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Biomedical subjects

C Perret

Publications and source records attributed to C Perret.

At least 73 records · Page 4Linked to original sources
PubMed1997

Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus--a meta-analysis.

OBJECTIVE: To describe the relative risk for venous thrombosis (VT) associated with antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE). DESIGN: Systematic review and meta-analysis of 26 articles that examined the association between aPL and VT in SLE. SETTING: Mostly secondary and tertiary referral centres. PATIENTS: 2249 patients with SLE, 1120 tested for LA (lupus anticoagulant) and 1563 tested for aCL (anticardiolipin antibodies). MAIN OUTCOME MEASURES: A summary of study characteristics and a critical appraisal of study quality were done. Two statistical combinations of 18 primary studies that examined the association of VT and LA and of 14 studies that examined the association of VT and aCL were performed to estimate the risk for VT associated with aPL. RESULTS: The odds ratios of the risk of VT related to the LA summarized from 18 studies were 5.61 [95% CI; 3.80-8.27] overall, 6.32 [CI; 3.71-10.78] for deep venous thrombosis and pulmonary embolism, 11.6 [3.65-36.91] for recurrent venous thrombosis after the first event. The odds ratios of the risk of VT related to aCL summarized from 14 studies were 2.17 [95% CI; 1.51-3.11] overall, 2.50 [CI; 1.51-4.14] for deep venous thrombosis and pulmonary embolism, 3.91 [1.14-13.38] for recurrent venous thrombosis after the first event. CONCLUSIONS: Patients with SLE and LA are at approximately six times greater risk for VT than patients without LA, whereas patients with SLE and aCL are approximately two times greater risk for VT than patients without aCL. We have identified important methodologic limitations and differences in study characteristics. Other risk factors for VT have not been thoroughly evaluated in these studies. Further studies are needed that provide an accurate estimate of the absolute risk for aPL related VT.

Antibodies, Anticardiolipin↗
PubMed1997

Safety of combined heat and moisture exchanger filters in long-term mechanical ventilation.

STUDY OBJECTIVE: To evaluate the safety of a combined heat and moisture exchanger filter (HMEF) for the conditioning of inspired gas in long-term mechanical ventilation (MV). DESIGN: Randomized controlled trial. SETTING: Medical ICU in a large teaching hospital. PATIENTS: One hundred fifteen consecutive patients who required > or = 48 h of MV. INTERVENTIONS: Patients were randomized at intubation time (day 1) to receive inspired gas conditioned either by a water-bath humidifier heated at 32 degrees C (HWBH) or by an HMEF (Hygroster; DAR; Mirandola, Italy). MEASUREMENTS AND MAIN RESULTS: The two study groups were comparable in terms of primary pathologic condition at the time of hospital admission, disease severity as measured by the Simplified Acute Physiology Score, and ICU mortality. They did not differ with respect to ventilator days per patient (mean +/- SD: HMEF, 7.6 +/- 6.5; HWBH, 7.8 +/- 5.8), incidence of endotracheal tube obstruction (HMEF, 0/59; HWBH, 1/56), and incidence of hypothermic episodes (HMEF, five; HWBH, two). In 41 patients receiving MV for > or = 5 days, the morphologic integrity of respiratory epithelium was evaluated on day 1 and day 5, using a cytologic examination of tracheal aspirate smears. The state of ciliated epithelium was scored on a scale from 0 (poorest integrity) to 1,200 (maximum integrity), according to a well-described method. In both patient groups, the scores slightly but significantly decreased from day 1 to day 5 (mean +/- SD: HWBH, from 787 +/- 104 to 745 +/- 88; HMEF, from 813 +/- 79 to 739 +/- 62; p < 0.01 for both groups); there were no statistically significant differences between groups. CONCLUSIONS: These data indicate acceptable safety of HMEFs of the type used in the present study for long-term mechanical ventilation.

Equipment Safety↗
PubMed1996

[Permissive hypercapnia. From choice to unavoidable decision].

