Significance of supraspinal control of reflex actions by impulses in muscle afferents

Zusammenfassung An decerebrierten und spinalen Katzen wurden diverse somatische Afferenzen in ihren synaptischen Wirkungen auf Vorderhornzellen verglichen. Bei der decerebrierten Katze waren deren erregende und hemmende Wirkungen stark herabgesetzt oder nicht nachweisbar. Somit werden Zwischenneurone im Reflexbogen durch supraspinale Zentren tonisch gehemmt. Die Bedeutung dieser Kontrolle für die Reflexregulierung wird besprochen.     

Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.     

Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations

Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.     

Integrative pattern of reflex actions by impulses in large muscle spindle afferents on motoneurones to hip muscles

Zusammenfassung Es werden die intrazellulären Potentiale an Motoneuronen von Hüftmuskeln abgeleitet. Motoneurone des HüftstreckersSemimembranosus werden von Ia-Impulsen der Hüftstrecker und Kniebeuger erregt, Motoneurone des HüftstreckersAdductor femoris dagegen von den Hüftstreckern und Kniestreckern. Motoneurone der Hüftbeuger werden von Ia-Impulsen gehemmt, nicht nur von deren Antagonisten, sondern auch vom KniestreckerVasto Cruralis.     

ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles

We screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and two in controls (P = 0.0047). The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.) = 1.51-3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer.