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PubMed1995

The distribution of alpha-helix propensity along the polypeptide chain is not conserved in proteins from the same family.

We address the question of whether the distribution of secondary structure propensities of the residues along the polypeptide chain (denominated here as secondary structure profiles) is conserved in proteins throughout evolution, for the particular case of alpha-helices. We have analyzed by CD the conformation of peptides corresponding to the five alpha-helices of two alpha/beta parallel proteins (ComA and Ara). The large alpha-helical population of peptide ComA-4 detected by CD in aqueous solution has been confirmed by NMR. These proteins are members of the CheY and P21-ras families, respectively, which have been studied previously in the same way (Muñoz V, Jiménez MA, Rico M, Serrano L, 1995, J Mol Biol 245:275-296). Comparison of the helical content of equivalent peptides reveals that protein alpha-helix propensity profiles are not conserved. Some equivalent peptides show very different helical populations in solution and this is especially evident in very divergent proteins (ComA and CheY). However, all the peptides analyzed so far adopted an important population of helical conformations in the presence of 30% trifluoroethanol, indicating that there could be a conserved minimal requirement for helical propensity.

Amino Acid Sequence↗

PubMed1999

Relapse in chronic myeloid leukemia after bone marrow transplantation: biomathematical modeling as a new approach to understanding pathogenesis.

A biomathematical model was developed to simulate relapse development in patients with chronic myeloid leukemia (CML) following bone marrow transplantation (BMT). The purpose of this study was to better understand the pathophysiology of the time evolution of CML relapse and to provide means whereby the outcomes of patients with CML relapse can be projected and treatment modified accordingly. The model consists of three parallel series of catenated compartments representing granulopoiesis in normal (donor) cells from the marrow, in CML cells from the marrow, and in CML cells from extramedullary sites. It was assumed that CML stem cells were resistant to feedback control and that CML-derived neutrophils, as well as normal neutrophils, exercised feedback regulation of normal stem cells. The known longer generation times for CML neutrophil precursors compared with normal neutrophil precursors were used, and it was assumed that 10(7) pluripotential stem cells were infused with BMT. The model was evaluated for its ability to simulate the reappearance of CML (Philadelphia chromosome positive) metaphases in the marrow and the recovery pattern in the blood neutrophil count in six patients who had relapsed following BMT (allogeneic in three patients, allogeneic with T-cell depletion in two patients, and syngeneic in one patient). The variables tested included the site of origin of the CML stem cells responsible for relapse (marrow alone versus marrow and extramedullary sites), the minimum number of CML stem cells responsible for relapse, and the time delay between BMT and the onset of relapse. Model profiles based on the observed values were obtained in each case. The simulations pointed to the fact that relapse began from a small number of CML cells in medullary and extramedullary sites. The time delay between BMT and the onset of relapse varied from 15 to 240 days. We suggest that this biomathematical model should be further investigated as a possible means of predicting outcome and guiding the treatment for patients with CML relapsing after BMT.

Adult↗

PubMed2005

Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats.

BACKGROUND/AIMS: Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats. METHODS: After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17beta-estradiol or a control solution. RESULTS: Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17beta-estradiol significantly reduced cholangiocyte apoptosis. 17beta-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17beta-estradiol. CONCLUSIONS: This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17beta-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.

Animals↗

PubMed1986

Sequential assessment of regional cerebral blood flow, regional cerebral blood volume, and blood-brain barrier in focal cerebral ischemia: a case report.

Regional CBF (rCBF) and regional cerebral blood volume (rCBV) were evaluated by N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-[123I]iodobenzyl-1, 3-propanediamine-2 HCl- and 99mTC-labeled red blood cells, respectively, and single-photon emission computerized tomography (SPECT) in a patient with focal cerebral ischemia. Sequential transmission computerized tomography (TCT) and SPECT functional data were compared with clinical findings to monitor the pathophysiological events occurring in stroke. A lack of correlation between rCBF-rCBV distributions and blood-brain barrier (BBB) breakdown was found in the acute phase. In the face of more prolonged alteration of BBB, as seen by TCT enhancement, a rapid evolution of transient phenomena such as luxury perfusion was shown by SPECT studies. Follow-up of the patient demonstrated a correlation between the neurological recovery and a parallel relative improvement of the cerebral perfusion.

