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Biomedical subjects

W Stein

Publications and source records attributed to W Stein.

At least 55 records · Page 3Linked to original sources
PubMed1985

Influence of autoantibodies to creatine kinase-BB on assays for MB isoenzyme.

We describe the influence of autoantibodies that bind creatine kinase BB (CK-BB) on the methods for MB isoenzyme. If these autoantibodies are present in patients' sera, they cause the formation of macro CK type 1 (immunoglobulin-linked CK-BB). In some of these cases they can bind not only endogenous CK-BB but also CK-MB without significantly affecting enzyme activity. Although these antibodies show distinctly less affinity for CK-MB than for CK-BB, they nevertheless bind CK-MB in these particular sera, because their concentration exceeds that of CK-BB isoenzyme. If a person with such autoantibodies has an acute myocardial infarction, the immunoinhibition method for CK-MB, which does not discriminate between CK-MB and CK-BB, will recognize the increase and peak of CK-MB with time, although persistent macro CK activity will be superimposed on the typical isoenzyme pattern. However, isoenzyme electrophoresis and recently introduced immunoenzymometric assays for CK-MB in these cases may be less sensitive for detecting myocardial infarctions, because the typical increase in CK-MB activity may be identified later in the progression of symptoms, or even be missed.

Autoantibodies↗
PubMed1985

Analytical patterns and biochemical properties of macro creatine kinase type 2.

Here we describe our findings for 105 patients' sera containing macro creatine kinase (CK) type 2, as confirmed by exclusion chromatography. Depending on the technique used for determining isoenzyme CKs (electrophoresis, ion-exchange chromatography, immunoinhibition), this variant CK shows characteristic patterns and interferes in CK-MB assays by different mechanisms and to various degrees, thus complicating test interpretation. Macro CK type 2 evidently is not of cytoplasmic origin; rather it is a separate CK activity of human serum, characterized by its heat stability and, especially, by its increased molecular mass and high energy of activation. These latter characteristics have never been associated with the normal-size, dimeric cytoplasmic CK isoenzymes, but are typical for mitochondrial CK isolated from human tissues. We conclude that mitochondrial CK released after severe cell damage usually appears in blood in macromolecular forms (macro CK type 2), not in a dimeric form.

Chromatography, Gel↗
PubMed1985

Macro creatine kinase type 2: results of a prospective study in hospitalized patients.

We determined total CK activity with the N-acetylcysteine-activated method and residual activity after immunoinhibition of the CK-M subunits in the sera of 2018 patients consecutively admitted to our university hospital for internal diseases, and of 936 outpatients, regardless of the patients' diagnoses. We could detect not more than two types of macro CK: macro CK type 2, which we observed in the sera of 85 patients (prevalence, 3.7% for hospitalized patients), and macro CK type 1. Most patients showing macro CK type 2 were older than 50 years, but we additionally observed a second peak at 20-30 years of age. We saw no preponderance by sex. We detected macro CK type 2 predominantly in severely ill patients of all ages, mainly those with malignant tumors or cirrhosis of the liver. Our findings support the assumption that macro CK type 2 is the manifestation of mitochondrial CK in serum. Occasionally, macro CK type 2 disappeared from the circulation after amelioration of the associated disease. Its occurrence in serum nevertheless is a sign of a serious illness with high mortality but not inevitably a sign of impending death.

Adult↗
PubMed1984

Prenatal diagnosis of neuroblastoma by sonography.

Herein we report the first case in the literature in which a neuroblastoma in a fetus was recognized before birth and its growth could be observed. The diagnosis was made by ultrasonography. Other helpful diagnostic procedures in prenatal diagnosis are: determination of catecholamines, sonographic examination of the placenta, and search for metastases. As more and more centers perform ultrasound examinations routinely in pregnancy, similar findings such as fetal tumors or congenital malformations are to be expected more frequently.

Adrenal Gland Neoplasms↗
PubMed1984

Immunological procedures in clinical enzyme diagnostics.

The paper presented deals with the general potentialities of the immunological determination of enzymes, using selected examples to describe the most important variants of the immunoassay for clinical chemical enzyme diagnostics. The principle of each test and the respective possibilities of interference are described. The analytical efficiency and applicabilities of these immunoassays are assessed critically.

Antibodies↗
PubMed1984

Determination of creatine kinase MB activity with the Du Pont aca: interferences from the sample matrix.

