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Biomedical subjects

J Bartek

Publications and source records attributed to J Bartek.

At least 91 records · Page 5Linked to original sources

[Benefit of direct determination of LDL-cholesterol (comparison with LDL measurement using calculated estimates].

Treatment of dyslipidemia and its frequently associated complications (manifest atherosclerosis) is very pretentious from the economic aspect. Diagnostic and therapeutic criteria are based mainly on biochemical analyses. Although demands on laboratories are relatively strict (respecting defined laboratory errors, analytical and preanalytical conditions), when defined diagnostic criteria are used, the results of biochemical analyses are not yet satisfactory. A typical example is the stratification of risk patients according to the LDL concentration which in our country is very often preferred, although the LDL concentration is based only on calculation (contrary to investigations from which the majority of recommendations was derived where the LDL concentration was assessed directly). We know from our own experience that a large percentage of results of estimated and assessed LDL differs significantly. Therefore we wanted to know whether the assessed LDL concentration correlates with its estimate according to Friedewald s formula and which analytes have the greatest impact on the LDL concentration. Our objective was also to assess th percentage of incorrectly listed patients (according to the LDL stratification scale). In 1997-1998 we examined a group of 4578 probands, patients of the consultant out-patient departments of the Sternberk hospital. Their mean age was 56 years. On average subjects with as slightly atherogenic phenotype were involved (classification A according to EAS). The values of lipid parameters did not differ significantly in the two sexes. The cholesterol, LDL and triacylglycerol concentrations increased with advancing age. The LDL values obtained by assessment and calculation correlated closely. The LDL value was influenced most by ApoB and total cholesterol. Triacylglycerols correlated with LDL assessment only up to a concentration of .3 mmol/l. HDL, ApoA-1 and higher triacylglycerol concentrations (1.3 mmol/l) did not correlate with the LDL value. The authors provided evidence that in subjects where it was possible to calculate LDL lege artis (2458 probands) were listed according to LDL calculation into a wrong group (stratification according to NCEP) whereby up to an LDL concentration .11 mmol/l this parameter cannot be predicted at all by calculation (error up to 85%). A satisfactory estimate is assumed only at LDL concentrations 5.2 mmol/l. Because the estimated LDL values are in the majority of patients lower than the calculated values, it may be assumed that during stratification of LDL obtained by calculation the patients are treated too aggressively. Assuming pharmacological treatment of all mentioned patients, it may be estimated that by using analyses of direct LDL for stratification of probands the costs of hypolipidaemic treatment will by reduced by about 1/4-1/3 (in the catchment area of the Sternberk hospital this would save more than 10 million crowns). The costs of LDL analyses per year are about 180,000 crowns (in the Sternberk hospital--which amounts to cca 1.5% of the money saved on pharmacotherapy).

Adolescent↗

Biochemical findings in the ejaculate of men with non-obstructive azoospermia.

In men with non-obstructive azoospermia, testicle biopsy can provide isolated sperm which can be used for fertilization of an oocyte. The male seminal plasma was examined for adequate biochemical parameters and then tested as potential diagnostic parameters for prediction of sperm presence in non-obstructive azoospermia. Sperm was obtained by preparation of the testicular tissue. Biochemical parameters in men with found sperm were compared to findings obtained from men without sperm in the testicular tissue. The following parameters were analysed: fructose, lactate dehydrogenase, total acid phosphatase, Zn, K, Na, Cl, pH. No statistically significant differences were found in both groups under study. Biochemical examination of the ejaculate cannot provide any prediction of sperm retrieval in non-obstructive azoospermia.

Humans↗

[Determination of cardiac troponin-I in prediction of thrombolysis].

