CTG expansion & haplotype analysis in DM1 gene in healthy Iranian population

Myotonic dystrophy type 1 (DM1) is due to an unstable expansion of CTG repeat in the DMPK gene (19q13.3). The CTG repeat is highly polymorphic (5 to 37) in healthy individuals. According to the hypothesis that expanded (CTG)n alleles originated from larger normal alleles, there may exist a correlation between the prevalence of DM1 and the frequency of large size normal alleles. Strong linkage disequilibrium between different length alleles and the three biallelic markers, Alu, Hinf1 and Taq1, has been reported. OBJECTIVE: To determine the distribution of normal alleles, the frequency of larger normal alleles and analysis of the three biallelic markers, in healthy Iranian controls. MATERIAL AND METHODS: Polymerase chain reaction (PCR) was conducted on two hundred unrelated healthy individuals from different ethnic groups living in Iran to determine the size of the alleles. Markers were analyzed by PCR/RFLP on 174 chromosomes from other control healthy individuals. RESULTS: Our data reveals that 23.7% of alleles had 5 CTG repeats and 7.2% of alleles had > 18 CTG repeats. The analysis of haplotypes revealed that 75% of CTG5 and 80% of CTG > 18 had the (+++) haplotype. CONCLUSION: The frequency of alleles with CTG > 18 in Iran is similar to that of Western Europe and Japan.     

18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: comparison with long-term clinical outcome.

Extraaxillary metastases (i.e., in the absence of axillary involvement) are more likely to develop in patients with inner-quadrant (IQ) breast cancer than in patients with outer-quadrant (OQ) primary tumors. The relative difficulty of identifying extraaxillary metastases may lead to understaging of cancer in these patients. This study examined whether (18)F-FDG PET findings were differentially associated with the location of primary tumors, and with long-term prognosis, in IQ and OQ patients. METHODS: Follow-up data were obtained for 141 patients whose breast cancer was staged by PET and who were documented to have IQ (n = 42) or OQ (n = 99) primaries. Results were stratified according to PET findings consistent with different metastatic patterns. Data were further analyzed with respect to disease outcome after a mean 3-y follow-up period. RESULTS: Among IQ patients, progressive disease was identified in 26.1%, compared with 13.1% of OQ patients, for a relative risk (RR) of 2.0. Of patients with PET findings of isolated extraaxillary metastases, 36.1% had progressive disease, compared with 10.7% of other patients (RR = 3.4), and 61.9% of IQ patients had isolated extraaxillary metastases identified on PET, compared with 10.1% of OQ patients (RR = 6.1). CONCLUSION: IQ patients demonstrated a 6-fold greater frequency of PET findings of isolated extraaxillary metastasis, and such findings were associated with triple the risk for disease progression. Patients with IQ tumors could be vulnerable to understaging with conventional staging approaches and may particularly benefit from PET during the staging process.     

Chirurgische Therapie der pathologischen Adipositas durch laparoskopisches ?gastric banding“Technik und Ergebnisse in 370 F?llen Technik und Ergebnisse in 370 F?llen

Die Gewichtsreduzierung bei pathologischer Adipositas durch Anlage eines adjustierbaren Silikon-Magenbandes ist eine sehr effiziente und langfristige Methode. Sie ist chirurgisch anspruchsvoll; bei Standardisierung ist die Komplikationsrate minimiert. Im Zeitraum von Mai 1996 bis September 1997 wurden 370 Patienten bei bestehender pathologischer Adipositas mittels laparoskopischer Anlage eines Magenbandes operiert. Es kamen zwei verschiedene Bandtypen zum Einsatz, deren Ergebnisse in zwei Serien vorgestellt werden. Die Gesamtmorbidit?tsrate betrug 16,8 %, in der Serie II 4,5 %. Die Letalit?tsrate betrug 0 %. Der durchschnittliche Gewichtsverlust betrug nach 4 Wochen im Mittel 12 kg (5,3 %), nach 3 Monaten 18 %, nach 6 Monaten 37,4 % und nach einem Jahr 48,4 % des übergewichtes.     

Local self-renewal can sustain CNS microglia maintenance and function throughout adult life

Microgliosis is a common response to multiple types of damage in the CNS. However, the origin of the cells involved in this process is still controversial and the relative importance of local expansion versus recruitment of microglia progenitors from the bloodstream is unclear. Here, we investigated the origin of microglia using chimeric animals obtained by parabiosis. We found no evidence of microglia progenitor recruitment from the circulation in denervation or CNS neurodegenerative disease, suggesting that maintenance and local expansion of microglia are solely dependent on the self-renewal of CNS resident cells in these models.     

Autosomal Recessive Nonsyndromic Arrhythmogenic Right Ventricular Cardiomyopathy without Cutaneous Involvements: A Novel Mutation

The arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic disease frequently associated with desmosomal mutations, mainly attributed to dominant mutations in the Plakophilin‐2 (PKP2) gene. Naxos and Carvajal are the syndromic forms of ARVD/C due to recessive mutations. Herein, we report an autosomal recessive form of nonsyndromic ARVD/C caused by a mutation in the PKP2 gene. After examination and implementation of diagnostic modalities, the definite diagnosis of ARVD/C was confirmed by detection of ventricular tachycardia with a left bundle branch configuration and a superior axis, T‐wave inversion in right precordial leads (i.e., V1‐V3) in a 12‐lead electrocardiogram, and a right ventricle outflow tract dilatation. Neither cutaneous involvement nor other abnormalities were observed. Genetic testing was performed during which an intronic mutation of c.2577+1G>T in the PKP2 gene was observed homozygously. The c.2577+1G>T disrupts PKP2 mRNA splicing and causes a nonsyndromic form of ARVD/C.