In order to clarify the role of cell mediated immunity in autoimmune diseases concanavalin A-induced suppressor T cell function (Con A-Ts) was investigated by the Shou's method and autologous mixed lymphocyte reaction (AMLR) which is induced between T and non T cells, Tγ and non T cells, and non Tγ and non T cells. The patients studied included 26 cases of systemic lupus erythematosus (SLE), 27 of Sjögren's syndrome (SJS), 10 of progressive systemic sclerosis (PSS), 17 of polymyositis (PM) and together with 20 of healthy volunteers as control group.
Both Con A-Ts and AMLR between Tγ and non T cells in the patients with SLE were significantly decreased than those in the control group. The study on lymphocytes from the patients with SLE during both active and inactive phase of this disease revealed that the patients with active SLE showed the defects in Con A-Ts and in the ability of both T and Tγ cells to respond in AMLR. The patients with inactive SLE, however, exhibited inresponsiveness of Tγ cells alone. But Con A-Ts tended to be increased in inactive SLE than in active SLE. So far as the SJS was concerned, both sicca alone and sicca complex exhibited the decreased Con A-Ts and AMLR between Tγ and non T cells. Moreover, the significant correlations of Con A-Ts to AMLR between Tγ and non T cells were found in SLE (r=0.51, p<0.05), and in SJS (r=0.61, p<0.02). On the contrary, in PSS and PM, AMLR remained within normal range in spite of a decrease in Con A-Ts.
These results might suggest that the similar defects of cellular immunity exist in SLE and SJS.

View full abstract

Our previous studies demonstrated both humoral and cell-mediated autoimmunity to the goblet cell of the colon to be recognized in ulcerative colitis. As one of the characteristics of this disease is ascending and continuous lesion that arises from the rectum to the oral parts of the colon, we consider that the boundary zone between the uninvolved and involved portion of the colon, in which an attack of immunocompetent cells to the goblet cell occurs and the mucosal defence is destroyed, has an important key to understand this disease. On the other hand, it has been reported that secretory component (SC) and IgA are important factors in the mucosal defence mechanism.
In this paper, 11 patients-three with proctitis, six with left-sided colitis, and two with total colitis-were investigated as for the correlation of SC, IgA, and goblet cell mucus in the colonic mucosa. Biopsy specimens, which were obtained from uninvolved, involved portions, and boundary zones with colonofiberscope, were examined regarding their distribution with immunofluorescent staining technique.
Both SC and IgA were decreased in distribution in mucosa of uninvolved portion and boundary zone, whereas goblet cell mucus was kept abundantly. And all of them were decreased in distribution in mucosa of involved lesion. So it seems that these three factors have an important relationship to each other in the colonic mucosal defence in ulcerative colitis.

View full abstract

Complex-release activity (CRA) of complement was measured in 30 systemic lupus erythematosus (SLE) patients by our simple method using peroxidase as an antigen in immune complex. We studied the relationship among CRA and other complement levels, and the influence of CRA on the pathogenesis of SLE was discussed. CRA in SLE was lower than that in normal subjects and correlated with CH 50, ACH 50, C3, C4 and factor B. In some patients with persistent hypocomplementemia, reduced CRA was normalized soon after the administration of corticosteroid. In other patients, CRA correlated with clinical manifestations such as lupus nephritis or skin erythema. These observation suggested that the measurement of CRA might be more useful than that of CH 50 in some SLE patients and that CRA would affect tissue injury due to immune complex.

