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M Wassef

Publications and source records attributed to M Wassef.

At least 19 recordsLinked to original sources

Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor.

During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At gastrulation, following endoderm induction and further cell interaction processes including a local release of Notch/Delta signaling, her5 expression is progressively excluded from the presumptive anterior- and posteriormost mesendodermal territories to become restricted to an adjacent subpopulation of dorsal endodermal precursors. Ectopic misexpressions of wild-type and mutant forms of her5 reveal that her5 functions primarily within the endodermal/endmost mesendodermal germ layer to inhibit cell participation to the endmost-fated mesendoderm. In this process, her5 acts as an active transcriptional repressor. These features are strikingly reminiscent of the function of Drosophila Hairy/E(spl) factors in cell fate decisions. Our results provide the first model for vertebrate endoderm patterning where an early regulatory step at gastrulation, mediated by her5 controls cell contribution jointly to the anterior- and posteriormost mesendodermal regions.

Amino Acid Sequence↗

Residual lesions after Kasabach-Merritt phenomenon in 41 patients.

BACKGROUND: Kasabach-Merritt phenomenon (KMP) is the association of a vascular tumor and thrombocytopenic coagulopathy. Vascular tumors are either kaposiform hemangioendothelioma or tufted angioma but not "true" common hemangioma of infancy. There is a conspicuous absence in the literature regarding the late outcome and possible residual lesions after apparent clinical cure of KMP. OBJECTIVE: The purpose of the study was to analyze these residua in a large number of patients. METHODS: Clinical data on 41 patients who had KMP were accrued in an international cooperative study. The emphasis was on the residual lesions after resolution of the thrombocytopenia and other coagulation abnormalities. Imaging studies (follow-up magnetic resonance imaging studies available for 10 patients) and histologic specimens (30 specimens available for 26 patients, 18 biopsies done during the KMP and 12 concerning the sequelae) were reviewed. RESULTS: Residual lesions after "cure" of KMP were common. They exhibited 3 clinical patterns: type I lesions (n = 28) showed a cutaneous red stain, with or without associated red papules. The stain might overlap a minor fibrotic infiltration or a significant poorly delineated diffuse fibrotic infiltration. These cutaneous vascular lesions varied in size and appearance over time and were occasionally painful. Type II lesions were telangiectatic streaks and swelling (n = 5), and type III lesions showed a minor, firm, irregular, subcutaneous mass assessed by palpation or deep infiltration evidenced by computed tomography or magnetic resonance imaging (n = 8). A fourth feature was sequelae in muscles and/or joints. Histologically, tufted angioma was more common in the specimens from residual lesions, whereas kaposiform hemangioendothelioma was more common during the active phase of KMP. Imaging findings were remarkably reproducible and revealed a persistent vascular tumor. CONCLUSION: Residua of tumors associated with KMP are common after the resolution of thrombocytopenia and coagulopathy. They are (more or less) prominent dormant vascular tumors, not "scars" and, clinically as well as histologically, they differ markedly from involuted hemangioma.

Adolescent↗

The vomeronasal cavity in adult humans.

We observed the surface of the anterior part of the nasal septum of living subjects using an endoscope. In approximately 13% of 1842 patients without pathology of the septum, the vomeronasal pit was clearly observed on each side of the septum, and in 26% it was observed only on one side. The remaining observations indicated either the presence of putative pits or no visible evidence of a pit. However, repetitive observations on 764 subjects depicted changes over time, from nothing visible to well-defined pits and vice versa. Based on 130 subjects observed at least four times, we estimate that approximately 73% of the population exhibits at least one clearly defined pit on some days. By computer tomography, the vomeronasal cavities were located at the base of the most anterior part of the nasal septum. Histological studies indicated that the vomeronasal cavities consisted of a pit generally connected to a duct extending in a posterior direction under the nasal mucosa. Many glands were present around the duct, which contained mucus. There was no sign of the pumping elements found in other mammalian species. Most cells in the vomeronasal epithelium expressed keratin, a protein not expressed by olfactory neurons. Vomeronasal epithelial cells were not stained by an antibody against the olfactory marker protein, a protein expressed in vomeronasal receptor neurons of other mammals. Moreover, an antibody against protein S100, expressed in Schwann cells, failed to reveal the existence of vomeronasal nerve bundles that would indicate a neural connection with the brain. Positive staining was obtained with the same antibodies on specimens of human olfactory epithelium. The lack of neurons and vomeronasal nerve bundles, together with the results of other studies, suggests that the vomeronasal epithelium, unlike in other mammals, is not a sensory organ in adult humans.