During the last three years we and other have observed discrepancies between results for creatine kinase isoenzyme MB as measured with the mechanized ion-exchange chromatographic method in the Du Pont aca and those by other techniques. These observations prompted us to investigate the influence of the matrix on the Du Pont CK-MB assay. We conclude that, apart from possible interferences by CK-MM, CK-BB, and both types of macro CK, the aca will give apparent CK-MB activities that are directly related to protein concentration and inversely related to sodium chloride concentration. Practical consequences for the routine and emergency laboratories are: no diluted samples are allowed; application is restricted to samples from patients suspected of acute myocardial infarction which show upper-normal total CK activity; and multiple timed samples are run, in order to recognize the typical change in enzyme pattern with time.

Autoanalysis↗
PubMed1983

Response of metastatic breast cancer to tamoxifen withdrawal: report of a case.

This case history describes a patient with metastatic breast cancer treated sequentially with diethylstilbestrol, drug withdrawal, tamoxifen, and drug withdrawal again. An objective response was observed in all four instances. Withdrawal responses to tamoxifen exist and should be kept in mind for selected patients.

Aged↗
PubMed1983

Concentrations of prostaglandin E2 and F2 alpha in the cardiovascular system of infants with persisting patent ductus arteriosus.

The distribution of prostaglandin E2 and F2 alpha was examined in the peripheral veins and in several positions of the cardiovascular system before and after the blood had passed through the lungs in 37 infants. Prostaglandin E2 varied from 0.25 +/- 0.09 ng/ml to 0.44 +/- 0.09 ng/ml when measured in the pulmonary artery, the ductus arteriosus, the right atrium, the right ventricle, the left atrium, the left ventricle, the inferior vena cava and the descending aorta. Prostaglandin F2 alpha was much higher in these positions of the cardiovascular system. The range was 0.99 +/- 0.36 ng/ml to greater than 2.0 ng/ml. The vascular tissues produced virtually identical high amounts of prostaglandin E2 and F2 alpha, but there were no significant differences in prostaglandin E2 and F2 alpha, concentrations, in venous blood as well as in systemic arterial blood. The results suggest that prostaglandin E2 is not responsible for the persisting patency of the ductus arteriosus in infants. There is no explanation for the increased prostaglandin F2 alpha concentrations in these patients.

Aorta, Thoracic↗
PubMed1983

Definition of clinically relevant lactic acidosis in patients with internal diseases.

In order to define clinically relevant lactic acidosis, 12 biochemical variables, eight clinical symptoms and signs, leading diagnoses, and mortality were evaluated prospectively in approximately 2,000 unselected patients with internal diseases, consecutively admitted to the hospital. Patients with incomplete data sets were not considered. Of those patients who repeatedly were admitted to the hospital during the time of the study, only the first admission was included for statistical analysis. In addition to 11 definitions of lactic acidosis given in the literature, sequential cluster analyses of the biochemical variables were used to estimate the incidence of lactic acidosis in 1,467 patients. Depending upon which definition was used, 0.5-3.8% of all patients were classified as suffering from lactic acidosis, with a mortality rate ranging from 30-88%. From this study it is concluded that a limit of less than or equal to 7.35 for pH and of greater than 5-6 mmol/L for the concentration of lactate in whole blood will minimize false-negative or false-positive classifications.

Acidosis↗
PubMed1983

Evaluation of the optimized bioluminescent assay for the determination of total creatine kinase and creatine kinase MB activities.

A very sensitive, optimized bioluminescent assay for certain kinase and creatine kinase MB activities is tested. We evaluated reagent blanks, sensitivity, precision and compared the results with those of the spectrophotometric immunoinhibition test. The main advantage of the new method is a detection limit of less than 1 U/l which, together with a high precision (s = 0.1 at detection limit), allows determinations of the creatine kinase MB activity even in normal sera in about 20 minutes. A disadvantage of the manual procedure is that it may be necessary to include up to five pipetting steps.

Creatine Kinase↗
PubMed1983

Creatine kinase variants. Report on the workshop conference of the German Society for Clinical Chemistry held on September 19 to 21, 1982 in Tübingen, FRG.

