Biomedical subjects
Publications and source records attributed to M Wassef.
Hypersensitivity to zidovudine is an uncommon complication of antiretroviral therapy. Manifestations range from isolated fever to anaphylaxis. Fever and rash are the most common features. Diagnosis is made by rechallenge, although some patients have antibodies to zidovudine. Treatment is supportive, and symptoms resolve on withdrawal of the medication.
The diagnosis of acute Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy is based on clinical characteristics, abnormalities on nerve conduction studies, and nerve biopsy specimens indicating demyelination. Inflammation and edema are also common findings in nerve specimens. Immunotherapy is helpful in these dysimmune conditions. Occasionally the diagnosis is difficult to make, particularly when electrophysiological testing or nerve biopsy findings are not characteristic. The authors found contrast enhancement of lumbosacral roots in patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome, but not in those with other demyelinating neuropathies. Contrast-enhanced magnetic resonance imaging could be a useful tool in the diagnosis of the dysimmune inflammatory neuropathies.
To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone.
Primary cutaneous adenoid cystic carcinoma is a rare tumor, even if its frequency has often be underestimated, its localization in the external auditory meatus being generally considered separately. The results of the histological and ultrastructural study of two cases of adenoid cystic carcinoma, arising in the external auditory meatus, are presented, confirming the essential morphological similarity of adenoid cystic carcinoma of the skin and salivary glands. In these two cases, the ultrastructural study revealed two types of unique intra luminal inclusions, composed respectively of parallel straight tubular arrays and paracrystalline quadrangular structures, probably corresponding to a peculiar organization of secretion products or cellular debris. The review of 126 published cases of adenoid cystic carcinoma of the skin, including 89 cases developed in the auditory canal, shows that 78% of the cases were located in areas containing numerous apocrine glands, supporting an apocrine gland origin for this tumor. Contrasting with the low (8%) metastatic potential of cutaneous adenoid cystic carcinomas of other locations, adenoid cystic carcinoma of the auditory meatus present a 30% metastatic risk, similar to those or adenoid cystic carcinoma of salivary glands.
The mammalian neocortex is subdivided into functionally distinct areas differing in cytoarchitecture and connectivity. Areal specification is thought to occur late in development and to be controlled by extrinsic cues, particularly thalamic afferents. We have produced a transgenic mouse line in which beta-galactosidase expression in the neocortex is largely restricted to layer-IV neurons of the somatosensory area. Transgene expression in these mice may be considered as an intrinsic marker of a somatosensory cortex identity. We investigated whether the fate of pieces of embryonic cortex from transgenic embryos is modified after transplantation to ectopic locations. Parietal or occipital cortex obtained on embryonic days 14-16 maintained their characteristics with respect to transgene expression after heterotopic transplantation to the cerebellum or neocortex of newborn hosts. This shows that the specification of neocortical areas involves a previously unsuspected early step of areal determination.
RATIONAL AND OBJECTIVES: The feasibility of tubal occlusion by selective salpingography was tested in an animal model; three novel occluding materials also were tested for this application. METHODS: Unilateral selective salpingography was performed in three groups of six rabbits; fallopian tubes were embolized with ethanol (group 1), a hydrogel (group 2), or an occluding emulsion (Ethibloc, Laboratoire Princeps, Neuilly sur Seine, France) (group 3). Animals were killed 2 days or 30 days after the procedure, according to randomization; tubal patency and histologic modifications were evaluated. RESULTS: Selective tubal catheterization was obtained in 100% of the cases. In group 1, no satisfactory occlusion was obtained; in group 2, 65% of the tubes were occluded with little histologic damage; in group 3, 80% of the tubes were occluded, but significant inflammation and tissue necrosis were noted. CONCLUSION: Selective salpingography proved a suitable method for gaining access to the fallopian tube and allowed selective injection of occluding materials. More research is needed to determine a suitable occluding material, focusing on biocompatibility and on long-term efficacy.
When grafted ectopically into the diencephalon of a chick host embryo, a portion of met-mesencephalon straddling the met-mesencephalic constriction has the capacity to induce En-2 expression in the surrounding host tissue. Subsequently, tectal and cerebellar structures, composed of both host and grafted cells, are reconstructed in this ectopic location at the expense of the host diencephalon. Previous experiments indicated that the induction of En-2 was correlated with Wnt-1 expression within the graft. The aim of the present study was: (i) to determine whether Wnt-1 expression was spatially regulated within the graft, (ii) to investigate whether host Wnt-1-expressing cells were also involved in the ectopic met-mesencephalic development and, if so, (iii) to localize these Wnt-1-positive domains in relation to the patterning of the ectopically developing met-mesencephalic territory. We studied the expression profile of Wnt-1, in relation with that of other positional markers, in quail/chick chimeras where various portions of met-mesencephalon had been grafted into the diencephalon. We found that Wnt-1 expression was reorganized within the graft, and that it was also induced in the host in contact with the graft. Moreover, these ectopic expressions of Wnt-1, in both the grafted and the surrounding host tissues, were organized in concert to form a continuous positive line at the host/graft junction, the location of which depended on the precise origin of the graft. Finally, we found that this line was frequently located at the limit between territories expressing different positional markers. We propose that Wnt-1 expression is turned on at the junction between domains of different phenotypes, and may be used as a border to stabilize these adjacent differently committed territories.
The authors report a case of laryngeal rhabdomyoma occurring in a young female adult, revealed by a dysphonia. The review of literature shows that both immunohistochemical and electron microscopy studies have rarely been performed for this benign but infrequent tumour in this localization.
RATIONALE AND OBJECTIVES: Various materials have been used to perform intracerebral and cervical arterial embolization for head and neck tumors and vascular malformations. This preliminary prospective study was designed to analyze the clinical and histopathologic consequences of arterial embolization into the brain using biodegradable starch microspheres. METHODS: A new arterial embolization procedure which ensured the integrity of the common and internal carotid arteries, without modifying the arterial flow, was designed. The procedure allowed for cerebral arterial microembolization in 20 Sprague-Dawley rats. Various amounts of biodegradable starch microspheres (Spherex) were introduced into the brain via the left external carotid artery. RESULTS AND CONCLUSIONS: Clinical and histopathologic results suggested that: 1) consequences of cerebral embolization using biodegradable starch microspheres are related to the amount of material embolized; and 2) Spherex microspheres behave differently from degradable microspheres in the brain. Despite the rapid biodegradability of the material, permanent damage from ischemia to the brain was noted.
Atherosclerosis is a common feature of autogenous vein bypass grafts resulting in their long-term failure. Arterial pressure-induced distension is thought to play a major role in the wall thickening of vein grafts, which may in turn favor atherosclerotic complications. In this study, we evaluated the influence of vein distension on the development of atherosclerotic lesions in jugular vein grafts interposed into the common carotid arteries of rabbits. The proximal half of each vein graft was wrapped with a 4-mm-diameter polytetrafluoroethylene graft that reduced the vein graft diameter by 46 +/- 5%. Fourteen animals were fed a 1% cholesterol-rich diet for 8 weeks, and five animals were fed a normal diet. In normocholesterolemic and hypercholesterolemic animals, the wall thickness and the total cross-sectional area were significantly reduced in wrapped compared with unwrapped segments. Foam cells were never observed in normocholesterolemic animals. In hypercholesterolemic rabbits, the sudanophilic lesions covered 62 +/- 4% of the luminal surface in unwrapped segments and 31 +/- 7% in wrapped segments (p < 0.0001). In transverse sections, the surface areas of foam cells were also markedly reduced in wrapped compared with unwrapped segments. Reduction of the wall distension using a rigid external support protected the vein grafts from atherosclerosis, possibly as a result of the decrease in wall thickening that occurred in response to arterialization.
