[Drug induced lupus erythematosus].
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Biomedical subjects
Publications and source records attributed to Y Shoenfeld.
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The existence of subpopulations of macrophages which express a variety of regulatory activities of other branches of the immune system is suggested in a comparative study of a human macrophage long term culture ZI and a macrophage cell line DAB-1. Both cell cultures were derived from pleural effusions of patients with diffuse histiocytic lymphoma. DAB-1 cells were found to secrete factors which strongly suppress the response of normal T and B lymphocytes to the mitogens PHA, Con-A and pokeweed mitogen (PWM) (by 96-98%) and to stimulate the cytotoxic activity of NK cells. ZI cells secrete factors which have a mild inhibitory effect on the response of lymphocytes to the T-cell mitogens PHA and Con-A and a stimulatory effect on the response to PWM, whereas very little effect could be detected on the activity of NK cells. While DAB-1 cells form large clusters during growth in culture, and are capable of inducing the formation of lymphocyte rosettes around the tumor cells, ZI cells grow as a homogeneous monolayer and could not be shown to form such rosettes. The differences in the behavior of the two cell populations suggest that the malignant transformation may have affected different subsets of macrophages in each case. Cells from histiocytic lymphoma patients may therefore be a source for homogeneous subpopulations of macrophages and their isolation and propagation in culture is one approach by which such subsets can be defined characterized and classified. The biological characterization of macrophage subsets may also be of clinical importance since a transformed subset with broad suppressory activities may lead to a violet and rapidly deteriorating course of disease, as was in the case of the patient from whom the DAB-1 cell line was derived.
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13 patients with adult non-lymphocytic leukemia (ANLL) who developed central nervous system (CNS) involvement during the course of their illness are reported and compared with a control group of 26 ANLL patients without CNS involvement. The incidence of CNS involvement was 13/510 patients (2.5%). Initial symptoms and signs and routine laboratory data were not helpful in predicting which patients would ultimately develop CNS involvement. Almost 1/2 of the patients were in clinical and haematological remission at the time of the diagnosis of CNS involvement. Specific treatment to the CNS including intrathecal cytotoxic drugs and/or radiotherapy failed to increase the survival rate significantly. Whether the establishment of an early diagnosis of CNS involvement and the institution of appropriate treatment may improve the prognosis of this complication is a question which presently remains unanswered.
Salt tablets are habitually ingested by some people while doing physical exercise in hot climate, in order to prevent sodium depletion. The effects of supplementary salt on the intraocular pressure was investigated on 5 healthy acclimatized subjects who rode a bicycle ergometer at temperature of 35 degrees C and relative humidity of 40%. A significant decrease of 1.0 mmHg in their mean intraocular pressure was detected when 10.2 gm NaCl was added daily to the normal diet. The pressure reduction was associated with changes of the body fluid balance.
The review of the pertinent literature disclosed 36 reports of familial multiple myeloma, described mostly in siblings, to which the authors add one more family. These patients did not differ significantly from those with non-familial myeloma with regard to sex, age, distribution of monoclonal proteins, clinical and laboratory data, and the course and prognosis of the disease. An increased incidence of immunoglobulin abnormalities was observed in healthy relatives of patients affected with familial myeloma. In most cases the time interval of the diagnosis of myeloma in a family member of a known patient was under 4 years. These observations, in conjunction with reports of myeloma occurring in clusters in a community and the appearance of myeloma in spouses raise the possibility of an environmental factor (virus?) which may contribute to the pathogenesis of myeloma in genetically predisposed individuals. Multiple myeloma should be added to the list of neoplastic diseases in which the family history is relevant and in which genetic and possibly environmental factors may be pathogenetically involved.
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A patient with thrombotic thrombocytopenic purpura was treated with 8 U of fresh frozen plasma, resulting in a rapid improvement in her condition and subsequently followed by a prolonged clinical remission. The transmission and scanning electron microscopic examinations of the platelets performed before treatment demonstrated marked anomalies of the platelet morphology, namely, an increased number of abnormally elongated pseudopods with terminal knobs, a decreased number of platelet granules and excess of glycogen and marked anisocytosis. These anomalies remained unchanged when reexamined 2 months after the achievement of the clinical remission. The question whether these platelet abnormalities are an integral part of thrombotic thrombocytopenic purpura and play a role in its pathogenesis, is raised.
Peripheral blood lymphocytes and splenocytes of patients with autoimmune disease were used to prepare human-human hybridomas that produce autoantibodies. Because exogenous immunization was not used, the hybridoma antibodies were derived from B cells that spontaneously produced autoantibodies. 108 hybrids grew from 4,254 wells (2.5%). Optimal conditions for obtaining hybridomas with the GM 4672 myeloma line included initial growth in 2-ml wells, the use of 44% polyethylene glycol, a mononuclear cell/GM 4672 cell ratio 5:1, and prior stimulation of the B lymphocytes with pokeweed mitogen. Hybridoma supernatants had activity against ssDNA, platelets, and erythrocytes. The results demonstrate the feasibility of producing human-human hybridomas from lymphocytes of patients with various autoimmune diseases.
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Concentrations of IgA, IgG, and IgM were measured in 25 patients with Gaucher's disease. The mean of each was significantly higher than that generally observed in healthy adults. A direct correlation was noted between IgA and IgG concentrations and age. Patients who underwent splenectomy had IgM concentrations significantly lower than those of persons who did not. In two of 25 patients, multiple myeloma of the nonsecretory type developed. The migration inhibition factor (MIF) test performed with the lymphocytes of our patients was positive to glucocerebroside in four of 17 patients, to glucocerebrosidase in four of 19 patients, and to the extracts of the spleen of a patient with Gaucher's disease in three of eight patients. The results of al MIF tests were negative in six control subjects with splenomegaly of other causes. Our results suggest that in Gaucher's disease there is chronic stimulation of the humoral immune system. The first expression of this stimulation is the production of polyclonal immunoglobulins and, in due time, the development of monoclonal immunoglobulin as well as multiple myeloma.
Benign familial (hereditary) leukopenia and neutropenia (BFLN) have been reported in some ethnic groups, including black Americans and Yemenite Jews. The bone-marrow response of 34 Yemenite Jews (with and without neutropenia) to an intravenous injection of 200 mg of hydrocortisone sodium succinate was studied and compared with the response of 18 healthy control subjects. The mean +/- SEM of the increments in polymorphonuclear cells (PMNs) following injection of hydrocortisone in Yemenite Jews (2,413 +/- 245/mm3 in neutropenic subjects and 2,187 +/- 343/mm3 in nonneutropenic subjects) were significantly lower than in the control subjects (4,431 +/- 467/mm3), without significant differences among the subgroups of the Yemenite Jews. The decreases in monocytes, lymphocytes, and eosinophils were similar in all groups. No correlation was found between baseline PMN levels and the increments following hydrocortisone administration. These results suggest a lowered bone-marrow response to hydrocortisone in subjects with BFLN, indicating some defect in PMNs release from the bone-marrow storage pool to the peripheral blood. It seems that this defect characterizes all members of the ethnic group, whether they have "overt" neutropenia or not.