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PubMed1997

[Measurement of arteriovenous oxygen difference in the monitoring of patients with subarachnoid hemorrhage due to cerebral aneurysm].

The arterious venous oxygen difference (AVDO2) due to the close relationship with cerebral metabolic rate of oxygen and cerebral blood flow shows metabolic alterations that occur in some pathological situations in the brain including subarachnoid haemorrhage. The AVDO2 was calculated by the Fick equation and the results evaluated by the Glasgow outcome scale. Measurements of arteriojugular oxygen difference were carried out in 30 patients with subarachnoid haemorrhage due to rupture of intracranial aneurysms, as an attempt to monitor the relationship between changes in AVDO2, clinical picture, and evolution of the patients. The subarachnoid haemorrhage was diagnosed by CT scan in 17 patients and by lumbar punction in 13 and the diagnosis of arterial vasospasm was carried out by clinical evaluation and confirmed by four vessels angiogram in only eight patients. Eighteen patients were admitted with Hunt & Hess (H&H) I/II, seven with H&H III and five with H&H IV/V. Nineteen patients had AVDO2 normal and this group had three deaths; five patients had AVDO2 continuously low with three deaths; and six patients had AVDO2 continuously high with two deaths. The patients with normal AVDO2 had better prognosis and clinical evolution than the patients with abnormal values of AVDO2. In conclusion, AVDO2 measurements could not be correlated with the diagnosis of vasospasm, but was useful in the early identification of metabolic changes that occur after subarachnoid haemorrhage and could be used as an supplementary monitoring in the clinical evaluation of patients with this pathology.

Adult↗
PubMed1976

The evolution of one- and two-locus systems.

Assuming age-independent fertilities and mortalities and random mating, continuous-time models for a monoecious population are investigated for weak selection. A single locus with multiple alleles and two alleles at each of two loci are considered. A slow-selection analysis of diallelic and multiallelic two-locus models with discrete nonoverlapping generations is also presented. The selective differences may be functions of genotypic frequencies, but their rate of change due to their explicit dependence on time (if any) must be at most of the second order in s, (i.e., O(s2), where s is the intensity of natural selection. Then, after several generations have elapsed, in the continuous time models the time-derivative of the deviations from Hardy-Weinberg proportions is of O(s2), and in the two-locus models the rate of change of the linkage disequilibrium is of O(s2). It follows that, if the rate of change of the genotypic fitnesses is smaller than second order in s (i.e., o(s2)), then to O(s2) the rate of change of the mean fitness of the population is equal to the genic variance. For a fixed value of s, however, no matter how small, the genic variance may occasionally be smaller in absolute value than the (possibly negative) lower order terms in the change in fitness, and hence the mean fitness may decrease. This happens if the allelic frequencies are changing extremely slowly, and hence occurs often very close to equilibrium. Some new expressions are derived for the change in mean fitness. It is shown that, with an error of O(s), the genotypic frequencies evolve as if the population were in Hardy-Weinberg proportions and linkage equilibrium. Thus, at least for the deterministic behaviour of one and two loci, deviations from random combination appear to have very little evolutionary significance.

Biological Evolution↗
PubMed1992

[Dynamic continuous vectorcardiography].

Continuous dynamic vectorcardiography is an ideal method for monitoring patients with myocardial ischemia. The monitoring is a non-invasive and real time registration and simultaneously safe and reproducible. The method has proved valuable for describing the evolution in different ischemic heart diseases. The method measures the electric myocardial activity in three orthogonal leads and a computer calculates the different vectorcardiographic parameters for the ST- and QRS-complexes. Vectorcardiographic registration is feasible for computer analysis, because it can summarize all information in a few parameters. Using continuous registration, the different parameters can show dynamic evolution and, in this way, describe the variability during acute myocardial infarction and unstable angina pectoris. The method also made it possible to evaluate anti-ischemic treatment in patients, as for example thrombolytic therapy.

Humans↗
PubMed2004

Evolution of the MAT locus and its Ho endonuclease in yeast species.

