Renal cyclic GMP and cholinergic mechanisms in erythropoietin production.

Cobalt treatment in rats produced sequential elevations in both renal cyclic GMP concentration and lysosomal enzyme activity in plasma. These effects of cobalt were significantly inhibited by atropine pretreatment, as was cobalt-mediated erythropoietin (ESF) production. Physostigmine, an inhibitor of acetylcholinesterase, potentiated the erythropoietic effect of cobalt. These data are consistent with the hypothesis that the erythropoietic effect of cobalt is associated with a cholinergic mechanism involving cyclic GMP-mediated lysosomal enzyme release. These cholinergic events may precede a previously described cyclic AMP activation of a renal erythropoietic factor.     

Xeromammography in the Early Detection of Breast Cancer: Community Hospital Experience and Approach

Community hospitals can do much in the general effort toward earlier detection of breast cancer. Using xeromammography in the department of general radiology of one community hospital, 21 cases of occult carcinoma were detected in 2,392 patients in a two year period. Patients were both symptomatic and asymptomatic. This percentage is comparable to results in previously published series of similar patient populations, and can be expected to be slightly higher than screening populations of totally asymptomatic patients. In 24 percent of cases of occult carcinoma there was axillary node involvement, compared with 42 percent axillary node involvement in cases of nonoccult carcinoma.Early detection efforts are currently centered on improving thoroughness in physical examinations, stressing breast self-examination and identifying patients in high-risk categories. These, together with proper periodic use of mammograms, will yield the highest rate of early carcinoma detection until more sensitive biologic markers are developed.     

Studies on closure of the ductus arteriosus. XII. effect of indomethacin and sodium salicylate in rats and rabbits

Administration of prostaglandin synthetase inhibitors to pregnant does and dams in late gestation was followed by contraction of the fetal ductus arteriosus when studied by the whole-body freezing method. In the rat this contraction was well established within 6 h and persisted up to 36 h following 15 mg/kg indomethacin p.o. No effect was observed in the 18 d rat fetus but fetuses at 20 d and 22 d of gestation responded significantly to indomethacin. Doses of indomethacin approaching clinical usage (2.5 mg/kg) also caused a positive response . The rat was found to be sensitive also to sodium salicylate and in the rabbit both indomethacin and sodium salicylate were effective. Exposure to prostaglandin synthetase inhibitors with resulting contraction of the ductus may seriously disturb cardiac function in the fetus.     

Ultrastructure of the Bacterial Symbiotes in the Pharyngeal Diverticulum of Dacus oleae (Gmelin) (Trypetidae; Diptera)

Abstract The ultrastructure of the bacterial symbiotes in the pharyngeal diverticula of adult olive flies [Dacus oleae (Gmelin)] was examined. The diverticulum was an extension of the foregut formed by a row of epithelial cells bounded by an inner layer of cuticle. Towards the hemolymph, the epithelial cells showed an infolding of their basement membrane while adjacent to the cuticular lining, the cells contained a zone of extensive membrane proliferation. The diverticula were packed with bacterial rods which possessed elongate filamentous and short catenulate appendages. The function of these appendages is unknown. They did not resemble fimbriae (pili), flagella or prosthecae described from other bacteria.     

Non-coding RNAs and ferroptosis: potential implications for cancer therapy

Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways and molecules are involved in the regulation of ferroptosis, including enzymes that control the cellular redox status. Alterations in the ferroptosis-regulating network can contribute to the development of various diseases, including cancer. Evidence suggests that ferroptosis is commonly suppressed in cancer cells, allowing them to survive and progress. However, cancer cells which are resistant to common chemotherapeutic drugs seem to be highly susceptible to ferroptosis inducers, highlighting the great potential of pharmacologic modulation of ferroptosis for cancer treatment. Non-coding RNAs (ncRNAs) are considered master regulators of various cellular processes, particularly in cancer where they have been implicated in all hallmarks of cancer. Recent work also demonstrated their involvement in the molecular control of ferroptosis. Hence, ncRNA-based therapeutics represent an exciting alternative to modulate ferroptosis for cancer therapy. This review summarizes the ncRNAs implicated in the regulation of ferroptosis in cancer and highlights their underlying molecular mechanisms in the light of potential therapeutic applications.Subject terms: Tumour biomarkers, Oncogenes     

A Double-Isotope Procedure for Examining Protein Microheterogeneity: Multiple Forms of Fast-Transported Glycoproteins and Sulfoproteins Possess a Common Polypeptide Chain

Several fast-transported proteins that appear as single bands after sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolve into multiple spots during isoelectric focusing. A method was devised for determining if such microheterogeneity in net charge indicates that individual polypeptides have been posttranslationally modified to differing extents. Dorsal root ganglia were pulse-labeled with [35S]methionine and either [3H]leucine or [3H]proline, proteins fast-transported into peripheral sensory axons were separated by two-dimensional gel electrophoresis, and isotope incorporation ratios of proteins associated with individual gel spots were determined. When four microheterogeneous glycoproteins were analyzed, each protein "family" showed markedly similar isotope ratios for its three to seven characteristic spots. Such ratios differed between families by almost twofold. In addition, a group of nonglycosylated, sulfate-containing proteins was identified as a family on the basis of the similar isotope incorporation ratios of its component spots. These results suggest that protein microheterogeneity can result from variable sulfation of tyrosine residues as well as from variation in sialic acid-containing oligosaccharide side-chains. More generally, the method can be utilized to test for protein microheterogeneity in cases where the amounts of protein are too low to permit peptide mapping analysis and where the nature of the charge-altering modification is unknown.     

Fingerprinting of Mixed Bacterial Strains and BIOLOG Gram-Negative (GN) Substrate Communities by Enterobacterial Repetitive Intergenic Consensus Sequence-PCR (ERIC-PCR)

PCR-based genomic fingerprinting by use of enterobacterial repetitive intergenic consensus primers (ERIC-PCR) was evaluated for its use in fingerprinting DNA of mixed Gram-negative bacterial strains and BIOLOG Gram-negative (GN) microplate substrate communities. ERIC-PCR fingerprints of six different pure bacterial strains and a combined mixture of the strains were compared with fingerprints obtained by two more established methods: amplified ribosomal DNA restriction analysis (ARDRA) and random amplified polymorphic DNA analysis (RAPD-PCR). The ERIC-PCR fingerprint of the mixed strains was highly reproducible and was more species-specific and representative of the individual strain fingerprints than the ARDRA and RAPD-PCR fingerprints, respectively. ERIC-PCR fingerprinting of model and rhizosphere BIOLOG GN substrate communities also provided clearly distinguishable fingerprints. Results of this study suggest that ERIC-PCR represents a rapid and highly discriminating method for fingerprinting DNA of mixed Gram-negative bacterial strains and BIOLOG GN substrate communities. Received: 11 September 1998 / Accepted: 29 October 1998