Middle ear adenoma is a rare benign tumor that exhibits a pleomorphic histological pattern, with solid, cribriform, tubular and trabecular features, which often lead to a diagnosis of a malignant tumor. We report a case of middle ear adenoma, displaying the typical amphicrine biphasic cell growth, better visualized by immunohistochemical and ultrastructural studies. These tumors are composed of two cell types, endocrine B cells containing neurosecretory granules and labelled with anti-keratin, anti-vimentin and anti-neuron specific enolase antibodies, and exocrine A cells containing mucous granules and immunoreactive with anti-keratin and anti-epithelial membrane antigen antibodies. These immunohistochemical and/or ultrastructural characteristics may be helpful to confirm the diagnosis of middle ear adenoma which should be treated by local excision without additional therapy. The essential identity of middle ear adenoma and so called carcinoid tumors of the middle ear is highlighted. We propose to name these tumors middle ear amphicrine adenoma which better reflects their benign and biphasic nature.
Erdheim-Chester disease is an endogenous, non-genetically-determined lipidosis characterized by infiltrates of foamy, lipid-laden histiocytes and by bilateral symmetric foci of sclerosis in appendicular long bones. The clinical spectrum ranges from focal bone lesions to systemic disease with life-threatening visceral involvement. In one third of patients, roentgenograms show focal osteolysis within areas of sclerosis. Authors report a new case of Erdheim-Chester disease documented by two bone biopsies in different sites. Features in their patient included: 1) osteolysis and sclerosis of the long bones of the limbs and maxillas, with CT scan evidence of cortical rupture; 2) on magnetic resonance imaging studies, heterogeneous foci of decreased signal intensity on T1 images and heterogeneous areas of moderately increased signal intensity on T2-weighted images; 3) increased serum osteocalcin levels; 4) laboratory evidence of chronic inflammation with no extraosseous manifestations. The clinical, radiological, and pathological features of Erdheim-Chester disease are different from those of Langerhans cell histiocytosis. However, three cases of patients with both conditions have been reported in the literature, suggesting that there may be links between the two diseases.
At early phases of development (stage HH12 of chick and quail embryos) the rostral part of the cerebellar anlage extends into the caudal third of the mesencephalic vesicle. This region is characterized by its high level of expression of the Wnt-1 and engrailed genes, which encode, respectively, for a secreted molecule and for a homeodomain protein. In order to analyze the potentialities of various parts of the cerebellar anlage, pieces of quail or mouse embryonic neural tubes have been transplanted heterotopically in the prosencephalon of HH12 chick embryos. These experiments indicated that signals operating in the plane of the neural tube are still operating in the donor avian and murine embryos. The met- mes- and prosencephalic territories of HH12 chick embryos are still competent to change their fates under the influence of these signals. It was also found that the Wnt-1 expression domain, the caudal mesencephalic vesicle, has striking organizing properties until late stages of development in avian and rodent embryos. The exact role of Wnt-1 in these inductive interactions is still unknown. Wnt-1 influence on cell fate could be mediated by the engrailed genes. Observations suggesting a later role of en-2 in the regionalization of the cerebellar cortex are also reported.
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In the present study the early phases of the development of the inferior olive were examined by using immunocytochemical techniques. We observed that, from embryonic day 16 onward, antibodies against the calcium binding proteins parvalbumin and calbindin and the calcitonin gene related peptide stain partially overlapping territories of the inferior olive. This staining delimits a biochemical zonation of the inferior olive which is combinatory and transient. We have previously observed a biochemical parcellation of the cerebellar Purkinje cells which, like that of the inferior olive, is first observed at E16, involves the combined expression of marker proteins and is also transient. In order to know whether the biochemical compartmentations of the cerebellum and inferior olive arise independently, the time course of the development of the olivocerebellar projection was studied by anterograde and retrograde in vitro axonal tracing by using the fluorescent carbocyanine dye DiI. The olivocerebellar axons were found to reach the limit of the cerebellar plate at E16 and to enter it at E17. Even at this age the great majority of the climbing fibers are tightly fasciculated, which minimizes their interactions with the PC clusters. These observations indicate that the topographical heterogeneity of Purkinje cells and inferior olive neurons arise independently. The transient biochemical individualization of subgroups of neurons during development could contribute to recognition mechanisms.