Acute myocardial infarction (AMI) is a disease with high morbidity and mortality. Diagnosis of AMI using common methods (classical biochemistry, ECG) fails even in the fifth part of patients so that other noninvasive diagnostic methods are preferred. Recently, the biochemical analysis has been restored in the case of AMI diagnostics and also in prediction of coronary reperfusion after administration of a fibrinolytic agent. A suitable markers of AMI diagnostics is a combination of myoglobin and cardial troponin-I which is reported as a marker with high specificity and sensitivity. To determine coronary reperfusion, the examination of cardial troponin-T and CK-MB mass is recommended. In the literature, there exist isolated papers dealing with dynamics of cTn-I suitable for prediction of coronary revascularization. However, these papers do not report any adequate algorithm and subsequently mathematical differences between successful thrombolysis and failing thrombolysis. Therefore the aim of our study was to describe dynamics of cTn-I changes in AMI patients treated by thrombolysis. The study comprised of 8 AMI patients with delay from the occurrence of pains to fibrinolysis application under 4 hours (delay 4 hrs). These probands were examined for concentration of cTn-I and CK-MB mass in 3-hour intervals in the first 48 hours after admission to the clinic and further in 6-hour intervals from the hour 48 to the hour 90 after admission. All probands had a successful reperfusion (estimated using CK-MB peak, in 4 patients reperfusion was verified by subsequent coronarography). However, a simple mathematical prediction of coronary reperfusion after acute myocardial infarction by means of cTn-I dynamics determination is not possible due to relatively low cTn-I differences in individual analyses (CK-MB mass analysis shows more significant differences). Thus, in order to determine coronary revascularization, we recommend to use common analyses of dynamics of cTn-T or CK-MB mass.

Biomarkers↗

[Leptin, insulin and proinsulin--their relationship].

Leptin is protein produced by mature adipocytes into the system circulation and gives information to hypothalamic centers about fat amount in the organism. Leptin is supposed to play a causal role in energy output of the organism and influences the appetite (antiobese effect). Obese individuals were proved to have frequently hyperleptinemia. This disease is caused by a postreceptor disorder (however, several obese families had also normoleptinemia or even hypoleptinemia which is caused by polymorphism of Ob-gene). It was also found that leptin administration in animals leads to reduced appetite and decreased body weight. Interpretation of leptinemia in human is very complicated because leptinemia is influenced by many independent regulations (hormones, stress, food intake, motor activity atc.). Obesity is often associated with hyperinsulinemia and insulin resistance (a frequent cause of human mortality) so that correlations between insulin and leptin are intensively studied. Experimental models and animal studies revealed the existence of adipoinsular axis and it was found that insulin and leptin are contrahormones. In human studies, the majority of authors did not find correlation between leptinemia and markers of insulin secretion. Similar conclusions were drawn out in our previous paper [118]. This may be due to complex regulations of leptinemia in the organism and the use of biochemical markers with limited validity (insulin, C-peptide in fasting state and after stimulation). Therefore we decided to study correlation between leptinemia and intact proinsulin in the serum which is now considered to be the most valid marker of insulin secretion and provides information about an average "daily" insulinemia. This study was stimulated by the fact that increased leptinemia is found also in persons with prolonged hyperinsulinemia (a short-term hyperinsulinemia does not affect leptin concentration so that no available marker of insulin secretion is valid). We examined the group of 31 probands, patients of the Metabolic and Diabetologic Center at the hospital in Sternberk. They were diabetic patients of type 2 who were treated by peroral antidiabetics and insulin and who met criteria of good compensation. However, no correlation between leptinemia and proinsulinemia was found. We suppose that this failure was due to complicated fine regulations affecting leptinemia and also to the fact that intact proinsulin is not an "ideal" marker of a long-term hyperinsulinemia (correlation between insulin and leptin at euglycemic clamp indicates that there exist correlation between these parameters in human).

Adipose Tissue↗

The retinoblastoma protein pathway in cell cycle control and cancer.

Recent discoveries in diverse fields of biomedical research have merged to reveal the molecular basis of cell cycle control and a critical role of subverting this homeostatic mechanism in cancer development. At the heart of these processes lies a late G1 checkpoint governed by the "RB pathway" whose molecular composition, functions, and cancer-associated defects are briefly evaluated in this review. This exciting new knowledge raises a plethora of conceptual issues in cell biology, with potential practical implications for biotechnology and medicine.

Animals↗

[p16 and p53 genes transferred with the help of adenovirus to induce apoptic tumor cell death].

Based on studies of the cell cycle in tissue cultures of cancer cell lines and cells from normal tissue interference in the regulatory network of pRB/cdk4/cyclin D1/p16 in combination with the tumour suppressor gene p53 was investigated. It was shown that overexpression of p53 and p16, but not p53 on its own, induced apoptotic cell death only in tumour cells. Gene transfer of the same two genes to tumours transplanted subcutaneously in mice also caused fast regression of some of the tumours.

Adenoviruses, Human↗

Cyclin D1 expression in mantle cell lymphoma is accompanied by downregulation of cyclin D3 and is not related to the proliferative activity.

