The levels of histamine and leukotriene C₄ (LTC₄) in bronchoalveolar lavage (BAL) fluid and the release of these mediators from BAL cells stimulated by Ca ionophore A 23187 were examined in 22 athmatic subjects. In BAL fluid, histamine was detectable in 9 (40.9%) and LTC₄, was detectable in 10 (45.5%) of the 22 asthma patients. BAL cells from patients with detectable histamine (DH), many of whom were evaluated as atopic, released more histamine and less LTC₄ than those of patients without DH. In contrast, BAL cells from patients with detectable LTC₄ (DL), many of whom were assessed as nonatopic, released more LTC₄ and less histamine than those of patients without DL. These results suggest that histamine and LTC₄ levels differ in relation to the IgE-mediated allergic reaction.

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In radioimmunoassay or enzyme-linked immunosorbent assay (ELISA) for IgG rheumatoid factor (RF), IgM RF may interfere the results by binding of non-RF IgG. In order to destroy the IgM RF activity, dithiothreitol (DTT), a reducing agent, was used for testing IgG RF by means of IgG RF kit ED 001 (Eizai). In DTT-untreated and treated sera from 18 patients with RA, titers of IgG RFs were compared with the disease activity of rheumatoid arthritis (RA) assessed with Lansbury's activity index (AI). With DTT treatment of sera from 18 RA patients, IgM RF activity was completely abolished but the mean IgG RF activity was modestly decreased by 32.3%. The change in titers of DTT-untreated IgG RFs correlated significantly with the change in AI (68.6%, p<0.05%) and the change in titers of DTT-treated IgG RFs correlated also significantly with the change in AI (73.5%, p<0.01). In gel filtration analysis of IgG RF positive sera treated and untreated with DTT, from representative seropositive RA, IgG RFs were suggested to be present in serum as monomer, dimer, trimer or tetramer in forming self-association and some of IgG RFs bound to IgM RF in forming large complexes. From these data, it was suggested that DTT treatment was effective to assess the false positive serum for IgG RF. However, DTT treatment did not seem to be necessary to evaluate the relationship between IgG RF and AI.

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It is known that human lymphotropic virus type I (HTLV-I) is closely associated with adult T cell leukemia (ATL). The immunological abnormality of T lymphocytes in patients with ATL is characterized by their abnormal expression of the 55 kDa chain of the receptor for interleukin 2 (IL-2 R/p55 (Tac)), and the down-regulation of CD 3 antigen. HTLV-I gene products such as p 40^tax or ATL-derived factor (ADF) have been shown to enhance the expression of IL-2 R/p55 (Tac). However, the mechanism of down-regulation of CD 3 antigen on T lymphocytes in ATL patients still remains unclear. We found that CD 3 expression on peripheral blood mononuclear cells (PBMC) in healthy individuals was decreased significantly by treatment with sera and cell culture supernatants from ATL patients whose CD 3 expression on PBMC was decreased markedly, but not by sera and cell culture supernatants from ATL patients whose CD 3 expression was normal. Gel-chromatography for cell culture supernatant showed that CD 3 down-regulating activity was fractioned in the fraction number 11 which arrowed 40-60 kDa. Next, after culture with various cytokines (IL-1, IL-2, IL-4, IL-6, IFNγ and TNFα), the expression of CD 3 on normal PBMC was not reduced significantly. Furthermore, by treatment of cell culture supernatant with various anti-cytokine antibody, the expression of CD 3 antigen on normal PBMC was down-regulated. As mentioned above, there are novel factor (s) with CD 3 down-regulating activity in the sera and cell culture supernatants of those acute ATL patients. In this study, we tried to clarify the mechanism of down-regulation of CD 3 expression on ATL cells, based on the finding of soluble factor (s) down-regulating CD 3 molecule.

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Peptide histidine isoleucine (PHI) as well as vasoactive intestinal peptide (VIP) is considered to be a neurotransmitter of non-adrenergic and non-cholinergic inhibitory nerves in the respiratory tract. We tried to measure PHI like immunoreactivity in the respiratory tracts from guinea pigs to evaluate the movement of PHI. A high titer of PHI antiserum which did not react with VIP was obtained from a rabbit immunized with rat PHI, and PHI like immunoreactivity in the respiratory tract from guinea pigs was measured by radioimmunoassay. Tracheas, extrapulmonary bronchi and lungs were dissected and treated by microwave irradiation. They were homogenized with 0.5 N acetic acid and centrifuged at 35, 000×g. Lyophilized supernates were used as samples for the radioimmunoassay. PHI like immunoreactivity per g wet weight tissue was 6.85±2.75 (mean±SD) ng in the tracheas, 2.26±0.27 ng in the extrapulmonary bronchi and 0.75±0.90 ng in the lungs, indicating that PHI like immunoreactivity is present more in the central airways than in the peripheral ones. Intravenous administration of leukotriene C₄ (3μg/kg/hr) reduced significantly PHI like immunoreactivity in the tracheas and the extrapulmonary bronchi in parallel with the significant increase of dynamic respiratory resistance.

