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Biomedical subjects

I Tsuboi

Publications and source records attributed to I Tsuboi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Nonsteroidal anti-inflammatory drugs differentially regulate cytokine production in human lymphocytes: up-regulation of TNF, IFN-gamma and IL-2, in contrast to down-regulation of IL-6 production.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known as immunoregulators, but the mechanisms of their action are not fully explained by the inhibition of PG synthesis. We have investigated the effect of NSAIDs on cytokine production in human PBMC and T cell clones (TCC). NSAIDs up-regulated TNF, IFN-gamma and IL-2 production at both the mRNA and protein levels, and IL-12 expression at the mRNA level. In contrast, NSAIDs down-regulated IL-6 production both at the mRNA and protein levels, and down-regulated IL-4 mRNA expression. The modulation at the mRNA level became detectable 1 h after culture. This modulation was also observed at the level of TCC. Indomethacin (IM) enhanced TNF production in all the eight TCC that were established from a patient with human T lymphotrophic virus type 1 uveitis or pulmonary sarcoidosis, and suppressed IL-6 production in six of the eight TCC, without affecting their low levels of PGE2 production. IM also enhanced TNF and suppressed IL-6 production, respectively, in both IL-2-activated PBMC and IL-2-dependent NK cell line, with the inhibition of their high levels of PGE2 production. Culture with PGE2 alone suppressed TNF production by three of the six TCC and NK cell lines, which was neutralized by addition of IM. It had, however, no effect on TNF production by the remaining three TCC or IL-2-activated PBMC. The effects of PGE2 on IL-6 production also varied among TCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic virus type 1 and human immunodeficiency virus type 1 infections.

In serum, the enzyme adenosine deaminase (ADA) is known to be divided into two isoenzymes, ADA1 and ADA2, which have different molecular weights and kinetic properties. The present study investigated ADA isoenzyme levels in the sera of patients infected with retroviruses associated with adult T-cell leukemia (ATL), human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), and AIDS, ADA isoenzyme activities were found to be significantly (P < 0.001) higher in the sera of patients with ATL, HAM, and AIDS than in the sera of healthy controls. In the case of the ADA subtypes in the sera of patients with ATL, ADA1 activity was significantly (P < 0.001) elevated in patients with the acute and lymphoma types of ATL compared with that in patients with the chronic and smoldering types of ATL. ADA2 activity was significantly elevated in the sera of patients with the acute, lymphoma, and chronic types of ATL (P < 0.001) compared with that in patients with smoldering ATL and HTLV-1 carriers. In the case of patients with human immunodeficiency virus type 1 (HIV-1) infection, ADA1 and ADA2 activities in the sera of patients with AIDS and HIV-1 antibody-positive individuals were significantly (P < 0.001) higher than those in the sera of HIV-1 antibody-negative individuals. A significant elevation in ADA2 activity was also seen in the sera of AIDS patients (P < 0.01) compared with that in the sera of HIV-1 antibody-positive individuals. These results suggest that the magnitude of elevation of ADA isoenzyme levels in serum correlates well with the clinical conditions of the patients with these diseases. Measurement of the activities of ADA isoenzymes may therefore provide an additional parameter for distinguishing the subtypes of ATL and may prove to be useful as prognostic and therapeutic monitors in diseases associated with HTLV-1 and HIV-1 infections.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Long term remission following relapsed CNS lymphoma].

A case of NHL which has been in long-term remission following vigorous treatment for CNS relapse with intrathecal administration of Ara-C and focal irradiation to the brain is presented. The patient was a 61-year-old man, who was successfully treated with CHOP followed by MACOP-B for diffuse large cell NHL in 1988. Five months later he was admitted to our hospital because of loss of visual acquity and numbness in the right upper and lower extremities. The presence of lymphoma cells in CSF, abnormal shadow in the left frontal lobe on a cranial CT scan and MRI scan, and positive Ga scintigraphy yielded a diagnosis of CNS relapse of NHL. Twenty one whole brain and additional 1.0Gy to the left frontal lobe of irradiation were performed. Eight days later the left tumor disappeared. Neurological remission was obtained and has continued until now.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Daily oral low-dose etoposide therapy for aged patients with relapsed aggressive lymphoma].