The cell cycle regulatory protein cyclin D1 is essential for G1-S phase transition in several epithelial and mesenchymal tissues but is apparently not essential in normal mature B cells. An overexpression of cyclin D1 is induced by the chromosomal translocation t(11;14)(q13;q32), which characterizes non-Hodgkin's lymphomas (NHLs) of mantle cell type. We studied 26 cases of mantle cell lymphoma (MCL) for the expression of cyclins D1 and D3. A total of 23 lymphomas showed a nuclear staining for cyclin D1, whereas reactive B cells of residual germinal centers were constantly negative. When compared with cyclin D3, an inverse staining pattern emerged. Whereas the B cells of residual germinal centers reacted strongly positive for cyclin D3, there was low or missing expression of cyclin D3 in MCL cells. In other B-cell lymphomas (n = 55), including chronic lymphocytic leukemia, low-grade lymphomas of mucosa-associated lymphatic tissue, follicular lymphomas, and diffuse large B-cell lymphomas, no cyclin D1 expression could be detected and 89% of these cases displayed cyclin D3 positivity. Lymphoma cell lines harboring the t(11;14) showed cyclin D1 protein but no or very low levels of cyclin D3; three other B-cell lines, a T-cell line, and peripheral blood lymphocytes strongly expressed cyclin D3 and reacted negatively for cyclin D1. We conclude that the chromosomal translocation t(11;14) leads to an abnormal protein expression of cyclin D1 in the tumor cells of MCL and induces a consecutive downregulation of cyclin D3. In contrast to other B-NHLs, cyclin D1 and D3 expression in MCL is not related to the growth fraction.

Cell Division↗

Aberrant p21(CIP1/WAF1) protein accumulation in head-and-neck cancer.

p21(CIP1/WAF1) is an inhibitor of cyclin-dependent kinases and, in normal tissues including squamous epithelia, has been associated with cell-cycle exit and differentiation. As shown in this pilot study, however, the majority of head-and-neck squamous-cell carcinomas (HNSCC) display aberrant p21(CIP1/WAF1) expression: of 42 tumors analyzed by immunohistochemical staining, 28 (67%) over-expressed the p21(CIP1/WAF1) protein. Accumulation of p21(CIP1/WAF1) was independent of the histological grade of the tumors as well as the genetic status of the p53 gene. In many cases, most notably in poorly differentiated or undifferentiated HNSCC, p21(CIP1/WAF1)-positive cells were actively proliferating tumor cells, since they also expressed proliferating-cell nuclear antigen (PCNA) and Ki-67. Accumulation of p21(CIP1/WAF1) occurred through a post-transcriptional mechanism since, in contrast to immunohistochemical analysis of the p21(CIP1/WAF1) protein, in situ hybridization showed no increase of mRNA levels as compared with cells in normal mucosa (n = 25). Clinically, among the patients with p21(CIP1/WAF1)-over-expressing tumors, there was increased recurring disease (p = 0.03; chi2-test), shortened disease-free survival (p = 0.0019; log-rank test) and shortened overall survival (p = 0.0071; log-rank test). These in vivo data indicate that in many HNSCC, accumulated p21(CIP1/WAF1) is compatible with increased tumor-cell proliferation, and they provide preliminary evidence that p21(CIP1/WAF1) may be of prognostic and predictive significance.

Biopsy↗

[Magnesium balance in patients with spasmophilia. Relation to results of electromyography].

BACKGROUND: The pathophysiological basis of spasmophilia is frequently magnesium deficiency and the therapeutic administration of magnesium salts has usually a favourable effect. However the parameters of magnesium balance are not always consistent with the results of electromyography. The objective of the present work was to test and interpret the relationship of results of these two basic diagnostic procedures indicated when spasmophilia is suspected. METHODS AND RESULTS: Thirty-three subjects (9 men and 24 women) with suspected spasmophilia were examined by non-invasive electromyography, using the technique of surface electrodes. All subjects had concurrently biochemical examinations: serum calcium and ionized calcium, serum magnesium (S-mg), magnesium in erythrocytes (ery-Mg) and magnesium in the blood haemolysate (H-Mg). In 29 patients and oral magnesium loading test was made with evaluation of the urinary Mg excretion after a constant Mg load (U-Mg). Statistical evaluation of the investigated parameters of the magnesium balance revealed a highly significant relationship between ery-Mg and U-Mg and H-Mg and ery-Mg (p < 0.005). A less close relationship was found between H-Mg and S-Mg (p < 0.05). Total and ionized calcium was in all examined subjects within the range of the arbitrary normal range. The EMG finding was positive (the finding of two and more multiplets in the ischaemic and hyperventilation test resp.) in 30 instances, i.e. in 91% of the examined subjects. In 72% there was agreement of the positivity of the EMG and magnesium deficiency (i.e. reduced values of ery-Mg and U-Mg), positivity of EMG combined with normal parameters of the Mg balance was recorded in 18%. In 6.1% of the examined subjects magnesium deficiency was confirmed combined with a normal EMG finding. CONCLUSIONS: Concurrent positivity of EMG and magnesium deficiency in 72% justifies the therapeutic administration of magnesium. In patients with a normal magnesium deficiency and positive EMG another cause of spasmophilia must be taken into consideration, incl. technical errors of interpretation of EMG results. A negative EMG associated with magnesium deficiency can suggest the central form of tetany, where magnesium treatment is also unequivocally indicated.

