Suppressor of cytokine sigaling (SOCS) genes encode a family of protein recently identified as negative feedback inhibitors of signaling by eytokine receptors. We have previously shown that endotoxin markedly stimulates SOCS gene expression in rat liver, that correlates with observed resistance to growth hormone-signaling during endotoxemia. The objective of this study was to determine the expression of SOCS genes in state of fasting that have been shown to cause altered responses in pro-inflammatory cytokines and anzbolic hormones. Male Sprague-Dawley rats (～200g) were fasted for 1, 2 or 3 days, or refed for 3 days following a 3-day period of fasting. Liver and muscle mRNAs were determinedby Northern blotting using specific rat cDNA probes cloned in our laboratory. In liver, after a l-day lag period, there was a progressive 2-fold increase in SOCS-3 and 75% decrease in SOCS-2 mRNA afte 2 and 3 of fasting. Both SOCS mRNAs were normalized by 3 days of refeeding. There was no measurable changes in tyrosine phosphorylation of STAT1, STAT3, STAT5a or STAT5b, nor activation of MAP kinases including ERK 1/2, p38, and JUNK 1/2 in liver by 3 days of fasting. In muscle, there was a similar 75% decrease in SOCS-2 mRNA, but no change in SOCS-3 mRNA following 3 days of fasting. These data suggest that malnutrition regulates SOCS-2 and SOCS-3 in a different way, and this regulation is tissue specific. The changes of SOCS mRANs are independent of measurable phosphoryiation of multiple STATs and activation of MAP kinasea. The altered SOCS expressions during fasting may explain the changes of biological effects of multiple cytokines and anabolie hormones in malnutrition states.

No abstract available.
Germ Cells* ; Humans ; Neoplasms, Germ Cell and Embryonal* ; Treatment Outcome* ; Biomarkers, Tumor*

Results: Propensity matching led to two groups of 89 patients each. The UIV, pelvic incidence minus lumbar lordosis, sagittal vertical axis, pelvic tilt, age, and body mass index were similar in both groups (p >0.05). The incidence of PJK at postoperative one year was similar for SE (30.3%) and LF (22.5%) groups (p =0.207). The PJK angle was comparable (p =0.963) with a change of −8.2° (SE) and −8.3° (LF) from the preoperative measures (p =0.954). A higher rate of PJK after SE (p =0.026) was found only in the subgroup of patients with UIV levels between T9 and T12. Conclusions Instrumentation to the sacrum with or without iliac extension did not increase the overall risk of PJK. However, an increased risk for PJK was found after SE with UIV levels between T9 and T12.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors