This study was aimed to grasp the inflammatory characteristics of DPB and COPD, by measuring the serum protein levels of the immunoglobulins, immunoglobulin G subclasses, complement components and complement hemolytic activities. In spite of the small fluctuation of CH 50, CHT 1/2% and the serum protein levels of the complement components, ACH 50 showed high units in the patients with DPB. These facts suggested both of the high activation and the increase of the suppresive factors without the complement inhibitor proteins on the alternative complement pathway in the patients with DPB. There were no differences in the levels of the immunoglobulins and immunoglobulin G subclasses between the patients with DPB and COPD

View full abstract

Peripheral blood lymphocytes from 6 patients with typical drug fever due to antibiotics were studied by a 2-dimensional flow cytometry analyzer using monoclonal antibodies. The patients were diagnosed according to their clinical symptoms and the fever disappeared after discontinuation of the drug and no other cause for fever could be found. In all 6 patients the percentage of Leu-4⁺HLA-DR⁺ cells significantly increased (19.8±3.75%) at the onset of drug fever compared to that of the normal control group (5.8±2.15%) and acute bacterial infections group (7.0±2.59). The percentage of Leu-4⁺HLA-DR⁺ cells was on the decline after the discontinuation of the drug. Four out of 5 patients were completely normalized within two months after discontinuation of the drug. In the other patient with idiopathic interstitial pneumonitis, the percentage of Leu-4⁺HLA-DR⁺ cells decreased quickly but was not normalized. The higher percentage of Leu-4⁺HLA-DR⁺ cells were associated with an increase of Leu-3a⁺HLA-DR⁺ cells as well as Leu-2a⁺HLA-DR⁺ cells. More prominent increase was found in Leu-2a⁺HLA-DR⁺ cells in comparison to Leu-3a⁺HLA-DR⁺ cells.
Interleukin-2 receptor was also measured using monoclonal antibodies at the same time, but no significant change was revealed.
In conclusion, I consider the increased percentage of Leu-4⁺HLA-DR⁺ cells in total lymphocyte count to be useful method of diagnosing drug fever.

View full abstract

Effects of OK-432 and/or Nocardia rubra cell wall skeleton (NCWS) on superoxide generation from polymorphonuclear leukocytes (PMN) were studied by the new method of Cypridana luciferin analog-dependent chemiluminescence. Superoxide generation from the rat peritoneal PMN stimulated by phorbol myristate acetate or opsonized zymosan was augmented by the 8-day subcutaneous injection of OK-432 or NCWS in vivo, but neither by the 3-day subcutaneous injection nor by the incubation of PMN with OK-432 or NCWS in vitro. Combined 8-day subcutaneous treatment with OK-432 and NCWS induced marked increase in the superoxide generation from PMN stimulated by opsonized zymosan. OK-432 or NCWS did not directly stimulate PMN to generate superoxide under the condition we tested. It is suggested that the increased generation of oxygen radicals induced by OK-432 and/or NCWS may play a beneficial role in the tumoricidal activity exhibited by PMN, and that the augmentative offect of OK-432 and/or NCWS may not be direct.

View full abstract

Several kinds of killer cell activities including natural killer (NK) and lymphokine activated killer (LAK) activities, and subpopulations of lymphocytes were studied in 12 children with growth hormone (GH) deficiency before and during treatment with the intramuscular administration of 0.5U per Kg methionyl growth hormone weekly. The results as follows:
(1) The mean of natural killer (NK) activity against K 562 cells in 12 patients before GH therapy was significantly (p<0.05) lower than that in normal controls. NK activity in the patients, 3 months after initiation of therapy, was elevated to the level comparable to that in normal controls and persisted normally thereafter.
(2) No significant difference could be found in the mean value of interferon-γ, interleukin-2 (IL-2) or OK 432 augmented NK cell activity and prostaglandin E₂ producing suppressor cell activity to NK cells in the patients and in normal controls, and these augmented NK activities persisted normally during GH therapy in the patients.
(3) Although both the mean values of IL-2 and OK 432 induced LAK activities against Raji cells in 9 patients were significantly (p<0.01) lower before therapy, there were no appreciable differences between those in the patients during therapy and those in normal controls.
(4) NK and IL-2 induced LAK activities in each patient during therapy continued without difference with normal controls.
(5) A significant low percentage of Leu 7⁺ cells in 11 patients was observed in the patients both before and during GH therapy.
These data suggest that GH deprivation may cause the defective killer cell activities and number of killer cells, and that GH replacement therapy elevated the function of killer cells, though the number of killer cells remained at a low level.

View full abstract

To evaluate the clinical feature of pulmonary fibrosis and of the patients with the antibodies to 2 types of intermediate filaments (IFs), vimentin and cytokeratin filaments in mixed connective tissue disease (MCTD), we studied 44 patients who were followed at our hospital over 2 years.
Pulmonary fibrosis was diagnosed in 43% of MCTD patients by chest X ray and computed tomography. The intensities of pulmonary fibrosis in most of patients were not severe. PaO² levels of patients with pulmonary fibrosis were significantly lower than those without it, although there were no difference of values of vital capacity and diffusing capacity (DLco) between patients with and without pulmonary fibrosis. MCTD patients with pulmonary fibrosis had frequently proximal scleroderma, but fewer components of systemic lupus erythematosus (SLE).
The antibodies to vimentin and cytokeratin filaments, were assayed by western blotting in sera from 39 patients. The antibody to vimentin from HEL-299 cell was detected in sera of 56% and the antibody to cytokeratin from PtK-2 cell was present in 15% of patients' sera. These antibodies belonged mainly to IgG class. No healthy volunteer had anti-IFs antibody. The frequencies of proximal scleroderma, pulmonary hypertension and pulmonary fibrosis in patients with the antibody to vimentin were higher than the patients without it. This result suggests the possibility that the antibody to vimentin filament is associated with the pulmonary involvement in MCTD.

View full abstract

Sera from fifty-six patients with discrete speckled pattern in the indirect immunofluorescence (IF) test using HEp-2 cells as substrate were tested for antibody to centromere (ACA). Sera from fifty-four of these patients were found to contain ACA in the indirect IF tests using Wil-2 cell line. Thus, the discrete speckled patterns of fluorescence on HEp-2 cells correlated well with positive ACA IF tests on Wil-2 cell line.
ACA was found in sera from fourteen patients with progressive systemic sclerosis (PSS), seven with Raynaud's disease, nine with Sjögren syndrome, seven with SLE, three with RA and fourteen with various diseases. Thus, ACA tend to present most frequently in sera from patients with autoimmune diseases including PSS, SLE, RA, Raynaud's disease and Sjögren syndrome, but was also observed in sera from patients with none-autoimmune heart diseases.
Contrary to the previous reports none of the patients with ACA had all of features of CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia), though many patients had Raynaud's phenomenon.

View full abstract

The peroxidase-labelled IgG fraction of anti-nRNP serum obtaind from a MCTD patient was used to study the intracellular localization of n-RNP antigen. Nuclei of almost all kind of cells taken from man and rat were stained in a speckled pattern. The nuclei of the tonsil lymphocytes showed a various pattern of staining with thick and thin tone.
Cytoplasmic staining was observed in the anterior horn or rat spinal cord and this staining was abolished by treating the tissue sections with RNase for 90 min.
In the nodule of hepatocellular carcinoma, intensity of the staining by the labelled anti-nRNP antibody decreased from periperal to central zone.
During the cell differentiation of the cultured cells HeLa, the staining of nRNP antigen changed from nuclei to cytoplasma.
The presence of U1 nRNP antigen in different tissue distribution and durign cell cycle might be affect for the clinicophathology of patients with MCTD who have autoantibody to this antigen.