View full abstract

A case of SLE with simultaneous occurrance of interstitial pneumonitis and systemic angiitis after administration of antibiotics and antituberculous drugs is reported.
A 24-year-old woman developed fever and arthralgia during her first pregnancy. On admission in April 1980, she had a mild proteinuria, casturia, hypergammaglobulinemia, positive antinuclear antibodies, high titers of anti-DNA antibody and hypocomplementemia. Circulating immune complex was positive. Renal biopsy revealed mild mesangial proliferation and wire loop lesions in glomeruli. A diagnosis of SLE was made and prednisolone 40 mg daily was effective. In March 1982, fever relapsed when prednisolone was tapered to 10 mg daily. On the second admission, facial erythema was noted. Anti-DNA antibody was 304 U/ml (normal 10 U/ml), CH₅₀ 13.7 U/ml, CRP 2+ and the erythrocyte sedimentation rate 54 mm per hour. Prednisolone was increased to 30 ml daily. Fever subsided and titers of anti-DNA antibody decreased. In May 1982, fever, mononeuritis multiplex, dry cough and mild dyspnea developed when she was treated with Cefaclor for a carious tooth. In June, combination therapy with SM, INH and RFP was added because another SLE patient in the same ward was discovered to have pulmonary tuberculosis. Soon after psychosis, tremor and rigidity developed and dyspnea worsened. Blood gas analysis revealed severe hypoxemia and an X-ray film of the chest revealed diffuse interstitial infiltration in both lungs. Interstitial pneumonitis, CNS lupus and systemic angiitis were suspected. Pulse therapy with methylprednisolone was started with rapid improvement of hypoxemia and neurological symptoms. Interstitial pneumonitis relapsed again after slight reduction of prednisolone. The patient died after massive gastrointerstinal bleeding and anuria.
At autopsy, subacute interstitial pneumonitis was observed in both lungs without evidence of cytomegalic inclusion body, Pneumocystis carinii or other opportunistic infections. Generalized angiitis in healing phase with adventitial fibrosis, intimal thickening, mural thrombosis, and ruptured internal elastic laminae was found in small arteries of kidneys, heart, liver, pancreas, spleen, small intestine, adrenal glands and ovaries. However, no evidence of angiitis was found in pulmonary arteries. Ruptured internal elastic laminae were found in the main coronary arteries.
This case represents a rare combination of interstitial pneumonitis and systemic angiitis in SLE, in which antibiotics and antituberculous drugs were implicated as triggering factors.

View full abstract

Although anemia is commonly seen in SLE patients, the patogenesis of anemia is not clarified. In order to research the pathogenesis of anemia seen in SLE, and the effect of prednisolone on heme synthesis of patient's bone marrow erythroblasts, and patient's peripheral mononuclear cells were studied means of Krantz's method. Bone marrow erythroblasts (10⁶) were cultured with 1.0U of erythropoietin with Fe⁵⁹ in 1.0ml of pH 7.4NCTC 109, containing 20% human unactivated AB plasma, and added prednisolone or patient's mononuclear cells prior treated with prednisolone at 37°
C, containing 5% CO₂ in air for 72hours. Heme synthesis of the erythroblasts was measured by counting the radioactivity of Fe⁵⁹ incorporated into the heme with a γ-scintillation.
Results were as follows,
1. Prednisolone had no effect on heme synthesis of erythroblasts from normal human bone marrow.
2. Heme synthesis of patient's bone marrow erythroblasts was obviously improved adding prednisolone.
3. Patient's peripheral mononuclear cells treated with prednisolone did not suppress the heme synthesis of normal erythroblasts from human bone marrow. Theses results suggest that the patient's mononuclear cells affectionable with prednisolone may be participating in the pathogenesis of anemia seen in SLE patients.

View full abstract

Since 1965, Carcinoembryonic Antigen (CEA) was extracted from metastatic liver specimens of colon cancer and purified with several techniques.
But, several investigators have struggled with the characteristics of CEA. And CEA could be detected at high plasma level with the lung cancer patients. But the nature of CEA in the lung cancer specimens was not analyzed precisely related to CEA from tumors of colon or other organ.
In this paper, CEA in the human lung cancer cell line, HLC-1 (CEA) was purified from the spent culture medium.
HLC-1 (CEA) was purified with the combination of gel filtration chromatography, affinity chromatography, polyacrylamide gel electrophoresis (PAGE) and agarose-IEF electrophoresis. Physicochemical properties of HLC-1 (CEA) was found to be similar to those of CEA from colon cancer derived liver metastatic specimens at the point of amino acids compositions, but slightly different at molecular weight, HLC-1 (CEA)=27×10⁴ dalton, and pI, HLC-1 (CEA)=4.4.
HLC-1 (CEA) was similar to colon cancer-derived CEA but differed from NCA-1, NCA-2 by means of immunodiffusion method using guinea pig anti-[HLC-1 (CEA)] serum.
Immuno-histochemical studies also revealed that HLC-1 (CEA) was cancer specific antigen but not lung cancer specific antigen.

