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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 1,261 records · Page 70Linked to original sources

IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells.

rIL-6/B cell stimulatory factor 2 was found to augment CTL generation from mature as well as immature human T cells stimulated with UV-treated allogeneic cells. rIL-6 also acted on peanut agglutinin-positive murine thymocytes and Lyt-2-positive splenic T cells to give rise to CTL. rIL-6 alone could not induce CTL generation, the presence of IL-2 during the early phase of culture period was found to be essential for the IL-6 activity in the induction of CTL. The effect of rIL-6 was not mediated by the induction of IL-2 inasmuch as rIL-6 did not augment IL-2 production in MLC and anti-IL-2 antibody could not neutralize IL-6 activity. rIL-6 augmented CTL generation even when added 72 h after the initiation of cultures. The enhancing activity of rIL-6 could be neutralized with anti-IL-6 antibodies even when added 72 h after the initiation of cultures. The present data indicate that IL-6 acts in the late phase of CTL generation.

Adjuvants, Immunologic↗

Effects of interferon-alpha on the activity of preoptic thermosensitive neurons in tissue slices.

Effects of recombinant interferon-alpha (IFN-alpha) on the single activity of thermosensitive and thermally insensitive neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in rat's brain tissue slices. IFN-alpha, in doses of less than 5 x 10(3) U/ml, decreased the activity in 34 of 52 warm-sensitive neurons and increased the activity in 3 of 5 cold-sensitive neurons, but had no effect on the majority (12 of 17) of thermally insensitive neurons. The neuronal responses to local IFN-alpha could be observed in a Ca2+-free/high Mg2+ solution, suggesting the direct action of IFN-alpha. The actions of IFN-alpha on thermosensitive neurons were blocked by concurrent application of naloxone, but not by sodium salicylate in doses which effectively blocked the neuronal responses to endotoxin and leukocytic pyrogen in the previous studies. The fever induced by IFN-alpha may be explained, at least partly, by the direct actions of IFN-alpha on the PO/AH thermosensitive neurons, which involve the opiate receptor mechanisms.

Action Potentials↗

Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.

Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.

Antibodies↗

The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells.

The role of recombinant B cell stimulatory factor 2 (BSF-2/IL-6) in the regulation of growth and differentiation of B cells was investigated. rBSF-2 at 200 pg/ml could induce 50% of the maximum Ig production in B lymphoblastoid cell lines, the specific activity being estimated as 5 X 10(6) U/mg. rBSF-2 augmented PWM-induced IgM, IgG, and IgA production in mononuclear cells (MNC); the effect was exerted by directly acting on PWM-induced B blast cells to induce Ig production. However, rBSF-2 did not induce any growth of activated B cells. In contrast, rBSF-2 showed a potent growth activity on a murine hybridoma clone, MH60.BSF2. The concentration required for half-maximal [3H]TdR uptake was approximately 5 pg/ml, which was 40 times less than that required for Ig induction in a B cell line. Anti-BSF-2 antibody inhibited PWM-induced Ig production in MNC, but not PWM-induced proliferation. The antibody was effective even when added on day 4 of an 8-d culture, indicating that BSF-2 is one of the essential late-acting factors in PWM-induced Ig production.

Antibodies↗

Pericardium of rodents: pores connect the pericardial and pleural cavities.

Numerous circular fenestrations or pores were present in the pericardium of the rat, golden hamster, and mouse. The pericardial pores were most numerous in the mouse. They were usually less than 50 micron in diameter and situated in a meshwork formed by thick, wavy bundles of collagen fibers and thin, straight, elastic fibers. These pores directly connected the pericardial and pleural cavities and indirectly connected the right and left pleural cavities; i.e., the pericardial cavity in the rodents is not independent from but intercommunicates with the adjacent pleural cavities. There were many aggregates of free cells or milky spots in the pericardium. They principally consisted of lymphocytes, macrophages, and mast cells and were directly exposed to the pericardial cavity.

Animals↗

The mouse pericardium: it allows passage of particulate matter from the pleural to the pericardial cavity.