The genetics of the mating-type (MAT) locus have been studied extensively in Saccharomyces cerevisiae, but relatively little is known about how this complex system evolved. We compared the organization of MAT and mating-type-like (MTL) loci in nine species spanning the hemiascomycete phylogenetic tree. We inferred that the system evolved in a two-step process in which silent HMR/HML cassettes appeared, followed by acquisition of the Ho endonuclease from a mobile genetic element. Ho-mediated switching between an active MAT locus and silent cassettes exists only in the Saccharomyces sensu stricto group and their closest relatives: Candida glabrata, Kluyveromyces delphensis, and Saccharomyces castellii. We identified C. glabrata MTL1 as the ortholog of the MAT locus of K. delphensis and show that switching between C. glabrata MTL1a and MTL1alpha genotypes occurs in vivo. The more distantly related species Kluyveromyces lactis has silent cassettes but switches mating type without the aid of Ho endonuclease. Very distantly related species such as Candida albicans and Yarrowia lipolytica do not have silent cassettes. In Pichia angusta, a homothallic species, we found MATalpha2, MATalpha1, and MATa1 genes adjacent to each other on the same chromosome. Although some continuity in the chromosomal location of the MAT locus can be traced throughout hemiascomycete evolution and even to Neurospora, the gene content of the locus has changed with the loss of an HMG domain gene (MATa2) from the MATa idiomorph shortly after HO was recruited.

Deoxyribonucleases, Type II Site-Specific↗
PubMedDate not supplied

[Therapeutic effects of an antileukotriene in children with moderate-severe persistent asthma].

BACKGROUND: Asthma is a chronic inflammatory disease of the airways, in which participate many cells and cellular elements. OBJECTIVE: To assess the utility of the zafirlukast, an antagonist of the receivers of the leukotrienes, in asthmatic children of our environment and to evaluate the grade of safety of the medication in the preventive treatment of the asthma. MATERIAL AND METHODS: We selected 50 moderate-severe asthmatic children, between 12 and 16 years (of both sexes) with non satisfactory evolution, in spite of the conventional preventive treatment for the asthma. Zafirlukast were given in dose of 20 mg every 12 hours, far from the foods, during 12 weeks. We carried out laboratory studies, before and after the treatment, evaluating the hematic (Hb and Hto), renal (creatinine) and hepatic (TGP) functions. They were continued in allergy consultation at the 4, 8, and 12 weeks of treatment, to know their clinical evolution, the apparition of adverse reactions and the use of other asthmatic medications in the period of the treatment. RESULTS: The 88% of the children improved clinically. The patients decreased the use of oral steroids and only 4 adverse reactions (8%) were reported, with total regression of the symptoms when suppressing the medication. The averages of the laboratory results, before and after the treatment, reflected values into the established normal limits, Hb: 12.4 (before) and 12.1 g/L (later), creatinine: 63.2 and 67.1 mMol/1 and TGP: 2.1 and 3.6 units. CONCLUSIONS: We observed in our study that the preventive treatment with Zafirlukast is useful and well tolerated, representing a new expectation for the asthma, in pediatric ages.

Adolescent↗
PubMed2000

[Post-Doc (post-graduate training for medical doctors in Europe). The use of the Internet in the continuing education of general practice physicians: a European project of multimedia continuing medical education. The University of Aachen, Maastricht, Catholic University Leuven and the Central University Limburg (Diepenbeek) and EUREGIONET].

The continuing formation of the General Practitioners (GP) must stay in stride with the rapid evolution of society, technology, science and needs of the population. The Web allows on-line a rapid access to a pertinent and practical information whenever needed. PostDoc is a joint venture of the Universities of Aachen, Maastricht, Leuven and Diepenbeek. The Department of general medicine is associated with the Service of Technology of Education in this project. The interactivity of an Internet Website introduces a cooperative dimension in the work of the GP's centred on formation and discussion of problems encountered. This tool allows each GP to contribute to clinical cases and information.

Belgium↗
PubMed2005

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution.

Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.

Animals↗
PubMed2005

Rotational and vibrational relaxation of methane excited to 2nu3 in CH4/H2 and CH4/He mixtures at 296 and 193 K from double-resonance measurements.