Adult↗

PubMed2006

A generic 3-dimensional system to mimic trabecular bone surface adaptation.

The paper presents the structure optimizing system based on surface remodelling. The grounds for algorithm formulation are given by the bone remodelling phenomenon leading to optimization of trabecular network in the bone. The assumptions, algorithms and limitations of the own mesh generator Cosmoprojector are described. Unlike other approaches, the system is able to mimic real bone evolution including tissue consolidation and separation. The article presents a closed system consisting of finite element mesh generation, decision criteria for structure adaptation and finite element analysis in parallel environment. It also provides some computation results obtained by using specially designed software.

Adaptation, Physiological↗

PubMed2000

Aging exacerbates hydrogen peroxide-induced alteration of vascular reactivity in rats.

Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells under diverse physiological and pathophysiological situations. These species are known to exert various deleterious effects by which they might induce changes in vascular reactivity. The aim of the present study was to evaluate the evolution of vascular susceptibility to H2O2 during aging in rats. Catalase activity was assessed in aortas from young adult (4 months) and aged (24 months) Wistar rats. In parallel experiments, isolated rings from both age groups were exposed to increasing doses of H2O2 (0, 0.1, 1, 5, or 10 mM) for 20 min and the residual vascular response to phenylephrine (PE = 10(-6) M) and acetylcholine (ACh = 10(-6) M) was evaluated. Our results indicate that aging increases aortic catalase activity (4 months: 0.20 +/- 0.02 IU/mg prot versus 24 months: 0.46 +/- 0.06 IU/mg prot, p < 0.001) while it exacerbates vascular sensitivity to H2O2. These results suggest that the observed increased H2O2-induced alterations of vascular reactivity during aging in rats might be due to increased sensitivity of the vasculature to ROS rather than to a decrease in the defense systems against these species.

Acetylcholine↗

PubMed2005

Advances in epilepsy.

Advances in understanding of both the causes and consequences of epilepsy have been paralleled by a number of recent reports and clinical guidelines highlighting the complexities involved in both diagnosing and treating epilepsy. We review recent developments, including comments on the evolution of clinical guidelines, anti-epileptic drugs, epilepsy surgery and new treatment approaches in development. Epilepsy genetics and emerging evidence on mechanisms of drug resistance in epilepsy will also be discussed. Issues with respect to pregnancy and epilepsy are considered, together with more recently identified dilemmas including bone health in epilepsy and whether seizures themselves cause brain damage. Imaging in epilepsy has recently been reviewed elsewhere, and will not be discussed.

Anticonvulsants↗

PubMedDate not supplied

Sodium restriction decreases AP-1 activation after nephron reduction in the rat: role in the progression of renal lesions.

