Giant Mitochondria in a Cardiomyopathic Heart

Giant mitochondria (megamitochondria) measuring up to 14 µm in length and 3 µm in width are sporadically present in an exclusively interfibrillar position in the cardiomyocytes of a patient with restrictive cardiomyopathy. The number of cristae is augmented in the megamitochondria; these internal membranes are for the most part irregularly arrayed, but in certain giant mitochondria they run a parallel, zigzag course imparting a paracrystalline appearance to such organelles. Many of the giant mitochondria have one or several lucent, single membrane-bound inclusions that contain either &#102 - or &#103 -glycogen particles. Megamitochondria probably originate at least in part by fusion of adjacent organelles.     

Comparison of careHPV and Hybrid Capture 2 Assays for Detection of High-Risk Human Papillomavirus DNA in Cervical Samples from HIV-1-Infected African Women

The careHPV and HC2 assays were compared for high-risk human papillomavirus (HR-HPV) DNA detection in cervical samples from 149 HIV-1-infected African women. The HR-HPV DNA detection rates were 37.6% and 34.9% for careHPV and HC2, respectively. Agreement between the two tests was 94.6% (95% confidence interval [CI], 89.7% to 97.7%) with a kappa value of 0.88 (95% CI, 0.81 to 0.96), indicating an excellent agreement. careHPV may be considered as suitable as HC2 for cervical cancer screening among HIV-infected African women.     

Children's risk and resilience following a natural disaster: Genetic vulnerability,posttraumatic stress,and depression

Objective

We examined children’s risk and resilience following a natural disaster, evaluating the role of stress, social support, and two genetic markers: the short allele of the serotonin transporter gene (5-HTTLPR), and the met allele of the Brain-Derived Neurotrophic Factor (BDNF).Under high levels of hurricane exposure or hurricane-related stressors, we expected children displaying the markers would report greater symptoms of posttraumatic stress disorder (PTSD) and depression than children without these markers. Social support was explored as an additional moderating variable.

Method

Eight months after Hurricane Ike, 116 children (M age=8.85 years, SD=.89; 54% girls) residing in Galveston, Texas, provided saliva samples and completed measures of hurricane exposure and stress, and symptoms of PTSD and depression; 80 also completed a social support measure.

Results

For BDNF, analyses revealed several Gene by Environment interactions; greater stress was related to more symptoms of PTSD and depression, and this effect was stronger for children with the met allele. No findings emerged for 5-HTTLPR. Stressors and social support also were associated with children’s PTSD and depressive symptoms.

Limitations

Findings should be tempered by the relatively small sample, especially for analysis that included social support.

Conclusions

The met allele (BDNF) may play a role in children’s disaster reactions. Further research should consider the complex interplay between genes, stressors, support, and psychological outcomes over time.     

Analysis of Human Bone Sialoprotein in Normal and Pathological Tissues using a Monoclonal Antibody (BSP 1.2 mab)

Bone sialoprotein (BSP), a phosphorylated and sulphated glycoprotein that is expressed by mineralized connective tissues is also produced in tumors that metastasize to bone. To facilitate studies of BSP expression in normal and pathological human tissues a monoclonal antibody (BSP 1.2 mab) was raised against human bone BSP. BSP 1.2 mab was shown by ELISA assays to recognize the epitope “DEYSY” (amino acids 279–283) that is conserved in mammalian BSP sequences. However, whereas the antibody recognized recombinant BSPs expressed in bacteria, it did not recognize native forms of rat or pig BSP in which the first tyrosine of the DEYSY peptide sequence appears to be modified. Immunostaining of embryonic human tibiae and calvariae with BSP 1.2 mab showed strong reaction in osteoblasts and osteocytes with relatively weak staining of the bone matrix, suggesting that the BSP 1.2 mab epitope is partially masked in the bone matrix. BSP 1.2 mab also stained osteosarcoma cells and normal trophoblastic cells in the placenta in areas of microcrystalline deposits. Cancer cells in primary breast tumors, lymph nodes, and secondary bone metastases from individual patients were stained strongly by BSP 1.2 mab. Although BSP 1.2 mab also stained breast cancer carcinoma cell lines and SaOS2 osteosarcoma cells, biosynthesis of radiolabelled BSP could not be demonstrated in breast cancer cells. Notably, the staining of BSP in the breast cancer cells was diffuse contrasting the punctate staining, typical of secreted proteins, in SaOS2 cells. These studies, therefore, have identified a unique epitope in human BSP recognized by a monoclonal antibody, BSP 1.2 mab, which can be used for the unequivocal identification of BSP in normal and pathological human tissues.     

A continuous decline in menarcheal age in Denmark

We report a renewed decline in mean menarcheal age in a large Danish sample after a period with a halt in the trend towards earlier age at menarche in many North European countries. In our study based on retrospective data from six different samples constituting 42784 women, we find a continuously declining mean menarcheal age in Denmark among women born in the years 1964-1973. In a sample of textile workers born in the years 1939-1968 (n = 12605) we find a 1 year higher mean menarcheal age. This indicates that menarcheal age is still delayed in certain groups in Denmark. This leaves the possibility that the menarcheal age could fall even further in the future.     

Potential Mechanisms of Interferon-α Induced Autoimmunity

The type I interferons (IFN) are cytokines encoded by a multigene family comprising 13 closely related IFN-A genes, and a single IFN-B gene. These factors are rapidly induced upon viral infection, and have pleiotropic effects. Historically, the induction of a cell-autonomous state of antiviral resistance, the inhibition of cell growth, and the regulation of apoptosis were appreciated first. More recently, it became generally accepted that they can regulate immune effector functions. This latter feature led them to be reconsidered as signals linking innate and adaptive immunity, and potentially orchestrating autoimmunity associated with viral infection and IFN-α therapy. Common to almost all autoimmune diseases is their polygenic inheritance, incomplete penetrance, and evidence for the role of environmental factors, particularly viral infection. In addition, they are characterized by increased numbers of circulating autoreactive T- and B-cells. Endogenously produced or therapeutically applied IFN-α can tilt the usually tightly controlled balance towards activation of these autoreactive cells via a vast array of mechanisms. The genetic susceptibility factors determine which type of autoimmunity will develop. IFN-α induces numerous target genes in antigen presenting cells (APC), such that APC are stimulated and enhance humoral autoimmunity, promote isotype switching, and potently activate autoreactive T cells. Moreover, IFN-α can synergistically amplify T cell autoreactivity by directly promoting T cell activation and keeping activated T cells alive. In essence, type I IFNs may constitute one example of genes that have been conserved because they confer dominant disease resistance, but at the same time they can trigger autoimmunity in genetically susceptible individuals.