A series of time-resolved IR-IR double-resonance experiments have been conducted where methane molecules are excited into a selected rovibrational level of the 2nu3(F2) vibrational substate of the tetradecad and where the time evolution of the population of the various energy levels is probed by a tunable continuous wave laser. The rotational relaxation and vibrational energy transfer processes occurring in methane upon inelastic CH4-H2 and CH4-He collisions have been investigated by this technique at room temperature and at 193 K. By probing transitions in which either the lower or the upper level is the laser-excited level, rotational depopulation rates in the 2nu3(F2) substate were measured. The rate constants for CH4-H2 collisions were found to be 17.7 +/- 2.0 and 18.9 +/- 2.0 micros(-1) Torr(-1) at 296 and 193 K, respectively, and for CH(4)-He collisions they are 12.1 +/- 1.5 and 16.0 +/- 2.0 micros(-1) Torr(-1) at the same temperatures. The vibrational relaxation was investigated by probing other stretching transitions such as 2nu3(F2) - nu3, nu3 + 2nu4 - 2nu4, and nu3 + nu4 - nu4. A kinetic model, taking into account the main collisional processes connecting energy levels up to 6000 cm(-1), that has been developed to describe the various relaxation pathways allowed us to calculate the temporal evolution of populations in these levels and to simulate double-resonance signals. The different rate coefficients of the vibrational relaxation processes involved in these mixtures were determined by fitting simulated signals to the observed signals corresponding to assigned transitions. For vibration to translation energy transfer processes, hydrogen is a much more efficient collision partner than helium, nitrogen, or methane itself at 193 K as well as at room temperature.

Journal Article↗
PubMed2025

Evolution of SARS-CoV-2 in white-tailed deer in Pennsylvania 2021-2024.

SARS-CoV-2 continues to transmit and evolve in humans and animals. White-tailed deer (Odocoileus virginianus) have been previously identified as a zoonotic reservoir for SARS-CoV-2 with high rates of infection and probable spillback into humans. Here we report sampling 1,127 white-tailed deer (WTD) in Pennsylvania, and a genomic analysis of viral dynamics spanning 1,017 days between April 2021 and January 2024. To assess viral load and genotypes, RNA was isolated from retropharyngeal lymph nodes and analyzed using RT-qPCR and viral whole genome sequencing. Samples showed a 14.64% positivity rate by RT-qPCR. Analysis showed no association of SARS-CoV-2 prevalence with age, sex, or diagnosis with Chronic Wasting Disease. From the 165 SARS-CoV-2 positive WTD, we recovered 25 whole genome sequences and an additional 17 spike-targeted amplicon sequences. The viral variants identified included 17 Alpha, 11 Delta, and 14 Omicron. Alpha largely stopped circulating in humans around September 2021, but persisted in WTD as recently as March of 2023. Phylodynamic analysis of pooled genomic data from Pennsylvania documents at least 12 SARS-CoV-2 spillovers from humans into WTD, including a recent series of Omicron spillovers. Prevalence was higher in WTD in regions with crop coverage rather than forest, suggesting an association with proximity to humans. Analysis of seasonality showed increased prevalence in winter and spring. Multiple examples of recurrent mutations were identified associated with transmissions, suggesting WTD-specific evolutionary pressures. These data document ongoing infections in white-tailed deer, probable onward transmission in deer, and a remarkable rate of new spillovers from humans.

Animals↗
PubMed1998

Dictionary of recurrent domains in protein structures.

The rapid growth in the number of experimentally determined three-dimensional protein structures has sharpened the need for comprehensive and up-to-date surveys of known structures. Classic work on protein structure classification has made it clear that a structural survey is best carried out at the level of domains, i.e., substructures that recur in evolution as functional units in different protein contexts. We present a method for automated domain identification from protein structure atomic coordinates based on quantitative measures of compactness and, as the new element, recurrence. Compactness criteria are used to recursively divide a protein into a series of successively smaller and smaller substructures. Recurrence criteria are used to select an optimal size level of these substructures, so that many of the chosen substructures are common to different proteins at a high level of statistical significance. The joint application of these criteria automatically yields consistent domain definitions between remote homologs, a result difficult to achieve using compactness criteria alone. The method is applied to a representative set of 1,137 sequence-unique protein families covering 6,500 known structures. Clustering of the resulting set of domains (substructures) yields 594 distinct fold classes (types of substructures). The Dali Domain Dictionary (http://www.embl-ebi.ac.uk/dali/) not only provides a global structural classification, but also a comprehensive description of families of protein sequences grouped around representative proteins of known structure. The classification will be continuously updated and can serve as a basis for improving our understanding of protein evolution and function and for evolving optimal strategies to complete the map of all natural protein structures.

