Isoenzymes of lactate dehydrogenase in human leukemic cells in culture treated with inducers of differentiation.

The human leukemic cell lines HL60 and K562, were induced to differentiate terminally by chemical agents. The isoenzyme patterns of lactate dehydrogenase (LD) in the cells before and after differentiation were determined electrophoretically on agarose gels. In general, treatment of the leukemic cells with inducers of differentiation resulted in a quantitative shift of the isoenzyme pattern towards anodic or cathodic forms. This was correlated with the conversion of the chemically treated cells to morphologically more normal cells, as verified by light microscopy and/or synthesis of hemoglobin. The LD isoenzyme patterns of the chemically differentiated cells were: (a) characteristic for the particular cell type obtained rather than for the nature of the inducer used; and (b) not similar to those of normally differentiated cells of the corresponding lineage, indicating that incomplete differentiation had occurred.

Abnormal cerebrospinal fluid protein indices in schizophrenia.

Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective IgG production within the central nervous system (CNS). In comparison with previously determined reference values, 7 of 24 (29%) subjects showed increased blood-brain barrier permeability, and 8 of 24 (33%) demonstrated elevated endogenous CNS IgG production. One of these eight also demonstrated oligoclonal banding on high-resolution protein electrophoresis of the CSF.

CSF and serum concentrations of albumin and IgG in Alzheimer's disease.

Cerebrospinal fluid (CSF) and serum concentrations of albumin and immunoglobulin G (IgG) were measured in 31 patients with presumptive Alzheimer's disease (AD) and in 14 healthy control subjects. The albumin and IgG quotients, and IgG index were calculated to evaluate the permeability of the blood-brain barrier and the intrathecal production of immunoglobulins. X-ray computerized tomography (CT) of the head was performed to investigate the relation between cerebral atrophy and CSF protein concentrations. The albumin and IgG quotients, and the IgG index did not differ significantly between the AD and control groups. Cerebral atrophy, as measured by CSF volume, was not related to CSF protein concentrations in either group. The results do not support the hypothesized roles of blood-brain barrier disruption or of immunologically-mediated injury of the central nervous system in the pathogenesis of AD.

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome).

We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of-the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins.

Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment.

Total and low density lipoprotein cholesterol concentration reduction in patients with markedly increased levels of these substances, leads to a decline in the incidence of myocardial infarction and death. A unique cholesterol-rich lipoprotein, lipoprotein Lp(a), has been identified which not only can be confused with low density lipoproteins, but has also been associated with premature cardiovascular disease. Using the cholesterol-lowering drugs neomycin and niacin in 14 type II hyperlipoproteinemic subjects, we determined the effect of lipid-lowering therapy on lipoprotein Lp(a) concentrations. Neomycin (2g/day) reduced low density lipoprotein cholesterol and lipoprotein Lp(a) concentrations by 23% and 24%, respectively. Combination therapy with neomycin (2 g/day) and niacin (3 g/day) induced a 48% decline in low density lipoprotein cholesterol levels and a 45% reduction in the concentration of lipoprotein Lp(a). These changes in lipoprotein Lp(a) levels were associated with a striking decline in the intensity of the slow pre-beta-lipoprotein fraction determined Lp(a) by lipoprotein electrophoresis. This slow pre-beta-lipoprotein fraction contained Lp(a) determined by immunofixation. These observations indicate that lipoprotein Lp(a) concentrations can be altered pharmacologically and that the progression of cardiovascular disease may be altered through changes in lipoprotein (a) levels.

Lysozyme determination in parotid saliva from patients with Sjögren's syndrome.

Lysozyme and total protein concentrations in parotid saliva were measured in 17 patients with primary Sjögren's syndrome, in six patients with Sjögren's syndrome secondary to hyperlipoproteinemia and in 14 age- and sex-matched healthy control subjects. Increased lysozyme concentrations were found only in patients with primary Sjögren's syndrome and correlated well with the presence of parotid gland enlargement. The total protein concentration in the saliva of patients with Sjögren's syndrome was not different from that of the control subjects. Parotid saliva lysozyme determination may be useful as an early adjunctive diagnostic test of primary Sjögren's syndrome.

Prednisone effects on blood-brain barrier permeability and CNS IgG synthesis in healthy humans.

Corticosteroids reportedly decrease blood-brain barrier (BBB) permeability and/or IgG synthesis in patients with multiple sclerosis or brain tumors. However, these effects have not been studied in healthy humans. We investigated the effects of prednisone, 80 mg/day for five days, on the ratio of cerebrospinal fluid (CSF) albumin/serum albumin, a measure of blood-brain barrier (BBB) permeability, and on CSF and serum IgG levels in six healthy, normal volunteers. We found significant steroid-induced decreases in serum and CSF albumin levels and in serum IgG levels. However, we found only a nonsignificant decrease in BBB permeability and no significant change in CNS IgG synthesis. These findings, based on a small number of volunteers, suggest that it may be difficult to further decrease BBB permeability and CNS IgG synthesis in medically healthy subjects.

Evaluation of lactate dehydrogenase isoenzyme patterns in serum of patients undergoing cardiac surgery.

Serial determinations of serum lactate dehydrogenase (LD) isoenzymes were performed in 50 patients undergoing cardiac surgery for coronary artery bypass and heart valve replacement. A sequence of LD isoenzyme patterns was established in the patients with uncomplicated recovery. These patterns served as controls for the detection of abnormal patterns associated with clinical complications. Perioperative myocardial infarction was detected in seven patients by a characteristic reversal of the LD1:LD2 ratio. These studies established that accurate determination of LD isoenzymes improved their diagnostic specificity. These isoenzymes were determined by (1) using the same technique for tissues and for serum samples, (2) applying a volume of serum containing a standard amount of enzymatic activity, and (3) making a clear separation, which allows accurate quantitation. This test can provide useful information to the surgeon for the evaluation of operative procedures and to the clinician for the appropriate management of the patient undergoing cardiac surgery.

A comparison between chemical analysis and magnetic resonance imaging with the clinical diagnosis of multiple sclerosis.

Ninety-five patients suspected of having multiple sclerosis (MS) were evaluated by medical history and neurologic examination. Based on this evidence they were divided into three groups: clinically definite MS, not-definite MS, and not MS. The adjunct tests, chemical analysis, and magnetic resonance imaging (MRI), were also performed to assess the diagnosis of MS. Chemical analyses of paired serum and cerebrospinal fluid (CSF) samples were performed to identify oligoclonal immunoglobulin bands and to estimate both the albumin quotient and the IgG index. A positive correlation was found between the chemical test results and definite MS in 73 of 73 cases. In 11 of 12 cases of not-definite MS the chemical results were positive for MS. A positive correlation was also found between ten of ten cases that were not MS and negative chemical test results. MRI scans were positive for MS in 48 of 51 clinically definite MS cases and in 4 of 4 not-definite MS cases. MRI scans were negative for MS in five of six cases that were not MS. These findings demonstrate that combined determinations of serum and CSF proteins by simple zone electrophoresis and commercial immunochemical tests can be useful laboratory aids in the diagnosis of MS. The MRI scans provide additional evidence to support the diagnosis of MS.

Oligoclonal immunoglobulins in the sera of healthy subjects at risk for AIDS.

Analysis of serum samples from 68 healthy subjects seropositive for HTLV-III antibodies was performed by high-resolution zone electrophoresis. A high incidence of oligoclonal immunoglobulin bands was detected in the sera of these subjects compared with absence of these bands in the sera of healthy seronegative controls. Identification of the immunoglobulin bands by immunofixation revealed a single heavy chain IgG, single kappa and mixed kappa and lambda light chains. The presence or absence of oligoclonal immunoglobulin bands, determined by zone electrophoresis in serum samples from healthy subjects who have been exposed to HTLV-III, may prove to be a useful biochemical marker for following the course of infection and for determining a prognosis.

Monoclonal immunoglobulins in the serum of patients with primary Sjögren's syndrome.