Experimental and clinical evidence has led to a revision of conventional techniques used for mechanical ventilation in the treatment of respiratory failure due to severe asthma and acute respiratory distress syndrome. A common feature in these two clinical situations is the heterogeneous nature of the lesions, causing mechanical alterations which vary from one region to another. Thus the tidal volume is not equally distributed throughout the lungs and can lead to overdistension in some regions or functional exclusion in others. Hyperinflation then exposes the patient to barotrauma, cardiocirculatory and/or alveolocapillary complications. Controlled hypoventilation-or permissive hypercapnia-is a new approach aimed at preventing complications by supplying adequate oxygen while accepting or provoking a certain degree of hypercapnia by alveolar hypoventilation. The technique is based on restricting tidal volume and respiratory rate as long as is necessary to recover more favorable mechanical conditions. Results obtained with this method have been convincing for the treatment of decompensated asthma but preliminary data obtained in acute respiratory distress syndrome remain to be validated.

Acute Disease↗
PubMed1996

Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.

We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

Analysis of Variance↗
PubMed1996

Estradiol-dependent uterine leiomyomas in transgenic mice.

Uterine leiomyomas are a major health problem for women of reproductive age. The molecular biology of these tumors is poorly understood partly because of the lack of relevant animal models. We have produced transgenic mice expressing the simian virus 40 T antigen driven by the promoter of the Calbindin-D9K (CaBP9K) gene and either -1,000 or -117 bp of regulatory sequences so as to establish in vivo, uterine smooth muscle tumor models. Six transgenic mouse lines were obtained. Leiomyomas developed in all of them, with an almost complete penetrance of the phenotype. The smooth muscle tumors arose in different parts of the female reproductive tract. Leiomyomas usually developed in the corpus of the uterus, but one mouse line developed leiomyomas in the horn of the uterus, and another in the vagina. The CaBP9K regulatory sequences directing the expression of the Tag gene possess an estradiol responsive element, and accordingly, development of the tumors was strictly under the control of estrogen. Expression of the Tag gene is not only necessary for the initiation of the tumor but also for its development and maintenance. These transgenic mouse models should be useful for studying the pathobiology of uterine leiomyomas and could be instrumental in designing new therapeutic approaches to this disease.

Animals↗
PubMed1996

Tissue-specific and hormonal regulation of calbindin-D9K fusion genes in transgenic mice.

The rat Calbindin-D9K (CaBP9K) gene is mainly expressed in intestine, uterus, and lung and is regulated in a complex tissue-specific manner. To analyze the role of potential regulatory elements, previously defined by DNaseI hypersensivity, we made transgenic mice containing truncated rat CaBP9K fusion gene with simian virus 40 large T antigen and the chloramphenicol acetyltransferase as reporter genes. The transgenes contained CaBP9K promoter fragments with 5' end points at -4400, -1011, and -117 base pairs (bp), whereas the 3' end points was at +365 bp. Northern blot analysis of T antigen expression and chloramphenicol acetyltransferase enzyme-linked immunosorbent assay indicated that a positive element, probably the distal intestine-specific DNaseI HS, necessary to target the expression of the transgene in the intestine, is present between -4400 and -1011 bp. The cephalo-caudal gradient of expression of the transgene along the small intestine was similar to those of the endogenous gene, but an ectopic expression of the transgene was observed in the colon. The -1011 transgene was expressed in epithelial alveolar cells of the lung, in renal proximal tubule cells, and in uterine myometrium, as judged from immunocytochemical, histological, and Northern blot analyses. The shortest, -117 construct was only expressed in uterine myometrium, and it was under a strict estrogen dependence like the endogenous gene. Finally, responsiveness to vitamin D in the duodenum was observed with the largest, -4400 construct. Thus, different tissues utilize distinct cis-acting elements to direct and regulate the expression of the rat CaBP9K gene.

Animals↗
PubMed1996

cis-Acting elements and transcription factors involved in the intestinal specific expression of the rat calbindin-D9K gene: binding of the intestine-specific transcription factor Cdx-2 to the TATA box.

