The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Youhua Liu - One of the best experts on this subject based on the ideXlab platform.
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essential role of integrin linked kinase in podocyte biology bridging the integrin and slit diaphragm signaling
Journal of The American Society of Nephrology, 2006Co-Authors: Chunsun Dai, Shoukat Dedhar, Rene St-arnaud, Donna B Stolz, Sheldon I Bastacky, Youhua LiuAbstract:Integrin-linked kinase (ILK) has been implicated in the pathogenesis of proteinuria and congenital nephrotic syndrome. However, the function of ILK in glomerular podocyte in a physiologic setting remains unknown. In this study, a mouse model was generated in which ILK gene was selectively disrupted in podocytes by using the Cre-LoxP system. Podocyte-specific ablation of ILK resulted in heavy albuminuria, glomerulosclerosis, and kidney failure, which led to animal death beginning at 10 wk of age. Podocyte detachment and apoptosis were not observed at 4 wk of age, when albuminuria became prominent, indicating that they are not the initial cause of proteinuria. Electron microscopy revealed an early foot process effacement, as well as Morphologic Abnormality, in ILK-deficient podocytes. ILK deficiency caused an aberrant distribution of nephrin and α-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact. Co-immunoprecipitation demonstrated that ILK physically interacted with nephrin to form a ternary complex, and α-actinin-4 participated in ILK/nephrin complex formation. Therefore, ILK plays an essential role in specifying nephrin and α-actinin-4 distribution and in maintaining the slit diaphragm integrity and podocyte architecture. These results also illustrate that the integrin and slit diaphragm signals in podocytes are intrinsically coupled through an ILK-dependent mechanism.
Peter D Williamson - One of the best experts on this subject based on the ideXlab platform.
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medically intractable localization related epilepsy with normal mri presurgical evaluation and surgical outcome in 43 patients
Epilepsia, 2001Co-Authors: Adrian M Siegel, Barbara C Jobst, Vijay M Thadani, Harker C Rhodes, Petra J Lewis, David W Roberts, Peter D WilliamsonAbstract:Summary: Purpose: High-resolution magnetic resonance imaging (MRI) plays a crucial role in the presurgical evaluation of patients with medically refractory partial epilepsy. Although MRI detects a Morphologic Abnormality as the cause of the epilepsy in the majority of patients, some patients have a normal MRI. This study was undertaken to explore the hypothesis that in patients with normal MRI, invasive monitoring can lead to localization of the seizure-onset zone and successful epilepsy surgery. Methods: A series of 115 patients with partial epilepsy who had undergone intracranial electrode evaluation (subdural strip, subdural grid, and/or depth electrodes) between February 1992 and February 1999 was analyzed retrospectively. Of these, 43 patients (37%) had a normal MRI. Results: Invasive monitoring detected a focal seizure onset in 25 (58%) patients, multifocal seizure origin in 12 (28%) patients, and in six patients, no focal seizure origin was found. Of the 25 patients with a focal seizure origin, cortical resection was performed in 24, of whom 20 (83%) had a good surgical outcome with respect to seizure control. Six of the 12 patients with multifocal seizure origin underwent other forms of epilepsy surgery (palliative cortical resection in two, anterior callosotomy in two, and vagal nerve stimulator placement in two). Conclusions: Successful epilepsy surgery is possible in patients with normal MRIs, but appropriate presurgical evaluations are necessary. In patients with evidence of multifocal seizure origin during noninvasive evaluation, invasive monitoring should generally be avoided.
Imad A Tabbara - One of the best experts on this subject based on the ideXlab platform.
