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Biomedical subjects

F K Gorus

Publications and source records attributed to F K Gorus.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ektachem slides overestimate serum albumin in patients with nephrotic syndrome.

In a non-selected patient population (n = 140), serum albumin concentrations obtained with Ektachem slides were very significantly correlated with results determined with serum protein electrophoresis on Olympus Hite 200. In 7 patients with nephrotic syndrome, however, no such correlation existed, concentrations on Ektachem being 20 to 200% higher (up to 16 g/l difference). In other samples, albumin concentrations on Ektachem were 10 g/l lower. Between-method differences appeared most closely correlated with the sum of alpha 1- and alpha 2-globulins as determined by serum protein electrophoresis. Immunonephelometric determination of various serum proteins demonstrated that haptoglobin concentrations most closely paralleled the observed between-method differences.

Analysis of Variance↗
PubMed1992

Detection of autoantibodies against islet amyloid polypeptide in human serum. Lack of association with type 1 (insulin-dependent) diabetes mellitus, or with conditions favouring amyloid deposition in islets. The Belgian Diabetes Registry.

A radiobinding assay for the detection of autoantibodies against islet amyloid polypeptide was developed, analytically validated, and--in parallel with a similar assay for the detection of autoantibodies against insulin--applied to sera from recent-onset Type 1 (insulin-dependent) diabetic patients and from age- and sex-matched control subjects. There was no difference in islet amyloid polypeptide autoantibody titres between patient groups and matched control subjects, nor within subject groups according to age. At onset of Type 1 diabetes, elevated islet amyloid polypeptide-autoantibody levels (> 97th percentile of control subjects) were only detected in 1 of 30 patients aged 0-19 years and in 2 of 35 patients aged 20-39 years. By contrast, insulin autoantibodies were frequently demonstrated, in particular at onset of diabetes under age 20 (0-19 years: 18 of 30 patients; 20-39 years: 10 of 35 patients; p < 0.01 vs matched control subjects). Islet amyloid polypeptide autoantibodies were not detectable in 3 insulinoma patients nor in 37 patients (aged 33-70 years) with Type 2 diabetes (vs 1 of 40 in matched control subjects). In positive serum, adsorption onto protein A-Sepharose removed islet amyloid polypeptide binding activity, hereby confirming its antibody nature. In conclusion, Type 1 diabetes is associated with an age-dependent autoantibody reaction against insulin but not against islet amyloid polypeptide. Conditions associated with amyloid deposition in islets (Type 2 diabetes, insulinoma and ageing) do not favour the formation of autoantibodies against islet amyloid polypeptide.

Adolescent↗
PubMed1992

Spuriously low concentrations of serum iron measured with generation 14 Kodak Ektachem slides: prevalence, possible causes, and partial improvement with generation 16 slides.

For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides.

Ascorbic Acid↗
PubMed1992

Analytical and clinical evaluation of creatine kinase MB mass assay by IMx: comparison with MB isoenzyme activity and serum myoglobin for early diagnosis of myocardial infarction.

We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin.

Adult↗
PubMed1992

Increased concentrations of total IgM at clinical onset of type 1 (insulin-dependent) diabetes: correlation with IgM binding to cells. The Belgian Diabetes Registry.

Eighty patients with type 1 (insulin-dependent) diabetes (ages 0-39 years) were consecutively recruited by the Belgian Diabetes Registry. Sera obtained at clinically diagnosed onset (i.e., before start of insulin therapy or within 7 days of initial treatment) were analyzed for total IgM concentrations and for IgM binding to fixed rat splenocytes (IgM-LyAb) and permeabilized rat islet cells (IgM-ICAb). Comparison of results with those in age- and sex-matched control subjects, by fluorescence-activated cell-sorter analysis, indicated greater concentrations of IgM-LyAb and IgM-ICAb in sera from the patients. IgM antibodies reacted indiscriminately with islet beta and islet endocrine non-beta cells. The prevalence of IgM-ICAb, but not of IgM-LyAB, was significantly (P less than 0.05) higher in patients than in the control subjects. Of the ICAb-positive patients, 54% were also LyAb-positive, whereas none of the control subjects were doubly positive. IgM-ICAb and IgM-LyAb binding signals were positively correlated. Serum IgM concentrations were significantly (P less than 0.001) greater in patients than in control subjects and were significantly correlated with IgM-LyAb (P less than 0.001) and IgM-ICAb (P less than 0.01). The positivity for IgM binding was not, however, merely a reflection of total IgM, because no such correlation was found in sera from seven patients with Waldenström macroglobulinemia. Clinical onset of type 1 diabetes is apparently accompanied by increased production of IgM. The correlation between IgM concentrations and IgM binding to islet cells might reflect polyclonal activation or natural autoantibodies.

