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Biomedical subjects

G Csako

Publications and source records attributed to G Csako.

At least 19 recordsLinked to original sources
PubMed1997

Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women.

BACKGROUND: Plasma levels of plasminogen-activator inhibitor type 1 (PAI-1), an essential inhibitor of fibrinolysis in humans, increase in women after menopause, and this may contribute to the risk of cardiovascular disease. We studied the effects of hormone-replacement therapy on PAI-1 levels. METHODS: In a randomized, crossover study, we investigated the effects of oral conjugated estrogen (0.625 mg per day) in 30 postmenopausal women and transdermal estradiol (0.1 mg per day) in 20 postmenopausal women, either alone or in combination with medroxyprogesterone acetate (2.5 mg daily) for one month, on plasma PAI-1 antigen levels. Degradation products of cross-linked fibrin (D-dimer) were measured in serum as an index of fibrinolysis. RESULTS: PAI-1 levels were inversely associated with D-dimer levels at base line (r= -0.540, P=0.002). Conjugated estrogen, both alone and in combination with medroxyprogesterone acetate, reduced mean (+/-SD) plasma levels of PAI-1 from 32+/-34 ng per milliliter to 14+/-10 ng per milliliter (P<0.001) and from 31+/-29 ng per milliliter to 15+/-11 ng per milliliter (P=0.003), respectively; there was a significant inverse correlation between pretreatment PAI-1 levels and the degree of reduction in these levels during therapy (r= -0.631, P<0.001 for conjugated estrogen; r = -0.507, P=0.004 for combined therapy). The degree of reduction in PAI-1 levels was associated with increases in D-dimer levels both when conjugated estrogen was given alone (r= -0.572, P=0.001) and when combined hormone therapy was given (r= -0.541, P=0.002). Transdermal estradiol caused no significant changes in PAI-1 levels from base-line values. CONCLUSIONS: Conjugated estrogen, alone or combined with progestin therapy, reduced PAI-1 levels by approximately 50 percent in postmenopausal women and was associated with enhanced systemic fibrinolysis. These findings may partly explain the protective effect of hormone-replacement therapy with respect to coronary artery disease.

Administration, Cutaneous↗
PubMed1997

Gender-specific correlation of platelet ionized magnesium and serum low-density-lipoprotein cholesterol concentrations in apparently healthy subjects.

We previously found an inverse correlation between platelet ionized magnesium concentration ((Mg2+)i) and serum total cholesterol concentration in normal male but not female subjects. In the present study, we determined the platelet (Mg2+)i by using a fluorescent ionized magnesium (Mg2+) indicator, FURAPTRA, and measured the serum concentrations of the following: total cholesterol; very-low-density lipoprotein cholesterol (VLDL-C); low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); antioxidized low-density lipoprotein (LDL) autoantibodies; lipoprotein(a); apolipoproteins A-I (apo A-I) and B (apo B); triglycerides; estradiol-17 (E2); ceruloplasmin (Cp); and selected electrolytes, including total and ionized magnesium and calcium and total protein and albumin. In men, but not in women, platelet (Mg2+)i significantly inversely correlated with serum total cholesterol (r = -0.52, p < 0.02), LDL-C (r = -0.54, p < 0.009 by a "direct" method; r = -0.40, p < 0.05 by an electrophoretic method), and apo B (r = -0.42, p < 0.04). We found no significant correlations between platelet (Mg2+)i and any other variables, including serum total and ionized magnesium, antioxidized LDL autoantibodies, Cp, and E2. We speculate that decreased platelet (Mg2+)i is a possible marker for platelet membrane alterations that may affect platelet involvement in thrombosis and atherogenesis.

Adult↗
PubMed1995

Downward blotting of proteins in a model based on apolipoprotein(a) phenotyping.

Standard immunoblotting ("Western blot") involves electrotransfer of proteins from a separation gel (usually acrylamide) onto a membrane. Recently, a downward capillary method with increased hybridization efficiency was developed for DNA and RNA. The present work assessed the applicability of this method to proteins in a model based on human apolipoprotein(a)[apo(a)] isoforms which consist of a single, >200-kDa polypeptide chain varying in size with a repeat sequence. After reduction treatment and sodium dodecyl sulfate-agarose gel electrophoresis, serum proteins were transferred from the gel by upward or downward (Turboblotter) capillary action onto nitrocellulose membranes in Tris-buffered saline, pH 7.5, at room temperature. Increased detectability of apo(a) isoforms was achieved by substituting comparatively high molar concentrations of protein A for true second antibody. With downward capillary transfer and short 37 degrees C incubations, the apo(a) phenotyping could be completed in about 26 h and required less than 8 h effective processing time. The downward transfer was about twice as fast (complete within 1 h) as the upward version and with this speed it offers a good alternative to electroblotting as well.

Apolipoproteins↗
PubMed1994

Structure, biosynthesis, and function of salivary mucins.