View full abstract

The effects of intact immunoglobulin (pH 4-treated) preparation, F(ab')₂ (pepsin-treated) preparation, purified IgG and purified F(ab')₂ fragment on IL-1 production in human monocytes stimulated by silica suspension were investigated.
Measure of IL-1 activity was gauged by the proliferation ability of peanut agglutinin (PNA) non-agglutinating cells. High concentration (mg/ml) of either intact immunoglobulin preparation or F(ab')₂ preparation was unable to induce IL-1 production in unstimulated cells. However, both preparations enhanced IL-1 synthesis in human monocytes that had been stimulated by silica suspension. Incidentally, low concentration (μg/ml, ng/ml) of purified IgG boosted IL-1 production in such cells. On the other hand, low concentration of purified F(ab')₂ fragment had negligible effect. Also by the ELISA method, high concentration and low concentration of purified IgG enhanced IL-1 α and β productions in such cells, however, enhancement by low concentration of purified F(ab')₂ fragment was negligible.
These results suggest that the F(ab')₂ preparation is less potent than intact immunoglobulin preparation in inducing IL-1 production by monocytes.

View full abstract

A 30 years-old male was admitted to our hospital in 1985 with tonsilitis and fever. Because anti-neutrophil antibody was detected by cytotoxic assays, we diagnosed that he had autoimmune neutropenia (AIN). After treatment with predonisolone (60_??_100mg/day) for 34 days, neutrophil count (66/mm³) gradually returned to normal level, but abruptly platelet count abruptly decreased to 4, 000/mm³. Because platelet associated IgG turned positive at the level of 63.4ng/10⁷ cells, we diagnosed he had combined immunocytopenia.
Since any therapeutic trial was not responded with beneficial effects for thrombocytopenia, splenectomy and partial spleen autograft implantation (splenosis) were performed. Platelet and neutrophil counts were markedkly increased after the operation. He died of overwhelming post-splenectomy infection syndrome (OPSI) one week after the discharge. Autopsy revealed that his implanted spleens were intact. There were slight intravascular coagulation lesions in the lung and the kidney. Peptostreptococcus was detected from the blood specimen.
Fulminant bacterial infection called OPSI is reported in the splenectomized patients. It has been demonstrated that splenectomy is responsible for alteration in host defense especially opsonization and phagocytosis against bacteria. In this point of view, we performed splenosis not to deteriorate host defense mechanism. However, it is further recommended that the bacterial vaccination should be administrated to reduce the risk of OPSI.

View full abstract

We described an autopsy case of aortitis syndrome associated with Sjögren's syndrome. A 52 years-old female was admitted to our hospital with adult distress syndrome (ARDS). She had been diagnosed as aortitis syndrome, Sjögren's syndrome and pulmonary fibrosis from March 1985. She died of pulmonary hemorrage due to miliary tuberculosis. Autopsy revealed that 1) arteritis affecting the aortic arch and subclavian artery, 2) chronic siliatis in mandibular glands, 3) pulmonary fibrosis, 4) miliary tubercules in the multiple organs. Although certain rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and Behcet's disease have been reported to be associated with aortitis syndrome, this is a first case report of a patient with aortitis syndrome associated with Sjögren's syndrome.

View full abstract

A 70-year-old female patient with idiopathic interstitial pneumonia (IIP) was reported. After the diagnosis was confirmed, she was given oral prednisolone 60mg/day in April 1986. Her conditions improved with this treatment. In June 1986, however, when the dose of prednisolone was decreased to 45mg/day, she complained of severe dyspnea and PaO₂ was markedly decreased. Immediately after cyclophosphamide 400mg was administered intravenously, her conditions improved. In September 1986, when she developed actute exacerbation of IIP again, intravenous administration of cyclophosphamide (500mg) was effective as well. It is suggested that intravenous administration of cyclophosphamide might be very effective for acute exacerbation of IIP, although both corticosteroid and cyclophosphamide were unable to modify the on-going disease activity.