Amino Acid Sequence↗
PubMed1996

Synchronization affector of autonomous short-period-sustained oscillation of Saccharomyces cerevisiae.

When the yeast Saccharomyces cerevisiae was grown under aerobic continuous culture, an autonomous short-period-sustained oscillation appeared. This oscillation was observed in concentrations of various extracellular and intracellular parameters, such as ethanol, acetate, glycogen, dissolved oxygen and intracellular pH. In this work the synchronization affecter of this oscillation was investigated. Ethanol was found not to be the synchronizer of the oscillation because a pulse of ethanol did not affect the phase or period of the oscillation. The oscillation was dependent on the aeration rate, i.e., the oscillation occurred only between 150 and 600 ml min-1. However, the oxygen concentration did not influence synchronization as an upward shift in the oxygen concentration of the gas flow did not affect the sustainability of the oscillation. On the other hand, synchronization was stopped by an enhanced gas flow rate, keeping dissolved oxygen tension at the oscillatory condition, suggesting that synchronization was caused by a volatile compound in the culture. A stepwise increase in carbon dioxide concentration of the gas flow rate ceased synchronization, yet the oscillation seem to continue in each individual cell. Oscillatory behaviour of intracellular pH and carbon dioxide evolution rate showed a phase difference of 90 degrees. Based on these facts it is postulated that carbon dioxide, through the influence of its dissociation on intracellular pH, could be the synchronization affector of the autonomous short-period-sustained oscillation of S. cerevisiae.

Carbon Dioxide↗
PubMed1992

Emergence of myeloid stem cell line from T-lymphoid blastic phase of chronic myeloid leukemia in culture.

A new cell line designated JA-CML was derived from the peripheral blood of a patient with blastic phase CML. Sequential evolution of phenotypic and genetic markers was demonstrated during adaptation from primary to continuous culture in vitro. In the primary sample the majority of blast cells displayed the early T-cell markers, CD7, HLA-DR, and TdT, but were negative for the common ALL antigen (CALLA), CD4 and CD8. Simultaneously, unstimulated metaphase cells showed great karyotypic variation with a range of 43-46 chromosomes per cell. Clonal changes included the Ph chromosome t(9;22), loss of the Y and gain of several altered chromosomes. The cells grew slowly in suspension during the first 10 weeks of culture. During that time, cells still expressed the CD7 and HLA-DR antigens. Karyotypic analysis at ten weeks showed a pattern of 46,X,-Y,t(9;22),+8 in more than 90% of metaphases with disappearance of all other abnormal chromosomes noted in the original sample. A tetraploid subline exhibiting duplication of most chromosomes, including the Ph, comprised the remaining metaphases. Upon further cultivation in vitro, the cells transformed spontaneously over a period of several weeks, from T-lymphoid into myeloid cells. Expression of CD7 was lost, but reactivities with monoclonal antibodies to CD34, CD33 and CD13 were newly acquired. The karyotype was hypertriploid and all cells carried two copies of t(9;22) and lacked normal copies of No. 9 or Y. The cells have since maintained stable cytogenetic and phenotypic profiles. Molecular rearrangement of the breakpoint cluster region was identified in the primary blasts and the established line and T-cell receptor gene rearrangements were not found. These observations suggest that the leukemic blast arose from primitive stem cells, not irreversibly committed T cells, and that these stem cells retained the capacity to differentiate along the myeloid pathway.

Antigens, CD↗
PubMed1994

Vimentin-positive rosary-bead-like formations in the rabbit superior colliculus during postnatal development.

Strings of vimentin-positive rosary-bead-like formations in the rabbit superior colliculus were studied. The size and distance between beads varied from one string to another, and within a given string. The formations were similar in number and distribution in the two superior colliculi. Successions of beads were found mainly in the medial and deep layers, and represented not more than 1% of the radial glial fibers. The strings were in continuity at deep levels with segments of varicose fibers of radial glia, which in turn were continuous with fibers of normal appearance. These observations suggest a temporal sequence of evolution, starting with the normal radial glial fiber, which acquires swellings that in turn give rise to discrete beads; in subsequent stages, the beads become smaller and more widely separated. In the newborn rabbit, these formations are seen mainly in laterobasal regions of the superior colliculus, and spread throughout the colliculus by the end of week one of postnatal life, becoming more numerous in medial regions. We suggest that these formations represent a mechanism of removal of at least part of the radial glial fibers, and discuss the possible relation between these formations and the transformation of radial glia into astrocytes.