The glandular secretions of the oral cavity lining the underlying buccal mucosa are highly specialized fluids which provide lubrication, prevent mechanical damage, protect efficiently against viral and bacterial infections, and promote the clearance of external pollutants. This mucus blanket contains large glycoproteins termed mucins which contribute greatly to the viscoelastic nature of saliva and affect its complex physiological activity. The protein core of mucins consists of repetitive sequences, rich in O-glycosylated serine and threonine, and containing many helix-breaking proline residues. These features account for the extended, somewhat rigid structure of the molecule, a high hydrodynamic volume, its high buoyant density, and high viscosity. The oligosaccharide moiety of salivary mucins accounts for up to 85% of their weight. The oligosaccharide side chains exhibit an astonishing structural diversity. The isolation, composition, structure, molecular characteristics, and functional relevance of salivary mucins and their constituents is discussed in relation to recent advancements in biochemistry and molecular biology.

Amino Acid Sequence↗
PubMed1994

Pulsed-field gel electrophoresis for the separation of large protein molecules exemplified by the isoforms of apolipoprotein (a).

The performance of pulsed-field gel electrophoresis (PFGE) was assessed for the separation of protein molecules. The allelic isoforms of apolipoprotein (a) (apo[a]) served as a model for this study because apo(a) is an unusually large protein, consisting of a variable number of repeating units. PFGE and, for comparison, conventional electrophoresis of human sera were carried out under reducing conditions in agarose gel. After blotting proteins onto nitrocellulose membrane, a combination of monospecific rabbit anti-apo(a) antibody and alkaline phosphatase-conjugated protein A detected apo(a) isoforms in all sera tested. The various apo(a) isoforms were effectively resolved within two repeating units ("kringles") by both PFGE and conventional electrophoresis, but the type of agarose gel used greatly affected the speed of electrophoretic separation. In a series of 89 human sera, 59 double-band and 30 single-band patterns were seen using either electrophoretic system. However, one specimen produced double bands with PFGE, while only a single band could be detected by conventional electrophoresis, and with another specimen the opposite occurred. A total of 22 different apo(a) isoforms were identified among these patterns. It is concluded that the increasingly available PFGE technology is a practical alternative to conventional agarose electrophoresis for the separation of large protein molecules.

Apolipoproteins A↗
PubMed1994

Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data.

From 8322 patients for whom creatine kinase (CK; EC 2.7.3.2) isoenzyme analysis was ordered, we identified 136 patients with macro CK isoenzyme in their serum. There were 36 cases with type 1 (prevalence: 0.43%) and 100 cases with type 2 isoenzyme (prevalence: 1.20%). About three-fourths of the patients were ambulatory at the time of testing, and approximately 90% of the first 68 patients identified survived at least 1 year after macro CK was found in their serum. Age and gender did not differ significantly between the two groups. The serum total CK was significantly higher (P < 0.0005), and an increased CK-MB proportion (> 0.05 of total CK) was also significantly more common (P < 0.0005) in patients with macro CK type 1 than in those with type 2. On average, macro CK type 2 accounted for approximately 25% and macro CK type 1 for approximately 10% of the serum total CK activity. Patients with macro CK type 1 most often had myositis, whereas those with macro CK type 2 most commonly had a malignancy. We conclude that the presence of macro CK isoenzymes has a low prognostic value for impending death, but may support the diagnosis of an autoimmune process (type 1) or malignant cell proliferation (type 2).

Adenylate Kinase↗
PubMed1993

A 10-year analysis of "revenues," costs, staffing, and workload in an academic medical center clinical chemistry laboratory.

From 1980 to 1990 we found progressive increases in workload (number of billable tests; 12.1% per year), staffing [number of full-time equivalents (FTEs); 5.6% per year], "revenues" (gross billings; 25.8% per year), and direct cost (12.9% per year) in the clinical chemistry laboratory of a large tertiary-care university medical center. The increase in direct cost was mainly attributable to an increase in salary cost (23.7% per year), whereas the impact of increasing "consumable" cost was relatively small (5.3% per year). In fact, after adjustment for inflation, the consumable cost was virtually unchanged or decreased during the 10-year study period. Initially, consumables represented about 60% of the direct cost, and the remaining 40% was for salaries. After 1982/83, however, the relative contribution of consumables and salaries to direct cost gradually reversed. Because the workload grew at a higher rate than staffing, the workload per FTE increased from 1980 to 1990. This was paralleled by gradual increases in both "revenue" per FTE and salary per FTE in actual dollars, but by lesser increases to no increases in inflation-corrected dollars. After adjusting for inflation with different indices, the direct cost per test, the consumable cost per test, and the salary cost per test either remained unchanged or decreased in the 1980s. The findings are discussed in the context of technical advancements in laboratory testing, nationwide shortages of medical technologists, and implementation of prospective fixed-fee reimbursement practices during the study period.

Academic Medical Centers↗
PubMed1993

Biochemical analysis of thyroid cyst fluid obtained by fine-needle aspiration.

