stroma.

Adenocarcinoma, Scirrhous↗

Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201-995).

A case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201-995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long-term treatment with SMS 201-995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.

Female↗

Quantitation and characterization of serum transferrin receptor in patients with anemias and polycythemias.

Serum transferrin receptor concentration in patients with anemias and polycythemias was determined. The mean normal value was 258 +/- 82 ng/ml. Comparing with normal values, the higher values were obtained in patients with iron deficiency anemia, autoimmune hemolytic anemia, and polycythemias, while the lower values were obtained in patients with aplsatic anemia. During treatments of patients with iron deficiency anemia and autoimmune hemolytic anemia, serial change of serum receptor was paralleled with that of peripheral reticulocyte counts, suggesting that the circulating receptor values may reflect the activity of bone marrow erythropoiesis. The immunoreactive receptor was migrated at the position of alpha 1-globulin by agarose gel electrophoresis and the isoelectric point(pl) was 3.57 by isoelectric focusing. SDS-polyacrylamide gel electrophorogram of various patients' sera revealed that the autoradiographed band was migrated at the molecular weight of 110,000 daltons in the non-reducing condition and 46,000 and 23,000 daltons in the reducing condition. These bands were also capable of binding to 131I-labelled diferric transferrin. The proposed model of circulating transferrin receptor may be the nicked dimers of 55,000 daltons in which inter- and intra-disulfide bridges were present.

Anemia↗

Growth promoting activity of PDGF, EGF and TGF-beta on highly metastatic subline of Meth A cells.

The response of a highly metastatic cell line of methylcholanthrene induced A fibrosarcoma (Meth A) to growth factors from platelets was examined. The highly metastatic cell subline (MH) proliferated more rapidly than its parental counterpart cell subline (ML) in a medium containing platelet lysate. However, when the three major growth factors from platelets, ie, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta (PDGF, EGF, TGF-beta), were independently examined for their growth promoting activity, the former 2 growth factors preferentially stimulated the proliferation of ML and the latter growth factor rather suppressed the growth of both cells. On the other hand, the combined effects of these factors were more marked on MH. This combination effect was supported by the evidence that the number of receptors for EGF (which is probably an essential growth factor for the Meth A cell) was increased by pretreatment with PDGF or TGF-beta. Thus, the highly metastatic cells of MH were considered to be the most susceptible to growth factors released from platelets. This conclusion is consistent with the concept that platelets may play an important role in the formation of blood-borne metastasis by releasing growth factors to promote the proliferation of tumor cells, following aggregation with tumor cells.

Animals↗

[Property of scirrhous carcinoma of the stomach defined by collagen metabolism].

Scirrhous carcinoma of the stomach is characterized by the extensive deposition of collagen in the desmoplastic stroma. In the present study, we examined which cell types are responsible for the synthesis of collagen in tissue of scirrhous carcinoma. Furthermore, a RIA for carboxyterminal peptide of human type I procollagen (type I C-peptide) was developed and its clinical implication for serodiagnosis of scirrhous carcinoma of the stomach was evaluated. 1) The immunohistochemical localization of type I procollagen was investigated employing an antibody to procollagen. Strong staining was observed in the cytoplasma of scirrhous carcinoma cells. Furthermore northern blot technique using c-DNA probe of type I procollagen was performed. Tumor cells established from scirrhous carcinoma (KATO III) were expressing mRNA-procollagen type I as revealed by this technique. Thus in scirrhous carcinoma of the stomach, at least some portion of the increased collagen content is due to production by the tumor cells. 2) In scirrhous carcinoma of the stomach, serum type I C-peptide level appeared to increase, while in non-scirrhous carcinoma, serum type I C-peptide level stayed within normal range. Serum type I C-peptide levels corresponded to clinical course who underwent either operation or chemotherapy. Collectively, the measurement of serum type I C-peptide concentrations will provide a new means for diagnosis and monitoring the scirrhous carcinoma of the stomach.

Adenocarcinoma, Scirrhous↗

Expression of TGF-beta gene in adult T cell leukemia.

Peripheral mononuclear cells from adult T cell leukemia (ATL) patients were analyzed in comparison with other types of leukemia cells, for the expression of transforming growth factor-beta (TGF-beta) mRNA, for the presence of TGF-beta activity (colony stimulating activity for normal rat kidney fibroblasts [NRK]) in conditioned medium and for their susceptibility to exogenous TGF-beta. Highly elevated TGF-beta mRNA levels were observed in all five ATL cell samples tested; however, in three acute myelogenous leukemia (AML) samples, in one acute lymphatic leukemia (ALL), and one chronic myelogenous leukemia (CML), TGF-beta expression was relatively lower. In normal peripheral mononuclear cells TGF-beta mRNA was weakly detectable. Colony stimulating activity for NRK found in the conditioned medium from ATL cells as well as other leukemia cells correlated well with the levels of TGF-beta mRNA expression. In all three ATL samples tested, stimulation of 3H-thymidine uptake by purified TGF-beta from platelets was apparent. These results suggest that ATL cells are secreting active TGF-beta in a relatively high amount, as compared with other leukemia cells, and may proliferate in response to the factor via an autocrine manner. Furthermore, considering that TGF-beta stimulates bone resorption, we can speculate that the relatively high amount of TGF-beta in ATL cells contributes to the hypercalcemia frequently seen in ATL patients.

Cell Division↗

[Targeting chemotherapy with transferrin-neocarzinostatin conjugate].

In efforts to obtain preferential uptake of anticancer agents into tumors, we explored the possibility of delivering such agents by transferrin receptor-mediated endocytosis. Human diferric transferrin was conjugated with neocarzinostatin (NCS) using N-succinimidyl 3-(2-pyridyldithio)-propionate. This conjugate is capable of binding to the transferrin receptor and is internalized by endocytosis. The inhibitory effect of the conjugate on cell growth was remarkable when a human colorectal cancer cell line, M7609 was used as a target in vitro. In addition, in vivo efficacy of the conjugate in inhibiting the growth of M7609 cells implanted subcutaneously into nude mice was also observed when the conjugate was administered through a tail vein. The observed toxicity was a transient decrease in the red blood cell count, which returned to normal within 14 days. The half disappearance time of the conjugate was 55 min, while that of free NCS was 7 min. No serious side effects with regard to liver or kidney function were detected. This conjugate is an appropriate model for the receptor-mediated delivery of ligand-drug complex and may be useful for future clinical application.

Animals↗

[Induction of LAK cells by high density dialyzing culture device and its cytotoxicity].

Lymphokine activated killer (LAK) cells are generated by culture of lymphocytes with interleukin 2 (IL-2) in short term culture (3 to 5 days) and are used for adoptive immunotherapy for advanced cancer patients. The culture condition hitherto reported are essentially based on the rotating culture system, in which the maximum cell density was at 2 X 10(6) cell/ml and the cell recovery was usually less than 100%. The inability to induce LAK cells efficiently in vitro made the culturing of cells for therapy rather difficult and costly work because the mean infusion dose of LAK cells of one patient requires more than 1 X 10(10)/ml. We have therefore attempted to culture lymphocytes in 10 times higher concentration comparing with conventional methods. By using a new dialyzing culture system under continuous regulation of the amount of infused IL-2, nutrition medium, and pO2 and pCO2, we could culture cells at 2 X 10(7)/ml for more than 21 days and the resulted LAK cells showed a 100 times increase of activity on a per cell basis. By limiting dilution procedure, these killer cells mostly express T cell markers such as CD3 and CD8 but dose not express CD16.

Cell Division↗

Effect of combined administration of a prostacyclin analogue and adriamycin against the artificial metastasis of Meth A cell.

Antimetastatic effect of a stable prostacyclin analogue (PGI2-TEI8153) in combination use with adriamycin (ADM) was investigated. Meth A cell, which had membrane protein of 18,000 daltons specifically bound to platelets, induced platelet aggregation dose-dependently. This platelet aggregation was totally suppressed by PGI2-TEI8153. PGI2-TEI8153 also suppressed the pulmonary arrest as well as pulmonary metastasis of Meth A cells. Combined use of PGI2-TEI8153 and ADM exerted much less antimetastatic effect than that with PGI2-TEI8153 alone, indicating the counteracting effect of ADM against the PGI2-TEI8153. However, this combination use brought about additive antimetastatic effects with 2-fold reduction of pulmonary nodules compared to that of ADM alone. Consequently, even the anticancer drug itself has a negative influence on metastasis, the combined use of PGI2-TEI8153 with it is promising for the prevention of metastasis.

Animals↗

Externalization of transferrin receptor in established human cell lines.

The externalization of transferrin receptors was found in established human tumor cell lines at the rate of 10-35 ng/hour/10(6) cells, when they were incubated with transferrin at 37 degrees C. This externalization is inhibited by lowering the incubation temperature to 4 degrees C or eliminating the ligand from the culture medium. Metabolic inhibitors such as sodium azide, colchicine, cytochalasin B and chloroquine also decreased the rate of externalization. Almost 95% of released transferrin receptors were precipitated by centrifugation at 100,000 x g for 30 min, suggesting that transferrin receptor is externalized into the medium as a vesicular form.

Biomarkers, Tumor↗