Adolescent↗

Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc.

We demonstrate in this paper that CDK4 which is a G1 phase specific cell cycle regulator and catalytic subunit of D-type cyclins has oncogenic activity similar to D-type cyclins themselves and is able to provoke focus formation when cotransfected with activated Ha-ras into primary rat embryo fibroblasts. Surprisingly, using two different mutants we show that CDK4's ability to bind to p16INK4a and not its kinase activity is important for its transforming potential. In addition, p16INK4a but not a mutant form that is found in human tumours can completely abrogate focus formation by CDK4 suggesting that CDK4 can malignantly transform cells by sequestering p16INK4a or other CKIs. We demonstrate that both cyclin D1 and CDK4 functionally depend on active Myc to exert their potential as oncogenes and vice versa that the transforming ability of Myc requires functional cyclin D/CDK complexes. Moreover, we find that p16INK4a and the Rb related protein p107 which releases Myc after phosphorylation by cyclin D1/CDK4 efficiently block Myc's activity as a transcriptional transactivator and as an oncogene. We conclude that both p16INK4a and cyclin D/CDK4 complexes are upstream regulators of Myc and directly govern Myc function in transcriptional transactivation and transformation via the pocket protein p107.

3T3 Cells↗

Cyclin E-induced S phase without activation of the pRb/E2F pathway.

In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we performed microinjection and transfection experiments using rat R12 fibroblasts, their derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells, to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S-phase induction. We demonstrate that ectopic expression of cyclin E, but not cyclin D1, can override G1 arrest imposed by either the p16INK4a Cdk inhibitor specific for Cdk4 and Cdk6 or a novel phosphorylation-deficient mutant pRb. Several complementary approaches to assess E2F activation, including quantitative reporter assays in live cells, showed that the cyclin E-induced S phase and completion of the cell division cycle can occur in the absence of E2F-mediated transactivation. Together with the ability of cyclin E to overcome a G1 block induced by expression of dominant-negative mutant DP-1, a heterodimeric partner of E2Fs, these results provide evidence for a cyclin E-controlled S phase-promoting event in somatic cells downstream of or parallel to phosphorylation of pRb and independent of E2F activation. They furthermore indicate that a lack of E2F-mediated transactivation can be compensated by hyperactivation of this cyclin E-controlled event.

Animals↗

Aberrations of the G1- and G1/S-regulating genes in human cancer.

Deregulated cell proliferation is the hallmark of cancer, and convergent data from the fields of cell-cycle research and molecular oncology have revealed the key role played by abnormalities of the cell-cycle control genes in multistep tumorigenesis. Along with the p53-mediated DNA damage checkpoint, the G1-governing pathway of D-type cyclins, their partner cyclin-dependent kinases (Cdk), Cdk inhibitors, and the retinoblastoma protein constitute a functional unit and prominent oncogenic target. We have learned a great deal about the molecular basis of G1 phase progression and G1/S transition, their proto-oncogenic defects, and potential clinical significance including diagnostic and prognostic applications and new approaches to gene therapy of cancer.

Cyclin-Dependent Kinases↗

Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death.

Repression of cell cycle progression by tumor suppressors might provide a means for tumor therapy. Here we demonstrate that ectopic overexpression of the p16INK4/CDKN2 tumor suppressor from an adenovirus vector in various cell lines results in block of cell division and, subsequently, in a gradual reduction of the levels of the product of retinoblastoma susceptibility gene, pRb. Overexpression of p53 and p16INK4/CDKN2, but not p53 on its own, induces apoptotic death only in tumor cells. Simultaneous adenoviral transfer of p16 and p53 genes leads to inhibition of tumor growth in nude mice. These results suggest that combined delivery of two cooperating genes like p16 and p53 could be the basis for the development of a new strategy for cancer gene therapy.

