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Biomedical subjects

H Kaffarnik

Publications and source records attributed to H Kaffarnik.

At least 37 records · Page 2Linked to original sources

Low-dose oral contraceptives lower plasma levels of apolipoprotein E.

Three different oral contraceptive preparations were studied before and after a 3 month treatment period with respect to their effects on plasma lipoprotein parameters. A total of 58 healthy women requesting oral contraception were randomly assigned to three groups. Each woman received either monophasic preparations containing ethinylestradiol and desogestrel (M-DG); ethinylestradiol and gestodene (M-GD); or a triphasic preparation of ethinylestradiol and levonorgestrel (T-LN). As has been reported in other studies, the concentrations of total plasma cholesterol and apolipoproteins B and A-IV did not change significantly in any group. HDL cholesterol, triglycerides, apolipoproteins A-I and A-II increased or tended to increase. Despite the effects of the three hormone preparations on these lipoprotein parameters, however, each led to a highly significant decrease in apolipoprotein E plasma levels. Considering the recently reported observations that oral contraceptives increase the hepatic uptake of cholesterol-rich remnants, this decrease in apo-E plasma levels may in women that take oral contraceptives be directly correlated with increased hepatic lipoprotein metabolism.

Adolescent↗

Normolipemic dysbetalipoproteinemia and hyperlipoproteinemia type III in subjects homozygous for a rare genetic apolipoprotein E variant (apoE1).

A family with three heterozygote and two homozygote carriers of the rare apolipoprotein E1 isoform was detected by isoelectric focusing. One of the homozygous patients had type III hyperlipidemia, while the other showed normolipemic dysbetalipoproteinemia. Restriction fragment length analysis as well as allele specific oligonucleotides were used to identify the structural alterations forming the abnormal epsilon 1 genotype. Comparison with the most common epsilon 3 allele showed that two base exchanges A for G in codon 127 and T for G in codon 158 (Asp for Gly and Cys for Arg, respectively) are responsible for the amino acid substitution which causes the charge shift observed in isoelectric focusing. The same defects have been described in the only previously characterized apoE1 (Weisgraber et al. 1984. J. Clin. Invest. 73: 1024-1033). In addition to the study by Weisgraber and coworkers, who reported on a heterozygous patient, we here describe the metabolic and clinical consequences of a homozygosity for this rare allele. Changes in lipoprotein metabolism, as well as in clinical phenotypes, were exactly identical to those seen in patients homozygous for the epsilon 2 allele, which has in common with the epsilon 1 allele the mutation in codon 158, but lacks the substitution in codon 127. In addition, lipoprotein profiles of the epsilon 3/epsilon 1 heterozygotes were indistinguishable from those of epsilon 3/epsilon 2 heterozygotes. Therefore, we conclude that the additional mutation in codon 127 that characterizes the epsilon 1 allele is of no functional importance in vivo.

Adolescent↗

A rapid laser immunonephelometric assay for serum amyloid A (SAA) and its application to the diagnosis of kidney allograft rejection.

We set up a laser nephelometric assay for the quantitation of serum amyloid A (SAA) in human plasma. Therefore monospecific antibodies were raised in sheep and used in parallel to measure SAA concentrations by nephelometry and also by radial immunodiffusion, an assay usually applied for determination of SAA. The nephelometric method is precise, simple and unlike radial immunodiffusion results are obtained within an hour. The antigen concentrations determined both by laser nephelometry and radial immunodiffusion correlated highly (r = 0.98). As plasma SAA concentrations were reported to be a possible marker of kidney allograft rejection, the assay was applied to measure SAA concentrations in patients after kidney transplantation. Data were compared with clinical and other biochemical parameters. The period after kidney transplantation is reported for two cases, where SAA plasma concentrations were helpful in diagnosing allograft rejection. The rapid availability of the SAA plasma concentrations by nephelometry makes them a possible additional tool to decide quickly upon antirejection therapy.

Graft Rejection↗

Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate.

To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblotting and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the adult, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the epsilon 2 allele and lowest in individuals expressing apoE4, and vice versa for apoB. We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constant in utero environment.

Apolipoproteins B↗

Apolipoproteins in human amniotic fluid: concentrations, isoforms and polymorphism.

