Hesx1 gene in midline cerebral defects.
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Basic Helix-Loop-Helix Proteins↗
Biomedical subjects
M de Castro
Publications and source records attributed to M de Castro.
Mechanisms of glucocorticoid-resistant asthma.
The term "steroid- or glucocorticoid-resistant (GR) asthma" has been used to describe a group of asthmatics who demonstrate persistent airway obstruction and inflammation despite treatment with high doses of systemic glucocorticoids (GCs). There are at least two forms of GR asthma. The first group of patients has an acquired form of GC resistance. Analysis of their bronchoalveolar lavage (BAL) cells indicates an extremely high level of IL-2 and IL-4 gene expression as compared to BAL cells from GC-sensitive asthmatics. The incubation of T cells from normal individuals with the combination of IL-2 and IL-4 induces GC receptor binding defects, and concomitant GC receptor beta expression, in their cells. Similar abnormalities in GC receptor binding defects can be detected in freshly isolated cells from type 1 GR asthmatics, but this defect is reversible when their cells are cultured in the absence of IL-2 and IL-4. The second group involves patients with primary GC resistance who do not develop side effects on high-dose GCs and have very low numbers of GC receptors in their mononuclear cells. This defect is irreversible in culture and affects their T cells as well as non-T cells. The current studies provide new insights into mechanisms by which inflammation induces GC resistance and how defects in the GC receptor may contribute to chronic inflammation, creating the vicious cycle leading to chronic inflammatory diseases.
Asthma↗
Immediate reconstruction of the central segment of the mandible using the masseter osteomuscular flap.
We describe a new technique for reconstruction of the central segment of the mandible using a masseter osteomuscular flap. The advantages of this method are that bone viability is preserved, both form and function of the mandible are maintained, it is a local flap with low donor-site morbidity, and the operative time is shortened.
Bone Plates↗
Glucocorticoid resistance.
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Endocrine System Diseases↗
The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role.
BACKGROUND: Alternative splicing of the transcripts of the human glucocorticoid receptor gene results in two mutually exclusive products, the classic, ligand-binding glucocorticoid receptor (hGR alpha), and a dominant negative non-ligand-binding isoform, hGR beta. MATERIALS AND METHODS: We examined the existence of and quantified both hGR alpha and hGR beta isoforms in a panel of human tissues, as well as in intact and fractionated HeLa cells, using specific quantitative Western blots and/or immunocytochemistry. We studied the potential interactions of hGR beta with heat shock protein (hsp) 90 and/or hGR alpha using cross-immunoadsorption/precipitation procedures followed by Western blots. RESULTS: For the first time, we demonstrated the natural existence of the hGR beta protein, which was widely expressed in human tissues. The ratio of immunoreactive hGR alpha to hGR beta varied from 0.2 to 1.0 among different tissues, and was approximately 0.2 in HeLa cells. In the latter, both isoforms were distributed in the cytoplasm and nucleus in the absence of the hormonal ligand, and translocated into the nucleus after addition of dexamethasone. The cytosolic and nuclear hGR alpha-to-hGR beta ratio remained the same before and after dexamethasone exposure, suggesting that upon activation the two isoforms translocated into the nucleus in equal proportions. hGR alpha- and hGR beta-specific antibodies cross-adsorbed and precipitated cytosolic and nuclear glucocorticoid hGR alpha and hGR beta, respectively, as well as hsp90, suggesting that hGR alpha and hGR beta are in complex with hsp90 and/or each other. CONCLUSIONS: The hGR beta protein is widely expressed throughout the human body and present mostly in the cytoplasm of human cells, in complex with hsp90 and other proteins. In the presence of glucocorticoid, hGR beta probably heterodimerizes with ligand-bound hGR alpha and translocates into the nucleus to act as a dominant negative inhibitor of the classic receptor.
Alternative Splicing↗
Plicature of abdominoplasties with Marlex mesh.
We propose reinforcing the abdominal wall in abdominoplasties with a polypropylene mesh over three fusiform plications. A marked degree of musculoaponeurotic reinforcement is achieved and maintained postoperatively, especially if these layers are very flaccid. Indications for the procedure and patient selection are described.
Abdominal Muscles↗
Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans.
Alternative splicing of the human glucocorticoid receptor (hGR) pre-mRNA generates two highly homologous isoforms, termed hGR alpha and hGR beta. hGR alpha is a ligand-activated transcription factor which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element (GRE) DNA sequences. In contrast, hGR beta does not bind glucocorticoids and is transcriptionally inactive. We demonstrate here that hGR beta is able to inhibit the effects of hormone-activated hGR alpha on a glucocorticoid-responsive reporter gene in a concentration-dependent manner. [3H]-Dexamethasone binding studies indicate that hGR beta does not alter the affinity of hGR alpha for its hormonal ligand. The presence of hGR beta in nuclear extracts and its ability to bind to a radiolabeled GRE oligonucleotide suggest that its inhibitory effect may be due to competition for GRE target sites. Reverse transcription-PCR analysis shows expression of hGR beta mRNA in multiple human tissues. These results indicate that hGR beta may be a physiologically and pathophysiologically relevant endogenous inhibitor of glucocorticoid action, which may participate in defining the sensitivity of target tissues to glucocorticoids. They also underline the importance of distinguishing between the two receptor isoforms in all future studies of hGR function and the need to revisit old data.
Alternative Splicing↗
Hypo-osmotic swelling test: analysis of prevasectomy ejaculates.
The hypo-osmotic swelling (HOS) test was applied to 1,890 ejaculates obtained from previously fertile men who subsequently underwent a vasectomy. Less than 3% of the ejaculates produced an abnormal HOS test (less than 50% swelling), and more than 95% were normal (greater than or equal to 60% swelling). The sperm concentration and motility data were similar to those obtained by other investigators with prevasectomy ejaculates. Statistically significant but low correlation coefficients were present between the HOS test and these other sperm variables. On the assumption that the large majority of these men were fertile when the ejaculates were produced, the results support the contention that fertility is usually associated with normal or, occasionally, equivocal values in the HOS test.
Adult↗
[Intravesical echography. I. Anatomical correlation].
The scan images of the normal bladder were obtained by intravesical ultrasonography (IVU) and the ultrasonographic-anatomic correlation were defined based on 179 procedures. Except in bladder cancer, IVU did not prove to be useful in the evaluation of other bladder conditions or adjacent structures, including gynecological disorders.
Female↗
[Fever and pain in the left hypochondrium].
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Abdominal Pain↗
Abnormalities of muscle fibers in maple syrup urine disease.
Muscle fiber abnormalities are described in three cases of neonatal maple syrup disease. There were important variations in fiber diameters. Lesions consisted in focal or diffuse destruction of myofibrils. In view of recent biochemical and clinical data, a direct relation between elevated branched-chain amino acid levels and the muscular abnormalities seems improbable.
Amino Acids, Branched-Chain↗
[Not Available].
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Animal Population Groups↗
Abdominoplasty with two fusiform plications.
Two-fusiform plications are recommended for contouring the abdomen to produce a slimmer waistline in abdominoplasty, rather than the classical median xiphoid-pubic fusiform plication. This procedure was accomplished in 11 patients. After the dermoadipose flap was undermined, two fusiform shapes were marked at the transition of the sheaths of the rectus abdominis muscles with the external obliques. The slimmer waistline produced intraoperatively was maintained during the late postoperative period (mean 20 months), without loss of the natural contour between the rectus muscles. Maintenance of the natural contours of the abdominal muscles is of fundamental importance to reduce the embarrassment of a postabdominoplasty flat abdomen.
Abdominal Muscles↗