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J Bartek

Publications and source records attributed to J Bartek.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immunohistochemical analysis of the D-type cyclin-dependent kinases Cdk4 and Cdk6, using a series of monoclonal antibodies.

Cellular signal transduction cascades triggered by mitogenic or antiproliferative cues eventually converge on a biochemical mechanism centered around the retinoblastoma tumor suppressor (pRb), the so-called RB pathway that governs G1-phase progression and guards the commitment to enter S phase. pRb, together with its immediate upstream regulators, the D-type cyclins, their partner cyclin-dependent kinases Cdk4 and Cdk6, and the Cdk inhibitors, form a functional unit that is involved in major decisions about cellular fate, and whose components, including the proto-oncogenic cyclin D-dependent kinases, are commonly deregulated in many types of cancer. We report here the production and characterization of a series of 12 monoclonal antibodies (MAbs) that specifically recognize either Cdk4 or Cdk6. These antibodies are proving to be invaluable molecular probes for defining abundance, subcellular localization, binding partners, and ultimately the function(s) of these cell cycle-regulatory kinases. Localization of the target epitopes was mapped by peptide enzyme-linked immunoadsorbent assay (ELISA), and two antibodies recognizing sequences adjacent to N-terminus of Cdk4 can discriminate between the wild-type protein and the oncogenic, melanoma-associated R24C mutant of this kinase. Individual antibodies of our panel recognize distinct pools of Cdk4/6, a feature reflected by their differential applicability in immunoblotting, immunoprecipitation, kinase assays, and immunostaining including immunohistochemistry on archival paraffin-embedded tissue sections. Collectively, the antibodies described in this study provide the means for immunochemical analyses of the cyclin D-dependent kinases in human and animal cells, and represent useful molecular tools that should help better understand the biological roles of Cdk4 and Cdk6 in normal cell-cycle control, and their oncogenic activity in tumor cells.

Animals↗
PubMed1999

Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8.

Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, encodes a protein, referred to as HHV8-Vcyc, with sequence similarity to human G1 cyclins, in particular of the D type. HHV8-Vcyc is expressed in Kaposi's sarcoma and functional analysis suggests that it can activate cyclin-dependent kinases (cdk) and thereby trigger inactivation of the retinoblastoma protein (pRb), indicating that HHV8-Vcyc may contribute to the oncogenic potential of HHV-8. We show here that HHV8-Vcyc can activate transcription of the human cyclin A gene in quiescent cells, a property shared with known transforming oncogenes. Transcriptional activation by HHV8-Vcyc depends on an E2F-binding site in the cyclin A promoter, and cdk6 kinase activity is required. The ability of HHV8-Vcyc to activate cyclin A gene expression is shared by D-type cyclins and cyclin E. Unlike D-type cyclins, HHV8-Vcyc is unable to trigger phosphorylation of the pRb-related protein p107 and fails to induce dissociation of p107 from E2F. Unlike cyclin E, HHV8-Vcyc fails to interact physically with E2F complexes on the cyclin A promoter. These results provide additional evidence for the notion that the HHV-8-encoded cyclin differs in several properties from cellular G1 cyclins.

3T3 Cells↗
PubMed1999

Determination of leptin receptor in the serum and relations to laboratory and anthropological parameters in patients with atherosclerotic complications.

Leptin receptors are supposed to have signal effects and are located in most tissues in the organism but we failed to find literary data on concentration (measurement) of leptin receptors in the system circulation. We examined by the method of randomized selection the group of 20 patients with manifested atherosclerosis in whom BMI was calculated. Then we analyzed concentration of leptin receptor (double sandwich ELISA, standard recombinant human leptin), leptin, glucose, insulin, proinsulin, CRP and uric acid in the serum. The control group consisted of 103 probands without signs of atherosclerosis or other manifested diseases. The control group was subjected to determination of BMI, leptin and leptin receptor in the serum. Concentration of leptin receptor does not differ significantly between the patients with atherosclerosis and normal population. Probands with atherosclerosis showed a very close negative correlation between concentration of leptin receptor and leptinemia which is absent in normal population.

Arteriosclerosis↗
PubMed1999

[Leptinemia in individuals with hypertension (pilot study)].

UNLABELLED: During the last decade several papers were published where obesity in included among the building stones of the so-called metabolic cardiovascular syndrome (along with hypertension, dyslipidaemia, impaired glucose tolerance and hyperinsulinaemia). Several months ago it was also revealed that some patients with the metabolic syndrome suffer from hyperleptinaemia. Leptinaemia is considered by some authors as independent indicator of the risk of accelerated atherosclerosis. The cause of these hypothesis were (in addition to the known conclusions on the occurrence frequent incidence of leptin resistance and insulin resistance) in particular the results of experimental studies where evidence was provided that infusion induced hyperleptinaemia leads in animals to hypertension due to its direct effect on sympathicotonia and peripheral vascular resistance. The authors of these hypothesis assume that hyperleptinaemia (in particular in subjects with metabolic syndrome) in one of the basic causes of hypertension which is frequently encountered in these patients. OBJECTIVE: To assess the relations between leptinaemia and the blood pressure reading (actual and mean values) and leptinaemia and the classification of hypertension according to WHO. METHOD: The authors examined 35 hypertensive subject and 10 subject with tetanies (without hypertension). The blood pressure was assessed under standard conditions (rest, semi-recumbent position, three readings). The mean blood pressure readings during the last three months were obtained from case records. Leptin was assessed by the ELISA method of Bio Vendor Co. RESULTS: The group of hypertonic can be classified as subjects with mild obesity (BMI 30.1). The values of leptin were elevated but did not differ significantly from those of the normal population. No correlations were found between leptinaemia (incl. values calculated for BMI) and the actual and mean blood pressure readings. No correlations were found between leptinaemia (incl. BP calculated with regard to BMI) and the stage of hypertension according to WHO. CONCLUSION: Hypertonic subject do not differ significantly as to the serum leptin concentration from the general population. Leptinaemia does not correlate with the actual or mean blood pressure reading nor with stage of hypertension according to the WHO classification. Thus the authors did not confirm the hypothesis on the fundamental effect of leptinaemia on the genesis and development of hypertension. It is probable that leptin is only one of the many factors which have an impact on blood pressure.

Blood Pressure↗
PubMed1999

[Use of proinsulin analysis for estimates of insulin resistance].

INTRODUCTION: According to contemporary estimates diabetes is present in 120 million subjects. This disease is associated with the incidence of a number of very serious organ complications and very frequently is diagnosed late (several years after its development). Because despite increased diagnostic and therapeutic efforts the number of diabetic patients is increasing, new diagnostic and therapeutic means are sought. Evidence was provided that some complications of diabetes develop not only in case of poor compensation but also in hyperinsulinaemia (hypertension, ischaemic heart and coronary artery disease etc.). In clinical practice it is however possible to assess hyperinsulinaemia or incipient insulin resistance only with difficulty because classical examinations (insulin and C-peptide on fasting) have a very low specificity and sensitivity. Therefore for estimation of insulin resistance loading tests are used (e.g. examination of insulin after stimulation with glucose, or C-peptide after stimulation with glucagon, insulin tolerance and suppression tests, or in research projects so-called minimal models or clamp techniques). Any loading test is however demanding from the aspect of time, money, technical aspects and staff and therefore possibilities are sought how to estimate the degree of insulin resistance and sensitivity in a specimen of biological material under basal conditions. OBJECTIVE OF INVESTIGATION: Because in the literature only sporadically assessment of intact proinsulin is mentioned as the ideal marker of insulin resistance under basal conditions, the authors decided to assess the relations between intact proinsulin (PI) and other biochemical parameters in patients with type 2 diabetes and dyslipidaemia (200 probands) and to assess whether PI correlates with the results of loading tests (modified oGTT with calculation of the sum and delta-insulin--120 probands). RESULTS: It was revealed that PI (contrary to insulin, C-peptide and total proinsulin) correlates with the results of the loading test characterizing insulin resistance (sum and delta insulin, correlation coefficient 0.84) (n=120 subjects). It was furthermore found that probands (n=200 subjects) who are followed up on account of type 2 diabetes or dyslipidaemia (or both) differ from the control group (n=20 subjects) as regards biochemical parameters only in the PI concentration (dispensarized patients have higher levels, p>0.99), whereby in other standard basal characteristics of insulin secretion and resistance the groups did not differ. The differences were correlated with HOMA models of insulin secretion and resistance and no correlations were found. The PI concentration in this group correlated significantly with the cholesterol, fibrinogen and triacylglycerol concentration. No relations were found between the values of intact proinsulin with C-peptide and insulin. CONCLUSION: Based on the results of their study the authors assume that examination of intact proinsulin is a valid "basal" indicator of insulin resistance. From the results ensues also that intact proinsulin is probably a very good predictor as regards the risk of development of cardiovascular disease.

