In earlier work, a chemotactic factor (leucoegresin) had been isolated from the inflamed site of active Arthus reactions and cutaneous burns. Leucoegresin was specific for neutrophilic polymorphonuclear leucocytes, and fulfilled many of the criteria of a natural mediator of inflammatory leucotaxis. The substance shared antigenic sites in common with IgG, and was produced from IgG molecule by an inflammatory neutral SH-dependent protease, A minor structural change of the IgG molecule during chemotactic generation by the enzyme seemed to occur exclusively at the Fc portion. Most of chemotactic activity for PMN leucocytes in active Arthus reactions in rabbits was associated with leucoegresin itself, because the chemotactic activity of inflammatory extracts was significantly absorbed by anti-leucoegresin. Furthermore, the experiments using complement depleted rabbits by an anti-complementary factor from cobra venom revealed that production of leucoegresin or in vivo effects of protease and leucoegresin was not related to the complement system. It was thus indicated that leucoegresin played a significant and characteristic part in the inflammatory leucotaxis.

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Human polymorphonuclear leukocytes (PMN) have been reported to have lysosomal acid hydrolases and neutral proteases. The enzymes’ release has been observed when cells met with various substances such as microorganisms, latex, particles, crystals, zymosan and immune complex. The mechanism of the enzymes’ release would be thought as the result of phagocytosis. On the other hand, in the rheumatoid arthritis or SLE, when vasculitis or angiitis, is predominant, we find that there are always hypocomplementemia and high titer of auto-antibody and the deposition of immune complex on the vascular wall. Leukocytes are chemotactically attracted to sites of deposition and as the result of phagocytosis of complex, the enzymes, especially, neutral proteases, e. g. elastase and collagenase would be released and then direct damege of vascular construction is invited. We described in this paper 1) the granule fraction of human peripheral leukocytes contained neutral proteases, elastase and collagenase, 2) the chemotaxis of PMN was observed to the immune complex and gammaglobulin. fraction of synovial fluid of RA patient 3) enzymes’ release was occured when leukocytes were incubated with immune commplex and latex coated with heat aggregated globulin 4) leukocytes homogenate digested basement membrane in vitro 5) experimental arthritis was provoked by the injection of enzymes’ rich fraction to the knee joint of rabbit.

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Helping action by inflammatory exudate cells on lymphocyte triggering was shown in terms of lymphocyte DNA synthesis after stimulation with plant mitogen and of lymphotoxin production by antigen-stimulated lymphocytes. Thymocytes (4×10⁶) or spleen cells (1×10⁶) were cultured in RPMI 1640 with 5% heat-inactivated human serum (in case of mouse) or with 10 % syngeneic rat serum, and stimulated with various amounts of PHA-p with or without inflammatory cells which were collected from 0.2 % casein-induced peritoneal exudates. The DNA synthesis of lymphocytes was measured by the last 24 hr pulse exposure to ³H-thymidine at 72 hr stimulation. The inflammatory cells chiefly consisted of macrophages and lymphocytes. Thymocytes of mouse and rat were poorly triggered to induce DNA synthesis by PHA, but they were fairly well triggered when they were mixed with small number (5-15×10³) of inflammatory peritoneal exudate cells of syngeneic strain. The DNA synthesis of mouse spleen cells was also clearly enhanced by the addition of inflammatory cells. The same type of helping action to the DNA synthesis of thymocytes, spleen cells or lymph node cells were also accomplished by cell free exudate at 48-96 hr-age of inflammation. It was further demonstrated that a soluble lymphocyte helping factor was released in vitro from purified macrophages at 24 hr after stimulation with endotoxic lipopolysaccharide. Lymphotoxin in the culture supernatant after incubation of sensitized lymphocyte with antigen was measured by the method of Ruddle & Waksman, using the Coulter counter evaluation of survived target fibroblast monolayer. The lymphotoxin production was well achieved by whole sensitized lymph node cells with antigen but not by lymph node cells after removal of adherent cells and it was well restored by the addition of purified macrophages to this population. These findings offered a reason for the explanation why activity of lymphocytes in inflammatory sites are higher than that of cells in peripheral lymphoid organ. On the other hand, macrophages showed a suppressing effect against B-lypmhocyte triggering, only in the presence of T-lymphocytes (normal spleen cells) but not in the T-depleted (thymectomized, lethally irradiated and bone marrow cell-restored) spleen cells, when stimulated to induce DNA synthesis with endotoxic lipopolysaccharide. This may be attributed to the function of suppressor T-lymphocytes function which was also macrophage dependent.

