Frequency of the ΔF508 deletion and G551D,R553X and G542X mutations in Yugoslav CF patients

Summary A study was undertaken to find the frequency of the F508 deletion and those of the G551D, R553X and G524X mutations among the mainly Slavic population of Serbia, Bosnia, Herzegovina, and Montenegro and compare the frequencies determined with those in other European populations. The F508 mutation was found to account for about 70% of CF genes in central Jugoslavia, where its frequency is significantly higher than elsewhere in Southern European populations.     

Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila.

hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.     

Effect of cyclophosphamide on the candidacidal activity of rabbit peritoneal macrophages

Single and repeated intravenous administration of cyclophosphamide significantly decreased the candidacidal activity of rabbit peritoneal macrophages. Using higher doses of the drug, a more pronounced decrease, persisting up to 10 d, was observed. The phagocytic index has not changed significantly 10 d after cyclophosphamide injection as compared with controls. No changes in the phagocytic activity were recorded. The decreased candidacidal activity may be one of the causes of serious microbial infections in cyclophosphamide-treated patients.     

Radiation chemistry of a multicomponent aqueous system relevant to chemistry of cometary nuclei

Summary We have examined a water-dominated multicomponent system after irradiation in the multimegarad dose range with gamma rays from a⁶⁰Co source at both 77 and 310 K. The constituents were simple organic compounds in the proportions in which they appear in a dense interstellar cloud: HCN/CH₃OH/CH₃CN/C₂H₅CN/HCOOH=10.60.20.10.05. The total amounts were adjusted to correspond to a carbon to nitrogen ratio of 1.8 and a water content of about 50% in a cometary nucleus where the dust to volatiles ratio is 1; the total amount of CN-bearing compounds was taken to correspond to 0.4% of the cometary mass. In experiments at 310 K about 40 radiolytic products are identified, among them aldehydes and amino and carboxylic acids. Abundant polymeric material (M_w up to 80,000 daltons) is formed. The basic aspects of radiolysis of the liquid system are present also at 77 K, although at radiation-chemical yields that are lower by one to two orders of magnitude. We have considered the relevance of the present findings to the chemistry of a liquid-water core and the icy layers of a cometary nucleus.     

Radiation chemistry of an aqueous solution of glycine: compounds of interest to chemical evolution studies

Summary We have examined the radiolysis of an O₂-free aqueous solution of glycine at absorbed doses of⁶⁰Co gamma-radiation of up to 20 Mrad. At least 20 compounds are formed during radiolysis, among them several amino acids, an oligoamine, and the nitrogen-free polymers (M_w28,000 daltons). When dicyandiamide is present in the solution of glycine, various nitrogen-containing products, including some polymers (M_w12,000 daltons), are synthesized along with radiolytic products of glycine; polyglycines are not formed. We have determined the radiation-chemical yields of radiolytic-product formation and of decomposition of glycine, and have considered possible free-radical reactions leading to the radiation-induced changes observed.     

Sex differences in the response of rats to drugs affecting GABAergic transmission

The administration of diazepam 1.0 mg/kg decreased the level of plasma corticosterone in female but not in male Wistar rats. Picrotoxin, another drug affecting GABAergic transmission, also brought about an increase of plasma corticosterone in both sexes. However, in order to achieve a plasma corticosterone increase of similar magnitude (more than 500%) a threefold higher dose of picrotoxin had to be given to males. When the convulsive properties of picrotoxin were tested, it became evident that the dose of picrotoxin (2.5 mg/kg) which was subconvulsive in male was almost 100% convulsive in female rats. The existing sex differences in the response of rats to drugs affecting GABAergic transmission might have possible implications in the treatment of GABA system dysfunction.     

Action of neurotensin on size, composition, and growth of pancreas and stomach in the rat

Since the gastrointestinal peptide neurotensin has a stimulatory effect on the secretion of the exocrine pancreas and an inhibitory effect on secretion and motility of the stomach, we investigated whether chronic parenteral administration of neurotensin would affect pancreatic and gastric growth. We therefore infused synthetic neurotensin subcutaneously (dose, 43 and 282 pmol X kg-1 X min-1) in 20 Wistar rats for 2 weeks using Alzet osmotic minipumps and compared pancreatic weight, DNA, RNA, protein, lipase, amylase, pancreatic polypeptide and insulin with these parameters in 10 control rats from the same litter with subcutaneously implanted plastic cylinders approximately the size of the minipumps. In another experiment, synthetic neurotensin (836 pmol X kg-1) was injected intraperitoneally three times a day for 3 days in 12 rats. Thereafter, we measured pancreatic DNA and in vitro incorporation of [3H]thymidine into pancreatic DNA. These effects were compared with the actions of caerulein and normal saline. Long term infusion of the high neurotensin dose induced an increase of pancreatic weight (control: 0.87 g, neurotensin: 1.02 g) and of DNA (control: 2.5 micrograms; neurotensin: 3.5 micrograms) and pancreatic polypeptide (control: 2.4 ng; neurotensin: 7.4 ng) contents, whereas pancreatic protein, RNA, amylase and lipase contents were not stimulated. In relation to DNA, these parameters even were significantly depressed. Insulin remained unchanged. Intraperitoneal injection of neurotensin induced an increase of pancreatic DNA content and stimulated [3H]thymidine incorporation into DNA (control: 11 000 dpm/g; neurotensin: 15 800 dpm/g pancreas). Moreover, long-term neurotensin infusion with the high dose led to a rise in protein concentration and an increase in the thickness of the gastric antrum; antral DNA concentration was insignificantly stimulated. Parenteral neurotensin in the doses and at the times administered, led therefore, to hyperplasia of the pancreas and induced growth of the gastric antrum. It is concluded that neurotensin can act as a trophic factor on pancreas and gastric antrum of the rat. It remains to be determined whether this represents a physiological effect of neurotensin.     

Formation of autophagosomes in the pinealocytes of the rat and Mongolian gerbil (Meriones unguiculatus): A lysosome wrapping mechanism?

Summary Autophagosome formation in rat and gerbil pinealocytes is described. It starts with the setting up of a tubular acid phosphatase-rich cisterna which gradually wraps around cytoplasmic areas to be catabolized. In light of obtained findings, it seems that the autophagosome formation in pinealocytes is a type of lysosome wrapping mechanism.