Apolipoproteins were determined in 50 human amniotic fluids obtained by amniocentesis during weeks 16 and 22 (n = 26) or 33 and 41 (n = 24) of gestation. Whereas apo A-I, A-II, A-IV, and E were identified at levels of 1, 0.7, 0.8 and 1% of normal human adult plasma, respectively, apo B levels were only 0.04% of plasma concentration and apo C-III levels were below the detection limits of the assay. Amniotic fluid levels of apo A-II, A-IV and E did not differ between early and late stages of pregnancy, but levels of apo B decreased and apo A-I increased significantly in late pregnancy. Isofocusing showed apo A-I, A-II and A-IV in identical positions as compared to human adult plasma. Furthermore the known genetic polymorphism of apo A-IV was detectable. Individuals heterozygous, for the variant form apo A-IV-2, showing the phenotype apo A-IV (2-1), had significantly higher levels of apo A-I and A-II as compared to the common phenotype apo A-IV (1-1). We conclude that human amniotic fluid contains the major plasma apolipoproteins at about 1% of plasma levels with the exception of apo B which shows a level at an order of magnitude less than high-density lipoprotein apoproteins in comparison to their plasma counterparts.

Amniotic Fluid↗

[Does determination of atrial natriuretic factor have significance in the assessment of cardiac stress in apnea in sleep apnea patients?].

It has long been known that the heart is involved volume regulation. This fact took on new importance when, in 1981, de Bold discovered the existence of ANF. Apnea-associated cardiovascular changes make the treatment of apnea necessary to prevent the occurrence of cardiovascular sequelae. What is needed, however, is a parameter which, non-invasively, reflects both the cardiac loading during apnea and effects of treatment. Krieger succeeded in demonstrating that the commonly observed nycturia regresses under nasal cPAP therapy. This prompted us to consider whether the ANF factor might not be involved. In an attempt to find an answer, we have, up to now, investigated six patients prior to and during nCPAP therapy. On the basis of the results we obtained, the following conclusions may be drawn: 1. During apnea, the patients show sometimes dramatic increases in ANF plasma levels. 2. Under nasal CPAP treatment, these elevated levels decrease again, in some cases by as much as 50%. 3. The ANF plasma level correlates with pulmonary arterial pressure. This suggests to us that ANF determination is of importance for the assessment of cardiac loading during apnea, and represents a parameter that reflects the effects of therapy.

Atrial Natriuretic Factor↗

[Hyperestrogenemia following various shunt operations: on the role of estrogens in the development of focal nodular hyperplasia of the liver].

Hormones especially estrogens have been suspected to induce liver cell tumours or hepatic focal nodular hyperplasia (FNH). In rats 6 months after portocaval anastomosis (PCA) the occurrence of FNH has been observed. Modified portocaval anastomosis (mPCA) does not lead to FNH. To test the concept of estrogen induced tumour formation we measured in both groups as well as in a shamoperated control group (SOP) the levels of estradiol (E2), estrone (E1) and of testosterone (T). In a further experiment the hormone levels were measured in rats with portocaval transposition (PCT), an operation which leads to high gonadal hormone production. In groups of 6 male rats each (280-300 g) either SOP, PCA, mPCA or PCT were performed. 30 days later the blood levels of E2, E1, and of T were measured by radioimmunoassay. In PCT-rats hormone levels were measured in the blood synchronously taken from the inferior vena cava (prehepatic) and from the heart (posthepatic), to get an information of the hepatic hormone degradation. After PCA the median level of E2 (77 pg/ml) and E1 (63 pg/ml) are significantly elevated when compared with SOP-rats (41 and 43 pg/ml). Equally after mPCA the E2 and E1 levels are significantly higher (61 and 70 pg/ml) than in controls rats. In contrast the concentrations of T are significantly reduced (PCA 0.03, mPCA 0, 10, SOP 1.0 ng/ml). PCA as well as mPCA result in a hyperestrogenic and hypoandrogenic status. When PCA and mPCA are compared, only the testosterone blood levels are significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Apoprotein AII in acute pancreatitis: intriguing improvement in the prediction of fatal outcome.

In spite of significant advances in the past decade, assessing of severe prognosis in acute pancreatitis remains an improvable problem. Actually the standardized means are clinical, multiple laboratory and peritoneal lavage. In a series of 20 subsequent cases of acute pancreatitis with a lethality of 30%, apolipoprotein AII has proven to be a predictor of fatal outcome with a sensitivity in the range of all other methods together. Competitive replacement of Apo AII by serum amyloid like substance A as an indicator for the amount of necrosis would explain this relation. Whether this suggestion can be confirmed by ongoing work or not, apolipoprotein AII merits attention in this context.