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We measured serum levels of IgG-RF of the patients with rheumatoid arthritis and other collagen diseases (systemic lupus erythematosus, Behcet's disease, Sjögren's syndrome, progressive systemic sclerosis, mixed connective tissue disease). In RA, 25.5% (24/94) exceeded cut-off value. On the other hand, 0-5.6% patients exceeded cut-off value in other groups of collagen diseases except for Sjögren's syndrome. In two cases of allergic granulomatous angiitis, the levels of IgG-RF exceeded cut-off value. The levels of IgG-RF were gradually higher following progression of X-ray stage and ADL class of RA. The levels of IgG-RF correlated with Lansbury's activity index, joint point, grip power, erythrocyte sedimentation rate, IgM-RF, C-reactive protein and TNF-α in sera. Circulating ICAM-1 in the sera was considered to be concerned with vasculitis based on our investigation. In this study, it was measured to show correlation with the levels of IgG-RF. It was suggested that the levels of IgG-RF were concerned with vasculitis as well as circulating ICAM-1.

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Using rabbits, this study was undertaken to ascertain whether various physical conditions of the host, as well as pretreatment with prednisolone, affect the glucocorticoid receptor (GR) content of the bronchoalveolar lavage (BAL) cells. Our results have shown that BAL-cells from rabbits of various ages were found to exhibit an age-dependent reduction of the GR content. As for the effect of nutritional deprivation, the GR content tended to increase during the initial phase of malnutrition (days 4 to 8), and then return to the control level after day 12. Most significantly, the GR content of the BAL-cells from malnourished rabbits showed a limited response to cellular activation. Further, chronological changes were seen in the GR content of BAL-cells from non-treated rabbits and from sensitized rabbits that were given an intravenous injection of prednisolone (2mg/kg). In both instances, the GR content showed a transitory decrease after 3 hours, and a rapid increase by day 4, followed by a return to the control levels. In contrast, no significant changes in the dissociation constant were seen among the BAL-cells from each experimental procedure. These results indicate that the GR content of BAL-cells are greatly influenced by the conditions of the host, such as aging, cellular activation from a sensitization, malnutrition, and pretreatment with a steroid, so that these factors should be considered before deciding on a regimen of steroid therapy.

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Serum anti-streptococcal antibodies were examined by the enzyme-linked immunosorbent assay. Levels of IgG and IgA antibodies in sera of patients with Behçet's disease against crude cell walls of Streptococcus salivarius (strain HHT) were significantly higher than those of healthy controls and patients with chronic recurrent aphthosis. IgA antibody titers of Behçet's patients against crude cell walls of S. pyogenes (M1, ATCC 19618) and S. sanguis (biotype A, serotype I, strain ST 3) were also significantly higher than those of healthy controls, but not higher than those of patients with chronic recurrent aphthosis.
The correlation between anti-streptococcal antibody titers and clinical findings of Behret's disease was investigated, and it was revealed that most of Behçet's patients having had high titer of IgG antibody against S. salivarius belonged to the complete type of Behçet's disease. Sera from Behçet's patients with high titer of IgG antibody against S. salivarius reacted with a 48 kDa antigen of the crude cell wall by using Western blotting. However, this antigen also reacted with sera of patients with chronic recurrent aphthosis. Therefore, the antibody to the 48 kDa antigen was not considered as the pathognomonic finding in sera of patients with Behçet's disease.

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This report described five old aged patients with acute hypoxia, thrombocytopenia, liver dysfunction and hypergammaglobulinemia in the passage of parainfluenza (III) infection. They were treated with steroid pulse therapy (methylprednisolone 1 g/day×3 days) with symptomatic and laboratory improvement.
On physical examination, skin eruption was noted, and it improved after steroid pulse therapy. Serological studies revealed an elevated titer of serum antibodies to parainfluenza virus type (III) with improvement after treatment.
The effective steroid pulse therapy in these cases might provide an explanation of the pathogenesis for an abnormal allergic state caused by viral infection or drug allergy. Further investigation is necessary to make adequate understanding of this pathogenesis.

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Sjögren's syndrome (SjS) associated with primary biliary cirrhosis (PBC) with normal liver function is reported.
A 67-year-old female who had been suffered from xerostomia for eighteen years, and Raynaud's phenomenon and telangiectasias for four years, and pururitis for three years, was admitted because of right hypochodralgia. Laboratory findings on admission were as follows: antinuclear antibody 1:640 (discrete speckled), anti-centromere antibody 1:2, 560, antimitochondrial antibody 1:160, RAPA 1:80, antibodies to SS-A and SS-B negative, liver function normal. Abdominal echography showed a gall stone and chronic liver disease. Her labial salivary gland biopsy was consistent with SjS. Liver biopsy was performed during a cholecystectomy and showed chronic nonsuppurative destructive cholangitis.
Our case is diagnosed as SjS associated with primary biliary cirrhosis with normal liver function and is regarded as an interesting case on thinking about clinicopathology of early PBC and clinical significance of anticentromere antibody

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A 58-year-old female was admitted to our hospital on February 18, 1991 because of punched out lesions. No abnormal cells were revealed in the peripheral blood and bone marrow. Serum levels of BUN (93.1mg/dl), creatinine (2.7mg/dl) and calcium (14.5mg/dl) were elevated. M-component in her serum was not detected. X-ray of the skeleton revealed prominent punched out lesions in the skull and long tubular bones. On March 11, peripheral blood suddenly showed marked leukocytosis and hypercalcemia (21.0mg/dl). The flower cells appeared. Serum anti-HTLV-I antibodies was positive and HTLV-I proviral DNA was demonstrated in the peripheral lymphocytes. She was diagnosed as adult T-cell leukemia (ATL). Serum PTHrP level (319.0pmol/l) was also elevated. She was treated with CHOP regimen, but the patient died of disturbances of respiratory function due to brain metastasis. This might be a fairly rare case of ATL with punched out lesion.

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A 2 month old infant, who developed bronchial asthma in several months post RSV infection with IL 2-induced responsiveness by peripheral mononuclear cells stimulated with allergen such as OVA, α-casein and Df is reported. He complained of first wheezing on admission and was diagnosed of bronchitis with atelectasis of right upper lung. Viral studies showed positive RSV antigen in nasal smear as determined by ELISA and FA. Although IgE RAST score of HD, mite, egg white, cow milk and soy bean, and serum level of IgE were low, IL 2 responsiveness by the patient's lymphocytes was induced upon stimulation with allergens such as dermatophagoides farinae (Df) and α-Casein. The OVA-and JC-induced response followed several month later. Such responses were not induced in age-matched lymphocytes from other viral infection. Maximum responses were shown over the course of 4 to 5 months after RSV infection, which corresponded to increased frequency of wheezing, resulting in diagnosis of bronchial asthma. The results indicate that RSV-sensitized lymphocytes from the patients have acquired hypersensitivity to allergens such as food and mite antigens, which might involved in the onset of stopic diseases.

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Two cases of fatal virus-associated hemophagocytic syndrome (VAHS) were reported.
Case 1. A 2-year-old boy was admitted to our hospital with hepatic failure and sepsis. Bone marrow examination revealed typical hemophagocytes, and both EBV VCA-IgM and EBNA were negative. Despite the combined administration of antiviral agents, interferon alpha, high dose of γ-globulin and liposteroid, the patient rapidly developed multiple organ failure and died after a total clinical course of 37 days. The autopsy showed that all of the organs examined were infiltrated with atypical lymphoid cells with prominent necrosis. The EBV genome was demonstrated in the lymphoid tissue, kidneys and salivary glands by Southern hybridization technique.
Case 2. A 2-year-old girl was refered to our hospital with persistent high fever of unknown origin. The laboratory examination revealed anemia, leukopenia and abnormal liver function tests on admission, and deteriorated to typical signs of VAHS. Interstitial pneumonia appeared and she was treated with high-dose γ-globulin and methylprednisolone pulses. However, respiratory failure was progressed. Lung biopsy revealed giant-cell pneumonia, and measles virus was detected in the viral culture despite the lack of skin rashes. The immunosuppressants, VP-16 and liposteroid, were administered to the patient, but failured.
They manifested similar clinical course and the etiologic agent were varied. Since the pathophysiology of VAHS is believed to be immunologically a hyper reactive status to the infected virus, the immunosuppressive therapy was employed, but failed. The immunological mechanism of VAHS should be investigated.

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