Adolescent↗
PubMed1992

Method-dependent differences in apparent sodium concentrations in plasma after exchange transfusions with citrated blood.

Shortly after exchange transfusions (n = 7) with citrate-dextrose-phosphate (CDP)-treated blood, but not after regular transfusions (n = 9), sodium concentrations in plasma were significantly and paradoxically lower (3-10 mmol/L) by Ektachem 700 XR determination [with use of electrolyte reference fluid (ERF) generation 00] than by flame photometry. Similar between-method differences could also be generated by in vitro supplementation of plasma pools with CDP solution, with trisodium citrate, or to a lesser extent with Na2HPO4. For four potentiometric methods the analytical recovery of sodium added as CDP was significantly lower than by flame photometry. Within each potentiometric method the recovery was also less than the value for sodium added as NaCl. A significant association of sodium ions with citrate3- ions and, to a lesser extent, HPO4(2-) ions could theoretically account for at least part of the observations, conferring greater medical relevance to potentiometric measurements in this particular clinical situation.

Citrates↗
PubMed1992

Ektachem slides for direct potentiometric determination of sodium in plasma: effect of natremia, blood pH, and type of electrolyte reference fluid on concordance with flame photometry and other potentiometric methods.

With electrolyte reference fluid (ERF)00, results from Kodak Ektachem slides for the direct potentiometric assay of sodium in plasma were significantly correlated with results from flame photometry, but also appeared to be systematically higher, especially in hypernatremic patients. Indirect potentiometry with the Technicon RA-1000 yielded intermediate values. In 23 hypernatremic patients with greater than or equal to 6 mmol/L difference in sodium between Ektachem ERF00 and flame photometry, a clinical survey disclosed the frequent association of large between-method differences with renal failure, diabetes mellitus, and gastrointestinal disease. However, there was no correlation between differences in sodium on the one hand and anion gaps or (lipo)protein concentrations on the other, nor did in vitro addition studies implicate metabolites that often accumulate in the above-mentioned disorders. Unlike indirect methods, sodium measurements by direct potentiometry on Ektachem and Corning were influenced by in vitro changes of pH between 7.0 and 7.9. However, in a group of patients that included many acidotic individuals, between-method differences in sodium appeared not significantly correlated with in vivo blood pH. Use of the equitransferant ERF04 on Ektachem strongly diminishes the systematic differences with flame photometry, reduces the pH-dependency of the results to that of the direct Corning method, and brings the mean analytical recovery of sodium to below 95% (instead of 115% previously) without affecting the ability of Ektachem slides to avoid spuriously low results in the presence of increased (monoclonal) protein concentrations.

Blood↗
PubMed1991

Macromolecular creatine kinase type 1: a serum marker associated with disease.

The prevalence of circulating macromolecular creatine kinase type 1 (macro CK type 1 or CK-immunoglobulin complexes) is significantly higher in a patient population selected for CK isoenzyme assay than in age- and sex-matched blood donors (n = 1304). In greater than 8000 patients studied, 49 individuals with macro CK type 1 were identified, yielding an overall prevalence of 0.61%. Macro CK type 1 complexes occurred more frequently in women and in patients older than 70 years, and were often associated with complications of cardiovascular disease, life-threatening conditions, and poor outcome. These latter clinical associations could arise, at least partly, from the selection of patients for whom CK isoenzyme analysis was ordered.

Adult↗
PubMed1990

Effect of isoenzyme composition on Kodak Ektachem test results for creatine kinase, lactate dehydrogenase, alkaline phosphatase, and amylase.

Seventy-four patients' sera containing macroenzymes or other uncommon enzyme forms were analyzed for total creatine kinase, lactate dehydrogenase, alkaline phosphatase, or amylase activity on an Ektachem 700XR analyzer. The Ektachem test results correlated well with activities obtained by means of liquid reagents on RA-1000. For each enzyme tested, linear-regression analysis yielded data comparable with those for sera containing exclusively the more common isoenzymes. Increased concentrations of intestinal ALP, however, resulted in higher activities of total ALP being reported for the Ektachem.

Alkaline Phosphatase↗
PubMed1988

Interaction of sulfonylureas with pancreatic beta-cells. A study with glyburide.