Acute Disease↗

Ultrasonography of achilles tendons in primary hypercholesterolemia. Comparison with computed tomography.

Tendon xanthoma are a hallmark of familial hypercholesterolemia and are among its earliest clinical manifestations. Achilles tendon size, advanced to a generally accepted marker, is virtually specific for the disease and easily accessible for measurement. Hypercholesterolemic patients with coronary heart disease have been reported to have larger diameters of the Achilles tendons than patients without coronary problems. Furthermore, Achilles tendon xanthomas have been shown to regress with treatment of the lipid disorder. Mainly radiological procedures were applied in the past to evaluate the diameters of the Achilles tendon but their use is limited by radiation protection. We have used real-time ultrasonography to evaluate the Achilles tendons of 38 patients with primary hypercholesterolemia and 32 normocholesterolemic controls. The anterior posterior diameter in the patients was 13.4 +/- 5.9 mm (range 6-20 mm) and 5.7 +/- 0.7 mm (range 5-8 mm) in the control group. In 8 patients with newly diagnosed and previously untreated hypercholesterolemia the thickness correlated highly with their age. The Achilles tendons in about half of the patients (n = 21) showed a homogeneous thickening, whereas the others revealed an inhomogeneous thickening indicating the presence of circumscribed xanthoma. Upon comparison of the ultrasonographic procedure with an established method (computed tomography) in 18 patients and 8 normal volunteers a highly significant correlation (r = 0.96) proved the validity of the sonography. We show that real time ultrasonography is a valid procedure to assess Achilles tendon diameters in patients with primary hypercholesterolemia. It can be applied frequently and may be useful to follow xanthoma regression during lipid lowering treatment.

Achilles Tendon↗

Changes of apolipoprotein A-IV in the human neonate: evidence for different inductions of apolipoproteins A-IV and A-I in the postpartum period.

The levels, isoforms and distribution of apolipoprotein A-IV (apo A-IV) were investigated in 127 term human umbilical cord sera. In addition, apo A-IV levels and isoforms were determined on the 3rd (n = 82) and 6th (n = 68) day following parturition and compared to apo A-I concentrations. Levels of apo A-IV were low in umbilical cord serum (5.7 +/- 1.9 mg/dl) as compared to adult serum (17.6 +/- 4.8 mg/dl). No difference was found between male and female neonates. The serum distribution of apo A-IV closely resembled that seen in the adult human. Apo A-IV concentrations dramatically increased during the first week of life reaching levels of 13.4 +/- 4.1 mg/dl on day 3 and 16.7 +/- 3.4 mg/dl on day 6 post-partum. During this time apo A-I levels did not change significantly (81.0 +/- 16.5 mg/dl in cord serum, 75.3 +/- 10.6 mg/dl and 84.2 +/- 14.5 mg/dl on day 3 and 6, respectively). Cord serum already exhibited the major serum apo A-IV isoforms seen in the adult. Isofocusing of apo A-IV also identified the known genetic polymorphism of apo A-IV. Among 127 cord sera studied we identified 109 homozygote normal patterns, apo A-IV (1-1), 16 heterozygotes, apo A-IV (1-2) and 2 individuals homozygote for the variant peptide, apo A-IV (2-2). We provide evidence that apo A-IV and apo A-I are differently induced in the human neonate during the beginning of the feeding period.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

[Sex hormones and the hypophyseo-gonadal axis in females with liver cirrhosis in postmenopause].

The hormonal status of men with cirrhosis of the liver has been investigated in numerous studies. Little, however, is known about changes of sexual hormones in women afflicted by this disorder. In a study of 31 postmenopausal women (mean age 63 +/- 8 years) suffering from cirrhosis of various etiology (alcoholic, n = 8; posthepatitic B, n = 1; PBC, n = 5; cryptogenetic, n = 17) the blood levels of estradiol (E2), estrone (E1), androstenedione (A), testosterone (T) and basal and stimulated values of gonadotropins are reported and compared with the data obtained in an age-matched control group (n = 9). In cirrhosis a significant increase of the median E2 (28 vs 12 pg/ml, P less than 0.01) was found, whereas the changes of the blood levels of E1 (88 vs 76 pg/ml), A (63 vs 111 ng/dl), and T (0.30 vs 0.15 ng/ml) did not attain statistical significance in comparison to controls. Within the study group, however, a significant positive correlation with the degree of decompensation of cirrhosis (Childscore A-C) was observed for the steroid hormones measured. Thus, in subgroup C the hormone levels are higher than physiologically expected for postmenopausal women. On the other hand the median FSH (32 vs 48 mU/ml, P less than 0.05) is significantly lower in cirrhosis compared to controls with a trend to decreased values of LH. Very low levels of LH and FSH are found in decompensated cirrhosis. The decrease of LH and FSH can partly be explained by the rise of peripheral hormones (i.e. E2, E1, and in some cases T and A).(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Hormonal and cardiovascular variations during a public lecture.