A transient biochemical parcellation has been observed by immunocytochemical methods, during the perinatal development of both the inferior olive and the cerebellum. In the present study, we sought a relationship between this developmental compartmentation and the organization of the olivocerebellar projection. In the inferior olive, a transient parvalbumin immunoreactivity restricted to the dorsal cap of the medial accessory olive is observed around birth. The climbing fiber projection of the dorsal cap was identified in the cerebellum of newborn rats based on its parvalbumin immunoreactivity. The pattern of this projection, restricted to lobules IX and X of the vermis, and to the flocculus, is indistinguishable from that of the adult medial accessory olive, which was previously described from axonal tracing experiments. The parvalbumin immunoreactive climbing fibers were followed between birth and postnatal day 7. In the caudal vermis, Purkinje cell subpopulations can be identified between embryonic day 20 and postnatal day three, on the basis of their differential immunostaining with an antibody directed against a specific peptide, PEP 19. In lobule X, the parvalbumin immunoreactive climbing fibers form two sagittal bands on each side of the midline, one medial and one lateral. The medial parvalbumin immunoreactive climbing fiber band is coextensive with a PEP 19 negative Purkinje cell cluster, indicating a clear relationship between the biochemical parcellations of the cerebellum and inferior olive.
Grafting a met-mesencephalic portion of neural tube from a 9.5-day mouse embryo into the prosencephalon of a 2-day chick embryo results in the induction of chick En-2 (ChickEn) expression in cells in contact with the graft (Martinez et al., 1991). In this paper we investigate the possibility of Wnt-1 being one of the factors involved in En-2 induction. Since Wnt-1 and En-2 expression patterns have been described as diverging during development of the met-mesencephalic region, we first compared Wnt-1 and En-2 expression in this domain by in situ hybridization in mouse embryos after embryonic day 8.5. A ring of Wnt-1-expressing cells is detected encircling the neural tube in the met-mesencephalic region at least until day 12.5. This ring consistently overlapped with the En-2 expression domain, and corresponds to the position of this latter gene's maximal expression. We subsequently studied ChickEn ectopic induction in chick embryos grafted with various portions of met-mesencephalon. When the graft originated from the level of the Wnt-1-positive ring, ChickEn induction was observed in 71% of embryos, and in these cases correlated with Wnt-1 expression in the grafted tissue. In contrast, this percentage dropped significantly when the graft was taken from more rostral or caudal parts of the mesencephalic vesicle. Taken together, these results are compatible with a prolonged role of Wnt-1 in the specification and/or development of the met-mesencephalic region, and show that Wnt-1 could be directly or indirectly involved in the regulation of En-2 expression around the Wnt-1-positive ring during this time. We also provide data on the position of the Wnt-1-positive ring relative to anatomical boundaries in the neural tube, which suggest a more general role for the Wnt-1 protein as a positional signal involved in organizing the met-mesencephalic domain.
Vein grafts undergo early intimal thickening and accelerated atherosclerosis. To assess the role of increased wall stress and distension in the pathogenic responses, 11 New Zealand white rabbits underwent interposition of an autologous jugular vein graft in the left common carotid artery. To relieve wall stress and reduce distension, the half proximal part of the vein was wrapped with a polytetrafluoroethylene graft (i.d. 4 mm). Animals were fed 1% cholesterol for 8 weeks. Vein graft and carotid artery were perfusion fixed with Karnovsky solution at 100 mmHg. They were stained with Sudan IV, and 5-microns cross sections were stained with hematoxylin-eosin and orcein. The internal diameter was reduced by 46 +/- 10% in wrapped vein graft segments as compared with unwrapped ones. The percentage of luminal surface covered by sudanophilic lesions (%AS) was assessed by automatic planimetry. Results (mean +/- SD) were as follows. [table: see text]. Abundant foam cells were found in the intima of unwrapped veins, whereas they were absent or rare in wrapped segments. We concluded that atherosclerotic lesions could be prevented in vein grafts by reducing wall stress and distension.