Renal hyperplasia and hypertrophy are early events after nephron reduction which precede progressive destruction of the remnant kidney. Restriction of dietary sodium content was shown to reduce renal lesions following nephron reduction. AP-1 is a transcription factor, resulting from heterodimerization of fos and jun proteins, which mediates the effects of mitogenic growth factors. To elucidate the role of AP-1 in growth processes involved in renal deterioration, we evaluated whether restriction of dietary sodium content (0.25 vs. 0.50% sodium w/w) affected AP-1-DNA binding and hyperplasia in the remnant kidney after nephron reduction (70% nephrectomy). Cell proliferation, evaluated by PCNA immunostaining, increased progressively from day 7 to day 60 in glomeruli, proximal and distal tubules and loops of Henle of nephrectomized (Nx) rats compared to control sham-operated (C) animals. AP-1-DNA binding activity increased 7 and 14 days after surgery, but it was reduced below C values at day 60. c-fos and c-jun expression were also reduced in Nx rats at day 60. Sodium restriction significantly reduced the number of PCNA-stained cells in glomeruli and tubules at days 14 and 60, but not at day 7, whereas it decreased AP-1 activation at all times of the study. This effect was associated to a marked reduction of renal lesions in Nx rats. In conclusion, we showed that, after nephron reduction, the beneficial effect of sodium restriction was associated with a reduction of hyperplasia and AP-1 activation, but that the latter did not parallel delayed cell proliferation rate in remaining nephrons. Thus, we propose that different transduction pathways are involved in cell proliferation after nephron reduction, according to the time of evolution of renal lesions.

Animals↗

PubMed1975

The immune cellular response tested by lymphocyte transformation in the streptococcal infections.

Thirty-five children between 6 and 17 years treated in the clinic for scarlet fever, rheumatic fever and other non-streptococcal infections as controls, were tested by lymphocyte transformation to four streptococcal antigens. In all cases of scarlet fever and especially of rheumatic fever the lymphocytes were better stimulated by streptococcal products than in the control group. The SO and the MAP fraction showed a good stimulating activity. The response in the rheumatic fever patients was not influenced by the steroid treatment, nor by the stage of the illness. A parallelism with high humoral and cellular responses to SO at the beginning of the acute rheumatic fever was observed, followed by a dissociation of both responses during the evolution with the maintenance of the cellular one and the decrease of the ASO titre.

Adolescent↗

PubMed1992

[Diurnal variations in circulating leukocytes and subsets: relation to plasma cortisol and ACTH].

Surface cellular antigens of leukocytes, lymphocytes and corresponding subpopulations have been analysed by using monoclonal antibodies marked with fluorescein (PITC), parallel to those marked with phycoerythrin (PE). Cortisol and ACTH plasmatics have also been determined through RIA, on two samples at 8am. and 8pm. During this twelve hour evolution, a highly significant dependence of the leukocytes, T, T4 and T8 lymphocytes on the circulating ACTH has also been found. In general during the experiment time leukocytes, lymphocytes and subpopulations, have experimented an increase which is significantly related to the pituitary hormone secretion. The existence of this significant correlation establishes the presence of a possible mechanism that connects the cellular immunity to determined hypothalamus hormones.

Adrenocorticotropic Hormone↗

PubMed1983

Coronary arteriographic findings in acute transmural myocardial infarction.

To describe the coronary arteriographic findings during early transmural myocardial infarction and to define the prevalence of coronary thrombosis by arteriography, we performed coronary arteriography and left ventriculography within 24 hours from symptom onset of transmural myocardial infarction in 517 patients. The coronary arteriographic findings included total and nontotal coronary occlusion with and without coronary thrombosis. Coronary spasm or severe stenosis in the affected vessel were discovered in a minority of patients. The coronary arteriographic characteristics of thrombus included persistent staining of intraluminal material by the contrast material, local retention of the contrast agent in the involved coronary artery, and intracoronary filling defect occurring mostly in nontotal occlusion. Of the 517 patients, 368 were studied within 6 hours of symptom onset, 85 within 6-12 hours and 64 within 12-24 hours. There was a systematic difference between total coronary occlusion and coronary thrombosis in each group. This was determined by arteriographic findings (judged positive or negative) relative to surgical findings. Both total coronary occlusion and coronary thrombosis were more prevalent in the early treatment (within 6 hours from symptom onset) group. Total occlusion and thrombosis declined significantly in the 6-12- and 12-24-hour groups. These data suggest that thrombus is encountered by arteriography and confirmed by surgical exploration within the first 6 hours from symptom onset of transmural infarction in approximately 80% of patients. Coronary thrombosis by coronary arteriography decreases in parallel with total coronary occlusion during the first 24 hours after acute transmural infarction, suggesting that coronary spasm or thrombus formation with subsequent recanalization are important in the evolution of transmural infarction. Despite many factors involved in the pathogenesis of transmural myocardial infarction, coronary thrombosis appears to be the final common pathway converting chronic coronary disease to acute myocardial infarction in the majority of patients.

