Detection of the Glanzmann's thrombasthenia mutations in Arab and Iraqi-Jewish patients by polymerase chain reaction and restriction analysis of blood or urine samples.

Severe Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews--an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs--a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.     

Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse

Cyclic nucleotides are important second messengers that mediate a number of cellular responses to external signals. Cyclic nucleotide phosphodiesterases play a role in signal transduction by regulating the cellular concentrations of these messengers. Here, we have applied Southern analyses of somatic cell hybrid lines and of recombinant inbred (RI) mouse strains as well as fluorescence chromosomal in situ hybridization (FISH) to chromosomally localize five cAMP-specific nucleotide phosphodiesterase genes in human and mouse. GenesDPDE1, DPDE2, DPDE3, andDPDE4 that share sequence homology with theDrosophila dunce gene were assigned to human chromosomes 19 (DPDE1 andDPDE2), 5q12 (DPDE3), and 1p31 (DPDE4) and to mouse chromosomes 8, 9, 13, and 4, respectively. The high-affinity cAMP-specific phosphodiesterase gene (HCP1) was mapped to human chromosome 8q13-q22. Since these genes are potential candidates for involvement in psychiatric or behavioral disorders, knowledge of their chromosomal localizations will facilitate the discovery of their association with disease genes as they are being mapped by linkage studies.     

Time related bias in longitudinal studies using dual photon absorptiometry.

Examining the bone mineral density (BMD's) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July-December 1989, January-June 1990 or July-December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p < 0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p < 0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait.

The aim of this study was to examine the association between freezing of gait (FOG) and quality of life (QoL) in patients with Parkinson's disease (PD). PD patients (n = 118) completed the PDQ-39 (QoL) and FOG-Q questionnaires. Disease severity was assessed by the Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS). The relations between those parameters were assessed using regression models. 66 men and 52 women (mean age 65.8 +/- 10.2 years, UPDRS total score 48.4 +/- 17.1, disease duration 8.5 +/- 5.8 years, H&Y stage 2.7 +/- 0.8) participated. FOG severity had a significant effect on QoL (P < 0.0015), accounting for disease severity assessed by UPDRS. Specifically, FOG severity was correlated with all the dimensions of the PDQ-39 except for stigma and social support, as follows: with mobility, bodily discomfort, activity of daily living (ADL) (P < 0.005 in all), with emotional, communication, and cognition (P < 0.05 in all). FOG severity (FOG-Q) was also found to affect a modified PDQ total score, without the mobility aspect (P = 0.0081). FOG should be viewed as a highly important symptom with regard to QoL of PD patients beyond its effect on gait and mobility. On the basis of the present results, special attention should be given to FOG in the treatment of patients with PD.     

Raising awareness and providing free screening improves cervical cancer screening among economically disadvantaged Lebanese/Armenian women.

Women need to practice cervical screening regularly to reduce morbidity and mortality. The purpose of this study was to examine the impact of an intervention program on knowledge, attitude, and practice of cervical screening in the population of Lebanese/Armenian women. The design was a cross-sectional, quasi-experimental posttest survey following a year long intervention program. The sample included 176 women, who were members of the Armenian Relief Cross in Lebanon. Interventions consisted of educational classes, media messages, and free screening. The instrument was a self-administered questionnaire. Knowledge of women with intervention was higher (p > .05) and practice rate increased between intervention and comparison groups. No difference in attitude was noted. The study was successful in raising awareness and increasing screening in the sample. It is recommended to continue helping women to overcome barriers for cervical screening.     

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.     

Familial Mediterranean fever gene and protection against asthma.

BACKGROUND: Asthma is an inflammatory airway disease caused by interaction between susceptibility genes and diverse environmental factors. In Israel, asthma seems to be familial and more severe in patients of Iraqi Jewish descent. On the other hand, asthma is less frequent in individuals with familial Mediterranean fever, an autoinflammatory disease prevalent in the Iraqi Jewish community and linked to mutations in the familial Mediterranean fever gene, designated MEFV. OBJECTIVES: To explore a possible role for mutated MEFV in the reduced susceptibility to asthma and to determine its expression in Israeli subjects of Iraqi origins. METHODS: Using a case-control approach, we studied the presence of the 3 most common MEFV mutations (M694V, V726A, and E148Q) in DNA samples from 75 patients with asthma and 45 asymptomatic first-degree relatives, all of Iraqi Jewish origin. The severity of asthma was evaluated using a published severity score. RESULTS: Eleven patients with asthma and 14 of their relatives carried 1 or 2 mutations in the MEFV gene, a carrier rate significantly lower in patients with asthma than in their first-degree relatives and in ethnically matched healthy individuals (P < .03 and P < .003, respectively). Carriers of MEFV mutations had less severe disease, compared with noncarriers (P < .002). CONCLUSION: These findings suggest that MEFV mutations may have a protective effect in the pathogenesis of asthma.     

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (<1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16–F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread. This revised version was published online in July 2006 with corrections to the Cover Date.