The calbindin-D9K (CaBP9k) gene is mainly expressed in differentiated duodenal epithelial cells and is used as a model for studying the molecular mechanisms of intestine-specific transcription. The gene has been cloned, two major DNase-I-hypersensitive sites in the duodenum have been described, and a vitamin-D-response element has been identified. We have now analysed the transcription factors and regulatory sequences involved in the transcription of the CaBP9k gene in the intestine in ex vivo and in vitro experiments. Transfection experiments in intestinal (CaCo-2) and non-intestinal (HeLa) cell lines defined two regions in the 5'-flanking sequences of the rat CaBP9k gene. A minimal proximal region (-117 to +20) promoted transcription in both intestinal expressing and non-expressing cell lines. Tissue specificity was conferred by the sequences situated further upstream, which are responsible for complete repression in the non-intestinal cells. Intestinal transcription was specified by the proximal region, containing a specialized TATA box, and a distal region, which contains a previously described intestinal DNase-I-hypersensitive site. In vitro DNase I footprinting, electrophoretic mobility shift assays and antibody supershift assays were used to examine the factors bound to the proximal promoter region (-800 to +80 bp). Rat duodenal nuclear extracts protected 12 sites. Some of them appear to be binding sites for ubiquitous (nuclear factor 1) or hepatic-enriched sites (hepatocyte nuclear factors 1 and 4, enhancer binding protein alpha and beta factors. DNA binding studies and transfection experiments indicated that an intestine-specific transcription factor, caudal homeobox-2, binds to the TATA box of the rat CaBP9k gene. These data contribute to our understanding of the control of the intestinal transcription of the CaBP9k gene and demonstrate that several trans-acting factors, other than the vitamin D receptor, may be factors for intestine-specific CaBP9k gene expression.

Animals↗
PubMed1996

Nutritional factors and prostate cancer: a case-control study of French Canadians in Montreal, Canada.

The relationship between the risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Montreal (Quebec), Canada. French Canadians aged 35 to 84 years with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate were identified through the admission offices of five major francophone teaching-hospitals in Montreal from 1989 to 1993. Population-based controls matched for age (+/- five years), language, and place of residence were selected by a modified random-digit dialing method. The study included 232 cases and 231 controls. Information on dietary intake was collected by means of a quantitative dietary history. No association was evident between energy intake and the risk of prostate cancer. In contrast, there was some evidence of an inverse association with intake of total fat, animal fat, monounsaturated fat, and particularly saturated fat (odds ratio = 0.69, 95 percent confidence interval = 0.40-1.18, P = 0.05), while a nonsignificant positive association was found with polyunsaturated fat. In addition, high intake of retinol and vegetable protein (highest cf lowest quartile) was associated with reduced risk, but was not statistically significant. No associations were established between intake of other nutrients and risk. These patterns persisted after adjustment for a number of potential confounding factors.

Adenocarcinoma↗
PubMed1996

Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families.

The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Adult↗
PubMed1996

Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, during rodent endotoxaemia.

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an inducible nitric oxide synthase. In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable. The aim of this study was to evaluate the effects of L-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock. 2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously. One hour later, they randomly received a 5 h infusion of either L-canavanine (20 mg h-1 kg-1, n = 15), nitro-L-arginine methyl ester (5 mg h-1 kg-1, n = 13) or 0.9% NaCl (2 ml h-1 kg-1, n = 21). Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by a significant lactic acidosis and a marked rise in plasma nitrate. All these changes were significantly attenuated by L-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolaemia. In addition, L-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide. In contrast to L-canavanine, nitro-L-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis. This agent did not improve survival of endotoxaemic mice. In additional experiments, we found that the pressor effect of L-canavanine in advanced endotoxaemia (4 h) was reversed by L-arginine, confirming that it was related to nitric oxide synthase inhibition. In contrast, L-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent. 3. In conclusion, L-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock. The actions of L-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-L-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, in similar conditions.

Acidosis, Lactic↗
PubMed1996

Functional and growth properties of a myometrial cell line derived from transgenic mice: effects of estradiol and antiestrogens.

This study describes the properties of a myometrial cell line, m-M116, that was derived from a leiomyoma developed in an adult female transgenic mouse harboring the simian virus 40 large T antigen (Tag) under the control of the 5'-regulatory sequence of the calbindin D9k (CaBP9k) gene. As the expression of this transgene is governed by the CaBP9k estrogen-responsive element, m-M116 cells were grown in medium supplemented with 17 beta-estradiol. The cells were long lived, had Tag-positive nuclei, and were nontumorigenic when injected into nude mice. They formed irregular layers of elongated cells with typical features of uterine, smooth muscle cells, as assessed by the presence of alpha-smooth muscle actin and desmin filaments, estradiol and progesterone receptors, and expression of the CaBP9k gene. The rate of cell doublings and the expression of the Tag gene in early passaged cells depended on the presence of 17 beta-estradiol. Tamoxifen, a mixed estrogen agonist-antagonist, also stimulated the growth of m-M116 cells, whereas ICI 182 780, a pure antiestrogen, blocked cell growth. Later passages of m-M116 cells still had a smooth muscle phenotype, but proliferated even in the absence of 17 beta-estradiol. These mouse uterine smooth muscle cells obtained by targeted oncogenesis provide a useful model for studies of the progression of steroid-independent carcinomas.

