Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression

To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild-type mice (WT). These parameters were similarly studied in insulin-like growth factor-1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell (CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were detected in myocytes of young WT mice, and their expression increased with age. IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC-mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy.     

Quantitative analysis of myelin and axolemma particle distribution in C57BL/Ks diabetic mice and the effects of ganglioside treatment

By freeze-fracture technique we estimated myelin and axolemma intramembranous particle density in C57BL/Ks mice. A decrease in myelin particle content compared to controls is present in both 180 and 280 day old genetic diabetic mice. In addition, the axolemma of myelinated axons is affected in interparanodal regions while no modification was detected at nodal level. Such alterations of myelin membrane structure may also be responsible for the lower motor nerve conduction velocity (MNCV) observed in these diabetic mice; however this hypothesis cannot be taken into consideration for the reduction in MNCV at the early stage of the neuropathy (prior to 180 days of life). Therefore the structural changes of both myelin sheath and interparanodal axolemma as visualized by freeze-fracture are most likely related to late complications of the disease instead of being responsible for the changes in excitability. The low myelin and axolemma particle density of diabetic mice was found normal after 30 days' treatment with gangliosides. Such findings are in agreement with previous results on a significant effect of ganglioside treatment on MNCV and axonal area alterations in 180 and 280 day old genetic diabetic mice.     

免疫金-银染色在组织病理学中的应用

本文介绍在福尔马林固定的石蜡切片上用间接免疫组化技术显示抗原的一种新方法——免疫金-银法。免疫金与抗原结合后用银复染,可大大提高灵敏度。在肝、胃组织用免疫金-银法确定HBsAg及5-HT抗原取得满意结果。     

Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system

The ether-à-go-go-related gene (erg) K+ channels are known to be crucial for life in Caenorhabditis elegans (mating), Drosophila melanogaster (seizure), and humans (LQT syndrome). The erg genes known to date (erg1, erg2, and erg3) are highly expressed in various areas of the rat and mouse central nervous system (CNS), and ERG channel blockers alter firing accommodation. To assign physiological roles to each isoform, it is necessary to design pharmacological strategies to distinguish individual currents. To this purpose, we have investigated the blocking properties of specific peptide inhibitors of hERG1 channels on the human and rat isoforms. In particular, we have tested ErgTx1 (from the scorpion Centruroides noxious), BeKm-1 (from the scorpion Buthus eupeus), and APETx1 (from the sea anemone Anthopleura elegantissima). Because these peptides had different species-specific effects on the six different channels, we have also carried out a biophysical characterization of hERG2 and hERG3 channels that turned out to be different from the rat homologs. It emerged that APETx1 is exquisitely selective for ERG1 and does not compete with the other two toxins. BeKm-1 discriminates well among the three rat members. ErgTx1 is unable to block hERG2, but blocks rERG2 and has the lowest KD for hERG3. BeKm-1 and ErgTx1 compete for hERG3 but not for rERG2 blockade. Our findings should be helpful for structure-function studies and for novel CNS ERG-specific drug design.     

Is the occurrence of the empty follicle syndrome a predictor that a subsequent stimulated cycle will be an unfavourable one?

Several hypotheses have been advanced to explain empty follicle syndrome (EFS) but it remains a controversial topic. This paper reports experience with three IVF cycles in which no oocytes were collected. In all cases, an additional IVF cycle was performed. The ovarian stimulation protocol, ultrasound and hormonal surveillance methods, human chorionic gonadotrophin timing and oocyte retrieval technique were similar in all patients. The assessment of additional cycles demonstrated a poor response in terms of oocyte quality, since the number of mature oocytes was low despite the high number of oocytes collected. Thus, the data suggest that in these patients, EFS should be considered as a borderline form of poor response to ovarian stimulation. If this is confirmed, EFS should be a recurrent event and an empty cycle could be a good predictor that a subsequent stimulated cycle will be an unfavourable.     

A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of patients with primary biliary cirrhosis and pruritus

A single nucleotide polymorphism characterized by the substitution of valine for glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was found in a group of patients with primary biliary cirrhosis. This heterozygous mutation was significantly associated with the presence of pruritus.     

Expression of Carbohydrate Antigens in Human Esophageal Squamous Cell Carcinoma: Prognostic Application and Its Diagnostic Implications

Background Tumor markers whose antigenic determinants have been demonstrated to consist of carbohydrates are probably one of the most extensive tools that have been used in routine cancer diagnosis. In this study, the relevance of carbohydrate antigen expression profile was examined in esophageal squamous cell carcinoma together with prognosis in 130 patients. Methods The expression of carbohydrate antigens was estimated immunohistochemically by anti–sialyl Lewis a (sialyl Le^a) and anti–sialyl Lewis x (sialyl Le^x) monoclonal antibodies, and correlation between their staining and clinicopathological status was examined. In addition, the correlation of both carbohydrate antigens expression was evaluated with microvessel density (MVD). Results Expressions of sialyl Lewis antigens and MVD were associated with several clinicopathological features that reflect the tumor aggressiveness in esophageal cancer. The 5-year survival rate of patients was found to be associated with expression of sialyl Le^a and sialyl Le^x antigens and with MVD; thus, all of them were revealed to be independent prognostic factors. Conclusions Combination of these factors offered a better prediction of prognosis of esophageal squamous cell carcinoma. Further, carbohydrate antigens represent a promising target for therapeutic approaches against the disease.