Thyroglobulin polymorphisms in Tunisian patients with autoimmune thyroid diseases (AITD)

The thyroglobulin (Tg) gene was reported to be linked and/or associated to autoimmune thyroid diseases (AITD) development in European Caucasian populations. Here, we attempt to replicate this finding and to evaluate the contribution of the Tg gene in the genetic susceptibility of AITD in the Tunisian population. We examined the genomic region (11.5cM) containing the Tg gene by genotyping seven microsatellite markers and four SNPs located respectively at exon 10 (Ser715Ala), exon 12 (Met1009Val), exon 21 (Ala1483Ala) and exon 33 (Arg1980Trp) in 15 Tunisian multiplex families affected with AITD including Graves' disease (GD) and Hashimoto's thyroiditis (HT) (members: 87; patients: 27 GD and 16 HT). A case-control study was performed by genotyping the Tgms2 intragenic microsatellite marker (intron 27) and four intragenic SNPs on 108 unrelated patients affected with GD and 169 normal controls. Analysis of family data did not show linkage of the thyroglobulin gene with AITD nor did analysis of case-control data show association of Tgms2 or SNPs with GD. In contrast to the European Caucasian population, we failed to detect any contribution of Tg gene in the genetic component of Tunisian AITD.     

Clinical and single-photon emission computed tomography study of pure akinesia with freezing of gait

The clinical syndrome of pure akinesia (PA) is considered the third phenotype of progressive supranuclear palsy (PSP), and is characterized by freezing of gait and prominent speech disturbance without rigidity or tremor. It is frequently considered one of the dopamine resistant motor syndromes, and its pathophysiology remains unclear. We report a patient followed in the Department of Neurology of Razi Hospital, Tunisia, with PA with gait freezing (PAGF) with a frontal hypoperfusion on single photon emission CT and non-responsive dopa therapy. We discuss the clinical features of PAGF and efficiency of treatment options.     

Methicillin resistance in Staphylococcus aureus: emergence and molecular basis

Methicillin-resistant Staphylococcus aureus (MRSA) is often the severe causal agent in nosocomial infections that are becoming increasingly difficult to cure because of emerging resistance to all current antibiotic classes. Geographic spread of several MRSA clones between countries and continents has been reported and proven by molecular evidence. Several strains have been isolated from patients in the community without established risk factors for MRSA acquisition. Some of them may have origins in the hospital but others appear to be community-acquired strains. Community MRSA strains have several distinguishing characteristics that may enable them to more readily colonize and infect otherwise healthy hosts. Molecular typing approaches have been used with great advantage in studying of the MRSA epidemiology. It appears that a complete characterization of MRSA requires not only identification of the genetic background of the bacteria but also identification of the structural types of Staphylococcal Cassette Chromosome mec element (SCCmec), which carries methicillin resistance determinant mecA. Rapid and precise identification of MRSA is a prerequisite for control of hospital infections. This article reviews recent publications addressing the epidemiology markers of MRSA, specially of community-acquired strains, and the genetic diversity of SCCmec for identifying MRSA. It appears that MRSA will be an increasing important pathogen in the community.     

Sex chromosomes-linked single-gene disorders involved in human infertility

Human infertility is a healthcare problem that has a worldwide impact. Genetic causes of human infertility include chromosomal aneuploidies and rearrangements and single-gene defects. The sex chromosomes (X and Y) are critical players in human fertility since they contain several genes essential for sex determination and reproductive traits for both men and women. This paper provides a review of the most common sex chromosomes-linked single-gene disorders involved in human infertility and their corresponding phenotypes. In addition to the Y-linked SRY gene, which mutations may cause XY gonadal dysgenesis and sex reversal, the deletions of genes present in AZF regions of the Y chromosome (DAZ, RBMY, DBY and USP9Y genes) are implicated in varying degrees of spermatogenic dysfunction. Furthermore, a list of X-linked genes (KAL1, NR0B1, AR, TEX11, FMR1, PGRMC1, BMP15 and POF1 and 2 regions genes (XPNPEP2, POF1B, DACH2, CHM and DIAPH2)) were reported to have critical roles in pubertal and reproductive deficiencies in humans, affecting only men, only women or both sexes. Mutations in these genes may be transmitted to the offspring by a dominant or a recessive inheritance.     