In this study on purified rat pancreatic beta-cells, we show that the second-generation sulfonylurea glyburide stimulates insulin release through a direct interaction with the beta-cells. During static incubations, 2 microM glyburide releases 0.16 pg insulin per beta-cell, which corresponds to a half-maximal glucose stimulation. This effect occurs independently from the glucose-recognition unit, being detectable at both nonstimulatory and stimulatory glucose concentrations and proceeding without alterations in the rate of glucose oxidation. The secretagogue action of glyburide appears not to be mediated through cAMP but is potentiated by cAMP-generating substances such as glucagon (10(-8) M; 0.31 pg insulin released per beta-cell). Its 10-fold higher potency in isolated islets is attributed to the markedly higher cAMP levels that are maintained in islet beta-cells under the influence of locally released glucagon. Perifused pancreatic beta-cells respond to glyburide with a biphasic insulin release. After removal of the drug, the cells continue to secrete insulin at the same rate for greater than or equal to 30 min. This prolonged secretory activity coincides with a cellular accumulation of the drug, primarily in association with membranes of secretory vesicles and mitochondria. Tolbutamide also stimulates insulin release from pure beta-cells, but it is less powerful on a molar basis and does not lead to a sustained hormone release after its removal from the extracellular medium. We conclude that the hypoglycemic action of glyburide is at least partly the result of a direct interaction with pancreatic beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Alloxan toxicity in human and canine spermatozoa. Possible biochemical basis for a species difference in sensitivity.

In view of the well known species differences in the sensitivity of pancreatic B-cells to the toxic glucose analogue alloxan, it was tested whether spermatozoa from two species with a different diabetogenic effect of alloxan displayed a similar difference in their sensitivity to this drug. In canine spermatozoa, less than 2 mM alloxan profoundly reduced the rate of glucose oxidation and cellular motility whereas more than 5 mM was required to significantly alter these parameters in human spermatozoa. Such species difference was not observed in spermatozoal sensitivity towards the inhibitory effects of tert-butyl hydroperoxide. The phenomenon is not attributable to a different rate of alloxan uptake since the drug is not incorporated by dog or human spermatozoa. The alloxan toxicity was counteracted by D-glucose and its 3-O-methyl analogue in both species, and was potentiated by ascorbic acid; however, only in man. The protective effect of D-glucose was much less marked in tert-butyl hydroperoxide-cytotoxicity. It is concluded that the observed species difference in spermatozoal alloxan sensitivity is not related to differences in alloxan uptake or in sensitivity to organic peroxides; differences in cellular scavenging of superoxide anion radicals and/or ascorbic acid metabolism may explain the lower sensitivity of human spermatozoa for alloxan.

Adult↗
PubMed1986

Glucose metabolism in human spermatozoa: lack of insulin effects and dissociation from alloxan handling.

The role of glucose metabolism in sperm cell motility was examined in purified human spermatozoa from the perspective of elucidating its possible significance in spontaneous and experimental diabetes. After a 4-h incubation in the absence of D-glucose, the mean progressive velocity of human spermatozoa was 40% lower than that of control cells kept in the presence of D-glucose. The decline was rapidly overcome by the addition of D-glucose or D-fructose, the amplitude of this stimulatory effect being independent of the ambient hexose concentration. Between 1.4 and 16.7 mM glucose, spermatozoal glucose oxidation also proceeded independently of the extracellular glucose levels, whereas both insulin (100nM) and glucagon (100nM) failed to significantly affect the rate of glucose metabolism or cellular motility. It is speculated from these results that an alteration in seminal hexose concentrations or pancreatic hormone levels may be an unlikely cause for the reduced sperm motility that is characteristically observed in diabetic patients. Human spermatozoa rapidly incorporated D-glucose and 3-O-methyl-D-glucose but excluded the glucose-analogue alloxan, which may explain their resistance against the toxic effects of this diabetogenic drug, in spite of their intrinsic sensitivity to organic peroxides such as tert-butyl hydroperoxide.

Adult↗
PubMed1984

Differences in glucose handling by pancreatic A- and B-cells.