Adolescent↗

Role of matrix metalloproteinases in blood flow-induced arterial enlargement: interaction with NO.

Tears in the internal elastic lamina (IEL) can be observed after chronic increases in arterial blood flow, suggesting a potential role for matrix metalloproteinases (MMPs) in flow-induced vascular remodeling. We undertook to study this phenomenon by constructing an arteriovenous fistula (AVF) between the left common carotid artery (CCA) and the external jugular vein in rabbits. The diameter of the flow-loaded left CCA increased by 13.6+/-1.8% by day 3 after construction of the AVF compared with the right CCA (n=4, P:<0.01) and by 40.7+/-7.5% by day-15 (n=10, P:<0.0001). Increased CCA diameter also coincided with IEL fragmentation. Three days after construction of the AVF, gelatin zymography of protein extracts from left CCAs of untreated rabbits showed a significant increase in the 62-kDa (active MMP-2) activity and the appearance of a lytic band at 92 kDa (pro-MMP-9). In further experiments, MMP activity was inhibited by treatment with doxycycline (DOX) or BB-94, a specific MMP inhibitor. The increase in the 62-kDa gelatinolytic band was abolished in DOX- and BB-94-treated rabbits. The 92-kDa gelatinolytic band was also reduced in DOX-treated animals. Furthermore, both increased left CCA diameter and IEL fragmentation were abolished in DOX- and BB-94-treated rabbits. To evaluate whether nitric oxide was involved in blood flow-induced MMP activation, the rabbits were treated with N:(G)-nitro-L-arginine methyl ester to inhibit nitric oxide synthesis. MMP activities were significantly decreased in the left CCAs of N:(G)-nitro-L-arginine methyl ester-treated animals. Hence, blood flow-induced MMP activation is critical in flow-induced vascular enlargement and IEL fragmentation, and blood flow-induced nitric oxide participates in MMP activation.

Animals↗

Ectopic engrailed 1 expression in the dorsal midline causes cell death, abnormal differentiation of circumventricular organs and errors in axonal pathfinding.

A series of gain- or loss-of-function experiments performed in different vertebrate species have demonstrated that the Engrailed genes play multiple roles during brain development. In particular, they have been implicated in the determination of the mid/hindbrain domain, in cell proliferation and survival, in neurite formation, tissue polarization and axonal pathfinding. We have analyzed the consequences of a local gain of En function within or adjacent to the endogenous expression domain in mouse and chick embryos. In WEXPZ.En1 transgenic mice (Danielian, P. S. and McMahon, A. P. (1996) Nature 383, 332-334) several genes are induced as a consequence of ectopic expression of En1 in the diencephalic roof (but in a pattern inconsistent with a local di- to mes-encephalon fate change). The development of several structures with secretory function, generated from the dorsal neuroepithelium, is severely compromised. The choroid plexus, subcommissural organ and pineal gland either fail to form or are atrophic. These defects are preceded by an increase in cell death at the dorsal midline. Comparison with the phenotype of Wnt1(sw/sw) (swaying) mutants suggests that subcommissural organ failure is the main cause of prenatal hydrocephalus observed in both strains. The formation of the posterior commissure is also delayed, and errors in axonal pathfinding are frequent. In chick, ectopic expression of En by in ovo electroporation, affects growth and differentiation of the choroid plexus.

