Risk of cardio-respiratory abnormalities in preterm infants placed in car seats: a cross-sectional study

Background  

Little is known about the factors that predispose to the occurrence and severity of cardio-respiratory symptoms during the placement of a prematurely born infant in a car seat. The impact of gestational age, weight at discharge and infant's pre-existing cardio-respiratory status (in the supine position) on cardio-respiratory function during pre-discharge testing in a car seat (semi-upright position) has not been investigated.     

Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage

To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.     

Contribution of phopholipase D and a brefeldin A-sensitive ARF to chemoattractant-induced superoxide production and secretion of human neutrophils

We show that blockers of phospholipase D (PLD) reduce fMLP-triggered exocytosis of secretory vesicles effectively. In accordance with this, the PLD product phosphatidic acid (PA) was able to induce mobilization of secretory vesicles. Although PLD seems to play a role in the release of all neutrophil granule types, exogenous PA alone was not sufficient to activate the exocytosis of primary and secondary granules, suggesting that in the case of these granules, additional signaling factors are required to initiate the secretory responses. The ADP-ribosylation factor (ARF)-inhibitor brefeldin A (BFA) inhibited the fMLP-stimulated O2*- production strongly, whereas it did not influence any of the exocytic responses, and no significant effect of BFA was detected on the O2*- generation induced by other stimuli. On the basis of these results, we propose that upon chemoattractant stimulation, PLD activity is involved in induction of degranulation and O2*- production, but a BFA-sensitive ARF is only required to the activation of the NADPH oxidase. This ARF action seems to participate exclusively in the signaling pathway between the fMLP receptor and the oxidase.     

Alpha2-macroglobulin exon 24 (Val-1000-Ile) polymorphism is not associated with late-onset sporadic Alzheimer's dementia in the Hungarian population

Several lines of biochemical evidence support a role of alpha2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (betaAP). Furthermore, A2M has been shown to reduce betaAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoE epsilon4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.     

Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22

We have developed an initial approach for annotating and surveying pseudogenes in the human genome. We search human genomic DNA for regions that are similar to known protein sequences and contain obvious disablements (i.e., mid-sequence stop codons or frameshifts), while ensuring minimal overlap with annotations of known genes. Pseudogenes can be divided into "processed" and "nonprocessed"; the former are reverse transcribed from mRNA (and therefore have no intron structure), whereas the latter presumably arise from genomic duplications. We annotate putative processed pseudogenes based on whether there is a continuous span of homology that is >70% of the length of the closest matching human protein (i.e., with introns removed), or whether there is evidence of polyadenylation. We have applied our approach to chromosomes 21 and 22, the first parts of the human genome completely sequenced, finding 190 new pseudogene annotations beyond the 264 reported by the sequencing centers. In total, on chromosomes 21 and 22, there are 189 processed pseudogenes, 195 nonprocessed pseudogenes, and, additionally, 70 pseudogenic immunoglobulin gene segments. (Detailed assignments are available at http://bioinfo.mbb.yale.edu/genome/pseudogene or http://genecensus.org/pseudogene.) By extrapolation, we predict that there could be up to approximately 20,000 pseudogenes in the whole human genome, with a little more than half of them processed. We have determined the main populations and clusters of pseudogenes on chromosomes 21 and 22. There are notable excesses of pseudogenes relative to genes near the centromeres of both chromosomes, indicating the existence of pseudogenic "hot-spots" in the genome. We have looked at the distribution of InterPro families and Gene Ontology (GO) functional categories in our pseudogenes. Overall, the families in both processed and nonprocessed pseudogene populations occur according to a similar power-law distribution as that found for the occurrence of gene families, with a few big families and many small ones. The processed population is, in particular, enriched in highly expressed ribosomal-protein sequences (approximately 20%), which appear fairly evenly distributed across the chromosomes. We compared processed pseudogenes of different evolutionary ages, observing a high degree of similarity between "ancient" and "modern" subpopulations. This may be attributable to the consistently high expression of ribosomal proteins over evolutionary time. Finally, we find that chromosome 22 pseudogene population is dominated by immunoglobulin segments, which have a greater rate of disablement per amino acid than the other pseudogene populations and are also substantially more diverged.     

