Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia.

Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study.     

Genomic studies on killer yeasts belonging to the genusPichia

Twenty-four species belonging to the genusPichia were investigated using restriction fragment length polymorphism (RFLP) and Southern blot hybridization of their genomic DNA.Saccharomyces cerevisiae, Kluyveromyces lactis, Williopsis mrakii andCandida albicans were also included in this study. The RFLP patterns were obtained from digestion of yeast DNA with several restriction endonuclease enzymes, and showed various bands with different mobility; in most isolates, the more deeply stained bands were species-specific. This observation was confirmed by the results obtained from Southern blot hybridization of theEcoRI andXhoI RFLP patterns withP. anomala UCSC 25F DNA, digested with the same enzymes, used as probes. These bands are likely to be ribosomal DNA as shown by hybridization of digested DNA from unrelated yeast species (S. cerevisiae, K. lactis andC. albicans). However, one hybridized band, located at 3.9–4.1 Kb, seems to be peculiar to thePichia species. Our study confirms the usefulness of molecular tools in studying genetic relatedness among yeasts.     

The effect of thymidine on the induction of micronuclei by alkylating agents in V79 Chinese hamster cells

Incubation in thymidine-containing medium resulted in increased lethality and micronucleus frequency in V79 cells treated with ethyl nitrosourea (ENU), methyl nitrosourea (MNU) and ethyl methanesulphonate (EMS) but not with methyl methanesulfonate (MMS). Thymidine had no effect in ENU treated HeLa cells. In V79 cells, the presence of thymidine during post-treatment DNA replication was necessary for the effect. It is suggested that the increase in chromosome damage was the result of an increased O⁶-alkylguanine-thymine mispairing in cells which are defective in the repair of O⁶-alkylguanine. Treatment of V79 cells with O⁶-ethylguanine resulted in increased production of both micronuclei and polyploid cells. These effects might be explained by spindle dysfunction caused by the alkylated guanine.     

Influence of low-dose beta-interferon on natural killer cell activity in breast cancer patients subjected to chemotherapy

Summary The present study was designed to test whether immunomodulating doses of human beta-interferon would affect the natural cell-mediated cytotoxic function in untreated breast cancer patients or in those subjected to antitumor therapy. Analyses were performed on 11 breast cancer patients, 3 at stage 1 and 8 at stage 2, the latter being subjected to cyclophosphamide, methotrexate, 5-Fluorouracil (CMF) adjuvant chemotherapy. Five patients treated with CMF and 3 patients not subjected to adjuvant chemotherapy, received human beta-interferon (IF, 2×10⁶ IU/patient, i.m.), on days 0,7, and 15 for 6 cycles of 31 days each. The natural killer (NK) activity (NKA) of peripheral blood mononuclear cells (MNC) was tested 24 and 48 h after low-dose IF administration. The results of NKA determinations carried out for the 6 cycles of treatment show that (1) chemotherapy alone depressed NKA; (2) IF alone increased NKA in stage 1 patients not treated with CMF; (3) IF antagonized the depressive activity of CMF on NK function and significantly augumented NKA in the case of low basal cytotoxic activity detectable in MNC collected before IF administration.Parallel in vitro studies showed that the inhibitory effect on NKA provoked by CMF is due to cyclophosphamide present in the association and is effectively antagonized by IF. These data provide rational bases for using IF in immunochemotherapy regimens, when tumor cells are supposed to be susceptible to host control by the natural resistance function.     

Localization of amplified CAD genes on rearranged chromosomes of Chinese hamster cells

Chinese hamster cell lines carrying an amplified CAD region were selected from V79,B7 cells by their resistance to N-phosphonacetyl-L-aspartate (PALA). In one of the selected cell lines, SP PALA _inf1 ^supR L, an acrocentric chromosome with abnormally elongated q arms was identified as a marker for the PALA-resistant phenotype. The marker chromosome carried a homogeneously staining region close to a telomeric nucleolar organizer region. In the same region, localization of amplified CAD sequences was demonstrated by in situ hybridization. The marker chromosome was found to undergo extensive rearrangements. In particular, dicentric chromosomes, occurring with an unusually high incidence, were found to originate from end-fusion of two homologous marker chromosomes.Abbreviations ATCase Aspartate Transcarbamylase - CAD Carbamyl-phosphate synthetase-Aspartate transcarbamylase-Dihydroorotase - MTX Methotrexate - NOR Nucleolar Organizer Region - PALA N-phosphonacetyl-L-Aspartate     

Deprivation of paradoxical sleep effect on weight and nucleic acid content of liver and brain

Male Wistar rats weighing between 200 and 350 g were deprived of paradoxical sleep (PS-D) by placing them on small platforms surrounded by water. In comparison with rats kept in similar cages but without water, PS-D animals manifested a marked decrease in body and liver weight, which depended on animal size and on time of exposure to the condition of PS-D. A comparable weight loss occurred in the spleen, while more limited effects were present in brain and cerebellum. Exposure to the condition of PS-D induced a pronounced increase in the concentration of liver DNA and RNA. The latter effect occurred considerably earlier. On the other hand, only limited and uncertain variations were noted in the DNA concentration of brain and cerebellum. Body and liver changes were readily reversed after a period of recovery lasting two days.