The role of mesenchymes in the course of wound repair is presented, basing on experiments performed mainly in our laboratory. Two constituents in the connective tissue are considered separately, i.e. collagen and fibroblasts. The contents of this review are summarized as follows: (1) Inactivation of cellular activities by collagen fibers. Collagen fibrils greatly suppress the rate of DNA synthesis and proliferation of fibroblasts and epidermal cells. This suppresive effect is expressed by a polymerized form of collagen, but not by denatured or monomeric collagen. (2) Wound contraction might be controlled by fibroblasts. Fibroblasts can bind to collagen fibrils and contract them, resulting in a reorganization of collagen. This contractile force of fibroblasts could be a source of wound contraction. Our study strogly suggests that fibronectin is not involved in the binding of fibroblasts to collagen. (3) Physiological activities of epidermal cells largely depend on factors from mesenchymes. Epidermal cells require the presence of fibroblasts as a feeder for their proliferation at a low cell density culture. Some of this effect of feeder cells can be replaced with diffusible factors from fibroblasts.

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Monoclonal antibodies, 1-7, 3-5 and 8-30, specific to Fc_ε receptor (Fc_εR) on human B cells were established. The two monoclonals (1-7 and 8-30) were directed to the IgE binding site of Fc_εR, and the other monoclonal (3-5) recognized the same molecules, but a different epitope. The molecules recognized by these monoclonals had M.W. of 46 Kd. as determined by SPS-PAGE analysis.
By employing these monoclonals, the distribution of Fc_εR⁺ cells was studied in various lymphoid tissues, and the results showed that Fc_εR is a B cell specific differentiation marker confined to matur μ⁺δ⁺ B cells and disappear after class-switching. The lymphokine respensible for Fc_εR expression was BSF-1 (IL-4) . It was also found that Fc_εR expression on peripheral B cells was much augmented in atopic patients than normals.
We isolated and sequenced a cDNA clone encoding the Fc_εR. The deduced protein sequence revealed that Fc_εR consists of 321 amino acids, and is oriented with its N-terminus on the cytoplasmic side and its c-terminus on the outside of the cell. This molecule showed striking sequence homology with chicken asialoglycoprotein receptor, suggesting a possible role for Fc_εR in endocytosis.

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A rapid microassay of whole blood luminoldependent chemiluminescence (CL) was carried out in the patients with bacterial infections, idiopathic pulmonary fibrosis (IPF), bronchial asthma, hypersensitivity pneumonitis (HP) and eosinophilia. CL to phorbol myristate acetate (CL-PMA) and CL to opsonized zymosan (CL-OZ) was significantly elevated in the whole blood assay during either acute infections or during acute exacerbation of IPF. CL-PMA not CL-OZ of the separated polymorphonuclear leukocyte (PMNL) was comparable to the whole blood CL responses. Both CL-PMA and CL-OZ in the whole blood assay but not in PMNL CL assay were moderately but significantly elevated in the patients with HP where this elevation of CL-OZ was correlated well with neutrophils (r=0.856) . In the patients with bronchial asthma, the elevation of CL-OZ was correlated well with eosinophil (r=0.98) but not with neutrophils. It is thus concluded that the elevation of CL-OZ in HP depended on neutrophils whereas that in bronchial asthma depended on eosinophils and that whole blood CL assay appeared to be more suitable for clinical evaluation of the disease or disease activities rather than that of PMNL CL assay, possibly through reflection of serum factors in the whole blood assay.

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Glycosaminoglycanpolysulfate (GAGPS) was used to study effects on the production of superoxide anion (O^-₂) in human peripheral neutrophils. Superoxide generation in response to activating factor, N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA) and PA68 (a seed extract) was inhibited by GAGPS and the quantitative analysis indicated that this effect was does-dependent. The concentration of cytosolic ionized calcium [Ca²⁺] i, was measured in intact neutrophils using a fluorescent indicator trapped in the cytoplasm. A given rise of [Ca²⁺] i elicited by FMLP was also inhibited by GAGPS, in a fashion similar to, that of the inhibition of O^-₂ generation in neutrophils. The results suggested that GAGPS induce both calcium-dependent FMLP and calciumindependent PMA response to inhibite [Ca²⁺] i released from neutrophils. These nonspecific effects, taken together with the increase in lactate dehydrogenase activity brought on by high concentrations of GAGPS, would appear to implicate GAGPS as having an important role in neutrophil cytotoxity. The results, thus, suggest that the actions of GAGPS are similar to those of superoxide dismutase (SOD), a scanvenger of O^-₂.

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To evaluate pathophysiological significance of anti-microsome antibody positive sera in Basedow's disease, we have examined the production of opsonized zymosan stimulated active oxygens in neutrophils and the chemotaxis stimulated by f-methyonylleucyl-phenylalanine. O^-₂ significantly increased with sera of Basedow's disease as compared with those of healthy subjects. However OH^⋅ production and chemotaxis have not significantly changed.
Productive-stimulating factors are, therefore, suggested to be present in the sera of Basedow's disease. The association of the factors with hyperthyroidism was discussed.

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Leukocytes from mite sensitive asthmatic patient were challenged with the allergen and the supernatant was assayed for histamine and immunoreactive-leukotriene C₄ (i-LTC₄) . i-LTC₄, which was measured by a commercial radioimmunoassay kit, was confirmed to consist of LTC₄ with a little amount of LTD₄ and the LTC₄ was derived from basophils. Allergen induced a concentration-dependent release of histamine and i-LTC₄. The maximal release of histamine and i-LTC₄ occured at the same dose of the allergen. At optimal concentration of the allergen, basophils produced 20.4±17.9 ng of i-LTC₄/10⁶ cells (mean±SD, n=39) and histamine release was 55.6 ±20.1% of total histamine. There was a significant correlation in the capacity of leukocytes to release histamine and i-LTC₄ (r=0.47, P<0.01) . The reactivity and the cell sensitivity of the cells to the allergen for histamine release paralleled the severity to symptoms of asthnia, but this correlation was not significant in i-LTC₄ generation.

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Disodium-4-chloro-2, 2'-iminodibenzoate, lobenzarit disodium (CCA) is an antirheumatic drug which was developed in Japan, and its effectiveness on patients with rehumatoid arthritis (RA) was confirmed.
It is known that the acting mechanisms of conventionally used antirheumatic drugs to regulate human immunological abnormalities are caused by the macrophage inhibitory action of gold preparations and the inhibitory action of D-penicillamine on helper T-cells. How a new antirheumatic drug acts on the normalization against the immunological abnormalities of RA patients is a rheumatologically important problem. From the above point of view, we investigated the action of CCA on peripheral blood mononuclear cells to compare with those of gold and D-penicillamine.

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It has been elucidated that phagocyte-released oxygen intermediates which are excessively generated to fuse invading agents in their phagosomes induce auto-oxidative damage such as tissue injury in several human cells in vivo. Dr. Yukie Niwa has found that AOA (anti-oxidants analogs) are potent scavengers of oxygen intermediates from many natural plants after the treatment that are heating with ultra red ray and brewing with Koji.
We tried to treat with AOA on the collagen disease patients. A patient with PSS was significant improvement in both their clinical symptoms and laboratory findings.
We think that AOA may be useful drug in collagen disease.

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Lobenzarit exerts various kind of modulating effect on lymphocyte and significantly therapeutic activity in rheumatoid arthritis. However it is not known yet whether lobenzarit affects some paticular mechanism on pathogenesis of rheumatoid arthritis by correcting some abnormality. A long term clinical study was performed to assess the effectiveness of lobenzarit taken over extended periods by patients with rheumatoid arthritis. Consequently, it was shown that lobenzarit has favorable characteristics as a second line drug, but usually affords greater clinical benefit when used as a first line drug in the early stage of rheumatoid arthritis.

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