Two patients with relapsed Non-Hodgkin's lymphoma (NHL) were treated with oral administration of etoposide. In these patients, long-term hematological remission was obtained. One patient was a 76-year-old man, who was successfully treated with CHOP for diffuse large cell NHL stage III B. One year after obtaining CR, he was admitted to our hospital for enlargement of lymph node. Rebiopsy of lymph node made a diagnosis of relapse from NHL. A new regimen of oral administration of etoposide treatment was employed. Hematological remission was obtained and continued for 3 years. Without interfering with his quality of life. The other patient was a 74-year-old man, who was treated with 6 cycles of CHOP for diffuse large cell NHL stage IV B. The patient attained complete remission following an additional 2 cycles of COMLA therapy. Eight years later, he was admitted for enlargement of lymph node. Rebiopsy of lymph node provided the basis for a diagnosis of relapse from NHL. Oral administration of etoposide treatment was started. Hematological remission was obtained and has been continued until now. These results show that oral administration of etoposide treatment is effective for some patients with recurrent NHL.

Aged↗
PubMed1994

Age-related decreases in the reconstituting ability of hemopoietic cells and the ability of hemopoietic microenvironment to support hemopoietic reconstitution in senescence accelerated (SAM-P) mice.

The effect of the aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to the reconstituting ability of hemopoietic cells and the ability of the microenvironment to support hemopoietic reconstitution was investigated by bone marrow transplantation (reconstitution assay). When the bone marrow cells, obtained from young or old mice, were transplanted to lethally irradiated young SAM-P mice no difference in the reconstituting pattern of femoral spleen colony-forming units (CFU-S), splenic CFU-S and splenic granulocyte macrophage colony-forming units (CFU-GM) was observed between the mice transplanted with young and old donor cells. However, the reconstitution of femoral CFU-GM in mice transplanted with old donor cells was delayed compared to that in mice transplanted with young donor cells. Moreover, the recovery of WBC in mice transplanted with old donor cells was noticeably delayed. When the bone marrow cells obtained from young mice were transplanted to young or old recipient mice, no difference in the reconstituting pattern of femoral CFU-S and CFU-GM as well as splenic CFU-S and CPU-GM was observed between young and old recipient mice. However, the recovery of WBC in old recipient mice was noticeably delayed. These data indicate that the functions of both the hemopoietic cells and the hemopoietic microenvironment deteriorated with age in SAM-P mice.

Aging↗
PubMed1994

Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus.

Adenosine deaminase (ADA) is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) is not yet characterized. We measured the serum levels of ADA isoenzymes (ADA1 and ADA2) in healthy donors (HD, n = 52), insulin-dependent diabetes mellitus (IDDM, n = 53) patients and non-insulin-dependent diabetes mellitus (NIDDM, n = 65) patients. The mean serum level of ADA1 in HD, IDDM or NIDDM patients was, respectively 6.5, 8.1 or 9.5 units/l (P < 0.001 vs. HD) and that of ADA2 in HD, IDDM or NIDDM patients was 7.0, 14.9 (P < 0.001 vs. HD) or 11.2 units/l (P < 0.001 vs. HD), respectively. Normalization of the blood glucose level by the hospitalization was associated with the decrease in ADA2 (but not ADA1) activity in 6 of 8 IDDM or 11 of 12 NIDDM poorly controlled patients. ADA2 (but not ADA1) activity in the poorly controlled NIDDM patients directly correlated with the hemoglobin A1c level (P < 0.002). Measurement of serum ADA2 activity may be important to better understand the clinical aspects of both IDDM and NIDDM. The pathogenic role of elevated ADA activity in the sera of DM patients was addressed.

Adenosine Deaminase↗
PubMed1994

[Massive skeletal invasion in Hodgkin's disease observed by MRI].

