Lactate dehydrogenase isoenzyme 1. A rapid assay for ischemic myocardial disease.

A rapid immunochemical method (Isomune-LD) for the determination of lactate dehydrogenase isoenzyme 1 (LD1) activity in serum was investigated, and the sensitivity and specificity of the assay were determined for the diagnosis of a myocardial infarction (MI). Multiple serum samples were obtained (on admission and at 12, 24, and 48 hours) from 85 patients (30 with proven MI and 55 without MI). The sensitivity of LD1 on admission and at 12, 24, and 48 hours was 43%, 84%, 96%, and 100%, respectively, and the specificity at these same time intervals was 95%, 100%, 97%, and 97%, respectively. Thus, the determination of LD1 by this rapid immunochemical method appears to allow a rapid laboratory evaluation of MI with a high degree of sensitivity and specificity.

Immune complexes: characteristics, clinical correlations, and interpretive approaches in the clinical laboratory.

Immune-complex-mediated injury is thought to play a role in diseases such as rheumatoid arthritis, systemic lupus erythematosus, serum sickness, various infectious diseases, and malignancies. With increased appreciation of the biological and pathological significance of circulating immune complexes has come efforts to develop appropriate techniques for identifying and measuring them. Common approaches exploit such phenomena as the attachment of complement components to antigen-antibody complexes, the presence of specialized receptors for immune complexes at the surface of cells, and the ability of rheumatoid factor to bind with immune complexes. This variety of assay systems for immune complexes has yielded abstruse results in numerous human pathological conditions. Unfortunately, these results seldom correlate with one another in a given disease. Thus, use of a panel of immune complex assays has been recommended. Indirect consequences of immune complex disease may still be appraised and evaluated with some confidence in clinical medicine: measurements of C3 and C4, cryoglobulins, serum viscosity, and turbidity of serum samples. Measurement of immune complexes may be useful in diagnosis, prognosis, and therapeutic monitoring, but it is the characterization of immune complexes that holds the greatest potential for better understanding of disease mechanisms.

Interferences of mannitol with phosphate determination.

Methods commonly used for serum phosphate analysis depend upon the combination of inorganic phosphorus with molybdate and subsequent quantitation of the resultant phosphomolybdate by spectrophotometry. This is a case report of mannitol interference with phosphate quantitation by a method not employing dialysis (DuPont ACA) but not with another method which includes a dialysis step (Technicon SMAC). This interference, occurring at an extremely high level of serum mannitol (3.5 g/dl) in a patient with acute renal failure, appears to be due to direct inhibition of the formation of the phosphomolybdate complex by mannitol.

HLA patterns and disease associations.

The a priori biologic significance of the histocompatibility complex with its excessive polymorphism remains unknown. Teleologically, however, the role of the HLA system may be viewed as vital for survival of the species and the individual by providing the host with a recognition system of and defenses against viruses, microorganisms, parasites, plant antigens, neoplastic cells, and others. HLA testing, in addition to its usefulness in donor selection for transplantation, has been recently applied to the diagnosis and differentiation of specific diseases, the prediction of disease development (risk prediction), and as a basis for prognostic evaluations. An increasing number of diseases is being shown to be linked by specific HLA antigens and certain common denominators, such as arthritides, autoimmune components or infections, suggesting common etiologic or pathogenic mechanisms or both. These diseases with HLA associations can be separated into those that appear certain, probable, or only statistically possible.

Therapy with gastrin antibody in the Zollinger-Ellison syndrome.

The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it futher to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion.

Thymosin-induced increase in E-rosette-forming capacity of lymphocytes in patients with malignant neoplasms.

Thymosin, a thymic hormone, restores decreased cellular immunity under various experimental conditions. The purpose of this study was to evaluate the effect of thymosin on the E-rosette-forming capacity in cancer patients. Peripheral blood lymphocytes obtained from eight patients with various malignant neoplasms were examined. One of these patients received thymosin intramuscularly; his E-rosette formation was examined serially. Eight normal adults served as controls. Patients with advanced stages of malignant tumors showed decreased E-rosette-forming capacity, which increased significantly under the influence of thymosin. Patients with less-advanced tumors, as well as normal adults, demonstrated normal E-rosette formation without further effects by thymosin. The in vivo administration of thymosin to one patient was followed by a marked increase of the E-rosette-forming capacity. These results suggest that the administration of thymosin, both in vivo and in vitro, significantly increases the circulating T-lymphocyte levels and/or functions in patients with advanced malignant neoplasms.

Lymphoid response of the burn patient.

Clinical observations have long suggested immunologic compromise in burned patients. Resolution of the immune system into cooperative dual components of T-cells mediating delayed hypersensitivity and B-cells mediating antibody responses prompted the present survey of T-cell and B-cell changes after acute thermal burn injury. Adults and children sustaining extensive burn injuries were studied for up to 60 days after injury. T-cell function was assessed by lymphocyte counts, in vitro lymphocyte synthesis of RNA and DNA with and without mitogenic stimulation, and lymphocyte response and stimulatory capacities in the mixed lymphocyte culture (MLC) reaction. B-cell function was studied by quantitation of the major classes of circulating immunoglobulins. Transient lymphocytopenia, increased RNA and DNA synthesis rates by both mitogenstimulated and unstimulated lymphocytes, and impairment of lymphocyte response and stimulation in the MLC were observed early in the postburn period. These parameters tended to normalize by the third week after injury. Immunoglobulin levels, particularly IgG, were depressed significantly the first week postburn, but were normal or elevated by 60 days. These studies document both T-cell and B-cell changes postburn,which appear to be reversible with the recovery phase. A transient shift of circulating lymphocytes toward the B-cell type is suggested and early depression of immunoglobulin levels is notable. Both types of changes likely contribute to the immunologic compromise of the acutely burned patient.