Monoclonal immunoglobulins (M Igl) were detected in the serum of 10 of 20 patients with primary Sjögren's syndrome (prim. SS), by using high resolution electrophoretic technique combined with immunofixation. The finding of three free lambda chains and two IgG lambda suggests that the lambda-expressing B-clones are involved in this process, but the class distribution is different from one series to another, and from one country to another. The prim. SS patients with multiogran disease have the higher incidence of M Igl.

Monoclonal immunoglobulins and autoantibodies in lymphoid malignancies.

The presence of serum monoclonal or oligoclonal immunoglobulins (paraproteins) was investigated in 38 non-Hodgkin's lymphoma and chronic lymphocytic leukemia patients, 33 patients with solid tumors and 33 healthy individuals. Seventy two percent of non-Hodgkin's lymphoma and 31% of chronic lymphocytic leukemia patients had serum paraproteins, in contrast to 21% and 15% of solid tumor patients and normal controls respectively. There was no significant prevalence of a certain isotype or light chain in the non-Hodgkin's lymphoma, chronic lymphocytic leukemia and solid tumor groups. In the healthy individuals all bands were monoclonal of the IgG isotype. No correlation was found between histologic grading of lymphoid malignancy or disease stage and serum monoclonality. No serologic or histologic autoimmune features were demonstrated in non-Hodgkin's lymphoma and chronic lymphocytic leukemia patients. In addition, no correlation was found between serum autoantibody activity and mono- or oligoclonal immunoglobulins.

Clinical applications of lactate dehydrogenase isoenzymes.

A quantitative electrophoretic test for the determination of lactate dehydrogenase isoenzymes was applied to the analysis of human tissues, cells and fluids in order to obtain their normal isoenzyme patterns and to form a reference record. The same test was employed in the analysis of serum samples from patients with defined pathological conditions. The abnormal serum isoenzyme patterns were correlated with the tissue patterns, thus indicating the origin of the abnormality. This type of correlation, together with the clear demonstration of the actual isoenzymes and their quantitation, improves diagnostic discrimination and enhances the early detection of a biochemical abnormality that aids in the prevention of disease.

Detection of lipoprotein abnormalities by a sensitive electrophoretic test system for the prevention of cardiovascular disease.

With the use of new and improved technology and methodology, an electrophoretic test system has been developed to determine serum lipoprotein patterns. The main features of this system, which distinguish it from other methods are: (1) high sensitivity and sharp resolution, which enable the identification in human serum of two beta, two pre-beta, and alpha lipoprotein fractions and additional subfractions; (2) rapid analysis of blood samples to demonstrate accurately the lipoprotein fractions as they circulate in the natural state in plasma; and (3) low cost of the test since the materials and supplies are inexpensive. The application of the test system to the analysis of serum samples from normal individuals and patients with defined pathologic conditions resulted in the following new developments: (1) the demonstration of abnormal lipoprotein patterns that aid the diagnosis of clinical disorders of lipid metabolism; and (2) the detection of abnormal lipoprotein fractions associated with atherosclerotic cardiovascular diseases (ACD). The determination of serum lipoproteins is an indispensable part of the evaluation of an individual for ACD because they are the native molecules in the circulation which are intimately associated with the blood vessels that become atherosclerotic.

[Monoclonal cryoglobulins in primary Sjögren's syndrome]. / Monoklonal'nye krioglobuliny pri pervichnom sindrome Shegrena.

Cryoglobulins were studied in the sera of 40 unselected pSS patients. The nature of the cryoglobulins was defined using a very fast and sensitive resolution electrophoresis technique combined with immunofixation. Thirty-five per cent of SS patients were shown to have circulating IgMk mixed monoclonal cryoglobulins. On the contrary, all the other tested cryoprecipitates were found to be mixed polyclonal, with the exception of one patient with SLE. The presence of cryoglobulins in the sera of SS patients correlated with extraglandular disease and with autoantibodies to Ro (SSA) cellular antigen and rheumatoid factor. Patients with cryoglobulins had lower serum C4 levels compared to patients without cryoglobulins. These findings suggest that SS in addition to polyclonal B-cell hyperreactivity expresses a monoclonal process preceding the development of lymphoid neoplasia. Extraglandular manifestations of the syndrome may be associated with an immune complex mediated pathology.