Biomedical subjects

S Bel

Publications and source records attributed to S Bel.

8 recordsLinked to original sources

PubMed2001

Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21.

We previously localized and fine-mapped Charcot Marie Tooth 4A (CMT4A), the autosomal recessive, demyelinating peripheral neuropathy, to chromosome 8. Through additional positional cloning, we have identified a good candidate gene, encoding ganglioside-induced differentiation-associated protein-1 (GDAP1). We found three different mutations in four different Tunisian families-two nonsense and one missense mutation. How mutations in GDAP1 lead to CMT4A remains to be understood.

Amino Acid Substitution↗

PubMed2001

Cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid-storage disease caused by mutations in the sterol 27-hydroxylase gene. The accumulation of cholestanol in various tissues characterizes this disease. Diagnosis is based on determination of urinary bile alcohols. Therapy with chenodeoxycholic acid may arrest the progression of the disease. A 55-year-old woman presented with a slowly progressive paraparesia and two firm subcutaneous tumors over the knees. Her medical history revealed difficulty in standing and walking since infancy, bilateral juvenile cataracts, and mental retardation. Histopathologic examination of one subcutaneous tumor was consistent with tendinous xanthoma. Substantial elevation of urinary bile alcohols confirmed the diagnosis. Treatment with oral chenodeoxycholic acid was started, with only mild improvement of spasticity. Recognition of tendon xanthomas in a young patient with neurologic symptoms or cataracts (or both) is crucial to start early treatment and to avoid irreversible neurologic sequelae.

Chenodeoxycholic Acid↗

PubMed1999

Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways.

To investigate eosinophil stimulation by chemokines we developed a sensitive assay of leukocyte shape change, the gated autofluorescence/forward scatter assay. Leukocyte shape change responses are mediated through rearrangements of the cellular cytoskeleton in a dynamic process typically resulting in a polarized cell and are essential to the processes of leukocyte migration from the microcirculation into sites of inflammation. We examined the actions of the chemokines eotaxin, eotaxin-2, monocyte chemoattractant protein-1 (MCP-1), MCP-3, MCP-4, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and IL-8 on leukocytes in mixed cell suspensions and focused on the responses of eosinophils to C-C chemokines. Those chemokines acting on CCR3 induced a rapid shape change in eosinophils from all donors; of these, eotaxin and eotaxin-2 were the most potent. Responses to MCP-4 were qualitatively different, showing marked reversal of shape change responses with agonist concentration and duration of treatment. In contrast, MIP-1alpha induced a potent response in eosinophils from a small and previously undescribed subgroup of donors via a non-CCR3 pathway likely to be CCR1 mediated. Incubation of leukocytes at 37 degrees C for 90 min in the absence of extracellular calcium up-regulated responses to MCP-4 and MIP-1alpha in the majority of donors, and there was a small increase in responses to eotaxin. MIP-1alpha responsiveness in vivo may therefore be a function of both CCR1 expression levels and the regulated efficiency of coupling to intracellular signaling pathways. The observed up-regulation of MIP-1alpha signaling via non-CCR3 pathways may play a role in eosinophil recruitment in inflammatory states such as occurs in the asthmatic lung.

Calcium↗

PubMed1998

Genetic interactions and dosage effects of Polycomb group genes in mice.

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes. These skeletal transformations are accompanied with an enhanced shift of the anterior limit of expression of several Hox genes in the somitic mesoderm. Our results demonstrate that in mice the Polycomb group genes act in synergy to control the nested expression pattern of some Hox genes in somitic mesodermal tissues during development.

Animals↗

PubMed1997

Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice.

In Drosophila, the trithorax-group and the Polycomb-group genes are necessary to maintain the expression of the homeobox genes in the appropriate segments. Loss-of-function mutations in those groups of genes lead to misexpression of the homeotic genes resulting in segmental homeotic transformations. Recently, mouse homologues of the Polycomb-group genes were identified including M33, the murine counterpart of Polycomb. In this report, M33 was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its function during development. Homozygous M33 (-/-) mice show greatly retarded growth, homeotic transformations of the axial skeleton, sternal and limb malformations and a failure to expand in vitro of several cell types including lymphocytes and fibroblasts. In addition, M33 null mutant mice show an aggravation of the skeletal malformations when treated to RA at embryonic day 7.5, leading to the hypothesis that, during development, the M33 gene might play a role in defining access to retinoic acid response elements localised in the regulatory regions of several Hox genes.

Animals↗

PubMed1991

Dorsal column stimulation (DCS): cost to benefit analysis.

In order to analyse the ratio of costs to clinical benefit of the implantation of a neurostimulator (type Medtronic SE-4) we examined a group of 14 patients who required treatment for chronic lumboischialgia after repeated surgery for herniated discs. Over a period of two years we evaluated the pre- and postimplantation costs. The implantation of a DC-Stimulator resulted in a striking decrease in drug requirements, in the total time of clinical treatment, and in the degree of disability. The DCS provides a satisfying method of treatment for chronic lumboischialgia after repeated surgery for herniated discs. Despite relatively high primary costs, treatment with a DCS results in a significant decrease in the accumulated expenses in comparison to other methods of medical treatment in similar cases.

Analgesia, Epidural↗

PubMed1990

[Prognosis in meningiomas. Relevance of morphologic studies and clinical risk factors].

Since the introduction of the WHO-classification of tumours of the central nervous system in 1979, meningiomas are subdivided in 8 histological types and graded I to IV. The basis for this classification were histopathological investigations combined with clinical follow-up data. Since the introduction of immunocytochemistry as a diagnostic tool in neurooncology, morphological methods have gained renewed interest among neurosurgeons and neurologists. Some of the more recent developments, as well as the classical methods of the neuropathologist, are discussed here, and the results of the impact of morphology on prognosis is discussed on 139 own cases. Beside the histopathological grading, the application of so called proliferative markers as Ki-67 and BUdR seems to be most promising in the prediction of recurrences. Clinical parameters as patients age, preoperative physical status, tumor size and location on the other hand are of particular importance concerning postoperative mortality.

Biomarkers, Tumor↗

PubMedDate not supplied

Vegetant bromoderma in an Infant.

Bromoderma is a cutaneous reaction caused by the use of products containing bromide. In this report we describe a 2-month-old girl who was admitted to our institution with vegetative lesions on the face and scalp owing to the administration of a syrup containing sodium bromide.

Abdominal Pain↗