Diabetes Mellitus, Type 2↗
PubMed1999

[Leptinaemia in the Czech population].

INTRODUCTION: Leptin is a protein, determined by the ob-gene which influences in a fundamental way the energy metabolism of the organism. A significant effect of leptin on the haematopoietic, immunological and endocrinological system cannot be ruled out nor its effect on the course of pregnancy and maturation of the organism. In humans leptinaemia correlates with the amount of subcutaneous fat which is due to a receptor or post-receptor disorder, obese subjects suffer frequently from hyperleptinaemia. OBJECTIVE: To assess the mean leptinaemia of the general population, seek relations between leptinaemia and anthropological indicators and age. METHODS: Using the method of random sampling the authors examined a group of 538 probands (252 males, 286 females) incl. 12% healthy students of the Faculty of Physical Culture in Olomouc, 37% subjects without acute or chronic complications feeling in good health and 37% patients of the metabolic and diabetological ambulance of the hospital in Sternberk. In each patient a detailed case-history was recorded, an anthropological examination was made and a venous blood sample was taken for leptin analysis (serum, ELISA-sandwich method of BIOVENDOR Co.) RESULTS: Spectrum of patients, whose condition and age distribution in our group corresponded to the general population of the Czech Republic. The mean age of the probands was 51 years (18 to 82 years), the examined group can be characterized as subjects lacking signs of obesity. Leptinaemia was on average about 10 ng/ml (minimum 0, maximum 97.9 ng/ml), whereby men had values round 6 and women round 14 ng/ml (women had also a greater adipose tissue mass). Non-obese subjects (BMI<26) had a mean leptinaemia of 5 (women cca 6, men cca 2 ng/ml), obese subjects (BMI>30) have a leptinaemia of cca 19 ng/ml (women about 26, men about 13 ng/ml). With advancing age the leptinaemia in adults rises up to the age of 70, in subjects above 70 years it does not change (in women it declines significantly). The dynamics of leptinaemia imitate the changes of BMI and percentage of adipose tissue (in men also a rise in WHR). Leptinaemia is associated with the BMI (correlation coefficient 0.55), with the percentage of body fat (correlation coefficient 0.75), and in men with the WHR (correlation coefficient 0.82). The association between ageand leptinaemia is only indicated (correlation coefficient 0.29) and is not very close. According to the authors results subcutaneous body fat is responsible for cca 60% of the variability of leptinaemia (in women as much as 74%), BMI for 23%, age and sex for cca 9% of the vriability of leptinaemia. In men the WHR is responsible for 66% of the variability of leptinaemia. With an increase of subcutaneous adipose tissue by 1% the leptinaemia increases by some 0.54 ng/ml (in men by 0.22 ng/ml, in women by 0.84 ng/ml), with increasing BMI leptinaemia rises by 0.44 ng/ml/u (in men by 1.3 ng/ml, in women by 1.72 ng/ml), with advancing age leptin rises by 0.24 ng/ml/year (in men by 0.16 ng/ml, in women by 0.28 ng/ml), changes of leptinaemia imitate changes of BMI and the percentage of body fat. With increasing WHR in men the leptinaemia rises by 2.6 ng/ml/0.1 WHR. CONCLUSION: Standards of leptinaemia for the general population of the Czech Republic were elaborated. Leptinaemia correlates most closely of all anthropometric indicators with subcutaneous fat and in men with the WHR index. With advancing age between 20 and 70 years leptunaemia rises and then decliunes insignificantly (in women the changes are however significant). The primary cause of the mentioned differencesare probably changes of the bodily constitution.