View full abstract

The measurement of intracellular ATP levels using luciferinluciferase induced bioluminescence was used for the evaluation of proliferative responses of human mononuclear cells to lectins. A linear relationship was observed between cell numbers and ATP contents in samples, and high reproducibility was confirmed. Lectin-stimulated mononuclear cells increased ATP contents with the passage of time, and a significant difference from non-stimulated cells was obtained 48hrs after culture. Furthermore an interesting results that the pre-treatment with mitomycin C strikingly increased the ATP level of lectinstimulated cells, but not that of lectin-non-stimulated cells was obtained. These findings suggest that proliferative response of mononuclear cells can be measurable without the use of isotope, and that more early event occurring in stimulated cells may be analyzed by this simple method.

View full abstract

On the decrease in polyclonal Ig levels in patients with multiple myeloma (MM), several hypotheses have been proposed. By measuring in vitro Ig synthesis by mononuclear cells from peripheral blood (PMC) and from bone marrow aspirates (BMC) in a patient with IgG K myeloma, interesting results were obtained.
The patient's WBC and lymphocytes are normal in number. Serum Ig levels were IgA 27, IgG 993 and IgM 58mg/dl. Urinary excretion of Bence-Jones protein was 7_??_10g/day. The amounts of IgG synthesized by PMC were markedly reduced, while those of IgA and IgM were almost equal to normal values. Hyperactivity of IgG specific suppressor T cells was responsible for the impairment of IgG synthesis. The amounts of Ig synthesis by BMC were markedly impaired for IgA and IgM and some what low for IgG. BMC could synthesize IgG without PWM-stimulation and moreover, B cells in BMC could synthesize IgG in the absence of T cells. Therefore, IgG synthesized by BMC was probably myeloma protein, not polyclonal IgG.
Considering these results, we proposed a hypothesis that low levels of polyclonal IgA and IgM in this case were certainly caused by decreased synthesis of them in the bone marrow. Low level of IgG was caused by impaired synthesis of polyclonal IgG in PMC and also reduced synthesis of myeloma protein in the bone marrow. As myeloma protein synthesis by BMC was reduced, this case seems to belong to so called “oligo-M-component type” in multiple myeloma.

View full abstract

This 53 year-old female had been admitted to our hospital in 1975 with the complaints of general malaise, hoarseness and facial edema. She was diagnosed of Hashimoto's thyroidits, chronic active hepatitis and Sjögren's syndrome by biopsies of the thyroid glands, the liver and the salivary glands and was administered prednisolone, azathioprine and thyroid hormone.
In 1981, she was admitted to our hospital for the second time with the complaint of left upper quadrant pain. The X-ray examination of the upper gastrointestinal tract and gastric endoscopy showed multiple ulcers with submucosal tumor at the gastric antrum. The biopsy specimen of the gastric mucosa suggested the diagnosis of malignant lymphoma of the stomach. However, subtotal gastrectomy was performed and surgical specimen demonstrated diffuse infiltration of plasma cells with pleomorphism. Immunohistochemical staining revealed in_??_ra cytoplasmic immunoglobulin, mainly IgM kappa and she was diagnosed of malignant extramedullary gastric plasmacytoma. Liver biopsy performed simultaneously showed characteristic changes of the primary biliary cirrhosis.
We believe that this case is the first case of Sjögren's syndrome associated with extramedullary plasmacytoma of the stomach, Hashimoto's thyroiditis and the primary biliary cirrhosis.

View full abstract