A 35-year-old female developed cervical adenopathy and mediastinal tumor in 1988. A lymph node biopsy specimen showed nodular sclerosing Hodgkin's disease. She received combination chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisolone, and radiotherapy for mediastinal tumor. She had a complete remission (CR). In September 1990, she developed swelling of the left hip and felt pain in the left hip and thigh. She also noticed swelling of the left inguinal lymph nodes. MRI T2-weighted images showed enlargement and destruction of the fascia and hyperintense signal of the left iliac and gluteus muscle. A biopsy specimen of the inguinal lymph node showed recurrence of Hodgkin's disease of mixed cellularity. She received salvage therapy with ifosfamide, methotrexate, etoposide and procarbazine, and achieved a second CR. The clinical appearance of the skeletal muscle involvement by lymphoma is uncommon, especially in Hodgkin's disease.

Adult↗
PubMed1993

Isolation and characterization of a sialic acid-specific binding lectin from the hemolymph of Asian horseshoe crab, Tachypleus tridentatus.

A lectin was isolated from the hemolymph of Asian horseshoe crab Tachypleus tridentatus by using glycophorin HA affinity chromatography and Sephacryl S-300 gel filtration. The lectin's molecular weight was approx. 533 kDa; being a simple protein comprised of two non-identical subunits with molecular weights of 30 and 32 kDa. The hemagglutinating activity of the lectin against equine erythrocytes was strongly inhibited by several sialoglycoproteins and weakly inhibited by sialic acid, although not inhibited by neutral sugars, hexosamines, N-acetylhexosamines, glucuronic acid, or several asialoglycoproteins. In addition, glycophorin HA was more effective than glycophorin HA digested with trypsin in inhibiting hemagglutination of the lectin. These results suggest that the purified lectin specifically reacts with sialic acids containing glycoprotein.

Animals↗
PubMed1993

Isolation and characterization of a sialic acid-specific lectin from hemolymph of the Southeast Asian horseshoe crab Tachypleus gigas.

A lectin was isolated from hemolymph of the Southeast Asian horseshoe crab Tachypleus gigas by using glycophorin HA affinity chromatography and Sephacryl S-300 gel filtration. The purified lectin had a molecular mass of approximately 396kDa and was composed of 13 identical subunits with molecular masses of 31 kDa. The serological specificity of the purified lectin was specifically inhibited by sialic acids sialoglycoproteins, but not by neutral sugars, hexosamines, N-acetylhexosamines, or asialoglycoproteins. Although the N-terminal amino acid sequence of the lectin from T. gigas was identical to that from American horseshoe crab (liphemin) by the same purification method and cross reacted with the anti-liphemin serum, the calcium concentration of hemagglutinating activity of the purified lectin showed a smaller optimal concentration than that of liphemin.

Amino Acid Sequence↗
PubMed1992

Treatment of diffuse non-Hodgkin's lymphoma with combined chemotherapy using methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin (MACOP-B).

Forty-nine previously untreated adult patients with diffuse non-Hodgkin's lymphoma were treated with MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin) between December 1986 and December 1990. Forty patients (82%) achieved a complete response (CR), three (6%) a partial response (PR), while four (8%) had either no response or progression of disease, one (2%) patient ceased MACOP-B therapy and received other chemotherapy because of sustained neutropenia, and one patient (2%) died of sepsis during therapy. The factors that adversely affected the CR rate were by stage IV, the presence of B symptoms, the presence of a large mass (greater than 5 cm), and low serum total protein level. The 4-year survival for all 49 patients was 70% and the 4-year disease-free survival (DFS) for the 40 CR patients was 77%. Relapses were higher in patients whose initial serum lactic dehydrogenase (LDH) level was higher than 660 IU/1 (DSF 89% vs. 49%). Toxicity was substantial but acceptable, with neutropenia and mucositis proving to be the most frequent severe side-effects. These preliminary results confirmed the effectiveness of MACOP-B therapy for diffuse non-Hodgkin's lymphoma.

Adolescent↗
PubMed1991

Rapid method for preparing a beta-glucan-specific sensitive fraction from Limulus (Tachypleus tridentatus) amebocyte lysate.

By separating Limulus amebocyte lysate by cation-exchange chromatography with an SP-Toyopearl 650C column, a fraction insensitive to endotoxin, yet specifically sensitive to beta-glucan, was successfully obtained in the unadsorbed portion. This fraction showed beta-glucan dose-dependent clotting enzyme activity, although no sensitivity to endotoxin. This beta-glucan-dependent reaction showed no interference in the presence of endotoxin, with the fraction also showing sensitivity towards various kinds of beta-glucan, i.e. curdlan, pachyman, laminaran and lichenan. The sensitivity towards curdlan was approximately 10(-10) g/ml.