Animals↗
PubMed1996

Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine.

The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine (NAC) have been described in experimental and clinical ARDS. NAC could act in part by replenishing the intracellular stores of glutathione (GSH) in activated granulocytes, leading to detoxification of oxygen radicals produced by these cells. To test this hypothesis, 16 patients in the early phase of ARDS were randomized to receive either NAC (n = 8) or placebo (n = 8); granulocyte GSH, granulocyte oxygen radical production, and plasma levels of granulocyte elastase were measured in blood samples drawn sequentially within 8 h after the onset of ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) after the first sample; treatment with NAC or placebo was started immediately after day 0 and stopped just after day 3. Granulocyte GSH was significantly higher on days 1 and 3 when NAC was received by the patient. Unstimulated oxygen radical production, as measured ex vivo by luminol- and lucigenin-amplified chemiluminescence (CL), was higher in granulocytes from ARDS patients than from healthy control subjects, but was not influenced by NAC. The plasma levels of granulocyte elastase were five to eight times above the upper normal limit on day 0, decreased steadily until day 5, and were uninfluenced by NAC. In summary, parenteral NAC treatment started within 8 h of diagnosis increases the intracellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells. The mechanisms of the protective effects of this drug previously reported in experimental and clinical ARDS remain to be established.

Acetylcysteine↗
PubMed1996

Volemic status influences the response of plasma atrial natriuretic factor to positive airway pressure.

UNLABELLED: STUDY OBJECTIVE; To evaluate interactive effects of volemic status and positive end-expiratory pressure (PEEP) on the plasma levels of atrial natriuretic factor (ANF) in assist-controlled mechanical ventilation (MV). DESIGN: Three successive protocols applied in randomized order to each participant. SETTING: Clinical investigation laboratory. PARTICIPANTS: Twenty-one young, healthy adults. INTERVENTIONS: The three protocols were as follows: (1) MV+PEEP, normovolemia; (2) MV+PEEP, hypervolemia; and (3) spontaneous breathing (SB), hypervolemia. In protocols 1 and 2, a preliminary period of SB lasting 2 h was followed by MV alone (0.5 h), MV+20 cm H2O PEEP (1 h), and a recovery period of SB (1.5 h). Hypervolemia was induced by the continuous i.v. infusion of 3 L of 0.9% NaCl in 5 h (protocols 2 and 3). MEASUREMENTS AND RESULTS: Heart rate, BP, and the plasma levels of immunoreactive ANF and catecholamines were measured serially. During hypervolemia, ANF significantly decreased when PEEP was added to MV (protocol 2: from 31.1 +/- 2.7 to 20.7 +/- 1.5 fmol/mL; p < 0.01). This did not occur in normovolemia (protocol 1: from 20.0 +/- to 16.7 +/- 1.2 fmol/mL; p = NS). The different effects of MV+PEEP in normovolemia and hypervolemia were not related to differences in circulating catecholamine levels. CONCLUSIONS: These results demonstrate for the first time (to our knowledge) that volemic status modulates the response of plasma ANF to PEEP in humans. The role of ANF in the water and salt retention induced by MV with PEEP might be limited to hypervolemic conditions.

Adult↗
PubMed1996

Endothelin-1 does not mediate the endothelium-dependent hypoxic contractions of small pulmonary arteries in rats.