Adolescent↗
PubMed1998

p21WAF1/CIP1 mutants deficient in inhibiting cyclin-dependent kinases (CDKs) can promote assembly of active cyclin D/CDK4(6) complexes in human tumor cells.

The cyclin-dependent kinase (CDK) inhibitor p21WAF1/CIP1 is a multidomain, multifunctional protein and a candidate tumor suppressor. Here, we show that, among rationally designed and tumor-associated mutants of human p21 ectopically expressed in U-2-OS cells, those that are selectively deficient in binding to either cyclin or CDK are partially impaired in inhibiting endogenous CDK activities but efficiently promote assembly of active cyclin D/CDK4(6) complexes. These results provide mechanistic insights into the p21-cyclin/CDK interplay in vivo and suggest a functional subclassification of tumor-specific aberrations of p21. Intriguingly, the subclass exemplified by the melanoma-derived N50S mutant may promote tumorigenesis, by both attenuating CDK-inhibitory function and concomitantly activating the proto-oncogenic cyclin D-dependent kinases.

Cyclin D↗
PubMed1998

Expression of a p16INK4a-specific ribozyme downmodulates p16INK4a abundance and accelerates cell proliferation.

The pl6INK4a tumor suppressor negatively regulates progression through the G1 phase of the mammalian cell cycle. To mimic the downmodulation of p16INK4a commonly seen in cancer, we designed and characterized a hammerhead ribozyme against exon E1alpha of the murine pl6INK4a transcript. Stable expression of the ribozyme in murine erythroleukemia (MEL) cells reduced the endogenous pl6INK4a protein by more than 70% and significantly accelerated cell cycle progression. The specificity and efficiency of our new ribozyme suggest its possible application in elucidating the role of p16INK4a in fundamental biological processes including homeostatic tissue renewal, protection against oncogenic transformation, and cellular senescence.

Animals↗
PubMed1998

Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation.

The mammalian D-type cyclins D1, D2, and D3 activate the cyclin-dependent kinases CDK4 and CDK6 in G1 and thereby promote the cell's commitment to enter S phase. To elucidate the extent of functional overlap among the D-type cyclins, we have examined several aspects of the least characterized member of this subfamily of G cyclin proteins, cyclin D3. Microinjection of cyclin D3-neutralizing antibody inhibited G1/S transition in human (IMR-90) and rat (R12) diploid fibroblasts, indicating that analogous to cyclins D1 and D2, cyclin D3 is essential for timely progression through G1. In contrast to cyclins D1 and D2, cyclin D3 was (i) ubiquitously expressed among a panel of 70 human cultured cell types; (ii) strongly upregulated upon induction of HL-60 leukaemia cells to differentiate; and (iii) accumulated to high levels in a wide range of quiescent cell types in mouse and human differentiated tissues. Complementary analyses of human biopsies and mouse tissues at different stages of foetal and postnatal development revealed lineage-dependent transient or long-term accumulation of the cyclin D3 protein, correlating with initiation/establishment or maintenance of the mature phenotypes, respectively. Our data support the notion that the biological roles of the individual D-type cyclins are not fully redundant, and suggest a possible dual role for cyclin D3 in cell proliferation and induction and/or maintenance of terminal differentiation.

Antibodies, Monoclonal↗
PubMed1998

Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours.

Cell cycle proteins regulate the transitions from G1 to S and G2 to M phases. In higher eukaryotes, their function is controlled by intracellular cascades regulated by extracellular growth factors. We have studied in previously described transgenic mouse models for thyroid proliferative diseases the expression of the key proteins regulating the cell cycle by Western blotting and immunohistochemistry, and have correlated the observations with the known actions of the transgenes on the signal transduction cascades. In the adenosine A2a receptor model, the cyclic AMP pathway, upstream of the Rb family cell division block, is constitutively activated. In the model expressing HPV 16 E7 protein, the Rb-like proteins are inhibited. Cyclin-dependent kinases cdk4, cdk2 and cdc2, and the associated cyclins D, E and A have been studied. Cyclin D3 appears as the major cyclin D subtype expressed in mouse thyroid epithelial cells in normal and transgenic mice. In the adenosine A2aR model, all cell cycle proteins tested were accumulated. In the E7 model, all cell cycle proteins except for D-type cyclins and cdk4 were also accumulated. A similar pattern was observed in thyroids coexpressing both transgenes, suggesting a dominant effect of E7 over the consequences of the cAMP cascade activation. The cyclin-dependent kinase inhibitors p21cip1/waf1 and p27kip1 were not downregulated in these proliferating thyroids which suggest other roles than the inhibition of the cell cycle progression.

Animals↗
PubMed1998

Rac and Cdc42 are potent stimulators of E2F-dependent transcription capable of promoting retinoblastoma susceptibility gene product hyperphosphorylation.

The Rho family of GTPases plays an important and diverse role in reorganization of the actin cytoskeleton, transcriptional regulation, and multiple aspects of cell growth. Our study has examined their potential links to the cell cycle machinery. We find that constitutively active mutants of Rac and Cdc42, but not Rho, are potent inducers of E2F transcriptional activity in NIH 3T3 fibroblasts. Furthermore, activated Rac and Cdc42, but again not Rho, are capable of inducing cyclin D1 accumulation and pRB hyperphosphorylation in serum-deprived cells, outlining one route leading to enhanced E2F-mediated transcription. The inhibitory effect of the cyclin-dependent kinase inhibitors, p16(ink4), p21(cip1), and p27(cip) on Rac/Cdc42-mediated E2F transcription corroborates a role for pRB family members and their functional inactivation by cyclin-dependent kinases in generating E2F activity. While the up-regulation of E2F transcriptional activity by Rac or Cdc42, not Rho, suffices for entry into S phase and DNA synthesis in Rat-1 R12 cells, this is clearly not the case in NIH 3T3, where additional requirements must exist.

3T3 Cells↗
PubMed1998

A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes.

In different systems, cyclic adenosine monophosphate (cAMP) either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S prereplicative phase progression by cAMP as a second messenger for thyrotropin (TSH). The cAMP-dependent mitogenic pathway is unique as it is independent of mitogen-activated protein kinase activation and differs from growth factor-dependent pathways at the level of the expression of several protooncogenes/transcription factors. This study examined the involvement of D-type G1 cyclins and their associated cyclin-dependent kinase (cdk4) in the cAMP-dependent G1 phase progression of dog thyroid cells. Unlike epidermal growth factor (EGF)+serum and other cAMP-independent mitogens, TSH did not induce the accumulation of cyclins D1 and D2 and partially inhibited the basal expression of the most abundant cyclin D3. However, TSH stimulation enhanced the nuclear detection of cyclin D3. This effect correlated with G1 and S phase progression. It was found to reflect both the unmasking of an epitope of cyclin D3 close to its domain of interaction with cdk4, and the nuclear translocation of cyclin D3. TSH and EGF+serum also induced a previously undescribed nuclear translocation of cdk4, the assembly of precipitable cyclin D3-cdk4 complexes, and the Rb kinase activity of these complexes. Previously, cdk4 activity was found to be required in the cAMP-dependent mitogenic pathway of dog thyrocytes, as in growth factor pathways. Here, microinjections of a cyclin D3 antibody showed that cyclin D3 is essential in the TSH/ cAMP-dependent mitogenesis, but not in the pathway of growth factors that induce cyclins D1 and D2. The present study (a) provides the first example in a normal cell of a stimulation of G1 phase progression occurring independently of an enhanced accumulation of cyclins D, (b) identifies the activation of cyclin D3 and cdk4 through their enhanced assembly and/or nuclear translocation, as first convergence steps of the parallel cAMP-dependent and growth factor mitogenic pathways, and (c) strongly suggests that this new mechanism is essential in the cAMP-dependent mitogenesis, which provides the first direct demonstration of the requirement for cyclin D3 in a G1 phase progression.