Frog erythrocytes injected into the pleural cavity of mice reached the pericardial cavity. Pericardial pores that connect the two cavities were the routes of the migration. As soon as 5 minutes after injection, frog erythrocytes were surrounded and phagocytosed by attached macrophages in milky spots facing the pericardial cavity. The pericardial pores may function in an allied self-defense mechanism between the pleural and pericardial cavities in this species.

Animals↗

Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies.

Murine hybridomas producing monoclonal antibodies (mAb) specific to human interleukin 6 (IL 6/BSF-2) were established. One of these hybridomas (MH60.BSF2) was found to be dependent on IL 6 for its in vitro growth. None of the known biological factors tested, such as recombinant (r) human (Hu) IL 1 alpha, rHuIL 1 beta, rHuIL 2, rHuIL 3, rHuIL 4, rHu interferon (IFN)-gamma, HuIFN-beta, rHuG-CSF, or recombinant murine (Mu) IL 3, MuIL 4, rMuIL 5, could induce the in vitro growth of MH60.BSF2 cells. The half-maximum tritiated thymidine uptake by MH60.BSF2 cells could be achieved by picogram amounts of rIL 6, making this hybridoma clone an indicator cell for specific and sensitive detection of the IL 6 activity in test samples. The MH166.BSF2 clone was found to produce IgG1,chi type mAb (alpha BSF2-166) capable of neutralizing IL 6 activity. The other clone, MH60.BSF2, produced IgM,chi type mAb (alpha BSF2-60) unable to neutralize IL 6 activity. Both mAb specifically reacted with IL 6 as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis. An enzyme-linked immunosorbent assay (ELISA) utilizing alpha BSF2-166 and rabbit anti-IL 6 antibodies was established which could detect as low as 50 pg/ml of IL 6. Since both the ELISA and MH60.BSF2 hybridoma could detect small amounts of IL 6 in biological fluids, they constitute powerful tools in exploring the presence or the role of IL 6 in various immunological disorders.

Animals↗

Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis.

High levels of interleukin 6 (IL 6/B cell stimulatory factor-2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL 6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL 6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL 6. The data indicate that IL 6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL 6 can function as B cell growth and differentiation factor as well as hepatocyte-stimulating factor.

Antigens, CD20↗

The follow up study of intra-arterial infusion chemotherapy with local vein blocking as a surgical neo-adjuvant treatment for locally advanced breast cancer.

Preoperative intra-arterial infusion neo-adjuvant chemotherapy, in combination with local vein blocking, was administered to thirty-one patients with locally advanced stage III breast cancer. The anti-cancer drugs and dosages used were 500 mg of 5-Fluorouracil (5FU), which was infused daily for 7-14 days, and 20 mg of Adriamycin (ADM), which was administered as a bolus dose twice into the subclavian and internal mammary arteries. The response rate of this method on the primary tumor was 48.4 per cent, and, histologically it was found to be as high as 90.3 per cent. The response rate of the clinical effects on the regional lymph nodes was 50.0 per cent, however, histologically, it was found to be lower than that of the primary tumor. In the long-term follow-up study the 5-year survival rate was 72.2 per cent. Thus, this method seems to be effective as a combined modality in cases of locally advanced stage III breast cancer.

Breast↗

Difference between neuronal and nonneuronal (Na+ + K+)-ATPases in their conformational equilibrium.

Several experiments were carried out to study the difference between two isozymes (alpha(+) and alpha) of (Na+ + K+)-ATPase in the conformational equilibrium. Rat brain (Na+ + K+)-ATPase was much more thermolabile than the kidney enzyme. Both enzymes were protected from heat inactivation not only by Na+ and K+, but also by choline in varying degrees, though there was a difference between the two enzymes in the protection by the ligands. The brain enzyme was partially protected from N-ethylmaleimide (NEM) inactivation by both Na+ and K+, but the effects of the ligands on NEM inactivation of the kidney enzyme were more complex. Though ligands differentially affected the thermostability and NEM sensitivity of the two enzymes, the effects were not simply related to the conformational states. The sensitivity of phosphoenzyme (EP) formed in the presence of ATP, Na+, and Mg2+ to ADP or K+ and K+-p-nitrophenyl phosphatase (pNPPase) was then studied as a probe of the differences in the conformational equilibrium between the two isozymes. The EP of the brain enzyme was partially sensitive to ADP, while those of the heart and kidney enzymes were not. At physiological Na+ concentrations the percentages of E1P formed by the brain and kidney enzymes were determined to be about 40-50 and 10-20% of the total EP, respectively. The hydrolytic activity of pNPP in the presence of Li+, a selective activator at catalytic sites of the reaction, was much higher in the kidney enzyme than in the brain enzyme. The inhibition of K+-stimulated pNPPase by ATP and Na+ was greater in the latter enzyme than in the former. These results suggest that neuronal and nonneuronal (Na+ + K+)-ATPases differ in their conformational equilibrium: the E1 or E1P may be more stable in the alpha(+) than in the alpha during the turnover, and conversely the E2 or E2P may be more stable in the latter than in the former.