Animals↗
PubMed1991

In vivo effect of a large amount of allogeneic granulocytes on reconstitution of hemopoietic cells of irradiated mice.

The in vivo effects of allogeneic granulocytes on the reconstitution of splenic and bone marrow CFUs and CFUc numbers were investigated using irradiated mice. When allogeneic granulocytes were intraperitoneally injected into irradiated BDF1 mice (260 rads), the reconstitution of CFUs in both spleen and bone marrow as well as the hematocrit were enhanced, while the reconstitution of splenic or bone marrow CFUc numbers was transiently suppressed and then enhanced. The magnitude of enhancement was dose-dependent. These results suggest that granulocytes injected into irradiated mice might act as enhancing effectors on the in vivo reconstitution of hemopoietic cells.

Animals↗
PubMed1991

Effects of irradiation on marrow stromal cells with respect to committed granulocyte-macrophage progenitor cells.

The effects of irradiation on the growth regulatory function of marrow stromal cells (MSC), and on the committed granulocyte-macrophage progenitor cells (GM-CFC), were investigated using a liquid culture system. CSF activity in the supernatant of irradiated MSC (0-900 rads) increased markedly with the increase of MSC irradiation dose. CSF-inhibitory activity in the supernatant of irradiated MSC (0-900 rads) also increased with the increase of MSC irradiation dose. Furthermore, the activity of exogenous CSF added to the supernatant of 900 rad-irradiated MSC was lost more slowly than that of non-irradiated MSC. These data suggest that irradiation affected CSF production, inhibitor production and consumption of CSF by MSC.

Animals↗
PubMed1991

Age-related changes in various hemopoietic progenitor cells in senescence-accelerated (SAM-P) mice.

The effect of aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to numbers of hemopoietic progenitor cells was investigated. The numbers of femoral granulocyte-macrophage colony-forming cells (CFU-GM), mast cell progenitors (mast colony-forming units, CFU-Mast), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) in old mice (30-35 weeks old) decreased to 96%, 81%, 83%, and 87% of those of young mice (8-12 weeks old), respectively. The numbers of femoral fibroblast colony-forming cells (CFU-F) in old mice increased to 315% of those of young mice. The numbers of splenic CFU-GM, CFU-Mast, BFU-E, and CFU-E in old mice decreased to 7%, 43%, 25%, and 40% of those of young mice, respectively. In contrast, significant changes in these progenitor cells were not observed in the bone marrow. These findings suggest that the effect of the aging process on hemopoietic tissues in SAM-P mice is predominantly in the spleen.

Aging↗
PubMed1990

Colony promoting activity: differences from interleukin-3 and similarities to interleukin-6.

The supernatant of long-term bone marrow culture contains colony promoting activity (CPA) which does not have granulocyte-macrophage colony stimulating activity (CSF) but which enhances granulocyte-macrophage (GM) colony formation in the presence of CSF. CPA might consist of IL-3 or IL-3-like activity, since CPA stimulates proliferation and differentiation of more immature cells to CSF-responding granulocytes-macrophage progenitors (GM-CFC), and since IL-3 also stimulates immature hemopoietic cells to proliferate and differentiate to functional blood cells. IL-1 and IL-6 are also known to enhance GM colony formation. One or both of these molecules can accordingly be another candidate for CPA. In the present study, GM-CSF activity of IL-3 was dependent on the batch of serum: it was negative in the presence of fetal calf serum, but positive in the presence of horse serum. In contrast, GM-CSF and CPA showed no such dependence on the batch of serum. The addition of IL-3 to GM colony assay system did not enhance but rather suppressed GM colony formation. The supernatant of long-term bone marrow culture which contains substantial levels of CPA did not stimulate proliferation of IL-3 dependent DA-1 cells, but facilitated the proliferation of IL-6 dependent, MH60.BSF2 cells. No detectable level of IL-1 activity was found in the supernatant. These results indicate that CPA is different from IL-1, IL-3 or GM-CSF, but similar to or the same as IL-6.

Animals↗