IGFBP-2 expression in a human cell line is associated with increased IGFBP-3 proteolysis,decreased IGFBP-1 expression and increased tumorigenicity

Insulin-like growth factors (IGF-I and -II) play an active role in cell proliferation. In biological fluids, they are non-covalently bound to high-affinity binding proteins (IGFBPs), at least 6 species of which have been identified to date, but with poorly defined functions. One of these IGFBPs, IGFBP-2, is secreted by most cell lines and appears to be involved in cell proliferation. A human epidermoid carcinoma cell line, KB 3.1, which produces IGFBP-1 and -3 and small amounts of IGFBP-4, but no IGFBP-2, was stably transfected with an expression vector comprising IGFBP-2 complementary DNA (cDNA), whose expression was placed under the control of the constitutive and ubiquitous cytomegalovirus promoter. After an s.c. injection of these IGFBP-2-expressing KB 3.1 cells into nude mice, tumours developed more quickly than in controls, they were 3 to 4 times larger and grew about 3 times as fast. Concomitant with IGFBP-2 expression in these tumours, were a decrease in IGFBP-1 expression and an increase in IGFBP-3 proteolysis, both of which increase the bioavailability of the IGF-II produced by the cells. The increased IGFBP-3 proteolysis most probably resulted from amplified expression of tissue-type plasminogen activator (t-PA) and depression of its inhibitor (PAI-1) observed in IGFBP-2-expressing xenografts. Our findings suggest that IGFBP-2 plays a role in this model of experimental tumorigenesis via a mechanism that remains unclear, but appears to involve increased protease activity and IGF-II bioavailability. Int. J. Cancer 77:874-879, 1998.© 1998 Wiley-Liss, Inc.     

EGF‐related peptides are involved in the proliferation and survival of MDA‐MB‐468 human breast carcinoma cells

A majority of human breast carcinomas co‐express the epidermal growth factor (EGF)‐like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor α (TGF‐α). MDA‐MB‐468 breast carcinoma cells express CR, AR and TGFα, while SK‐BR‐3 cells express CR and TGF‐α. Anti‐sense phosphorothioate oligodeoxynucleotides (AS S‐oligos) directed against either CR or TGF‐α inhibit the proliferation of both cell lines. A 40–50% growth inhibition was observed at a 2‐μM concentration of each AS S‐oligo. Treatment with the AR AS S‐oligo also resulted in a significant inhibition of MDA‐MB‐468 anchorage dependent growth (ADG). No significant growth inhibition was observed when MDA‐MB‐468 or SK‐BR‐3 cells were treated with a mis‐sense S‐oligo. The AS S‐oligos inhibited the expression of AR, CR or TGF‐α proteins and mRNAs, as assessed by immuno‐cytochemistry and semi‐quantitative RT‐PCR. An additive growth‐inhibitory effect was observed when MDA‐MB‐468 cells were treated with a combination of EGF‐related AS S‐oligos. Indeed, treatment of MDA‐MB‐468 cells with a combination of AR, CR and TGF‐α AS S‐oligos resulted in about 70% growth inhibition at a concentration of 0.7 μM each. Finally, treatment of MDA‐MB‐468 cells with a combination either of the 3 AS S‐oligos or of an EGF receptor‐blocking antibody (MAb 225) and either CR, AR or TGFα AS S‐oligos resulted in a significant increase in DNA fragmentation. Our data suggest that the EGF‐related peptides are involved in the proliferation and survival of breast carcinoma cells. Int. J. Cancer 80:589–594, 1999. © 1999 Wiley‐Liss, Inc.