The world according to PARP

An immediate cellular response to DNA damage is the synthesis of poly(ADP-ribose) by the enzyme poly(ADP-ribose) polymerase (PARP). This nuclear enzyme and the unique post-translational modification it catalyzes have long been considered to function exclusively in cellular surveillance of genotoxic stress. The recent identification of multiple members of a PARP family might force a revision of this concept. The novel primary structures and subcellular localizations for some of these PARPs suggests new and unexpected roles for poly(ADP-ribosyl)ation in telomere replication and cellular transport.     

New synthesis of somatostatin according to the S-tert-butylthiocysteine procedure

To exemplify the usefulness of the S-tert-butylthio group for a reversible blocking of the cysteine thiol function in peptide synthesis, fully protected dihydrosomatostatin was prepared by the fragment-condensation procedure. The experimental results confirm the excellent stability of the asymmetric disulfide under the normal conditions of peptide synthesis and prove that the selective, acid-catalyzed nucleophil removal—as well as by mercaptans—of the 2-nitrophenylsulfenyl group proceeds smoothly in the presence of this thiol protection. Thus, the strategy of overall acid-labile side-chain protection in combination with the N^α-2-nitrophenylsulfenyl group for the chain-elongation steps can be successfully applied to the synthesis of cysteine-containing peptides using their S-tert-butylthio derivatives. Removal of the acid-labile groups, followed by reductive cleavage of the asymmetric disulfides and successive air oxidation, allowed a clean conversion of protected dihydrosomatostatin into somatostatin at a high degree of purity and in good yields.     

Effectiveness of murine leukemia chemotherapy according to the immune state

Summary Cyclophosphamide (CPM) chemotherapy (134 mg/kg) of L1210 leukemia is less efficient in mice previously immunodepressed by anti-thymocyte serum (ATS) than in non-ATS pre-treated mice. On the other hand, administration of a higher dose of CPM (403 mg/kg), which kills a greater number of leukemic cells but induces an immunodepression, according to the skin graft test, results in a shorter survival time than does the administration of a lower dose of CPM (134 mg/kg), capable of killing fewer leukemic cells but not inducing such an immunodepression. Thus it appears that: a) the antileukemic effect of the same dose of a chemotherapeutic drug is less efficient in immunodepressed than in non-immunodepressed hosts; b) calculation of the number of neoplastic cells killed by a given chemotherapy by extrapolation from the survival time may lead to erroneous conclusions.     

Should the definition of micropenis vary according to ethnicity?

OBJECTIVE: We determined whether the existing reference values for the diagnosis of micropenis are appropriate for optimal care of neonates in a multiethnic environment like Vancouver. METHODS: The stretched penile length and width were measured in 105 full-term newborn males of Caucasian (n = 40), Chinese (n = 40) and East-Indian origin (n = 25). RESULTS: Mean length -2.5 SD was used for the definition of micropenis and was 2.6, 2.5 and 2.3 cm for Caucasian, East-Indian and Chinese babies, respectively (p < 0.05). This is close to the widely accepted recommendation that a penile length of 2.4- 2.5 cm be considered as the lowest limit for the definition of micropenis. CONCLUSION: Mean penile length and diameter are slightly but significantly smaller in newborns of Chinese origin compared to newborns of Caucasian and East-Indian origins.     

Chromatin fractionation according to the strength of its matrix bond

Extraction in low salt concentration followed by centrifugation allows rat liver nuclear chromatin to be divided into two fractions: the supernatant chromatin and matrix chromatin. The former fraction contains about 60-70% of initial DNA and about 15% of initial protein along with all five histones, and an insignificant amount of non-histone proteins. RNA synthesis in the matrix chromatin fraction is 2-3 times more intense than that in the original nuclei. The data on gradient centrifugation do not suggest the elongation of RNA molecules synthesized in the matrix fraction. The results obtained as compared with the literature data suggest that the matrix chromatin fraction is enriched with active genes.