PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CONSTANS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed2004

Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML).

Fms-like tyrosine kinase 3 (FLT3) receptor mutations as internal tandem duplication (ITD) or within the kinase domain are detected in up to 35% of patients with acute myeloid leukemia (AML). N-benzoyl staurosporine (PKC412), a highly effective inhibitor of mutated FLT3 receptors, has significant antileukemic efficacy in patients with FLT3-mutated AML. Mutation screening of FLT3 exon 20 in AML patients (n = 110) revealed 2 patients with a novel mutation (Y842C) within the highly conserved activation loop of FLT3. FLT3-Y842C-transfected 32D cells showed constitutive FLT3 tyrosine phosphorylation and interleukin 3 (IL-3)-independent growth. Treatment with PKC412 led to inhibition of proliferation and apoptotic cell death. Primary AML blasts bearing FLT3-Y842C mutations showed constitutive FLT3 and signal transducer and activator of transcription 5 (STAT-5) tyrosine phosphorylation. Ex vivo PKC412 treatment of primary blasts resulted in suppression of constitutive FLT3 and STAT-5 activation and apoptotic cell death. Inspection of the FLT3 structure revealed that Y842 is the key residue in regulating the switch from the closed to the open (= active) conformation of the FLT3 activation loop. Overall, our data suggest that mutations at Y842 represent a significant new activating mutation in AML blasts. Since FLT3 tyrosine kinase inhibitors (TKIs) such as PKC412 are currently being investigated in clinical trials in AML, extended sequence analysis of FLT3 may be helpful in defining the spectrum of TKI-sensitive FLT3 mutations in AML.

Animals↗
PubMed2006

Involvement of cholecystokinin 2 receptor in food intake regulation: hyperphagia and increased fat deposition in cholecystokinin 2 receptor-deficient mice.

The role of cholecystokinin (CCK) as a satiety factor has been extensively documented. Although most work implies that CCK1 receptor mediates the control of food intake, a contributing role for CCK2 receptor (CCK2R) in the CCK-induced satiety cannot be totally excluded. The hypothesis that CCK2R invalidation disrupts regulatory pathways with impact on feeding behavior was examined in CCK2R(-/-) mice. CCK2R(-/-) mice developed obesity that was associated with hyperphagia. Obesity was related with increased fat deposition resulting from adipocyte hypertrophy. Expression of several adipokines was dysregulated consistently with obesity. Moreover, obesity was associated with disturbed glucose homeostasis as revealed by increased fasting glycemia and insulinemia, impaired glucose tolerance, and hepatic insulin resistance in CCK2R(-/-) mice. In vitro analysis of isolated adipocytes metabolism was consistent with increased storage but preserved insulin sensitivity. Suppression of feeding and concomitant increased expression of hypothalamic proopiomelanocortin after intracerebroventricular injection of gastrin into control mice demonstrates that hypothalamic CCK2 receptors mediate inhibition of food intake. Comparative analysis of hypothalamic mediator gene expression in fed knockout and control mice demonstrated overexpression of ghrelin receptors in CCK2R(-/-) mice, indicating up-regulation of orexigenic pathways. This effect was also observed after body weight normalization, indicating a causative role in the development of hyperphagia and obesity of CCK2R(-/-) mice. Our results give evidence that CCK2 receptor activity plays a contributing regulatory role in the control of food intake.

Adiposity↗
PubMed1987

Intracorneal correction of aphakia: paraxial approach at null incidence.

The technique of intracorneal implantation, recently proposed by de Laage de Meux and Cinquin [Implants, 2, 26 (1984)] for the correction of aphakia, is analyzed in terms of geometrical optics. The analysis is done by using matrix optics and by assuming a null incidence. The characteristics (diameter, radii of curvature, axial thickness) of the hard or soft lens to be implanted are determined and given. The aniseikonia of such lenses is shown to be nearly the same as that of contact lenses.

Aphakia↗
PubMed1992

Clinical pharmacokinetics of alpha 1-antitrypsin in homozygous PiZ deficient patients.

A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks.

Adult↗
PubMed1995

Asymptomatic atherosclerosis in HIV-positive patients: A case-control ultrasound study.

Atherosclerosis has been reported in some HIV-positive subjects without any known risk factor. The purpose of the present study was to investigate cervical arteries, abdominal aorta and femoral arteries by B-mode ultrasonography and doppler in 30 HIV-positive subjects matched to 18 controls for sex, age, tobacco consumption and arterial hypertension. Although no haemodynamically or clinically relevant lesions were found, plaques occurred more often in patients than in controls (11 patients, 36.7% vs. 2, 11.1%; P = 0.05). Compared to the HIV-positive patients without plaques, those with plaques had a tendency to have decreased lower HDL cholesterol, higher tobacco consumption and lower CD4-cell count (77 +/- 85/mm3 vs. 220 +/- 202/mm3). The patients with plaques (but not those without plaques) had lower HDL cholesterol than controls (P = 0.03). Asymptomatic atherosclerosis seems to be more frequent in HIV-positive patients and is associated to lower HDL cholesterol.