B-lymphocytosis factor in human plasma.

Patients with acute thermal burns experience an increase of serum immunoglobulins associated with marked B-lymphocytosis during the recovery phase from the burn injury. This study was performed to delineate humoral factors which may induce the B-lymphocytosis in such patients. Plasma samples were obtained serially from 14 adult patients and 14 adult controls. One-half ml of plasma was injected intraperitoneally into C3H/He male mice, and absolute numbers of surface immunoglobulin-bearing cells in the mouse peripheral blood were counted. Fractionation of plasma samples was performed. The biologically active plasma fraction, tentatively termed B-lymphocytosis factor (BLF), was cultured with normal human peripheral blood lymphocytes to determine in vitro lymphocyte transformation. The solubility of 125I-labelled BLF in various organic solvents was examined. Plasma obtained from burned patients induced a marked increase of IgG, IgA, and IgM-bearing cells in the peripheral blood of mice within 3 hours after injection. The B-lymphocytosis activity of normal plasma was not significant. The molecular weight of BLF was estimated to be close to that of ribonuclease A (M.W. 13,400). Transformation of normal human peripheral blood lymphocytes was observed when cultured with BLF. 125I-labelled BLF was not soluble in organic solvents. These data suggest that BLF is not a lipopolysaccharide, and plays a role in regulation of B-lymphocyte levels in burned patients.

Methodologic differences in values for M-proteins in serum, as measured by three techniques.

Accurate and reproducible measurement of M-proteins is essential for managing patients with monocional gammopathies, but serum protein electrophoresis, radial immunodiffusion, and electroimmunodiffusion yield comparatively divergent results. We have studied these differences and their causes. Sera from cases of IgG-monoclonal gammopathy, IgA-monoclonal gammopathy, and IgM-monoclonal gammopathy were assayed by each of the three techniques. Results indicated inter-method discrepancies as great as fivefold for all proteins studied. For IgG-monoclonal gammopathy, radial immunodiffusion values were less consistently so. For IgA-monoclonal gammopathy, both radial immunodiffusion and electroimmunodiffusion gave lower results than did serum protein electrophoresis. For IgM-monoclonal gammopathy, results were variable, but values by radial immunodiffusion tended to be higher than, and electroimmunodiffusion comparable to, those for serum protein electrophoresis. The differences were not correlated with protein abundance, serum freshness, immunoglobulin class, light-chain type, ultracentrifugal characteristics, or electrophoretic mobility. Clearly, values for M-protein concentration depend on the techniques used to obtain them. We postulate that subclass differences may contribute to the diversity of radial immunodiffusion results, and that for electroimmunodiffusion the fixed electrophoretic mobility of M-proteins leads to unpredictable results. We conclude that serum protein electrophoresis is the best of the three assay techniques for M-proteins.

Idiopathic (asymptomatic) monoclonal gammopathies.

Asymptomatic forms of monoclonal gammopathies (MG) are recognized with increasing frequency; their recognition and differentiation from the symptomatic forms of MG appear imperative, since the therapeutic approaches are different. Available clinical and laboratory indexes lack specificity required for useful and practical discrimination; presently, we must still rely on the timecourse monitoring of such laboratory values as hemoglobin levels, M-protein concentrations, and presence of Bence Jones proteins. Elucidation of histocompatibility A and W antigenic profiles, as well as the functions and kinetics of B-lymphocytes from such patients, appear most promising. Evidence of the causative role of extrinsic and intrinsic antigenic stimulation in MG production is increasing; segregation into two distinct concentration ranges of M-proteins in the asymptomatic and symptomatic groups suggests two control levels of the expression of immune response (Ir) genes, due to partial or complete derepression of the latent Ir gene function, reflecting "partial" (asymptomatic, benign MG) and "complete" (symptomatic, malignant MG) monoclonal immune responders.

Skylab experiment results: hematology studies.

These studies were designed and coordinated to evaluate specific aspects of man's immunologic and hematologic systems which might be altered by or respond to the space flight environment. The biochemical functions investigated included cytogenetic damage to blood cells, immune resistance to disease, regulation of plasma and red cell volumes, metabolic processes of the red blood cell, and physical chemical aspects of red blood cell functions. Only minor changes were observed in the functional capacity of erythrocytes as determined by measuring the concentrations of selected intracellular enzymes and metabolites. Tests of red cell osmotic regulation indicated some elevation in the activity of the metabolic dependent Na-K pump, with no significant alterations in the cellular Na and K concentrations or osmotic fragility. A transient shift in red cell specific-gravity profile was observed on recovery, possibly related to changes in cellular water content. Measurements of hemoconcentration (hematocrit, hemoglobin concentration, red cell count) indicated significant fluctuations postflight, reflecting observed changes in red cell mass and plasma volume. There was no apparent reticulocytosis during the 18 days following the first manned Skylab mission in spite of a significant loss in red cell mass. However, the reticulocyte count and index did increase significantly 5 to 7 days after completion of the second, longer duration, flight. There were no significant changes in either the while blood cell count or differential. However, the capacity of lymphocytes to respond to an in vitro mitogenic challenge was repressed postflight, and appeared to be related to mission duration. The cause of this repression is unknown at this time. Only minor differences were observed in plasma protein patterns. In the second mission there were changes in the proteins involved in the coagulation process which suggested a hypercoagulative condition.