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Lymphocytes are particularly numerous in chronic inflammation, the role of the cells in the inflammatory sites is still unknown. It has frequently been suggested that small lymphocytes were primitive cells capable of transformation into other cell types; and that they acted as a mobile source of nutrients which promoted growth and proliferation of other cells. However, these still remain to be finalized. Lymphocytes undoubtedly play a key role in immunologic reactions, and they act as effector cells in graft reject reactions and GVHR. They stick to the target cells and lyse them. In vitro, lymphocytes produce many chemical mediators and it is suggested that they involve in the regulation of immune reactions. However, its relevance to in vivo events in cell-mediated immune reactions is quite unknown. In our laboratory, a chemotactic activity for macrophages and several proteases were found in the extract of tuberculin skin sites, and partially purified using ammonium sulfate and column chromatography. In addition, proteases of the lymphocytes were assayed in the extract of lymphoid cells from animals sensitized with heat-killed tubercle bacilli against hemoglobin and casein. Three peaks of the activities were found at pH 3, 6 and 9. The specific activities between pH 6-9 were higher in the sensitized cells than in the control cells. Proteases active at neutral and alkaline pH have been partially purified from the extract through a column of DEAE-cellulose and then GE-cellulose. They had pH optima of approximately 7.0 and 9.0, respectively, with casein, and their activities were stimulated by cysteine. Intradermal injection of the proteases into normal rabbits and guinea pigs induced an inflammation, with a peak around 6 hours after injection, and the lesions was characterized microscopically by a mixed mononuclear-polymorphonuclear. infiltrate in the deep dermis. The relevance of the proteases to in vivo events in cell-mediated immune reactions was discussed.

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The present investigation was undertaken to determine the kinetics of eosinophils and basophils in allergic reactions, the Rebuck’s skin window technique with the specific antigens being used. And the same procedures with known chemical mediators and histamine liberator were utilized on the non-allergic individuals in order to see which mediator was the most responsible to each cell dynamics.
1. Atopic hypersensitivity
Significant eosinophilia was seen in each preparation (Table 1). However, no basophilia was observed.
2. Delayed hypersensitivity
a) Response to streptokinase
By intradermal injection of 40 units/ml streptokinase saline solution (diluted from Varidase) beneath the denuded area, considerable basophilia was seen at late period in each subject (Table 2).
b) Response to tuberculin (PPD)
Moderate eosinophilia and basophilia were noticed in the preparation at 48 hours obtained from tuberculin-sensitive persons by the same procedure above-described (Table 3).
c) DNCB-contact allergy
As shown in Table 4 and Fig. 1, within first 24 hours, significant eosinophilia was observed in most specimens, then it decreased. Basophils began to accumulate at 24 hours, and this response intensified at 48 hours.
In this experiment the skin window technique was done on the chronic dermatitic lesion induced by 24-hour patch of 0.2 % DNCB aceton solution 10 days ago. And prior to performance of skin window technique, the same agent was reapplied on the lesion for 2 hours. Thereafter, the skin window was made on the site with a drop of saline.
3. Response to chemical mediators and compound 48/80
By the topical application of 20 μl of each agent, it was revealed that serotonin creatinine sulfate (15 %), acetylcholine (1 %), norepinephrine (1 %), kallikrein (40 units/ml), trafuril (1 %), prostaglandin El (0.1 %) and prostaglandine E2 (0.1 %) had no chemotactic activity for both eosinophils and basophils. Histamine phosphate brought about weak eosinophil-chemotaxis only when 10 % solution was used.
On the other hand, 1mg/ml compound 48/80 saline solution was able to cause significant eosinophilia in the skin window preparations (Table 5). These results suggested that eosinophilia seen in allergic reactions could be induced by histamine liberation, not by histamine itself. Basophilic response was characteristic in delayed hypersensitivity. This may show the mobilization pattern of basophils from the blood vessels in order to make up the mast cells depleted by long-lasting degranulation stimuli.

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A 20 year-old woman with histiocytic medullary reticulosis was reported. A biopsy taken from a skin lesion showed phagocytosis of erythrocytes by atypical histiocytes. Since this case started from cutaneous lesions, it may be named cutaneous reticulohistiocytosis with erythrophagocytosis. It is our conclusion that histiocytic medullary reticulosis belongs to malignant reticulohistiocytosis.

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A osseous tumor on the right external ocular angle which appeared in a 11-month old girl was reported. The tumor, 7 mm in diameter, had many long hairs on its surface and connected with the upper and lower eyelids. Complete excision and blepharoplasty was performed without recurrence afterwards. Histologically many mature hair follicles in the dermis and osseous structure in the subcutaneous tissues were observed. This hamartoma-like and non-neoplastic nature was discussed. It seems better to consider this case as a naevus or hamartoma rather than as a neoplasm, and a provisional term “naevus osseus” was proposed.

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The patient was an 11 year-old girl who complained of vesiculation on exposed areas. The disease had first occured during the spring at five years of age. Family history was negative for similar disease. Routine laboratory studies were within normal limits, except for slight elevation of SGOT, SGPT and γ-globulin. The examinations of urine, feces and blood porphyrins were within normal limits. Her general health was good. She had corneal turbidity in both eyes, but her visual acuity was normal. There were small scars and crustings on her face, and slight lichenification on the back of the hands. Affected sites were predominantly those of the exposed parts including the cheeks, chin, nose, ears and the back of the hands. Liver biopsy was performed and she was diagnosed as having chronic hepatitis (active form). Histopathologic studies of the skin on the back of the hand showed only lymphocytic infiltrations of the upper dermis. There were no PAS positive materials in the upper dermis. Thirty minutes of sun light exposure produced erythema with small vesiculations. This report was as follows:
1) It was considered that the mechanism of photosensitivity was different from hydroa vacciniforme and porphyria.
2) Hydroa vacciniforme has a high incidence of ocular complications, especially corneal abnormalities.
3) Although this patient had chronic hepatitis, the relation between hydroa vacciniforme and hepatitis is unknown.

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A case of 21 year-old woman with flat and tuberous xanthomas on the patellar and popliteal regions and buttock, on the flexor sides of legs and thighs, and in the region of Achilles’ tendons was reported. Orange-yellowish longitutinal lines were found on her palms. Chemical analysis of serum lipid revealed 484 mg/dl of total cholesterol, 1760 mg/dl of β-lipoprotein, and 450 mg/dl of phospholipid. Hyperlipoproteinemia with flat and tuberous xanthomas was also detected on her mother, elder brother and elder sister.