Animals↗

[An unusual primary vascular tumor: intimal sarcoma of the pulmonary artery].

Primary sarcomas of great vessels are rare and involve the aorta, pulmonary artery and inferior vena cava. The pathologic classification of these tumors can be made on the location of the sarcoma in relation to the vessel wall, luminal or mural. Luminal sarcomas are usually intimal sarcoma and mural sarcoma are most frequently leiomyosarcoma. The myofibroblastic or endothelial differentiation of these tumors is still debated. We report a case of intimal sarcoma of the pulmonary artery.

Adult↗

[Bilateral sino-orbital mucormycosis. A case report].

We report a case of mucormycosis in a 48 year-old diabetic woman. She presented with nasosinusal ulcer accompanied by panophthalmitis in the left eye and central retinal artery occlusion in the right eye. Left eye enucleation was performed and the diagnosis of mucormycosis was made on histopathologic examination displaying fungal micro-organisms in the optic nerve and in the retina. The patient died of stress ulcer hemorrhage. Mucormycoses are rare and severe diseases affecting immunocompromised hosts, especially diabetic patients during ketoacidosis. The treatment includes surgical debridement and amphotericin B but prognosis remains severe.

Amphotericin B↗

Specification of somatosensory area identity in cortical explants.

The H-2Z1 transgene is restricted to a subset of layer IV neurons in the postnatal mouse cortex and delineates exactly the somatosensory area. Expression of the H-2Z1 transgene was used as an areal marker to determine when the parietal cortex becomes committed to a somatosensory identity. We have shown previously that grafts dissected from embryonic day 13.5 (E13.5) H-2Z1 cortex and transplanted into the cortex of nontransgenic newborns express H-2Z1 according to their site of origin. Expression was not modified on heterotopic transplantation (). In the present study, whole cortical explants were isolated at E12.5 from noncortical tissues. The explants developed a regionalized expression of H-2Z1, indicating that regionalization takes place and is maintained in vitro. We used this property and confronted embryonic H-2Z1 cortex with presumptive embryonic sources of regionalizing signals in an in vitro grafting procedure. A great majority of E11.5-E13.5 grafts maintained their presumptive expression of H-2Z1 when grafted heterotopically on nontransgenic E13.5-E15.5 explants. However, a significantly lower proportion of E11.5 parietal grafts expressed H-2Z1 in occipital compared with parietal cortex, indicating that somatosensory identity may be partially plastic at E11.5. Earlier stages could not be tested because the E10.5 grafts failed to develop in vitro. The data suggest that commitment to the expression of a somatosensory area-specific marker coincides with the onset of neurogenesis and occurs well before the birth of the non-GABAergic neurons that express H-2Z1 in vivo.

Animals↗

Protective effects of Celsior in lung transplantation.

BACKGROUND: Celsior is a new preservation solution for heart transplants that recently has been shown also to improve protection of pulmonary grafts. As these data were obtained in isolated lung preparations, we sought to perform further tests with an in vivo model of allogeneic lung transplantation. METHODS: The left lungs of 41 rats were either transplanted immediately after harvest (controls) or flushed with and cold stored in Celsior or the blood-based Wallwork solution for 5 or 12 hours. Lungs were then reperfused for 30 minutes, after which ligation of the contralateral pulmonary artery and bronchus made the recipient rat exclusively dependent on the transplanted lung. Assessment of preservation was made on functional (blood gases, pulmonary hemodynamics) and structural (dry-to-weight ratio, light microscopy, myeloperoxidase [MPO] content) end points. RESULTS: The protective effects of Celsior were primarily manifest, once the contralateral lung had been functionally excluded, as a better preservation of oxygen tensions in the 5-hour storage experiments (416 +/- 52 mm Hg vs 406 +/- 59 mm Hg in controls [p = NS] and vs 239 +/- 34 mm Hg in Wallwork [p < 0.05 vs the 2 other groups]) and a smaller increase in pulmonary vascular resistance in the 12-hour storage experiments (10.2 +/- 4.1 mm Hg/mL/minute vs 3.2 +/- 1.1 mm Hg/mL/minute in controls [p = NS] and vs 23.1 +/- 4.3 mm Hg/mL/minute in Wallwork [p < 0.02 vs Celsior, p < 0.002 vs controls]). Survival was also longer in the 12-hour preserved Celsior group. Other end points were not significantly different between the two preservative solutions. CONCLUSION: These data support the efficacy of Celsior as a flush-out and storage solution for pulmonary grafts. Given its previously documented ability to adequately preserve heart transplants, Celsior might provide a unified "solution" to thoracic organ preservation.