Animals↗
PubMed1998

Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide beta-D-GalpNAc-(1-->4)[alpha-L-Fucp-(1-->3)]-beta-D-GlcpNAc.

The trisaccharide allyl glycoside 36 and related disaccharide part structures have been prepared using the 2-trichloroacetamido-2-deoxy-alpha-D-galactopyranosyl trichloroacetimidate derivative 9 as glycosyl donor under promotion with TMSOTf or Sn(OTf)2, respectively, to produce the beta-(1-->4) linkage to suitably protected glucosamine derivatives in fair yields. Fucosylation was effected employing the ethyl 1-thio glycosyl donor 20 in the presence of IDCP. Deprotection of the intermediates afforded the disaccharide allyl glycosides beta-D-GalpNAc-(1-->4)- beta-D-GlcpNAc 13, beta-D-GalpNClAc-(1-->4)-beta-D-GlcpNAc 14, alpha-L-Fucp-(1-->3)-beta-D-GlcpNAc 24, alpha-L-Fucp-(1-->4)-beta-D- GlcpNAc 31 and the branched trisaccharide allyl glycoside beta-D-GalpNAc-(1-->4)[alpha-L-Fucp-(1-->3)]-beta-D-GlcpNAc 36. The trisaccharide which corresponds to a structural motif occurring in N-glycoprotein glycans from human urokinase, human recombinant protein C, phospholipase A2 as well as O-glycans, was converted into a neoglycoprotein following introduction of a cysteamine-derived spacer group and subsequent activation with thiophosgene.

Carbohydrate Sequence↗
PubMed1998

Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers.

There is controversy concerning the prognosis of breast cancers arising in women carrying loss of function mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. This study was carried out to assess the likely hormone dependence of this group of tumours in comparison with an age and grade matched group of control sporadic tumours. We used quantitative immunohistochemical analysis for the oestrogen receptor (ER), progesterone receptor (PgR), cyclin D1 and pS2 on sections of primary tumours and ductal carcinoma in situ (DCIS). Expression of PgR (P < 0.05) and cyclin D1 (P < 0.01) was low in the BRCA1- and BRCA2-associated cancers compared with sporadic cases. The low frequency of expression of ER (9/40), PgR (2/40) cyclin D1 (5/36) and pS2 (5/36) in the familial tumours indicates that the majority of such tumours will be oestrogen insensitive and unlikely to respond to hormonal manipulation even at the in situ stage in their evolution. The low level of PgR (2/40 cases) suggests that there may be some abnormality of transactivating function of the ER in these tumours.

Adult↗
PubMed1998

[Serum leptin, early atherosclerosis and hypolipidemia (a new, previously undescribed effect of pravastatin, a hypolipemic agent)].

Hyperleptinemia is considered to be one of predictors of early atherosklerosis complications. This stimulated us to investigate differences between leptinemia in persons with accelerated atherosclerosis and leptinemia in probands without atherosclerosis complications. The study also verified whether leptinemia and its relationship to other anthropometric and biochemical parameters can differ in hypolipemic-treated probands and hypolipemic-untreated individuals. We examined 89 probands with accelerated atherosclerosis. The controls were 20 persons without any signs of accelerated atherosclerosis. Probands with accelerated atherosclerosis had a slight hyperglycemia and were slightly obese, but they did not meet criteria of metabolic cardiovascular syndrome. No significant differences between both groups under study were found in terms of anthropometric and biochemical parameters (BMI, % body fat, glycemia, insulin, C-peptide, intact proinsulin, total proinsulin cholesterol, HDL, triglycerides, LDL, homeostatic model of insulin secretion and resistance). Leptin concentration was not different as well. Stratification into males and females showed that women had a significantly higher leptinemia and fat tissue mass. Other biochemical parameters were similar in both groups. We suppose that in individuals without signs of metabolic syndrome, leptinemia does not belong among predictors of accelerated atherosclerosis. The accelerated atherosclerosis persons were then divided into subgroups according to medication (28 probands--pravastatin Lipostat 20, 15 probands--phenofibrate Lipanthyl 200M, 9 probands--simvastatin Zocor 20, 47 probands--no hypolipemic medication). No significant differences between the groups were found in terms of the analysed anthropometric and biochemical parameters, except leptinemia. The pravastatin-medicated probands had a significantly lower leptinemia (significant at 99% significance level) which was evidently sex-related than other patients. The pravastatin-administered persons showed no correlation between leptinemia and body fat mass (in contrast to other groups where such a correlation was highly statistically significant). These findings can be explained by a still unclear effect of pravastatin on insulin metabolism and on other factors involved in leptin synthesis and elimination. Thus, a new therapeutic effect of pravastatin can be supposed. This may account for a highly favourable effect of pravastatin on reduced manifestations of atherosclerosis complications event at a low LDL cholesterol decrease (particularly in persons with metabolic cardiovascular syndrome).