Functional imaging of the rat cervical spinal cord

PURPOSE: To examine functional magnetic resonance imaging (fMRI) of the rat cervical spinal cord using painful stimulation. MATERIALS AND METHODS: fMRI of the rat cervical spinal cord was performed at 9.4 T. Stimuli included injection of 25 microL of capsaicin (128 microg/mL in 7.5% dimethylsulfoxide (DMSO)) into the right dorsal forepaw and electrical stimulation (15 V, 0.3 msec, 3 Hz) of the left dorsal forepaw. RESULTS: Activation in the dorsal horn of the spinal cord, which is known to be associated with the transmission of pain, was found in all rats (N = 4) following injection of capsaicin into the dorsal forepaw. It was possible to reproduce the pain response in a given animal several times throughout the course of an experiment, provided that sufficient time was allowed between capsaicin injections. Regions of the spinal cord associated with motor and pain response were observed in functional imaging experiments involving subcutaneous electrical stimulation of the dorsal forepaw. CONCLUSION: Spinal fMRI using electrical stimulation and capsaicin-induced painful stimulation can be a useful tool in an animal model of pain and injury.     

Histological and immunohistochemical structure of pulmonary tuberculotic granulomas in untreated cases and cases treated with antitubercular drugs

INTRODUCTION: The changes occurring in response to antituberculotic treatment and immune defence were studied in human tuberculotic granulomas. AIMS: To compare the possibilities of detection of Mycobacterium tuberculosis with the Ziehl-Neelsen staining technique and with an immunohistochemical method, and to assess the roles of lymphocytes and heat-shock protein 70. METHOD: 40 patients who had undergone lung resection (the postoperative histology confirmed tuberculosis) were divided into two equal groups, on the basis of whether they had received antituberculotic treatment preoperatively (group I) or not (group II). Customary histology was used to determine the Langhans cells, epitheloid cells and lymphocytes, and an immunohistochemical method was then applied to examine the heat-shock protein 70 production of these cells and the normal lung. The lymphocytes were divided into CD4+ T-helper, CD8+ T-cytotoxic and CD20+ B cells by means of immune examinations. M. tuberculosis was demonstrated by an immunohistochemical method, with antibody against the wall protein. RESULTS: Heat-shock protein 70 was produced by 17.6% of the Langhans cells and 94.4% of the epitheloid cells in group I, and by 100% of both cell types in group II. The bacterium could be detected in 40% of the total number of cases with acid-fast staining, and in 85% by immunohistochemistry. There was no significant difference in the qualitative distribution of the lymphocytes in the granulomas in groups I and II. The heat-shock protein 70 levels of the tuberculotic granuloma and the normal lung were significantly higher in group II. CONCLUSIONS: The production of heat-shock protein 70 is more enhanced in untreated tuberculotic cases. On the basis of their heat-shock protein 70 production, the authors assume that a majority of the Langhans cells have a resting protective function in medically treated cases. Independently of the stage of the infection and of the use or not of antituberculotic treatment, the number of lymphocytes participating in the immune defence is constant. By means of immunohistochemical examination of the wall protein of M. tuberculosis, the presence of the tuberculotic disease can be demonstrated with high reliability.     

Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: Comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen

Daily intraperitoneal treatment of female Sprague-Dawley ratswith either 5, 10 or 20 mg/kg tamoxifen (TAM) for 1 weeks increasedthe level of peroxidase activity in the uterus 2- to 10-foldcompared to the control level. Using uterine extracts preparedfrom control and TAM treated animals, we investigated the activationof 4-hydroxytamoxifen (4-HO-TAM) and (E, Z)-1, 2-dipheny-1-(4-hydroxyphenyl)-but-1-ene(cis/trans-metabolite E) to form DNA adducts. Activation of4-HO-TAM by uterine extracts prepared from either control orTAM-treated rats produced one major (a) and Two minor DNA (band c) adducts. A similar activation of cis/trans-metaboliteE produced two adducts (d and e). There was good correlationbetween levels of uterine peroxidase activity and levels ofDNA adducts formed by 4-HO-TAM and cis/trans-metabolite E. Activationof 4-HO-TAM and cis/trans-metabolite E with horseradish peroxidase(HRP) produced the same adducts as observed by activation withuterine extract Treatment of Sprague-Dawley rats with 5 and10 mg/kg for 7 days produced eleven DNA adducts in the liverwith no adducts detected in the uterus. However, treatment ofrats with 20 mg/kg of TAM for 7 days produced the same adductpattern in the liver and also one major adduct (1) in the uteruswith a relative adduct level of 6.4 ±4.1x10^–9.Tamoxifen-DNA adduct 1 detected both in the liver and in theuterus of treated rats was similar to adducts produced by activationof 4-HO-TAM with either uterine extract or HRP. The resultsof these studies suggest a general model whereby the tamoxifenmetabolite 4-HO-TAM is further activated in the uterus by peroxidaseenzymes to form DNA adducts.