336 research outputs found

    Mortality and incidence of second cancers following treatment for testicular cancer

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    We studied 5555 seminoma patients and 3733 patients with nonseminomatous testicular cancers diagnosed in Southeast England between 1960 and 2004. For both groups survival improved over time: 10-year relative survival increased from 78% in 1960–1969 to 99% in 1990–2004 for seminomas, and from 55 to 95% for nonseminomas. In the early period mortality was still significantly increased more than 15 years after diagnosis in both groups, whereas in more recent periods the excess deaths mainly occurred in the first 5 years after diagnosis. For seminomas, there was a significant excess of cancers of the colon (standardised incidence ratio (SIR) 2.36; 95% confidence interval (CI) 1.13–4.35), soft tissue (SIR 13.64; CI 1.65–49.28) and bladder (SIR 4.28; CI 2.28–7.31) in the long term (20+ years after diagnosis), of pancreatic cancer in both the medium (10–19 years) (SIR 2.91; CI 1.26–5.73) and long term (SIR 5.48; CI 2.37–10.80), of leukaemia in both the short (0–9 years) (SIR 3.01; CI 1.44–5.54) and long term (SIR 4.48; CI 1.64–9.75), and of testis cancer in both the short (SIR 6.69; CI 4.28–9.95) and medium term (SIR 3.96; CI 1.08–10.14). For nonseminomas, significant excesses were found in the long term for cancers of the stomach (SIR 5.13; CI 1.40–13.13), rectum (SIR 4.49; CI 1.22–11.51) and pancreas (SIR 10.17: CI 3.73–22.13), and for testis cancer in the medium term (SIR 5.94; CI 2.18–12.93). Leukaemia was significantly increased in the short term (SIR 6.78; CI 2.93–13.36). The better survival observed is largely attributable to improved treatment, and the trend in reducing the toxicity of therapy should continue to reduce future health risks in testicular cancer survivors

    High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

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    Collagen synthesis is severely diminished in osteoarthritis; thus, enhancing it may help the regeneration of cartilage. This requires large amounts of glycine, proline and lysine. Previous works of our group have shown that glycine is an essential amino acid, which must be present in the diet in large amounts to satisfy the demands for collagen synthesis. Other authors have shown that proline is conditionally essential. In this work we studied the effect of these amino acids on type II collagen synthesis. Bovine articular chondrocytes were cultured under a wide range of different concentrations of glycine, proline and lysine. Chondrocytes were characterized by type II collagen immunocytochemistry of confluence monolayer cultures. Cell growth and viability were assayed by trypan blue dye exclusion method. Type II collagen was measured in the monolayer, every 48 h for 15 days by ELISA. Increase in concentrations of proline and lysine in the culture medium enhances the synthesis of type II collagen at low concentrations, but these effects decay before 1.0 mM. Increase of glycine as of 1.0 mM exceeds these effects and this increase continues more persistently by 60–75%. Since the large effects produced by proline and lysine are within the physiological range, while the effect of glycine corresponds to a much higher range, these results demonstrated a severe glycine deficiency for collagen synthesis. Thus, increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthriti

    Mutations in the Catalytic Loop HRD Motif Alter the Activity and Function of Drosophila Src64

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    The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele
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