View full abstract

A case of systemic lupus erythematosus (SLE) associated with idiopathic portal hypertention (IPH) was reported.
In February 1969, a 48 years old woman was admitted because of general fatigue and polyar-thralgia. She had polyarthritis, butterfly rash, splenomegaly, leucopenia and antinuclear antibody. She was diagnosed as SLE, and treated with paramethason. She responded rapidly to the treatment except splenomegaly. In 1974, she developed hair lossand thrombocytopenia. In 1977, esophagial varices were demonstrated by upper gastrointestinal X-ray examination. In April 1978, she was transfered to our hospital. The examinations of liver scan, celiacangiography and hepatic venography were performed, which demonstrated marked splenomegaly and esophagial varices due to portal hypertention. She was therefore diagnosed as SLE associated with IPH, and esophagial transection was done. In 1983, the patient was admitted because of nausea and vomitting. In October 1983, she was died due to hematoemesis. At autopsy there was a marked splenomegaly. Pathological findings of the liver were compatible with characteristic features of IPH.
Complication of IPH in SLE is rare and pathogenesis of IPH is unknown. It might be suggested that the common immunological mechanism playes a role on the etiology of both SLE and IPH because IPH developed at the onset of SLE in this case.

View full abstract

A 65 year-old-male with multiple polyposis of the gastrointestinal tracts, with hyper-γ-globulinemia and with generalized lymphadenopathy representing the histopathological characteristics of Castleman's lymphoma is described. The patient first complained general lassitude at his age of 64 with laboratory findings of anemia and hyperproteinemia. On admission, June 28th 1983, generalized lymphadenopathies (bilateral cervical, supraclavicular, axillary and inguinal) were noted. At the right lower abdominal quadrant, a soft tumor (8×8cm) with unclear margin was found. Digital examinations revealed multiple polyposis at the rectum. Laboratory data: Hb 7.3g/dll, thrombocytes 22.5×10⁴/μl, WBC 8, 400/μl with 11% of atypical lymphocytes. Bone marrow: nucleated cell count 33.7×10⁴/μl, plasma cells 7%, atypical lymphocytes 5%. ¹²⁵1-PVP test 2.39%, CRP 1.0mg/dl, cold agglutinin titer×1, 024, toxoplasma test×640. EBV antibody was strongly positive. Total proteins 9.2g/dl with 56.9% of γ-globulin. IgG 5, 090mg/dl, IgA 677, IgM 169. IgG-κ-type M protein was present. OKT 4: 10.7%, OKT 8: 17.6%, and OKT 4/8 ratio: 0.59, Upper GI: gastroptosis with giant folds and with polypoid changes was noted. Disseminated polyposis was also observed in the jejunum and in the ileum. Lower GI: multiple polyposis was observed in the colon and in the rectum. Lymph node biopsies: follicular hyperplasia was observed with the proliferation of blood vessels with partial hyalinization, and of plasma cells with cluster formation. Pathological cells resembling Warthin-Finkeldey's giant cells were also observed sporadically. Biopsies of the GI tracts: no epithelial changes were observed in the stomach, the duodenum and the rectum. Marked infiltration of plasma cells and lymphocytes was noted at the submucosal region. Hyalinization of blood vessels was also observed at the rectum. These findings at the GI tracts were identical to those at the lymph nodes.

View full abstract

An interspecies cross-reactive pancreas antigen (PA3) was prepared by a monoclonal antibody (SP 3-1, IgM), which reacted with duct cells of multiple exocrine organs. Specific cell-mediated immunity to PA3 was examined using lymphocyte proliferation test. Lymphocyte sensitization was demonstrated in five of 20 patients with idiopathic chronic pancreatitis, three of 12 patients with alcoholic chronic pancreatitis, and 10 of 15 patients with Sjögren syndrome, whereas only one of 8 patients with PBC, and none of 7 patients with stone related chronic pancreatitis and normal controls (n=14) showed positive results. These results revealed a possibility that PA3 was the target antigen for cellular immune-response in the pathogenesis of chronic pancreatitis and/or Sjögren syndrome.

View full abstract