Adenosine Diphosphate↗

Changes in levels of t-PA and alpha 2PI-plasmin complex in plasma in patients with DIC.

Levels of alpha 2PI-plasmin complex and tissue-type plasminogen activator (t-PA) in plasma were determined in 10 cases of acute promyelocytic leukemia (APL) with marked coagulopathy and in 10 cases of hematological malignancies with DIC to investigate relevance to fibrinolysis. In the both groups, levels of alpha 2PI-plasmin complex increased and were inversely proportional to levels of fibrinogen and alpha 2PI. Levels of t-PA in plasma increased moderately in the majority of the both groups. Serial observation of the concentrations of t-PA with corresponding changes in the levels of fibrinogen, alpha 2PI, alpha 2PI-plasmin complex and FDP could not demonstrate any significant relationship between levels of t-PA and the other parameters. From these results, it is unlikely that levels of t-PA in plasma directly influence on the degree of consumption of alpha 2PI or of formation of alpha 2PI-plasmin complex in most cases of DIC.

Anticoagulants↗

Secondary release of thromboxane A2 in aerosol leukotriene C4-induced bronchoconstriction in guinea pigs.

Effect of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4 and histamine was studied in anesthetized, artificially ventilated guinea pigs in order to examine whether secondary release of thromboxane A2 is produced by aerosol leukotriene C4 or not. 0.01-1.0 micrograms/ml of leukotriene C4 and 12.5-400 micrograms/ml of histamine inhaled from ultrasonic nebulizer developed for small animals caused dose-dependent increase of pressure at airway opening (Pao) which is considered to be an index representing bronchial response. Pretreatment of the animals with intravenous OKY-046 (100mg/kg) significantly reduced the airway responses produced by inhalation of 0.1, 0.33 and 1.0 micrograms/ml of leukotriene C4, while the pretreatment did not affect the histamine dose-response curve. Based on these findings and previous reports (6,7), it is suggested that aerosol leukotriene C4 activates arachidonate cyclooxygenase pathway including thromboxane A2 synthesis and the released cyclooxygenase products have bronchodilating effect as a whole.

Aerosols↗

Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2).

Recombinant B cell stimulatory factor 2 (rBSF-2) did not display any detectable level of antiviral activity when using human diploid fibroblasts, DIP-2, FS-4, FS-7, amnion-derived WISH and FL cells with vesicular stomatitis virus (VSV) and Sindbis virus as challenging agents (less than 2.5 X 10(2) IU/mg). Furthermore anti-IFN-beta could not neutralize the immunoglobulin-inducing activity of BSF-2. Moreover anti-BSF-2 could not neutralize the antiviral activity of IFN-beta. The data indicate that BSF-2 is functionally and immunologically not related to IFNs.

Cross Reactions↗

Eosinophilic sclerosing lipogranuloma of the male genitalia not caused by exogenous lipids.

A type of sclerosing lipogranuloma of the male genitalia that is different from cases caused by injection or application of foreign bodies is reported in 4 patients. The characteristics of the disease are a symmetrical Y-shape of the granuloma, spontaneous regression, severe infiltration of eosinophils in the granuloma, eosinophilia of the peripheral blood and absence of any exogenous lipids by chemical analyses of the granuloma tissue. Ultrastructural study showed intracytoplasmic fat vacuoles of varied size in histiocytes and multinuclear giant cells. This is a new type of sclerosing lipogranuloma of the male genitalia and the pathogenesis of the disease is still unknown.

Adult↗