It was the aim of the workshop to summarize present knowledge of the variant creatine kinases in human blood. Discussion was centered on the nature, measurement, and clinical significance of these variants. On the basis of the presented results, the different creatine kinase variants can be classified as follows: Normal size variants (80000 Daltons). These originate from postsynthetic modifications of the three dimeric isoenzymes creatine kinase-MM, MB or BB. The M subunit can be transformed by a serum constituent and these modifications result in at least three different creatine kinase-MM and two creatine kinase-MB variants, which still show catalytic activity. The mechanism of the postsynthetic alterations of creatine kinase-BB seems to be more complex: In vitro incubation of this isoenzyme even in a non-serum matrix changes its electrophoretic mobility and decreases activity. In vivo there is evidence that on the one hand intact creatine kinase-BB molecules are directly removed from the circulation. On the other hand, however, inactive creatine kinase-BB-protein is reported to occur in serum. Variants with higher molecular weights (greater than 200000 Daltons). These are termed macro creatine kinases. Macro creatine kinase type 1 comprises the immunoglobulin-bound creatine kinase isoenzymes. Of these immune complexes, IgG-linked creatine kinase-BB is well known and has been described in detail, whereas the occurrence of creatine kinase-MM-containing macro creatine kinases is still questionable. Macro creatine kinase type 1 is found in the blood of about 2% of all hospitalized patients. It occurs mainly in elderly women, but it is not known whether it has any special clinical significance. Macro creatine kinase type 2 is the term for an oligomeric form of mitochondrial creatine kinase released after breakdown of mitochondria in liver, heart and some tumours. After treatment with urea this oligomeric form is converted into a normal sized, dimeric creatine kinase-MiMi. Macro creatine kinase type 2 is found exclusively in seriously ill patients, and may occur in more than 3% of all hospitalized patients. This classification of the creatine kinase variants seems logical, since it takes into account the nature of the creatine kinase variants, and it permits the classification of all atypical creatine kinases described in the literature. As quantification and differentiation now become possible, further experimental and clinical investigations should provide the information necessary for a better understanding of the physiology and pathobiochemistry of these multiple forms of creatine kinase.

Creatine Kinase↗
PubMed1982

Macro creatine kinase: determination and differentiation of two types by their activation energies.

Determination of the MB isoenzyme of creatine kinase in patients with acute myocardial infarction may be disturbed by the presence of macro creatine kinase. The relative molecular mass of this form of creatine kinase in human serum is at least threefold that of the ordinary enzyme, and it is more thermostable. Here we describe our method for determination of macro creatine kinases and an easy-to-perform test for differentiating two forms of macro creatine kinase, based on their distinct activation energies. The activation energies of serum enzymes are mostly in the range of 40-65 kJ/mol of substrate. Unlike normal cytoplasmatic creatine kinases and IgG-linked CK-BB (macro creatine kinase type 1) a second form of macro creatine kinase (macro creatine kinase type 2) shows activation energies greater than 80 kJ/mol of substrate. The exact composition of macro creatine kinase type 2 is still unknown, but there is good reason to believe that it is of mitochondrial origin.

Activation Analysis↗
PubMed1982

Macro creatine kinases: results of isoenzyme electrophoresis and differentiation of the immunoglobulin-bound type by radioassay.

In 2.9% of sera from 1253 unselected patients we detected two different types of macromolecular creatine kinases (CK; EC 2.7.3.2). One macro type was represented by immunoglobulin-linked CK: in sera containing macro CK-BB isoenzyme, 125I-labeled CK-BB was bound with high affinity to the immunoglobulin fraction. Furthermore, during electrophoresis, macro CK-BB mostly migrated between CK-MB and CK-MM, and was fixed to Protein A from Staphylococcus aureus. We therefore propose radioelectrophoresis as a specific, highly sensitive, and simple method for detecting this type of macro CK. This form occurs predominantly in elderly women, is not correlated to any specific disease, and persists in blood over a long period of time. In contrast, a second type (macro-CK type 2) never bound radiolabeled CK isoenzymes, and was not adsorbed to Protein A. Electrophoretic migration of this macro-CK type 2 was generally cathodic to CK-MM. We observed this type in severely ill patients, frequently those suffering from malignant tumors. Clinical observations and biochemical data suggest that macro-CK type 2 is of mitochondrial origin.

Age Factors↗
PubMed1981

Stability of macro creatine kinases and creatine kinase isoenzymes compared: heat inactivation test for determination of thermostable creatine kinases.

Creatine kinase isoenzymes showed decreasing thermal stability and increasing lability towards pH changes in the order: MM, MB, and BB. The three isoenzymes exhibited their highest stability between pH 6.5 and 7.0. At 37 degrees C and an almost physiological pH of 7.5 the decay constants were 0.025, 0.164 and 0.580 h-1 (MM, MB, and BB isoenzyme), respectively. In contrast to free creatine kinase BB, immunoglobulin-linked creatine kinase BB (macro creatine kinase BB, type 1 macro creatine kinase) showed a markedly higher stability; this accounts for the persistence of creatine kinase BB activity in macro creatine kinasaemia. In addition we identified a second type of macro creatine kinase in patients' sera, which is also thermostable. A simple heat inactivation test (20 minutes, 45 degrees C, immunoinhibition of the M-subunits) differentiates thermostable macro creatine kinases from thermolabile creatine kinases and thus completes isoenzyme diagnosis.

Creatine Kinase↗