Albumins↗

Nasal haemangiopericytoma: report of two cases with literature review.

Haemangiopericytoma (HPC) is a rare vascular tumour produced by proliferation of pericytes. One hundred and thirty-three cases of HPC have been reported in the nose and the paranasal sinuses. We present two more cases. Wide surgical excision via lateral rhinotomy, midfacial degloving, or endonasal removal is the treatment of choice. Radiotherapy has been used post-operatively in cases of incomplete removal. Life-long follow-up is required to evaluate local recurrence and late metastases.

Aged↗

Spinal melanotic schwannoma: a tumour with poor prognosis.

AIM: To clarify the prognosis of melanotic schwannoma. This is a rare tumour which is generally considered as a benign lesion, reported in many cases with a short follow-up only. METHODS AND RESULTS: Five cases of spinal melanotic schwannoma were retrospectively studied. The tumours were examined using standard histological, immunohistochemical and ultrastructural methods. No features of malignancy (high mitotic count, atypia or necrosis) were found in the primary tumours. The follow-up period ranged from 3 to 7 years. Malignant clinical behaviour was clear-cut in four cases: three patients died from metastases to various sites and one presented several discrete spinal tumours of the same type seven years after the first operation. Only one patient presented no recurrence and was free of disease 6 years after initial diagnosis. The review of 57 cases of the literature (including our cases), showed that 15% of the cases had recurrences and 26.3% were complicated by metastasis. Only 53% of the cases followed for more than 5 years, were free of disease vs. 67.5% of the cases with shorter follow-up. Twenty additional cases had no follow-up. CONCLUSION: Appropriate long-term follow-up is required for all melanotic schwannomas, as it may recur or metastasize after more than 5 years, even in the absence of overt malignant histological features.

Adult↗

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Journal Article↗

Role of thalamic axons in the expression of H-2Z1, a mouse somatosensory cortex specific marker.

In the H-2Z1 mouse line, postnatal expression of the lacZ containing transgene in the cerebral cortex is restricted to layer IV neurons of the somatosensory area. We have used H-2Z1 embryos in previous heterotopic transplantation experiments to investigate the chronology of determination of areal identity. From the onset of neurogenesis, the cortex was regionalized in domains fated to express or not the somatosensory area-specific transgene. Determination occured 1 day later. In the present study, we show that, in vivo, H-2Z1 expression coincides with invasion of the cortical plate by thalamic afferents. We therefore investigated the role of thalamic innervation in the onset of H-2Z1 expression. For this purpose, we examined the pattern of H-2Z1 expression in perinatal cortical explant, in reeler mutant and MaoA deficient mice, or in animals which had received neonatal lesions affecting the somatosensory cortex or the thalamocortical projection. We found that, around birth, a switch occurs in the control of H-2Z1 expression: whereas H-2Z1 expression developed autonomously in embryonic parietal cortex in the absence of thalamic fibers, a transient requirement for a thalamic axon derived signal was observed postnatally. This property has interesting implications for the plasticity of cortical areas in development and evolution.

Animals↗