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hemolytic anemias diagnosis and management
Medical Clinics of North America, 1992Co-Authors: Imad A TabbaraAbstract:Hemolysis can be induced by two general mechanisms. In the first one, erythrocytes lyse intravascularly due to complement fixation, trauma, or other extrinsic factors. In the second mechanism, which is the most common, the red cells are removed from the circulation by the mononuclear-phagocytic system either because they are intrinsically defective or because of the presence of bound immunoglobulins to their surfaces. The diagnosis of hemolysis is not difficult to establish and is based on the presence of anemia with sustained reticulocytosis in the absence of blood loss. Additional findings can include marrow erythroid hyperplasia; increased unconjugated bilirubin, LDH, and free hemoglobin; decreased haptoglobin and hemopexin; hemoglobinuria and hemosiderinuria; and decreased 51Cr red cell half-life. Hemoglobinemia, hemoglobinuria, and hemosiderinuria occur only in the setting of severe and rapid intravascular hemolysis. Conditions associated with significant lysis of red cells in the circulation include incompatible transfusion, G6PD deficiency, PNH, severe burns, and certain infections. The morphology of the red cell is abnormal in almost all cases of hemolytic anemia. However, the Morphologic Abnormality can be, in certain cases, diagnostic of the underlying condition. Treatment is usually supportive, with effective therapy directed to treat the underlying cause of hemolysis.
Chunsun Dai - One of the best experts on this subject based on the ideXlab platform.
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essential role of integrin linked kinase in podocyte biology bridging the integrin and slit diaphragm signaling
Journal of The American Society of Nephrology, 2006Co-Authors: Chunsun Dai, Shoukat Dedhar, Rene St-arnaud, Donna B Stolz, Sheldon I Bastacky, Youhua LiuAbstract:Integrin-linked kinase (ILK) has been implicated in the pathogenesis of proteinuria and congenital nephrotic syndrome. However, the function of ILK in glomerular podocyte in a physiologic setting remains unknown. In this study, a mouse model was generated in which ILK gene was selectively disrupted in podocytes by using the Cre-LoxP system. Podocyte-specific ablation of ILK resulted in heavy albuminuria, glomerulosclerosis, and kidney failure, which led to animal death beginning at 10 wk of age. Podocyte detachment and apoptosis were not observed at 4 wk of age, when albuminuria became prominent, indicating that they are not the initial cause of proteinuria. Electron microscopy revealed an early foot process effacement, as well as Morphologic Abnormality, in ILK-deficient podocytes. ILK deficiency caused an aberrant distribution of nephrin and α-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact. Co-immunoprecipitation demonstrated that ILK physically interacted with nephrin to form a ternary complex, and α-actinin-4 participated in ILK/nephrin complex formation. Therefore, ILK plays an essential role in specifying nephrin and α-actinin-4 distribution and in maintaining the slit diaphragm integrity and podocyte architecture. These results also illustrate that the integrin and slit diaphragm signals in podocytes are intrinsically coupled through an ILK-dependent mechanism.
Karen A. Holbrook - One of the best experts on this subject based on the ideXlab platform.
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Characteristic Morphologic Abnormality of harlequin ichthyosis detected in amniotic fluid cells
The Journal of investigative dermatology, 1994Co-Authors: Masashi Akiyama, Dong Kun Kim, Denise M. Main, Carl E. Otto, Karen A. HolbrookAbstract:We have examined cells from amniotic fluid obtained at 17 and 21 weeks' gestation and fetal skin biopsy samples from a fetus at risk of harlequin ichthyosis by light and electron microscopy. Clumps of abnormally keratinized cells that had a large number of lipid droplets in the cytoplasm were seen within both the 17- and 21-week amniotic fluid cell pellets. The cells in these clumps were similar to the thick layers of keratinized cells observed in the skin biopsy and autopsy samples. Morphologic examination of the fetal skin biopsy samples obtained at 21 weeks gestation revealed the characteristic changes of harlequin ichthyosis. The intraepidermal portions of hair canals had an excessive number of layers of keratinized cells. Normal lamellar granules were absent but abundant membrane-bound vesicles of a similar size and a number of dense bodies were observed in the cells of the upper intermediate layers of the epidermis. Autopsy skin samples of the terminated fetus at the twenty-third week of gestation showed structural changes that corresponded to those of the amniotic fluid cells and the fetal skin biopsy samples, although the periderm was gone in all the regions. Our findings of amniotic fluid indicate that the characteristic epidermal Abnormality of harlequin ichthyosis has been expressed at 17 weeks gestation in some parts of the body or structures of fetal skin (e.g., hair canals) that keratinize before interfollicular epidermis. Moreover, the results suggest that harlequin ichthyosis can be detected in utero by Morphologic analysis of amniotic fluid cells obtained by amniocentesis.