A long-time electrocardiogram over a period of 12 h was recorded from ten test persons without cardiovascular diseases, and their blood pressure was checked at regular intervals on the day of a public speech. In order to determine plasma concentrations of epinephrine, norepinephrine, cortisol, human growth hormone (hGH), prolactin and gastrin, blood samples were taken from the subjects by inserting a venous catheter in the morning. The levels of epinephrine, norepinephrine and cortisol were also examined in urine collected from the volunteers. During the public speech there was a distinct increase in blood pressure and pulse rate. Epinephrine and cortisol showed the clearest increase in serum and collected urine, whereas norepinephrine, prolactin, hGH and gastrin reacted less strongly. The epinephrine/norepinephrine ratio value is discussed as a parameter for psychomental and emotional strain.

Adult↗

Activation of phosphatidylcholine-sterol acyltransferase by human apolipoprotein E isoforms.

The reaction catalysed by phosphatidylcholine-sterol acyltransferase (EC 2.3.1.43) is believed to be the major source of cholesteryl ester in human plasma; the enzyme requires a protein activator. Several human apolipoproteins were found to exhibit an activator function, the major one being apolipoprotein A-I. Human apolipoprotein E exists in the population mainly in three different genetic isoforms; apolipoprotein E-2, E-3 and E-4. These isopeptides were isolated from subjects homozygous for one of the isoforms, incorporated into phospholipid/cholesterol/[14C]cholesterol complexes by the cholate dialysis procedure and used to measure capacity to activate phosphatidylcholine-sterol acyltransferase in comparison to apolipoprotein A-I lipid substrate particles prepared by the same procedure. Acyltransferase activity was measured by the formation of [14C]cholesteryl ester from [14C]cholesterol using purified enzyme. With egg yolk phosphatidylcholine as acyl donor, apo E was 15-19% as efficient as apolipoprotein A-I for activation of the acyltransferase. Apo-E-stimulated cholesteryl ester formation by the enzyme was enhanced when 1-oleoyl-2-palmitoyl-glycerophosphocholine was used as a substrate phospholipid (45% of apo A-I/phosphatidylcholine control) and most pronounced with dimyristoylglycerophosphocholine (75% of apo A-I/phosphatidylcholine control). No significant difference in activation was found between apo E isoforms. It is concluded that apolipoprotein E activates phosphatidylcholine-sterol acyltransferase in vitro and that apolipoprotein E isoforms are similarly effective.

Apolipoproteins E↗

[Thyroid hormones in women with liver cirrhosis].

Basal thyroid hormone levels were measured in 68 women with liver cirrhosis (LC) of different etiology (alcoholic n = 34, posthepatitic B n = 9, PBC n = 5, cryptogenetic n = 18, M. Wilson n = 2). In addition the rise of TSH after 400 micrograms TRH was measured in 23 women with LC and compared with the data obtained from 17 women of a control group. There was no difference of the median T4-concentrations (LC 8.0 micrograms/dl versus 7.2 micrograms/dl) but a significant correlation of T4 to the grade of decompensation of LC. In contrast of T4 there was a marked decrease of T3 in LC-patients (109 ng/dl versus 143 ng/dl) and a rise of reverse T3 (0.21 ng/ml versus 0.13 ng/ml). The decrease of T3 and rise of reverse T3 equally correlated to the severeness of LC. TBG concentrations fell according to the grade of decompensation of LC and T4/TBG-quotient exhibited no difference to the control data (0.51 both). Though basal thyroid hormones and TSH show euthyroidism the significant augmented TSH release after TRH (delta-TSH 7.0 versus 3.2 microU/ml) indicate a status of latent hypothyroidism. In alcoholic cirrhosis the degree of TSH release was much higher than in non alcoholic cirrhosis. Estradiol and estrone levels correlated significantly negatively to T4, T3, estrone negatively to TBG and positively to reverse T3 but not to TSH and TSH release. Otherwise TSH release correlated positively to estradiol. The thyroid status in women with liver cirrhosis does not differ from the thyroid hormone profile found in men with cirrhosis.

Female↗