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.     

Endogenous polyamines are intimately associated with highly condensed chromatin in vivo. A fluorescence cytochemical and immunocytochemical study of spermine and spermidine during the cell cycle and in reactivated nuclei

Polyamines are low molecular weight aliphatic polycations essential for cell proliferation and differentiation. By immunocytochemistry, as well as by two independent fluorescence cytochemical methods, we show that polyamines are associated with highly condensed chromatin in nucleated erythrocytes and in metaphase and anaphase chromosomes. In other cells, polyamines mainly occur in cytoplasm. The association between polyamines and DNA in condensed chromatin is so close that DNase treatment is necessary for making polyamines available for reaction with antibodies. Studies of chick/HeLa cell heterokaryons reveal that polyamines disappear from the chick erythrocyte nuclei concomitantly with DNA decondensation and initiation of RNA synthesis. Our data strongly suggest that polyamines are important for chromatin condensation in vivo.     

Rhinitis,Ocular, Throat and Dermal Symptoms,Headache and Tiredness among Students in Schools from Johor Bahru,Malaysia: Associations with Fungal DNA and Mycotoxins in Classroom Dust

There are few studies on rhinitis and sick building syndrome (SBS) among students in tropical countries. We studied associations between levels of five fungal DNA sequences, two mycotoxins (sterigmatocystin and verrucarol) and cat allergen (Fel d 1) levels in schools and rhinitis and other weekly SBS symptoms in the students. Fungal DNA was measured by quantitative PCR and cat allergen by ELISA. Pupils (N = 462) from eight randomly selected schools in Johor Bahru, Malaysia participated (96%). Dust samples were collected by cotton swabs and Petri dishes exposed for one week. None of the schools had a mechanical ventilation system, but all classrooms had openable windows that were kept open during lectures and indoor CO₂ levels were low (mean 492 ppm; range 380–690 ppm). Weekly nasal symptoms (rhinitis) (18.8%), ocular (11.6%), throat (11.1%), dermal symptoms, headache (20.6%) and tiredness (22.1%) were common. Total fungal DNA in swab samples was associated with rhinitis (p = 0.02), ocular symptoms (p = 0.009) and tiredness (p = 0.001). There were positive associations between Aspergillus versicolor DNA in Petri dish samples, ocular symptoms (p = 0.02) and tiredness (p = 0.001). The level of the mycotoxin verrucarol (produced by Stachybotrys chartarum) in swab samples was positively associated with tiredness (p = 0.04). Streptomyces DNA in swab samples (p = 0.03) and Petri dish samples (p = 0.03) were negatively associated with tiredness. In conclusion, total fungal contamination, measured as total fungal DNA) in the classrooms, Aspergillus versicolor and verrucarol can be risk factors for rhinitis and SBS symptoms among students in the tropical country Malaysia.     

Differential changes in calcitonin, somatostatin and gastrin/cholecystokinin-like immunoreactivities in rat thyroid parafollicular cells during ontogeny

Immunocytochemical quantitative studies on the development of rat thyroid calcitonin (C) cells have been performed. In neonatal rat pups up to day 6 nearly 90% of all calcitonin cells are also somatostatin immunoreactive and 45% of these cells also show immunoreactivity to a C-terminal gastrin/cholecystokinin antiserum (CCK-4-like immunoreactivity). Already at day 8 the frequency of somatostatin immunoreactive calcitonin cells has dropped to 25%, whereas half of the calcitonin cells still display CCK-4-like immunoreactivity. In adult rats, less than 1% of the calcitonin cells are somatostatin immunoreactive, whereas 90% of the calcitonin cells display CCK-4-like immunoreactivity. These data show that between day 6-8 a pronounced change in the peptide repertoire of rat thyroid C cells occur and that these cells, prior to this time, mainly contain calcitonin and somatostatin immunoreactivity and after this time mainly contain calcitonin and CCK-4-like immunoreactivity. The time course of the change in the C cell peptides is similar to that observed with changes in transitory peptides of neonatal rat pancreas and duodenum, suggesting that possible hormonal mechanisms during this period act to change the peptide repertoire of several endocrine cell types simultaneously. It is possible that many of the transitory peptides exert actions in the developing individual that are necessary for growth and differentiation. Interestingly, many of these transitory peptides reappear in tumours, where theoretically they could exert similar actions.     