Various pulmonary artery preparations in vitro demonstrate sustained endothelium-dependent contractions upon hypoxia. To determine whether endothelin-1 could mediate this phenomenon, we examined the effect of bosentan, a new antagonist of both the ETA and ETB subtypes of the endothelin receptor. Small (300 pm) pulmonary arteries from rats were mounted on a myograph, precontracted with prostaglandin F2 alpha and exposed to hypoxia (PO2, 10 to 15 mm Hg, measured on-line) for 45 min. Endothelium-intact control rings exhibited a biphasic response, with a transient initial vasoconstriction (phase 1) followed by a second slowly developing sustained contraction (phase 2). Expressed in percent of the maximal response to 80 mmol/L KCl, the amplitudes of phase 1 (peak tension) and 2 (tension after 45 min of hypoxia) averaged 37 +/- 12% and 17 +/- 14%, respectively (n = 11). In endothelium-denuded rings, phase 1 persisted while the amplitude of phase 2 was reduced to 2 +/- 12% (p < 0.05, n = 8), showing the endothelium dependence of this contraction. Neither phase was significantly decreased in rings treated with 10(-5) mmol/L bosentan (38 +/- 15% and 17 +/- 12%, respectively, n = 6). The PO2 threshold for onset of hypoxic contraction was not significantly different among these three groups and averaged 32 +/- 24 mm Hg. In a separate experiment, we assessed the inhibitory effect of 10(-5) mol/L bosentan on the response to 10(-8) mol/L endothelin-I. Rings treated for 45 min with 10(-8) mol/L endothelin-1 alone exhibited a maximal contraction of 75 +/- 27% (n = 6). This was reduced to 4 +/- 17% (p < 0.01, n = 6) in rings treated with both 10(-8) mol/L endothelin-1 and 10(-5) mol/L bosentan. We conclude that complete blockade of all endothelin receptor subtypes has no effect on either endothelium-dependent or -independent hypoxic contractions in this preparation. This suggests that endothelial factors other than endothelin-I mediate the acute hypoxic contractions of small pulmonary arteries in the rat.

Animals↗
PubMed1996

[Role of the hemostasis laboratory in the etiologic approach to deep vein thrombosis].

Thrombophilia is characterized by an inherited or acquired defect in the blood coagulation pathway leading to an increased risk for thrombosis. The etiological approach following confirmed venous thrombotic events should rule out medical or chirurgical risk factors. Thrombophilia should be sought by laboratory tests. The recent discovery of a blood coagulation defect: inherited resistance to activated protein C which is found to 20% of patients with former thrombotic events has changed current laboratory approach. Deficiencies of one of the anticoagulant proteins (antithrombin III, protein C, protein S) are found in 10% of the patients, similar to the frequency of antiphospholipid antibodies. These tests may be difficult to interpret immediately after the thrombotic event because of various factors such as inflammatory states or anticoagulant treatments. Therefore this abnormal tests should be confirmed on a later sample analysis far from the event. The discovery of an inherited blood coagulation pathway defect may affect the duration of treatment, prophylaxis in situations with circumstantial risk factors and requires familial analysis. Inherited resistance to activated protein C may be associated with another inherited defect leading to an increased risk for thrombosis.

Antithrombin III Deficiency↗
PubMed1995

Identification of DNA sequences that bind retinoid X receptor-1,25(OH)2D3-receptor heterodimers with high affinity.

Vitamin D3 receptors (VDR) bind as heterodimers with retinoid X receptors (RXR) to vitamin D response elements (VDRE) and transactivate gene expression in a 1,25(OH)2D3-dependent manner. These elements are tandem direct repeats (DRs) of the hexamer RGGTCA separated by three nucleotides (DR3). We determined whether this DR3 was the optimal and/or only recognition sequence, by PCR-mediated binding site selection with reticulocyte lysate-expressed hVDR and mRXRalpha, and a pool of random sequences. We derived a consensus binding site for RXR-VDR heterodimers, RGGTCANN RRGTTCAB, and analyzed 10 of the 45 sequences slected by EMSA, methylation interference and transfection experiments: all the sequences were specific and acted as positive VDREs; the underlined purine of the spacer interacted with the heterodimer; the mutation of the third T in the second motif to a G did not influence VDRE activity. Thus, the selectivity of vitamin D pathway involving heterodimerization rather than VDR-homodimerization is not due to internal sequence variations. Except for mouse osteopontin VDRE, the natural VDREs would be efficient, only when helped by adjacent sequences and/or transactivators other than VDR and RXR.

Amino Acid Sequence↗