Adenoviridae↗

Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and p15CDKN2B genes in certain B cell non-Hodgkin's lymphomas. Functional studies in a cell line (Granta 519).

Abnormalities of several cell-cycle regulatory genes including cyclin D1, p16CDKN2 and p15CDKN2B have been described in B cell non-Hodgkin's lymphoma (B-NHL). We describe a new B-NHL cell line (Granta 519), with concurrent abnormalities of the cyclin D1, pl6CDKN2 and pl5CDKN2B genes. An independent clinical case of mantle cell NHL (Mc-NHL) with concomitant overexpression of cyclin D1, and deletion of the p16CDKN2 gene was also identified, suggesting that this combination of oncogenic aberration is a pathophysiologic contribution to a subset of NHL cases. More in-depth functional studies of this concept were facilitated by the availability of the cell line Granta 519 which was derived from a case of high-grade NHL and has a mature B cell immunophenotype. Cytogenetic analysis identified translocation t(11;14)(q13;q32) and complex rearrangements involving chromosomes 9p22, 13p21, 17pl1, and 18q21. Molecular analysis identified overexpression of cyclin D1 mRNA and biallelic deletion of the p16CDKN2 and p15CDKN2B genes. To elucidate the effect of these genetic abnormalities on the G1 control of Granta 519 cells, the level and function of the major components of the cyclinD/retinoblastoma (RB) pathway were investigated. Cyclin D1 was dominant among the D-type cyclins, formed abundant complexes with cyclin-dependent kinase (Cdk) Cdk4 rather than Cdk6, and the immunoprecipitated cyclin D1/Cdk4 holoenzyme was active as a pRB kinase. Electroporation of wild-type pl6CDKN2 arrested the Granta 519 cells in G1, consistent with the p16CDKN2 loss as a biologically relevant event during multistep evolution of the tumor, and with the expression of functional pRB. Direct cooperation of these distinct abnormalities to cell-cycle, deregulation in NHL cells was suggested by G1 acceleration upon inducible overexpression of cyclin D1 in a control breast cancer cell line lacking p16CDKN2, an effect which could be prevented by ectopic expression of p16CDKN2. Taken together, these data suggest that concurrent overexpression of cyclin D1 and functional elimination of p16CDKN2 and p15CDKN2B may characterize certain cases of mantle cell NHL, and that cooperation of the abnormalities is likely to provide a growth advantage of the tumour cells through more efficient inactivation of the RB tumor suppressor. Further clinicopathologic studies of this possibility are warranted.

Aged↗

Complementary insulin therapy improves blood glucose and serum lipid parameters in type 2 (non-insulin-dependent) diabetic patients. I. Effects on blood glucose control.

Aim of the present prospective study was to assess the potential benefits of complementary insulin therapy, consisting of a single dose of 1 to 8 units of shortacting insulin before each meal, on blood glucose, serum lipid parameters and on patient's well-being. A group of 251 type 2 (non-insulin-dependent) diabetic patients completed the study. The complementary insulin therapy was introduced in hospital in the course of one week. Number of injections per day was increased, the average dose of insulin per day and the average dose of glibenclamide decreased, amount of carbohydrates in food (adapted by patients themselves) diminished, mean blood glucose, number of hyperglycaemia's and number of hypoglycaemia's decreased. At a check-up 8 to 10 weeks later, a decrease of haemoglobin A1c, glycated proteins in serum and body mass index together with improved patient's well-being have been shown. These results demonstrate a good effectiveness of complementary insulin therapy in type 2 (non-insulin-dependent) diabetic patients. We assume this kind of therapy should be more often recommended.

Adult↗

Complementary insulin therapy improves blood glucose and serum lipid parameters in type 2 (non-insulin-dependent) diabetic patients. II. Effects on serum lipids, lipoproteins and apoproteins.