Despite the relatively ready availability of thyroid cyst fluid specimens, little has been published on their biochemical composition. We measured the concentrations of 18 analytes in thyroid cyst fluid specimens from benign (n = 17) and malignant (n = 3) lesions and in homogenates of normal thyroid tissue (n = 5). The concentrations of an additional five analytes were measured in selected cyst fluid specimens only. Compared with normal human serum specimens, we found that in thyroid cyst fluid specimens the activities of acid phosphatase, aspartate aminotransferase, amylase, and lactate dehydrogenase, and the concentrations of iron and total bilirubin were highly increased. The concentration of glucose was low. The gross appearance of the fluids and the presence of certain analytes were consistent with a hemorrhagic origin of most of the benign and malignant cyst fluid specimens. Other biochemical markers, however, indicated colloidlike features and/or an admixture of thyroid tissue components to the cyst fluid. Although we have limited data for cyst fluid specimens from malignant thyroid lesions, we found no evidence that the results of any of the common biochemical tests would distinguish benign from malignant lesions.

Biopsy, Needle↗
PubMed1992

In vitro inactivation of bacterial endotoxin by human lipoproteins and apolipoproteins.

A chromogenic Limulus amebocyte lysate assay was used to measure the recovery of 1 endotoxin unit of endotoxin per ml. Purified human high-density lipoprotein, low-density lipoprotein, and apolipoprotein A1 (apo A1) at a maximum concentration of 1 g of protein per liter reduced the recovery to less than 40% of baseline in a both dose- and time-dependent manner and in the absence of other serum components. Furthermore, the lapine fever response to a dose of 1 ml of 5-ng/ml endotoxin per kg was reduced by greater than 0.5 degrees C (P less than 0.005) when the solution was preincubated in vitro with 0.5 g of apo A1 per liter. By the Limulus test, a maximum concentration of 0.01 g of apolipoprotein B (apo B) per liter (which contained deoxycholate, a known endotoxin-disaggregating agent) reduced recovery to 0% in a dose- but not time-dependent manner. In heat-inactivated (56 degrees C, 1 h) normal human serum, high-density lipoprotein cholesterol (P less than 0.005) and apo A1 (P less than 0.05) correlated inversely with endotoxin recovery, but, paradoxically, apo B correlated directly with endotoxin recovery (P less than 0.05), while low-density lipoprotein cholesterol showed no significant correlation. INTRALIPID alone had no effect on endotoxin recovery. Addition of a maximum of 10 g of INTRALIPID per liter to 0.0042 g of apo B per liter increased endotoxin recovery from approximately 30 to 80% (P less than 0.001), but addition of INTRALIPID to 0.25 g of apo A1 per liter decreased recovery from approximately 30 to 20% (P less than 0.001). We conclude that (i) lipoproteins are endotoxin inactivators; (ii) this ability of lipoproteins may be modulated by their lipid component (lipid-endotoxin interaction); (iii) apo A1 is capable of directly inactivating endotoxin (protein-endotoxin interaction).

Animals↗
PubMed1992

New automated nonisotopic immunoassays for free thyroxin: effect of albumin and thyroxin-binding globulin concentrations.

Recently, nonisotopic (often automated) immunoassays for measuring serum free thyroxin (FT4) have become available. Though more costly than radioimmunoassays, they are considerably more convenient. We studied the influence of endogenous albumin and thyroxin-binding globulin concentration on five automated, nonisotopic methods of measuring FT4 [Enzymun on ES300 (one-step), Stratus I and II (essentially two-step), Delfia (two-step), and IMx (two-step)] in a mixed patient population. We observed that they (a) are influenced very little by endogenous serum binding proteins and (b) seem to have sufficient within-run precision to justify performing single measurements on patients' specimens.

Autoanalysis↗
PubMed1992

Evaluation of two over-the-counter natural thyroid hormone preparations in human volunteers.

OBJECTIVE: To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. DESIGN: In vitro analysis and a prospective, crossover study in vivo. SETTING: Tertiary care center. PARTICIPANTS: Two healthy adult volunteers. INTERVENTION: Three OTC preparations (Thyrotrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lymphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thyrotrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. MAIN OUTCOME MEASURES: The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. RESULTS: HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. CONCLUSIONS: Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown.

Drug Evaluation↗
PubMed1991

Interference by iatrogenically induced anti-mouse IgG antibodies in a two-site immunometric assay for thyrotropin.

Two-site immunometric assays using mouse monoclonal antibodies are gaining increasingly widespread popularity and use. Patients with circulating antimurine immunoglobulin antibodies capable of interfering in these assays have been encountered and described sporadically. Parenteral administration of murine monoclonal antibodies for imaging and therapeutic purposes is increasing and is known to induce human anti-murine antibodies frequently. We examined 60 serum samples from 48 individuals who received such murine immunoglobulin to determine whether iatrogenically induced anti-murine antibodies could interfere in a two-site (sandwich) immunoradiometric assay for serum thyrotropin. We found that these circulating antibodies can indeed interfere in an "unblocked" assay, but that the interference appears to be suppressed by including nonspecific IgG in the commercial version of the assay kit.

Animals↗