Cytogenetic sensitivity of G0 lymphocytes of Fanconi anemia patients and obligate carriers to mitomycin C and ionizing radiation

It is well known that Fanconi anemia (FA) patients show a hypersensitivity to the effect of cross-linking agents such as mitomycin C (MMC) and diepoxybutane (DEB), while the sensitivity of these patients to ionizing radiation is still controversial. Fanconi anemia heterozygotes do not show a hypersensitivity to the above mentioned agents compared to normal individuals. To examine the radio-sensitivity of Fanconi anemia patients and heterozygotes, ten patients and 13 heterozygotes were enrolled in this study. Standard metaphase analysis for detection and verification of radio-sensitivity was used to establish the relationship between γ-ray and chromosome breakages in these groups. Statistical analysis was used for the assessment of aberrations including chromatid and chromosome breaks and exchanges. Results of chromosome aberration yield that: (i) differentiation between obligate carriers and the control group after MMC treatment and gamma irradiation was not possible; (ii) homozygotes were clearly distinguishable from heterozygotes and controls after MMC treatment; (iii) FA patients don't show hypersensitivity to gamma irradiation compared to normal controls and heterozygous carriers. Copyright © 2008 S. Karger AG

Evaluation of Inhibitory Effects of Berberine on Apoptosis Due to Measles Virus Strain AIK-HDC

Background: Measles virus (MV) is a highly contagious agent which causes a major health problem in developing countries. We studied the effect of BERBERINE on the replication of an AIK-HDC strain of MV and its induced apoptosis in Vero cell lines. Methods: In this study, toxicity of BERBERINE on Vero cells was investigated first, resulted in determination of sub-lethal or non-toxic concentration zone of BERBERINE for cells. Next, anti-viral effect of BERBERINE at various time limits was evaluated and virus titer was determined at each stage either as 50% tissue culture infective dose TCID50 or by plaque assay method. Using specific anti-measles IgG, anti-viral effect of BERBERINE on MV replication cycle was evaluated through indirect immunofluorescence assay, meanwhile presence of viral RNA was investigated by RT-PCR and gel- electrophoresis. Results: According to the experiments, BERBERINE, at concentration of 50 μM, markedly inhibited the cytopathic effect (CPE) induced by MV. BERBERINE also significantly inhibited apoptosis induced by MV. BERBERINE either influences replication of MV genome, or may inhibit virion formation. Conclusion: These results suggest that the inhibition of CPE and apoptosis by BERBERINE induced by MV may be associated with the effect of BERBERINE on viral RNA genome. Therefore, it is suggested that MV infections can induce apoptosis through the activation of a common pathway that can be blocked by BERBERINE or some of its ingredients

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

Background: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder that shows an increased sensitivity to the intercalating agents such as mytomycin C (MMC), measured as chromosomal aberrations. This study was conducted to differentiate between FA and "idiopathic" aplastic anemia on the basis of induced chromosomal breakage study with MMC. Materials and Methods: MMC stress tests in different final concentrations of 20 and 50 ng/ml of MMC were conducted on peripheral blood lymphocytes from 32 patients with aplastic anemia and 13 healthy controls. Fifty nanograms per milliliter of MMC from old, fresh and frozen stocks was used to check the sensitivity of diagnosis on FA-diagnosed patients. Statistical analysis was used for the assessment of aberrations, including chromatid and chromosome breaks and exchanges. Results: Eight patients (25%) with a very high percentage of chromosomal breakage were diagnosed as FA on the basis of the chromosomal breakage study. Six of these patients exhibited congenital anomalies at presentation, while another two lacked such anomalies or had minor physical problems. Freshly made MMC has shown more sensitivity to detect FA patients compared with frozen or 1-week-old MMC stock. Conclusions: The study indicates that freshly made MMC stress test provides an unequivocal means of differentiation between FA and "idiopathic" aplastic anemia. Further, the study, the first of its kind from Iran, stresses on the need for conducting this test in all aplastic anemia cases, even those without congenital anomalies, for accurate and timely diagnosis of FA to implement appropriate therapy

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

Background: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder that shows an increased sensitivity to the intercalating agents such as mytomycin C (MMC), measured as chromosomal aberrations. This study was conducted to differentiate between FA and "idiopathic" aplastic anemia on the basis of induced chromosomal breakage study with MMC. Materials and Methods: MMC stress tests in different final concentrations of 20 and 50 ng/ml of MMC were conducted on peripheral blood lymphocytes from 32 patients with aplastic anemia and 13 healthy controls. Fifty nanograms per milliliter of MMC from old, fresh and frozen stocks was used to check the sensitivity of diagnosis on FA-diagnosed patients. Statistical analysis was used for the assessment of aberrations, including chromatid and chromosome breaks and exchanges. Results: Eight patients (25%) with a very high percentage of chromosomal breakage were diagnosed as FA on the basis of the chromosomal breakage study. Six of these patients exhibited congenital anomalies at presentation, while another two lacked such anomalies or had minor physical problems. Freshly made MMC has shown more sensitivity to detect FA patients compared with frozen or 1-week-old MMC stock. Conclusions: The study indicates that freshly made MMC stress test provides an unequivocal means of differentiation between FA and "idiopathic" aplastic anemia. Further, the study, the first of its kind from Iran, stresses on the need for conducting this test in all aplastic anemia cases, even those without congenital anomalies, for accurate and timely diagnosis of FA to implement appropriate therapy

A Fresh Look at the Male-specific Region of the Human Y Chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome’s length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein–protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping

A Fresh Look at the Male-specific Region of the Human Y Chromosome

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome’s length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein–protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping