Israel Medical Association Journal

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.

Background: The Bloom syndrome gene, BLM, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase. The Fanconi anemia complementation group C gene was mapped to chromosome 9q22.3, but its product function is not sufficiently clear. Both are recessive disorders associated with an elevated predisposition to cancer due to genomic instability. A single predominant mutation of each disorder was reported in Ashkenazi Jews: 2281delATCTGAinsTAGATTC for Bloom syndrome (BLM-ASH) and IVS4+4A®T for Fanconi anemia complementation group C.

Objectives: To provide additional verification of the mutation rate of BLM and FACC[1] in unselected Ashkenazi and non-Ashkenazi populations analyzed at the Sheba Medical Center, and to trace the origin of each mutation.

Methods: We used polymerase chain reaction to identify mutations of the relevant genomic fragments, restriction analysis and gel electrophoresis. We then applied the Pronto^TM kit to verify the results in 244 samples and there was an excellent match.

Results: A heterozygote frequency of 1:111 for BLM-ASH and 1:92 for FACC was detected in more than 4,000 participants, none of whom reported a family history of the disorders. The Pronto^TM kit confirmed all heterozygotes. Neither of the mutations was detected in 950 anonymous non-Ashkenazi Jews. The distribution pattern of parental origin differed significantly between the two carrier groups, as well as between each one and the general population.

Conclusions: These findings as well as the absence of the mutations in non-Ashkenazi Jews suggest that: a) the mutations originated in the Israelite population that was exiled from Palestine by the Roman Empire in 70 AD and settled in Europe (Ashkenazi), in contrast to those who remained; and b) the difference in origin distribution of the BS[2] and FACC mutations can be explained by either a secondary migration of a subgroup with a subsequent genetic drift, or a separate geographic region of introduction for each mutation.

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[1] FACC = Fanconi anemia complementation group C

Background: Prevention of cigarette smoking is an important issue in public health policy. Since most adult smokers began smoking in childhood, understanding behavor­ial factors associated with smoking initiation would contribute to smoking initiation programs. Health-related behavior may vary between different ethnic groups.

Objectives: To determine the prevalence of smoking among Jewish and Arab adolescents in Jerusalem, and whether there are differences in smoking initiation between the two ethnic groups.

Methods: We carried out a cross-sectional survey of all students in the 6th to 11th grades (age range 11-17 years) of a Jewish school and an Arab school in the Jerusalem area, using an anonymous self-completion questionnaire. A total of 791 questionnaires was analyzed, 479 from the Jewish students and 312 from the Arab students.

Results: The lowest prevalence of smoking was found among Arab female students and the highest among Jewish female students (9% vs. 41%, P<O.OO1). The prevalence of smoking among Jewish and Arab males was similar. More Arab female students smoked than their mothers. Peer pressure seemed to be a more important factor among Jewish students.

Conclusions: This study demonstrated the presence of ethnic differences in smoking prevalence and the reasons for smoking among adolescents in Israel. These results suggest the need for specific smoking prevention policies for different ethnic groups.

Background: The growth plate increases its activity in response to exercise. Likewise, decreased physical activity exerts a negative effect on bone growth and development, leading to rarefaction of the subepiphyseal bone. Limb immobilization inhibits the growth plate’s activity, indirectly shown by a recorded arrest in longitudinal growth of the long bones. However, there is no direct evidence concerning the growth plate itself.

Objective: To determine whether the growth plate exhibits measurable microstructural changes in response to decreased levels of physical activity.

Methods: Histomorphometric analysis was used to qualitatively and quantitatively assess the changes in the epiphyseal plate in response to single hind limb immobilization in the rat. In 16 of 25 Sprague-Dawley male rats the left hind limb was immobilized for 3 weeks; the remaining 9 rats served as controls. The left proximal tibia of each animal was examined by computerized image analysis.

Results: There was a decrease in epiphyseal height, cell column density and subepiphyseal trabecular area - all indices of growth plate activity. Metaphyseal cortical thickness was also depressed, thereby confirming the efficacy of the immobilization method applied.

Conclusions: Limb immobilization in the rat induces inhibitory histological changes in the epiphyseal growth plate, which are in contrast to the excitatory microscopic changes seen with exercise. These changes can be assessed quantitatively. Their potential for reversibility remains to be determined by future experiments.