Glucose exerts opposite effects upon glucagon and insulin release from the endocrine pancreas. Glucose uptake and oxidation were therefore compared in purified A- and B-cells. In purified B-cells, the intracellular concentration of glucose or 3-O-methyl-D-glucose equilibrates within 2 min with the extracellular levels, and, like in intact islets, the rate of glucose oxidation displays a sigmoidal dose-response curve for glucose. In contrast, even after 5 min of incubation, the apparent distribution space of D-glucose or 3-O-methyl-D-glucose in A-cells remains much lower than the intracellular volume. In A-cells, both the rate of 3-O-methyl-D-glucose uptake and glucose oxidation proceed proportional to the hexose concentration up to 10 mM and reach saturation at higher concentrations. Addition of insulin failed to affect 3-O-methyl-D-glucose or D-glucose uptake and glucose oxidation by purified A-cells. Glucose releases 30-fold more insulin from islets than from single B-cells, but this marked difference is not associated with differences in glucose handling. The rate of glucose oxidation is virtually identical in single and reaggregated B-cells and is not altered after addition of glucagon or somatostatin. It is concluded that the dependency of glucose-induced insulin release upon the functional coordination between islet cells is not mediated through changes in glucose metabolism.

3-O-Methylglucose↗
PubMed1984

Glucose metabolism in murine fetal cortical brain cells: lack of insulin effects.

Glucose uptake and oxidation were markedly higher in cultured than in freshly isolated neural cells, prepared from murine fetal brain cortices. The hexose transport process--measured as 3-O-methyl-D-glucose uptake--appeared comparable in both conditions, and proceeded proportionally to the extracellular sugar concentration up to 6 mM. In contrast, glucose oxidation occurred independently of the prevailing glucose concentration from 1.4 mM on. Acute or chronic exposure to insulin exerted no effect upon cellular glucose uptake or oxidation. These results suggest that glucose handling by maturing fetal cortical cells is mainly determined by the rate of cellular glucose breakdown rather than by the rate of glucose transport into the cell; the marked rise in cellular glucose metabolism during culture might result from the synthesis and/or activation of a key enzyme in glucose catabolism. Our observations also indicate that the previously described neurotrophic effects of insulin are not mediated via enhanced glucose handling.

Animals↗
PubMed1982

Selective uptake of alloxan by pancreatic B-cells.

Alloxan rapidly binds to or accumulates in pancreatic B-cells as distinct from non-B-cells. The selective uptake of this cytotoxic agent by the insulin-producing B-cells might account for its well-known diabetogenic effect.

Alloxan↗
PubMed1982

Effect of temperature, nutrients, calcium, and cAMP on motility of human spermatozoa.

The motility of human spermatozoa and its regulation were examined on cells isolated from other seminal components and purified into fractions of uniform progressive motility. The percent motile cells and estimates of their translational speed were determined by visual inspection, by stroboscopy, and by photon correlation spectroscopy; microcinematography and gradient centrifugation were occasionally used to clarify discrepancies. The motility of isolated spermatozoa could be maintained for periods up to 24 h at 4 or 37 degrees C; the presence of seminal fluid was not required and even provoked a reversible inhibition at 4 degrees C. Albumin facilitated cell movement between microscopic glass plates but had no effect on progressive motility per se, as evidenced by other techniques. During incubations of up to 2 h, progressive cell motility occurred independently of extracellular glucose and calcium but responded to variations in adenosine 3',5'-cyclic monophosphate and calcium. Dibutyryl cAMP increased forward motility, whereas ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid reversibly immobilized the spermatozoa in a calcium-dependent manner; phosphodiesterase inhibition resulted in increased vibration of sperm heads without any effect on progressive motility. Longer incubation periods required the presence of extracellular nutrients. These experiments further demonstrate that several motility measuring techniques should be used in parallel to distinguish the various components of cell movement, to exclude aspecific effects, and to supplement the shortcomings of each individual technique. Such procedure could clarify the various discrepancies that have been reported so far and should lead to a better understanding of the regulation of human sperm motility.

Calcium↗
PubMed1981

A rapid method for the fractionation of human spermatozoa according to their progressive motility.

A rapid and gentle procedure has been developed for the separation of spermatozoa from other seminal cells and for the preparation of purified spermatozoa with uniform progressive velocity. The method consists of the filtration of semen through an isotonic. Percoll layer and the subsequent centrifugation of the cell pellet on a preformed continuous Percoll gradient; after fractionation of the density gradient, immotile spermatozoa are recovered at density 1.06 to 1.09, whereas an increase in progressive velocity is measured for spermatozoa collected at higher densities. The usefulness of this simple method as a diagnostic aid in men with infertility and urogenital disease was illustrated by the analysis of two abnormal semen samples. This method for the preparation of homogeneous sperm cell populations might facilitate further (sub)cellular studies under normal and pathologic conditions.

Cell Separation↗