Adipose Tissue↗
PubMed1998

[Leptinemia in persons with acute myocardial infarct].

The purpose of the study was to verify whether the currently reported relationship between leptinemia and adipose tissue mass can be applied to cases of acute coronary attack. An increased number of cytokines has been reported in severe acute myocardial infarctions so that correlation between cytokines and leptin was investigated. Correlation between standard coronary markers and leptinemia was also studied. We examined 48 probands, patients of the Coronary Unit, Hospital, Sternberk, who were hospitalized for acute myocardial infarction (AMI--16 probands) or for unstable angina pectoris (UAP--22 probands). The persons with AMI had leptinemia and a higher concentration of interleukine-6 (Il-6) and of cardial troponine-I (cTn-I) than individuals without coronary accident (UAP). Early after the acute coronary lesion, leptinemia in persons with AMI displayed a statistically significant positive correlation with concentration of interleukine-6 and subsequently of markers of coronary lesion severity (cTnI). No correlation between leptinemia and body weight was found in those probands. This study proved that leptinemia in the AMI individuals is influenced directly by concentration of cytokines which leads to leptin superproduction by fat cells and leptin resistance.

Adipose Tissue↗
PubMed1998

[Serum leptin in women during the third trimester of pregnancy].

Leptin is a small protein produced mainly by adipocytes. Recently, its relationship to obesity has been studied extensively. It was proved that obese individuals have either relative or absolute leptin deficiency. Several years ago, leptin was found to be produced also by the placenta. This stimulated us to study relationship between leptinemia and placental hormones in 85 women in the second gravidity trimester. Within the prenatal screening, these pregnant women were subjected to analysis of AFP, hCG, SP-1 glycoprotein and leptin and the results obtained were processed statistically. The control group consisted of 20 nonpregnant women with tetany. Women in the second gravidity trimester were found to have a significantly higher leptinemia than nongravid women (even with respect to body weight). This may be due to a larger amount of adipose tissue during gravidity and also leptin-resistance. Moreover, we recorded a negative correlation between leptinemia related to body weight and concentration of SP-1 glycoprotein. This finding supports the presumption that mother's leptinemia correlated negatively in the second gravidity trimester with quality and quantity of the placental syncytiotrophoblast. Our findings can be explained as follows: the biological effect of leptin is metabolically unfavourable for the growth of the foetus and the placenta. An increased leptinemia with advancing gravidity can be caused by a larger fatty mass and an increased activity of adipocytes when leptin presence increases in system circulation but the organism begins to be leptin-resistant and an "unfavourable" metabolic effect fort the gravid woman and the foetus is not distinct. These findings thus support the hypothesis postulating the nonsignificance of leptin production in human placenta and on the contrary the necessity of leptin-resistance for foetus development from the metabolic point of view. Thus, a decreased leptinemia immediately before and after the delivery could be caused by the still unclear regulators of leptin sensitivity. This is again a metabolically highly favourable state (reduced appetite, decreased body weight, increased energy output and others).

Adipose Tissue↗