The aim of the present study was to evaluate the effects of complementary insulin therapy, consisting of a single dose of 1 to 8 units of shortacting insulin before each meal (4-6x daily) and sometimes at 02.30 h, on concentrations of serum lipids, lipoproteins and apoproteins in type 2 (non-insulin-dependent) diabetic patients, unsatisfactorily controlled either by oral hypoglycemic agents (OHA) or by longacting insulin 1-2x daily (INS 1-2). Compared means +/- SD. Patients on INS 1-2 (n = 82) had better baseline glycemic control than patients on OHA (n = 68) (HbAlc: 9.33 +/- 1.76% vs. 10.59 +/- 1.83%, p < 0.001 and fructosamine: 3.34 +/- 0.74 mmol/l vs. 3.85 +/- 0.84 mmol/l, p < 0.001) and serum triglyceride concentrations (3.03 +/- 2.05 mmol/l vs. 4.95 +/- 4.48 mmol/l, p < 0.001), in spite of longer duration of diabetes (13.35 +/- 8.07 years vs. 10.1 +/- 6.9 years, p < 0.001). After 8-10 weeks of complementary insulin therapy, OHA patients (n = 33) improved both the glycemic control (HbA1c: 10.5 +/- 1.78% vs. 9.0 +/- 1.75%, p < 0.001) and fructosamine: 4.0 +/- 0.85 mmol/l vs. 3.5 +/- 0.76 mmol/l, p < 0.001) and most of the lipid parameters (decreased serum triglyceride: 5.8 +/- 5.64 mmol/l vs. 3.6 +/- 4.69 mmol/l, p < 0.001, total cholesterol/HDL-cholesterol: 6.8 +/- 3.13 vs. 5.6 +/- 2.23, p < 0.01 and increased HDL-cholesterol: 1.0 +/- 0.30 mmol/l vs. 1.2 +/- 0.30 mmol/l, p < 0.001, apo AI: 1.6 +/- 0.26 g/l vs. 1.8 +/- 0.28 g/l, p < 0.001, LpAI particles: 0.6 +/- 0.1 g/l vs. 0.7 +/- 0.12 g/l, p < 0.001 and LDL-cholesterol/apo B: 2.1 +/- 0.67 vs. 2.7 +/- 0.67, p < 0.001). In patients previously on INS 1-2x (n = 34), complementary insulin therapy with reduced dose of insulin per day (49.6 +/- 22.5 U/d vs. 36.6 +/- 13.3 U/d, p < 0.001) did not further improve glycemic control but improved the number of proatherogenic and antiatherogenic lipoprotein particles (decreased apo B: 1.7 +/- 0.52 g/l vs. 1.5 +/- 0.94 g/l, p < 0.01, apo AI/Lp AI: 2.9 +/- 1.01 vs. 2.3 +/- 0.98, p < 0.01 and increased Lp AI particles: 0.6 +/- 0.10 g/l vs. 0.7 +/- 0.12 g/l, p < 0.0001); BMI also decreased (29.4 +/- 4.28 kg/m2 vs. 28.9 +/- 4.24 kg/m2, p < 0.05). These results demonstrate that complementary insulin therapy probably induces antiatherogenic lipoprotein changes in NIDDM patients previously treated by either OHA or INS 1-2x. Thus, this type of therapy should be used more often and start earlier, and should be preferred to longacting insulins.

Adult↗

p53 protein in endometrial cancer is related to proliferative activity and prognosis but not to expression of p21 protein.

Expression of the tumor suppressor gene product p53 and the cyclin-dependent kinase inhibitor p21, which is transcriptionally activated by p53, was investigated and compared with patient survival in a retrospective longitudinal study of 202 cases of endometrial carcinoma. The median duration of follow-up was 4.3 years. P53 was observed immunohistochemically in 63 (31%) of the tumors and was found by univariate analysis to be related to reduced adjusted survival (p = 0.00028) and disease-free survival (p = 0.04). However, p53 expression was not found by multivariate analysis to be an independent prognostic factor when compared with FIGO stage, histologic grade, and proliferative activity, as determined by immunoreactivity for topoisomerase IIalpha with the antibody Ki-S1. Overexpression of p53 was related to histologic grade (p < 0.00001), proliferative activity (p = 0.0071), and inversely to progesterone receptor content (p = 0.042). Immunohistochemical identification of p21 was investigated in 95 cases and found to be positive in 19 (39%) of 49 tumors with p53 overexpression and in 13 (28%) of 46 tumors without p53 overexpression (p = 0.28). Expression of p21 is therefore not related to p53 expression, nor was it found to be related to proliferative activity. Strong expression of p21 was observed in tumors negative for progesterone receptors (p = 0.0028). P53 in endometrial carcinoma is not associated with induction of the cell cycle inhibitor p21, but is associated with an enhanced proliferative activity. The findings of multivariate analysis suggest that the prognostic significance of p53 is related mainly to cell proliferation.

Adult↗