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Investigation of skin diseases in Western Samoa was performed during May to June, 1973. Examinations of skin diseases are carried out by the following three methods:
(i) Mass-examination of school children.
(ii) Observation of outpatients in Apia General Hospital and in some district hospitals.
(iii) Examination of households by house-to-house visits.
There are no conspicuous differences in the kind and the severity of skin diseases between urban and rural areas. Skin diseases which are common among outpatients of hospitals in Western Samoa are, in addition to eczema-dermatitis, which is also the most common in other countries, fungal infections (ringworms and tinea versicolor) and bacterial infections (pyodermas). Eczema-dermatitis is the most common skin diseases in Western Samoa, as it is in almost all countries. It includes infantile eczema, acute or chronic eczema of adults, various contact-type dermatitis clue to exogenous irritants and also secondary eczematization which is caused during the treatment of preexisting pyodermas or fungal infections. Tinea imbricata is not seen among infants under one year, very few in childhood, and gradually increase in school age. There is no apparent sexual difference and widespread, characteristic clinical features become outstanding in the middle age of life. Prevalence of tinea imbricata among inhabitants of Western Samoa may be under 5 % and is decreasing. There are also several cases of generalized tinea circinata, tinea pedis or tinea unguium. Some of them had been treated by physician with topical antifungal ointments or oral administration of griseofulvin and sometimes with a combination of these. Tinea versicolor is the most common fungal infection among the people of Western Samoa. The youngest of the patients observed was one-year old boy, but there were not so many cases among children before school age. The incidence of tinea versicolor patients then increases with age and comes to a peak at puberty. It seems that about a half of adult population was infected by tinea versicolor but usually they would not consult physicians. In almost all cases, the accumulation of tinea versicolor patients in a family was observed, so it was supposed that the majority of patients had been infected from their families. The great majority of school children have pyodermas which are caused spontaneously or by secondary infection following small injuries or insect bites.

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The patients with cosmetic dermatitis in our cosmetologic clinic are increasing in the ratio of the intractable cases such as melanosis faciei femini year by year, so that we keenly feel the difficulty of treatment of cosmetic-induced skin lesion. Women’s attachment to cosmetics is extremely deep, therefore, no effect can be anticipated only by the advise to avoid the use of causative cosmetics. It is necessary for complete elimination of causative cosmetics giving the patients satisfaction to some extent for the desire of cosmetics. In the treatment of cosmetic dermatitis, we devised, therefore, a system of serial use of the following external agents in place of cosmetics: adrenocorticoid containing ointment or cream → adrenocorticoid containing lotion → patch test negative ointment base or faintly perfumed cosmetics → patch test negative cosmetics according to skin condition. It was tried in 30 patients and obtained 90% efficacy for inflammatory condition and 66.7% for pigmentation. Treatment of dermatitis attributable cosmetics should be started with not only discovery of patch test positive cosmetics, but complete elimination of such cosmetics as well.

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The authors found chloride in the epidermal cysts of four patients with chronic pentachlorophenol (PCP) poisoning. In animal experiments with mice which were given PCP orally, we found PCP in the liver but not in the skin. In the same mice, we found changes, characteristics to PCB poisoning and PCP poisoning, in the liver and kidney but not in the skin and adrenal glands.

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Some properties of epidermal and hair root ribonuclease (RNase) were studied, Epidermal RNase showed an opimum pH around 6.0 and hair root RNase at 7.0 in Tris-Malate buffer. Although Ca⁺⁺ activated both RNases, other cations, Mg⁺⁺, Mn⁺⁺, Ca⁺⁺, Cu⁺⁺ inhibited these enzymes. Epidermal RNase as well as hair root RNase were heat-labile.

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A statistical survey of mycoses of Dermatological Clinic of Kyushu University Hospital for the last eight years (1966-1973) was reported. The proportion of mycoses to the outpatients has increased gradually since 1966. Especially, the increase of tinea on the face, erythema mycoticum infantile and intertrigo blastomycetica was very remarkable.

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In regard to 100 patients of urticaria treated with Histaglobin, vials of Histaglobin which were used till healing or showing effectiveness practically, and total vials used in course of treatment were examined in number. Results obtained were as follows. In 92 patients whose total vials used were numbered, 28 patients (30.4 %) with a vial, 26 patients (28.2 %) with 2 vials, 19 patients (20.6 %) with 3 vials and 15 patients (16.3 %) showed apparent effectiv eness with 4 vials respectively. On the other hand, it was also confirmed from the data examined in this study that the approximately necessary vials for treatment were in between 3 and 7 vials.

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