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.