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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 181 records · Page 10Linked to original sources
PubMed1995

Nicotine raises the influx of permeable solutes across the rat blood-brain barrier with little or no capillary recruitment.

Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (lCBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K1) and permeability-surface area (PS) products of [14C]antipyrine and [14C]-3-O-methyl-D-glucose (3OMG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of significantly increased PS products supports the capillary recruitment hypothesis. In 17 of 44 areas, nicotine treatment increased lCBF by 30-150%, K1 of antipyrine by 7-40%, K1 of 3OMG by 5-27%, PS product of antipyrine by 0.20% (mean 7%), and PS product of 3OMG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K1 of antipyrine were significant, whereas those in K1 of 3OMG and in PS for both antipyrine and 3OMG were not statistically significant. The lack of significant changes in PS products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capillaries were recruited and (b) blood flow within brain capillary beds rises by elevating linear velocity. The K1 results indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moderately permeable substances, and negligibly change those of solutes with extraction fractions of < 0.2, thereby preserving the barrier function of the blood-brain barrier.

3-O-Methylglucose↗
PubMed1995

Identification of a novel phospholipase C family gene at chromosome 2q33 that is homozygously deleted in human small cell lung carcinoma.

Since a considerably high incidence of allelic loss on chromosome 2q was detected in lung carcinoma and a homozygous deletion at chromosome 2q33 was detected in a small cell lung carcinoma cell line, NCI-H82, a novel tumor suppressor gene has been suggested to be present in this chromosomal region. In the present study, we constructed a cosmid contig map covering the homozygous deleted region, which was estimated as being 220 kbp in size, and identified a gene from the deleted region. All of the coding exons of this gene were homozygously deleted in this cell line, while a 5'-non-coding exons was retained. Since the gene encodes a protein with striking similarity to several members of a family of phospholipase C, we designated this gene as PLC-L (phospholipase C-deleted in lung carcinoma). The PLC-L gene was expressed in a variety of fetal and adult organs including the lung. However, its expression was greatly reduced in seven of 13 (53.8%) of small cell lung carcinoma and 13 of 15 (86.7%) of non-small cell lung carcinoma cell lines. Since its homology to phospholipase C genes suggests the involvement of the PLC-L gene in inositol phospholipid-based intracellular signaling cascade, it is possible that aberrant expression of the PLC-L gene contributes to the genesis or progression of human lung carcinoma.

Amino Acid Sequence↗
PubMed1995

High serum levels of granulocyte-macrophage colony-stimulating factor in patients with liver cirrhosis and granulocytopenia.

Leucopenia is often observed in patients with liver cirrhosis. We measured levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with liver cirrhosis by a sensitive enzyme linked immunosorbent assay. Eight out of 22 patients with liver cirrhosis had detectable serum GM-CSF (range, 55 to 245 pg/ml:mean, 135 pg/ml). Serum GM-CSF was detected in all patients with a granulocyte count below 2.0 x 10(9)/l, but in only one patient with a granulocyte count above 2.0 x 10(9)/l. Haemoglobin concentration, platelet count, serum albumin, total bilirubin and aminotransferase levels did not correlate with serum GM-CSF levels. These findings may reflect a feedback mechanism between the number of circulating granulocytes and serum GM-CSF levels in patients with cirrhosis.

Adult↗
PubMed1995

[Inhibitory effects of interleukin (IL) -10 and viral IL-10 (vIL-10) on the functions of monocytes/macrophages].

In this study, we examined the effects of IL-10 and vIL-10 on the production of superoxide anion (O2-) and nitric oxide (NO) by human monocytes and mouse macrophages. At an optimal concentration, human IL-10 (hIL-10) and vIL-10 significantly inhibited the production of interferon (IFN)-gamma by stimulated human peripheral blood mononuclear cells (PBMNCs). They also efficiently inhibited the production of O2- by both unstimulated and IFN-gamma-activated human monocytes. Mouse IL-10 (mIL-10) also significantly inhibited the production of NO by lipopolysaccharide (LPS) and IFN-gamma-stimulated mouse peritoneal macrophages. Moreover, the production of O2- and NO was effectively suppressed whether the IL-10 was added before or together with the stimulus, indicating that this cytokine acts primarily at an early stage of monocyte/macrophage activation by IFN-gamma and LPS. We also examined the effects of IL-4 and transforming growth factor (TGF)-beta on the production of O2- and NO by human monocytes and mouse macrophages, and found that they significantly inhibited both the production of O2- by human monocytes and the production of NO by mouse macrophages. Moreover, a combination of any two of IL-10, IL-4 and TGF-beta caused an additive effect on the inhibition of O2- production by human monocytes. These results indicated that IL-10 suppresses monocyte/macrophage activation either indirectly via an inhibition of the synthesis of IFN-gamma, a potent monocyte/macrophage activator, by PBMNCs, or directly via the deactivation of monocytes/macrophages. Moreover IL-10 may act in concert with IL-4 and TGF-beta to suppress monocyte/macrophage activation in vivo.

Animals↗
PubMed1995

Granulocyte colony-stimulating factor mobilizes primitive hematopoietic stem cells in normal individuals.

We studied the hematopoietic activity of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony-stimulating factor (G-CSF) using semisolid and long-term culture systems (LTC) in 5 normal individuals. Following 2 or 3 daily subcutaneous injections of G-CSF (filgrastim; 1.5 micrograms/kg), not only committed progenitors including CFU-GM, BFU-E, and CFU-Mix, but also long-term culture initiating cells (LTC-IC) were increased in the peripheral blood. When the cells derived from CFU-GM, BFU-E and CFU-Mix colonies were replated for secondary colony formation, a minor fraction of CFU-GM and CFU-Mix colonies formed after 3 days of G-CSF stimulation in vivo could produce secondary colonies. Moreover, the replating capacity of primary colonies from 5-week-old LTC initiated after 3 days of G-CSF stimulation was increased compared to that from 5-week-old LTC initiated in a 'steady-state'. These observations indicate that G-CSF can mobilize very primitive progenitors (LTC-IC) along with committed progenitors into the circulation and suggest that some of these G-CSF-mobilized progenitors may retain self-renewal capacity.

Adult↗
PubMed1995

[Endotoxin eliminating therapy in patients with severe sepsis--direct hemoperfusion using polymyxin B immobilized fiber column].

BACKGROUND AND METHODS: PMX is a blood purifier containing chemically immobilized polymyxin B fiber (PMX-F). To evaluate its effectiveness on the severe septic human, direct hemoperfusion (DHP) using a PMX-F was performed for 2 hours. The changes in various circulatory parameters, symptoms of septic shock, and blood endotoxin concentration and the survival rate, were evaluated. RESULTS: DHP was performed 61 times in 42 patients, of whom 38 had septic MOF, 25 with gram-negative bacterial infection. At the initiation of this treatment, 33 patients were receiving vasoactive agents, and 36 were under artificial ventilation via endotracheal intubation. The mean septic severity score (SSS) in all patients was about 46.6. Twenty-two of the 42 survived. The endotoxin concentration (mean +/- S.E.; pg/ml) was 85.0 +/- 27.2 immediately before treatment but significantly decreased to 57.5 +/- 28.4 after treatment (n = 50) and to 28.2 +/- 4.4 on the next day (n = 23) (p < 0.01). The endotoxin concentrations at the inlet and outlet of the PMX also significantly decreased 30 minutes after the initiation of DHP. Circulatory parameters, BP, CI, SVR and Vo2I demonstrated significant improvement. Body temperature also showed the same results. The removal of endotoxin in the blood using PMX was effective for severe sepsis or septic MOF. Various symptoms due to endotoxin was alleviated after this treatment.

Adolescent↗
PubMed1995

Structure of the most superficial layer of articular cartilage.

We studied the most superficial layer of macroscopically normal articular cartilage obtained from human femoral heads, using polarising microscopy and SEM. The most superficial layer, 4 to 8 microns thick, was acellular consisting of collagen fibrils. This layer could be peeled away as a thin film, with no broken collagen fibrils on its inferior surface or on the surface of subjacent cartilage layers. The orientation and diameter of collagen fibrils were different on these two surfaces. Our findings suggest that the most superficial layer is an independent one which is only loosely connected to the fibrous structure in the layer deep to it.

Cartilage, Articular↗
PubMed1995

[Oxygen transport pattern in burned patient with sepsis under inotropic support].

Hemodynamic and oxygen-kinetic data of 16 burn patients with sepsis were analysed to explore relationship between oxygen transport pattern and clinical outcome after dopamine and dobutamine therapy. Two patterns of oxygen transport were shown in the 16 patients. Of them, ten (62.5%) had optimal DO2 and VO2 values (model I), and six (37.5%) had lower DO2 and VO2 values than the optimal (model II). All of 6 patients with model II developed lactic acidosis, septic shock and MOF and died. Two of 10 patients in model I developed MOF, only one died. The results indicate that, in burn patient with sepsis, the decreased response of DO2 and VO2 to inotropic therapy suggests failure of tissue perfusion, oxygen extraction and utilization, and may possibly predict the outcome.

Adolescent↗
PubMed1994

G-CSF induces tyrosine phosphorylation of the JAK2 protein in the human myeloid G-CSF responsive and proliferative cells, but not in mature neutrophils.

Granulocyte colony-stimulating factor (G-CSF) stimulates a rapid phosphorylation on tyrosines of several proteins of Mr. 130, 100, 90, 70, 44 kd in human myeloid leukemia cell line cells, Kasumi-1, which respond to G-CSF to proliferate in vitro. In HL60 cells, only a 100 kd protein was phosphorylated, and no detectable phosphorylated proteins were observed in neutrophils by the stimulation of G-CSF. Among these proteins, the 130 kd protein was immunoprecipitated by anti- JAK2 serum. While JAK2 is a non receptor tyrosine kinase and is reported to be involved in the signal transduction by various cytokines including growth hormone, erythropoietin, and granulocyte-macrophage colony-stimulating factor/interleukin-3, it is strongly suggested that a signaling pathway that relates to the cell proliferation triggered by G-CSF in immature hematopoietic cells also involves JAK2.

Cell Division↗
PubMed1994

Surface phenotype and Ig heavy-chain gene usage in chronic B-cell leukemias: expression of myelomonocytic surface markers in CD5- chronic B-cell leukemia.

We investigated the surface expression of leukocyte differentiation antigens and the Ig heavy-chain variable region (VH) gene family use in leukemic cells from 26 Japanese patients with chronic B-cell leukemias with special reference to CD5 antigen expression. CD5 was expressed on leukemic cells in 21 of 26 cases (CD5+) but not in 5 cases (CD5-). Myelomonocytic marker, CD13 antigen was expressed on the leukemic cells in all 5 CD5- cases but in none of CD5+ cases. Leukemic cells in CD5- cases also expressed CD11b antigen more frequently than those in CD5+ cases (80% v 11%; P < .01). Another myeloid marker, CD33, was expressed neither on CD5+ nor CD5- leukemic cells. CD22, a restricted B-cell marker, was expressed more frequently on CD5- leukemic cells than on CD5+ leukemic cells (80% v 33%; P < .05). Another restricted B-cell activation marker, CD23, was expressed at similar frequency in both the CD5+ and CD5- groups (67% v 60%). Although CD45RA was expressed on the majority of leukemic B cells, the CD45RA expression level was significantly higher among CD5- cases than CD5+ cases (P < .01). In the analysis of VH gene expressed in chronic B-cell leukemias by polymerase chain reaction amplification, CD5+ cases preferentially used VH4 family members (48%; 10 of 21). CD5- cases, on the other hand, mainly used VH3 family (80%; 4 of 5). Thus, from our present observation of an albeit limited patient population, we have found an association between VH gene family use and CD5 antigen expression in chronic B-cell leukemias. We have also shown the differential expression of myelomonocytic markers in the CD5+ and CD5- chronic B-cell leukemias. These result are in agreement with previous suggestions that CD5 positivity is the hallmark for distinct clinical entity commonly referred to in the literature as chronic lymphocytic leukemia.

Adult↗
PubMed1994

Aberrant production of gliostatin/platelet-derived endothelial cell growth factor in rheumatoid synovium.

OBJECTIVE: To purify a protein inhibitor from rheumatoid arthritis (RA) synovial fluids which suppresses the apparent incorporation of 3H-thymidine into fibroblasts and synovial cells, and to define its biochemical features that have clinical relevance to the pathogenesis of RA. METHODS: Several standard chromatographic techniques were employed for the purification of the protein. Immunochemical methods with monoclonal antibody were used to quantify and visualize the protein in sera, synovial fluids, and tissues from RA patients. RESULTS: The chemical properties of purified inhibitor from RA synovial fluids confirmed its identity as gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF), a potent angiogenic factor. The gliostatin/PD-ECGF level in synovial fluid and serum was higher in RA patients than in osteoarthritis controls. CONCLUSION: These findings strongly suggest that gliostatin/PD-ECGF might play an important role in the aberrant neovascularization of rheumatoid synovium.

3T3 Cells↗
PubMed1994

Expression of the c-kit ligand and interleukin 6 genes in mouse bone marrow stromal cell lines.

The expression of c-kit ligand and interleukin 6 (IL-6) genes in mouse bone marrow-derived stromal cell lines was examined using quantitative polymerase chain reaction (PCR) analysis based on the design of an internal DNA control. The stromal cells studied included the 14F1.1 endothelial-adipocytes that support long-term hemopoiesis and two additional cell lines (MBA-1, MBA-13) which do not have this function. All the cell lines expressed c-kit ligand gene constitutively, and this expression was not increased by lectins. On the other hand, the expression of the IL-6 gene was markedly induced in all the lines by lipopolysaccharide (LPS) and by phorbol 12-myristate 13 acetate (PMA). The constitutive expression of c-kit ligand in 14F1.1 cells was the lowest among the three cell lines studied and could be increased by stimulation with IL-4. Thus, we observed some quantitative differences among the cell lines in their expression of cytokine genes. However, the unique capacity of 14F1.1 cells to support in vitro hemopoiesis cannot thus far be explained solely on the basis of the ability of these cells to secrete cytokines which are not produced by other stromal cell lines. c-kit ligand may be necessary, but its presence alone is not sufficient for 14F1.1 cells to support prolonged hemopoiesis.

Adipose Tissue↗