Adult↗
PubMed1983

Spinal metastases with neurological manifestations. Review of 600 cases.

The authors have studied 600 cases of spinal metastasis causing a neurological syndrome. The most significant statistical data are reviewed. The cases are examined according to clinical characteristics, type of primary tumor, site of lesion, and survival. Each of these factors influenced the choice and results of treatment. As a general rule, combined treatment (surgery and radiotherapy) was used. Preliminary surgery was performed as an emergency, designed to halt progression of the neurological syndrome and to prevent its more serious manifestations. The technique and usefulness of surgery are discussed for different situations and the short-term results of treatment are related to the various factors involved.

Adolescent↗
PubMed1985

Giant intradiploic epidermoid cysts of the skull. Report of two cases.

The authors describe two cases of giant intradiploic epidermoid cysts of the cranial vault in which there was massive intracranial extension causing signs of neurological involvement. The very slow growth and the benign histological nature of these tumors explain their long preoperative evolution and the mild neurological signs in some cases. Roentgenographic and computerized tomography findings permit a correct diagnosis. Complete removal of these cysts and their capsules can be easily accomplished, despite their large size. Total removal of these cysts is associated with a very good long-term prognosis.

Epidermal Cyst↗
PubMed1999

[Inflammatory arteriopathy of the arms in the course of Horton disease. Report of six cases].

We report 6 cases of upper limb involvement in giant cell arteritis; upper limb involvement revealed the disease in 4 cases and clinical symptoms were present in 5 (upper limb pain, Raynaud's phenomenon). Upper limb pulses were not palpable and blood pressure unmeasurable in all. Duplex ultrasonography found signs of inflammatory arteriopathy in 4 cases (hypoechogenous halo of the arterial wall and acceleration of flow velocity). Arteriography was performed in 5 cases and showed long and regular stenoses. In the last case, arteriography was not done because the duplex exploration gave an easier diagnosis. With this technique, the diagnosis of upper limb involvement, frequent in autopsy series of giant cell arteritis, might be made more often. Corticosteroid therapy is indicated and surgery should be discussed only in emergency situations.

Aged↗
PubMedDate not supplied

[Genetical and epidemiological study of uricaemia in a Pyrenean population. (Region of Sault - Pyrérées audoises) (author's transl)].

Serum uric acid levels were determined in 229 individuals of Rodome and 127 individuals of Camurace, in the french Pyrénées. The difference of average levels between these two populations was found to be due very likely to different way of life. Intra-familial correlations suggest a greater importance of environmental than genetic factors on serum uric acid levels.

Adolescent↗
PubMed1999

Effects of heparin and related sulfated polysaccharides on tissue factor expression induced by mitogenic and non-mitogenic factors in human vascular smooth muscle cells.

Smooth muscle cells (SMCs) of the intima are generally quiescent and non proliferative. Their proliferation due to different stimulations occurs in myointimal hyperplasia and is regularly present in atherogenesis or after transluminal angioplasty leading to vascular occlusive stenosis. In the course of these pathologies, the Tissue Factor (TF) synthesis was upregulated and rapidly expressed at the membrane of the SMCs. Heparin is known to inhibit SMCs proliferation induced by FCS. We evaluated the inhibitory effect of heparin on the expression of TF induced by various mitogenic (FCS, PDGF-BB and EGF) and non-mitogenic (bacterial LPS) agents. Inhibition by heparin of SMCs proliferation induced by the same agonists was also determined. Quiescent human vascular SMCs from normal adult arteries were treated for 1 h by heparin and related sulfated polysaccharides before stimulation by the agonists. All the agonists up-regulated the expression of TF antigen and activity. TF expression induced by the growth factors was inhibited by heparin (IC 50: 10-30 microg/ml), and other sulfated polysaccharides (IC 50: 1-5 microg/ml). SMCs proliferation, late activation of the extracellular signal-regulated kinases (ERK1/2), and PKC activity were inhibited by heparin (IC 50: 30-50 microg/ml) in SMCs stimulated by FCS but not in SMCs treated by PDGF or EGF. In contrast, heparin had no effect on LPS-induced TF expression nor on LPS-induced PKC activation. These results indicate that, besides its well known effect on SMC proliferation, heparin displays an inhibitory effect on cell mediated blood clotting processes through regulation of the TF expression.

Adult↗