Cardiac Catheterization↗

PubMed2005

Evolution of the trnF(GAA) gene in Arabidopsis relatives and the brassicaceae family: monophyletic origin and subsequent diversification of a plastidic pseudogene.

Recently, we used the 5'-trnL(UAA)-trnF(GAA) region of the chloroplast DNA for phylogeographic reconstructions and phylogenetic analysis among the genera Arabidopsis, Boechera, Rorippa, Nasturtium, and Cardamine. Despite the fact that extensive gene duplications are rare among the chloroplast genome of higher plants, within these taxa the anticodon domain of the trnF(GAA) gene exhibit extensive gene duplications with one to eight tandemly repeated copies in close 5' proximity of the functional gene. Interestingly, even in Arabidopsis thaliana we found six putative pseudogenic copies of the functional trnF gene within the 5'-intergenic trnL-trnF spacer. A reexamination of trnL(UAA)-trnF(GAA) regions from numerous published phylogenetic studies among halimolobine, cardaminoid, and other cruciferous taxa revealed not only extensive trnF gene duplications but also favor the hypothesis about a single origin of trnF pseudogene formation during evolution of the Brassicaceae family 16-21 MYA. Conserved sequence motifs from this tandemly repeated region are codistributed nonrandomly throughout the plastome, and we found some similarities with a DNA sequence duplication in the rps7 gene and its adjacent spacer. Our results demonstrate the potential evolutionary dynamics of a plastidic region generally regarded as highly conserved and probably cotranscribed and, as shown here for several genera among cruciferous plants, greatly characterized by parallel gains and losses of duplicated trnF copies.

Arabidopsis↗

PubMedDate not supplied

The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment.

Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus.

Autonomic Nerve Block↗

PubMed2001

Evolution of exclusive paternal care in arthopods.

Exclusive male care of offspring is the rarest form of postzygotic parental care among animals and has arisen independently in only 13 arthropod taxa. To distinguish the effects of sexual selection from those of natural selection on the evolution of arthropod paternal care, predictions concerning several life-history and behavioral traits resulting from both forms of selection are made and tested across all known taxa with exclusive paternal care. Comparisons suggest parallels between prezygotic nuptial gifts and exclusive postzygotic male care and support the hypothesis that, in arthropods, male behaviors that enhance female reproductive success either directly, by releasing females from the fecundity constraints of maternal care (enhanced fecundity hypothesis), or indirectly, by identifying mates with superior genes (handicap principle), are traits on which sexual selection has acted. Under such conditions, males that are willing to guard young become preferred mates for gravid females and enjoy greater promiscuity than males that are unable or unwilling to guard. Females use nest construction or the act of guarding another female's eggs as honest signals of paternal intent and quality.

Animals↗

PubMed2005

New maximum likelihood estimators for eukaryotic intron evolution.

The evolution of spliceosomal introns remains poorly understood. Although many approaches have been used to infer intron evolution from the patterns of intron position conservation, the results to date have been contradictory. In this paper, we address the problem using a novel maximum likelihood method, which allows estimation of the frequency of intron insertion target sites, together with the rates of intron gain and loss. We analyzed the pattern of 10,044 introns (7,221 intron positions) in the conserved regions of 684 sets of orthologs from seven eukaryotes. We determined that there is an average of one target site per 11.86 base pairs (bp) (95% confidence interval, 9.27 to 14.39 bp). In addition, our results showed that: (i) overall intron gains are approximately 25% greater than intron losses, although specific patterns vary with time and lineage; (ii) parallel gains account for approximately 18.5% of shared intron positions; and (iii) reacquisition following loss accounts for approximately 0.5% of all intron positions. Our results should assist in resolving the long-standing problem of inferring the evolution of spliceosomal introns.

Animals↗

PubMed1994

Exchanges of short polymorphic DNA segments predating speciation in feline major histocompatibility complex class I genes.

Sequence comparisons of 14 distinct MHC class I cDNA clones isolated from species representing the three major taxonomic lineages of Felidae (domestic cat lineage, ocelot lineage, and pantherine lineage) revealed that feline MHC class I alleles have highly mosaic structures with short polymorphic sequence motifs that are rearranged between alleles of individual MHC loci, between MHC class I genes within cat species, and between homologous MHC loci in different species. The pattern of sequence variation in felids supports the role of the following factors in production and maintenance of MHC variation: (1) gradual spontaneous mutation; (2) selective pressure to conserve certain residues but also to vary in hypervariable regions, notably residues that functionally participate in antigen recognition and presentation; and (3) recombination-mediated gene exchange between alleles and between related genes. The overall amount of genetic variation observed among MHC class I genes in the Felidae family is no greater than the amount of variation within any outbred cat species (i.e., domestic cat, ocelot). The occurrence of equivalent levels of polymorphism plus the simultaneous persistence of the same sequence motifs in divergent feline species suggest that most MHC class I nucleotide site polymorphism predated species divergences. Ancient polymorphisms have been transmitted through the speciation events and modern feline MHC class I alleles were derived by recombinational exchange of polymorphic sequence motifs. Moreover, some of these sequence motifs were found in other mammalian MHC class I genes, such as classical human HLA-B5, nonclassical human HLA-E class I genes, and bovine class I genes. These results raise the prospect of an ancient origin for some motifs, although the possibility of convergence in parallel mammalian radiations cannot be excluded.

Amino Acid Sequence↗

PubMed2002

Tympanal and atympanal 'mouth-ears' in hawkmoths (Sphingidae).

The labral pilifers and the labial palps form ultrasound-sensitive hearing organs in species of two distantly related hawkmoth subtribes, the Choerocampina and the Acherontiina. Biomechanical examination now reveals that their ears represent different types of hearing organs. In hearing species of both subtribes, the labral pilifer picks up vibrations from specialized sound-receiving structures of the labial palp that are absent in non-hearing species. In Choerocampina, a thin area of cuticle serves as an auditory tympanum, whereas overlapping scales functionally replace a tympanum in Acherontiina that can hear. The tympanum of Choerocampina and the scale-plate of Acherontiina both vibrate maximally in response to ultrasonic, behaviourally relevant sounds, with the vibrations of the tympanum exceeding those of the scale plate by ca. 15 dB. This amplitude difference, however, is not reflected in the vibrations of the pilifers and the neural auditory sensitivity is similar in hearing species of both subtribes. Accordingly, morphologically different - tympanal and atympanal - but functionally equivalent hearing organs evolved independently and in parallel within a single family of moths.

Acoustic Stimulation↗

PubMedDate not supplied

Proximodistal patterning of the limb: insights from evolutionary morphology.

There is an active debate about how skeletal elements are encoded along the proximodistal (PD) axis of the developing limb. Our aim here is to see whether consideration of the evolutionary morphology of the limb can contribute to our understanding of patterning mechanisms. Of special interest in this context are animals showing reiterated skeletal elements along the PD axis (e.g., dolphins and plesiosaurs with hyperphalangy). We build on previous hypotheses to propose a two-step model of PD patterning in which specification of broad domains in the early limb bud is distinct from subsequent processes that divides an initial anlage into a segmental pattern to yield individual skeletal elements. This model overcomes a major evolutionary problem with the progress zone model, which has not previously been noted: pleiotropy. Parallels with other developmental systems are briefly discussed.

Animals↗