Antinuclear antibodies were detected in 30 of 38 (79%) patients with scleroderma by indirect immunofluorescence using rat liver sections as a substrate. Seventeen of 30 patients who were positive for antinuclear antibodies also had antinucleolar antibodies. Antibodies to non-histone nuclear antigens were identified by double immunodiffusion in 0.45% agarose. The incidence of anti RNP antibody was 13%; anti SS-A antibody, 45%; anti SS-B antibody, 13%; anti Sm antibody, 0%; anti MU antibody, 0%; anti Scl-1 antibody, 58%. Scl-1 antigen was not found in isotonic saline soluble extracts of human spleen, human liver, rabbit thymus, rat liver or Raji cell. Alternatively, the antigen was extracted from these organs with hypertonic salt solutions (0.3M, 0.6M, 1.0M, NaCl). The antigen was inactivated by heating at 37 °C for 1 hour. It was resistant to digestion with deoxyribonuclease or ribonuclease, and was destroyed by trypsin digestion. Antibodies to Scl-1 antigen were detected in sera from 22 of 38 (58%) patients with scleroderma, 1 of 10 (10%) with sclerodermatomyositis, 1 of 26 (4%) with mixed connective tissue disease and 1 of 32 (3%) with undifferentiated connective tissue disease having anti RNP antibody. Anti Scl-1 antibody was not present in sera from 18 patients with polymyositis or dermatomyositis, 88 with systemic lupus erythematosus, 55 with rheumatoid arthritis, 44 with sicca complex or 24 with Hashimoto's thyroiditis. The patients with scleroderma had a significantly high incidence of the antibody (P<0.01). The present study suggests that anti Scl-1 antibody might be a useful marker for scleroderma.
In the previous paper, we reported that Neocarzinostatin (NCS) could bind covalently to rabbit anti-tumor IgG (Immune IgG) without losing its pharmacological activity. In this study, the complement dependent cytotoxicity and capping inhibition of the conjugate were evaluated. When antibody activity was measured by 3H-TdR uptake inhibition and 51Cr release tests in the presence of human complement, the cytotoxicity of the conjugate was significantly reduced in contrast to the antibody binding activity tested by immunofluorescence. In addition, an anti-complement immunofluorescent test showed that NCS-immune IgG fixed less complement on NALL-1 cells than immune IgG. These results indicate that complement fixing sites of NCS-immune IgG are damaged during chemical conjugation. The capping experiment demonstrated that NCS-immune IgG interfered with the capping of antigens on the NALL-1 cell surface, and that the capping inhibiting activity was almost the same degree as that of free NCS. This unique advantage of NCS-immune IgG may be useful for inhibiting the immunological escape of tumor cells from antibody attack in vivo.
Cytotoxic effects, chromosomal aberrations and malignant transformation in a cloned rat liver cell strain (Ac2F) were examined by treatment with an active metabolite of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), 3'-methyl-N-benzoyloxy-methylaminoazobenzene (3'-Me-N-benzoyloxy-MAB). The results are summarized as follows. 1) 3'-Me-N-benzoyloxy-MAB induced not only marked cytotoxic effects but also chromosomal aberrations on the cells when compared with 3'-Me-DAB. 2) The cells underwent malignant transformation at 51-53 days of culture after they had been treated three times with 6.9 ug/ml of 3'-Me-N-benzoyloxy-MAB. 3) 3'-Me-N-benzoyloxy-MAB-treated cells exhibited altered morphology, increased plating efficiency in liquid medium and increased size of aggregates in rotation culture, but not colony formation in semisolid agar medium or multinucleation by cytochalasin B. 4) These results strongly suggest that 3'-Me-N-benzoyloxy-MAB was an ultimate type carcinogen of 3'-Me-DAB.
The erythrophagocytic activity of peripheral blood monocytes in patients with Sjögren's syndrome (SjS) was investigated by using 51Cr-labelled SRBC sensitized with anti-SRBC antibody (IgG). The phagocytic activity of monocytes in patients with SjS alone was similar to that in healthy adults. On the other hand, the phagocytic activity of monocytes in patients with SjS associated with systemic lupus erythematosus or rheumatoid arthritis was lower than that in healty adults. There was no significant correlation, however, between phagocytic activity and several clinical parameters such as serum rheumatoid factor, erythrocyte sedimentation rate, serum complement level or the doses of prednisolone administered.