Combined non-radioactive detection of peptide hormones and their mRNA's in endocrine cells

Summary Non-radioactive in situ hybridization employing detection of biotin-labeled probes by an alkaline phosphatase-based procedure has proven useful for demonstrating a wide variety of mRNA species. With certain developers, the alkaline phosphatase reaction product is both light microscopically visible and fluorescent. We have exploited this to perform simple double-stainings for mRNA's and their corresponding peptide products in human insulin and gastrin cells and in rat ACTH, MSH and gastrin cells. Such stainings show that nearly all of these cells simultaneously contain both the peptide hormone and its corresponding mRNA. Human gastrin cells show a differentiated localization of gastrin mRNA and gastrin. Thus, while gastrin immunofluorescence predominates in secretory granules present in the basolateral region of the cells, gastrin mRNA is virtually restricted to the supranuclear region of the cells. Here it may be preferentially associated with granular endoplasmic reticulum. The strict subcellular localization of gastrin mRNA differs from that of general polyadenylated RNA in the G cells and raises questions whether specific transport routes or sites of accumulation for defined mRNA species exist.     

Electromyographic changes in work-related myalgia of the trapezius muscle.

In 11 patients, all women, 21-55 years of age, with unilateral work-related myalgia of the trapezius muscle, the right and left trapezius muscles were examined simultaneously for electromyogram (EMG) signs of localized muscle fatigue. All patients were tested with 0-kg hand load for 5 min, holding the arms straight at 90 degrees of elevation in the scapular plane. Only 4 of the patients tolerated exposure to higher load levels. They were tested with 1 kg hand load for 3 min and 2 kg hand load for 2 min, with a period of rest of 30 min between the trials. The EMG mean power frequency (MPF) and root mean square (rms) were calculated. Data were normalized with the initial value as a reference and regression analyses were performed. On both sides a decrease of MPF and an increase of rms were found with increasing time and load, i.e. classical EMG signs of localized muscle fatigue. Compared with the nonaffected side smaller changes were found on the affected side, possibly due to pain inhibition, impaired microcirculation and biochemical changes along the muscle fibres. At 0-kg hand load we found no change of MPF on either side despite subjective feelings of fatigue and pain. We interpreted these findings as an indication of reduced capacity of the affected trapezius muscle to sustain static load with early development of pain-associated local fatigue.     

Cloning, mapping and mutational analysis of the S-adenosylmethionine decarboxylase gene in Drosophila melanogaster

S-adenosylmethionine decarboxylase is a key enzyme in the synthesis of polyamines. These small cationic molecules are required for growth and development in all organisms. A wealth of biological processes, including synthesis of DNA and protein and condensation of chromatin, involve polyamines. Inhibition of polyamine synthesis has been proposed for treatment of cancer but this requires more knowledge about the in vivo function of polyamines. We report here the cloning of the S-adenosylmethionine decarboxylase gene from Drosophila melanogaster and the analysis of corresponding mutants. The mutant phenotypes are similar to those previously described for ribosomal protein genes (Minutes) and rRNA genes (bobbed?). This work elucidates the in vivo consequences of impaired polyamine synthesis with respect to the development of a whole animal.     

A cell cycle study of human mammary epithelial cells.

The growth regulation of human mammary epithelial cells (HMEC) cultured in a growth factor/hormone-enriched (e.g. EGF, insulin) medium with bovine pituitary extract as the only undefined supplement was studied. The doubling times of the cultures, in which the cells appear in colonies, was 55-72 h, and a considerable intercolonial heterogenecity in proliferative activity could be demonstrated. However, every colony, irrespective of the size of the growth fraction, comprised a sub-population of rapidly growing cells which had a mean generation time of approximately 22 h. When insulin was removed from the culture medium, HMEC proliferation was inhibited. This growth inhibition was shown to be a result of a cell cycle-specific block.