The effect of prednisolone (PSL) on clinical symptoms and laboratory parameters was studied in nineteen patients with Sjögren's syndrome (SjS) without associated diseases (SjS alone). The mean initial dose of PSL was 11.7±13.0 mg/day (M±SD), and the mean maintenance dose was 6.1±3.9 mg/day. The mean duration of the treatment was 25.2±14.1 months. Fever, polyarthralgia, elevated erythrocyte sedimentation rate, and hypergammagloblinemia were improved by the PSL treatment. However, no effect of PSL on the ocular and oral sicca symptoms including parotid enlargements, function of the exocrine glands and sialographical findings of parotid glands was observed. Neither Raynaud's phenomenon nor various autoantibodies detected in patients' sera was affected by this treatment.
A foreign soilor who had arrived by ship from Goa, India, was found to be infected with both Plasmodium falciparum and P. vivax. Although the P. vivax was a chloroquineresistant type, Fansidal ® was effective and the patient recovered. As it was the season for proliferation of mosquitoes in Japan, the patient was isolated so as not to become a source of secondary infection. Knowing the place where a patient with high grade fever comes from is of great help in diagnosing malaria, which is seldom seen in Japan.
Labial salivary gland specimens were obtained from 470 patients with sicca syndrome, collagen diseases and other diseases, and were analyzed according to the histological criteria reported by Chisholm and Mason. Abnormal findings were observed the labial salivary gland in 133 (55.0%) of 242 patient with xerostomia that were significantly higher (P<0.001) as compared with 64 (28.1%) of 228 patients without xerostomia. The histological findings correlated well with the findings of parotid sialography (p<0.001). In patients without xerostomia, abnormal histological findings were frequently observed in collagen disease; 8 (13.1%) of 61 patients with rheumatoid arthritis; 17 (22.7%) of 75 patients with systemic lupus erythematosus; and 9 (30.0%) of 30 patients with mixed connective tissue disease. In 193 patients with abnormal findings in the salivary gland, the average age of the patient with xerostomia at biopsy was higher than that of the patients without symptoms (p<0.001). Since it remains nuclear whether the patients who show abnormal findings of labial salivary gland without xerostomia have Sjφgren's syndrome, or whether these histological abnormalities represent part of the basic disease process, these patients should be oberved under the term of “subclinical” Sjφgren's syndrome.
We analyzed the clinical and laboratory findings of 160 patients with definite Sjφgren's syndrome, and examined the effect of corticosteroid therapy on these patients. One hundred and fifty nine were female, and the average age at the time of diagnosis was 46.2±12.2 years. The past histories disclosed gynecological diseases in 44 patients (29.9%) and appendicitis in 32 (21.8%); 10 (6.8%) with sinusitis; 10 (6.8%) with pleuritis. Complaints of oral dryness and decreased saliva were common in 73.8% of patients. Failure of lacrimation, redness, “film”, and increased dental caries were present in 20-30% of patients. In addition, systemic manifestations such as arthralgia, fever, Raynaud's phenomenon, and lymph node swelling were frequent. Abnormalities of Schirmer's test, gum test, histological findings of salivary glands, and of the sialogram were found in 80% of patients. Hyper γ-globulinemia was present in 81%. Anti SS-A antibody, rheumatoid factor, and total antinuclear antibodies were positive in 60-70%. Corticosteroid was effective for patients with the sicca syndrome; it relieved the symptoms of dry eye and dry mouth, and also tended to decrease the inflamation of the salivary glands. Serum γ-globulin and amylase were lower immediately after the corticosteroid treatment.
In order to study the transverse osseous architecture of the carpal region, eight wristhand specimens were obtained from four cadavers. The specimens were embedded in polyester resin after the soft tissues had been removed completely. The embedded specimens were cut into serial sections. The cutting was carried out perpendicular to the longitudinal axis of the third metacarpal bone. Each section was examined by microradiography. The shape of the bones, the width and the area of the carpal sulcus as well as the trabecular architecture were studied. The results were summarized as follows: 1. The bone shapes were divided into six groups, i.e. radio-ulnar joint level, proximal level of carpals, intermediate level of carpals, distal level of carpals, the first CM joint level and the metacarpal base level. The carpal sulcus corresponded to the intermediate, distal carpal level and to the first CM joint level. 2. Prominence of a volar arch of the carpal sulcus was observed not at the center of the arch but at the ulnar side. This prominence shifted more to the ulnar side in the distal level of carpals than in the proximal level. From these findings it was considered that the prominence of the volar arch functioned as a pulley for the flexor tendons of fingers in grasping. 3. Although the width of the carpal sulcus became narrower towards the distal level of the carpals, the largest area was obserbed at the distal level. From these observations, the cause of the carpal tunnel syndrome was considered to be an imbalance between the volume of the carpal tunnel and its contents such as flexor tendons and nerves. 4. The articulations of carpal bones indicated that the motion center of the carpal bones was situated at the head of the capitate. 5. The trabecular orientation was divided into three groups: trabeculae perpendicular to the joint surface, trabeculae crossing each other at right angles which were observed at radial and ulnar prominences of the carpal sulcus, and trabeculae arranged without interruption through the arch of the carpal sulcus.
An antagonistic relationship between epilepsy and psychosis has been claimed. On the other hand, abnormality of the N. accumbens is thought to be involved in schizophrenia and temporal lobe epilepsy. In order to examine the role of the N. accumbens in limbic seizure and psychosis, the following were studied: 1. Amygdaloid kindling and the functional change of the N. accumbens, 2. Accumbens kindling, 3. Functional change of limbic nuclei following the accumbens kindling, and 4. The effects of lesioning of the N. accumbens on the amygdaloid kindling. The results were as follows: 1. The amygdaloid kindling induced epileptic focus and positive transfer into the N. accumbens. 2. The kindling phenomenon was confirmed positive by repeated stimulation of the N. accumbens. Clinicoelectrographic seizure development during the N. accumbens kindling resembled that of amygdaloid kindling. The mean minimum intensities to induce afterdischarge and kindling rate were 620μA and 23days, respectively. 3. Positive transfer was found in the N. amygdala and hippocampus following the accumbens kindling. 4. Lesioning of the N. accumbens had no effect on amygdaloid seizure development, but lowered the threshold intensity to induce amygdaloid afterdischarge after kindling. It was concluded that the N. accumbens and the N. amygdala formed epileptic hyperexcitability reciprocally and that the N. accumbens had an inhibitory effect on the limbic seizure, but no effect on the developed amygdaloid kindling.
Monocyte chemotaxis to zymosan-activated serum was observed in 51 subjects including 31 patients with bronchial asthma, 7 patients with other respiratory diseases, and 13 normal adults as controls, using an agarose plate method. The results were as follows: 1) Monocyte chemotaxis in normal subjects showed no significant difference between females and males or between smokers and nonsmokers. 2) No significant difference was observed in monocyte chemotaxis between normal subjects and patients with bronchial asthma. 3) Monocyte chemotaxis was significantly increased after asthma attacks, although middle dose of glucocorticoid hormone were administered, compared with the non-attack stage and with during an attack. 4) Monocyte chemotaxis was not affected by serum IgE levels, although random migration of monocyte was significantly decreased in asthma patients who had serum IgE more than 500 IU/ml. 5) No significant difference was present in monocyte chemotaxis between two asthma groups defined by age of onset(<or≥40 years old). 6) There was no significant difference in monocyte chemotaxis between skin test positive and negative groups. 7) Small doses of glucocorticoid hormone did not affect the chemotaxis of monocytes from asthma patients. 8) Monocyte chemotaxis was decreased in 2 of 3 cases with hypersensitivity pneumonitis, and markedly increased in one patient with generalized aspergillosis.
Cells were taken from the peripheral lung by bronchoalveolar lavage in 43 subjects including 15 patients with bronchial asthma, 11 patients with sarcoidosis, 4 patients with hypersensitivity pneumonitis, 2 patients with lung fibrosis, and 11 normal adults as controls. Chemotaxis of alveolar macrophage to zymosan activated serum was observed, using an agarose plate method. The results were as follows. 1) The chemotaxis of alveolar macrophages from healthy smokers was increased, compared to that of nonsmokers. The alveolar macrophages from smokers with bronchial asthma or sarcoidosis also showed increased chemotaxis. 2) Alveolar macrophage chemotaxis was significantly decreased in asthma patients (nonsmokers) than in healthy nonsmokers. 3) Alveolar macrophage chemotaxis in asthma patients(nonsmokers) was not influenced by the regimen of small or middle doses of glucocorticoid hormone. 4) The chemotaxis of alveolar macrophages from patients with sarcoidosis(nonsmokers) was significantly decreased, compared to that of healthy nonsmokers. 5) Alveolar macrophage chemotaxis was increased in a patient with hypersensitivity pneumonitis, and decreased in patients with lung fibrosis.
Pulmonary lesions appearing in chest X-ray films were studied in 24 patients with progressive systemic sclerosis (PSS), 25 with polymyositis and dermatomyositis(PM-DM), 30 with rheumatoid arthritis (RA), 37 with Hashimoto's thyroiditis (HT), 59 with Sjögren's syndrome (SS) and 18 with Behçet's syndrome (BS). Pulmonary fibrosing changes were most common in these patients. The incidence of pulmonary fibrosis in connective tissue disease was as follows: 17 patients (71%) in PSS, 16 (64%) in PM-DM, 17 (57%) in RA, 10 (26%) in HT, 23(39%) in SS and 2 (11%) in BS. Pulmonary emphysema was observed in 2 patients with SS and pulmonary infarction was observed in one patient with BS. Fibrotic changes were most severe in PSS, in which positive anti-lung antibody and involvement of the alimentary tract were ofen detected in patients with pulmonary fibrosis. Pulmonary fibrosis in DM correlated well with the titer of anti-lung antibody, but not with other laboratory findings such as anti-nuclear antibody, CH50, RF, CRP, transaminase, LDH or γ-globulin level. In RA, HT, SS and BS, there was no significant correlation between pulmonary fibrosis and the laboratory findings.
The therapeutic effect of steroid hormone (STH) against pulmonary fibrosis was evaluated in 6 patients with dermatomyositis (DM), 6 with progressive systemic sclerosis (PSS), 3 with rheumatoid arthritis (RA) and 5 with idiopathic pulmonary fibrosis (IPF). Of these patients, 7 were male and 13 were female. The average age was 46.5, ranging from 24 to 66 years old. Dosage of STH varied between 10 mg and 40 mg/day in each patient and the mean administration period was 14 months. Clinical effects were determined using chest X-ray film, %VC, PaO2 and direct questioning. Twelve out of 20 patients improved after STH therapy. The clinical effectiveness of STH depended on the ground disease of patients with pulmonary fibrosis; that is, STH was most effective against pulmonary fibrosis in patients with DM and less effective in patients with PSS. STH was also effective in patients with acute stage IPF, but not in patients with chronic IPF. STH seemed to be dose dependent, being more effective in patients with the high dosage of STH. Nodular shadows on chest X-ray film were more sensitive to STH therapy than reticular shadows. Moreover, %VC and PaO2 seemed to be useful for judging the effectiveness of STH therapy.
A cloned strain, CL20, which was derived from the liver of rats fed 4-dimethylaminoazobenzene had low tumor-producing capacity, but had high tumor producing capacity after treatment of the cells with 3'-Me-DAB in the presence or absence of S15 mixture. The size of tumors produced at 60 days after back-transplantation of the cells treated with 3'-Me-DAB in the presence or absence of S15 mixture was larger than that of the non-treated control cells. Similar results were obtained for the weight of tumors produced at 90 days after back-transplantation. Treatment of the cells with 3'-Me-DAB in the presence or absence of S15 mixture produced morphological changes of cells in vitro. The plating efficiency and the size of aggregates formed by rotation culture were higher in treated cells than in control cells. A few differences in growth patterns and in the resistances to the toxic effects of 3'-Me-DAB in the presence or absence of S15 mixture were found between treated and control cells. These findings suggested that cell malignancy was promoted by the treatment of 3'-Me-DAB in the presence or absence of S15 mixture.