Aging↗
PubMed1996

Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome.

A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites.

Adult↗
PubMed2005

Large- and small-scale purification of mammalian 26S proteasomes.

The 26S proteasome is an ATP-dependent protease known to collaborate with ubiquitin, whose polymerization acts as a marker for regulated and enforced destruction of unnecessary proteins in eukaryotic cells. It is an unusually large multi-subunit protein complex, consisting of a central catalytic machine (called the 20S proteasome or CP/core particle) and two terminal regulatory subcomplexes, termed PA700 or RP/regulatory particle, that are attached to both ends of the central portion in opposite orientations to form an enzymatically active proteasome. To date, proteolysis driven by the ubiquitin-proteasome system has been shown to be involved in a diverse array of biologically important processes, such as the cell cycle, immune response, signaling cascades, and developmental programs; and the field continues to expand rapidly. Whereas the proteasome complex has been highly conserved during evolution because of its fundamental roles in cells, it has also acquired considerable diversity in multicellular organisms, particularly in mammals, such as immunoproteasomes, PA28, S5b, and various alternative splicing forms of S5a (Rpm 10). However, the details of the ultimate pathophysiological roles of mammalian proteasomes have remained elusive. This article focuses on methods for assay and purification of 26S proteasomes from mammalian cells and tissues.

Animals↗
PubMed1994

Carotid endarterectomy for unstable and compelling neurologic conditions: do results justify an aggressive approach?

PURPOSE: In a retrospective study the outcome of 70 carotid endarterectomies (CEA) in 68 patients with neurologically unstable conditions or anatomically compelling findings on carotid angiography was examined to more accurately identify patients who might benefit from CEA in this setting. METHODS: Out of a total of 1734 CEAs performed from 1978 to 1992, five groups of patients were selected: group A, stroke in evolution with tight stenosis (n = 5); group C, crescendo transient ischemic attacks (CTIA) continuing despite heparin (n = 14); group D, CTIA (above criteria) ceasing with heparin (n = 21); and group E, anatomically compelling situation on carotid angiography (n = 13). Data collected included preoperative and postoperative Neurologic Event Severity Score (NESS), CHAT classification, arteriosclerosis risk factors, demographics, and long-term overall and transient ischemic attack/stroke-free survival rates. RESULTS: Risk factors and demographics were similar in all groups. By NESS criteria the conditions of 97.3% of patients in the neurologically unstable groups A to C were improved or stabilized after operation, with one deterioration (2.7%). All patients in group B either stabilized or improved. In group D, one patient's NESS deteriorated, resulting in 3.5% overall morbidity rate and no deaths for groups A to D. Follow-up showed an overall survival rate by Kaplan-Meier analysis equivalent to a matched control population, with 85% alive at 5 years. The cumulative TIA/stroke-free survival rate at 5 years was 75%. CONCLUSIONS: In this retrospective series, CEA performed for compelling or unstable neurologic findings carried low morbidity and mortality rates. Early aggressive surgical therapy of neurologically unstable patients may be warranted because our results improved on the anticipated natural history of the conditions studied. Further clarification of proper patient selection is necessary before this principle can be applied broadly.

Adult↗
PubMedDate not supplied

Polymerase-chain-reaction-based semi-quantification of hepatitis D viraemia in patients treated with high doses of alpha 2b interferon.

To study the antiviral efficacy of high doses of alpha 2b interferon (alpha 2b-IFN) for chronic hepatitis D treatment, we used polymerase-chain-reaction(PCR)-based semi-quantitative detection of HDV RNA. The semi-quantification method used was based on the appearance of a positive amplification signal as a function of the number of PCR cycles. By amplifying dilutions (10(-1)-10(-8)) of an HDV-positive woodchuck liver RNA, we confirmed that exponential amplification efficacy occurred at between 20 and 30 cycles. Positive signals were observed from dilution 10(-2) (gel electrophoresis after 20 cycles of PCR) to dilution 10(-7) (hybridization after 30 cycles of PCR). To characterize the HDV RNA level in sera of 8 patients treated with alpha 2b-IFN (10 MU/3 times a week) for 1 year, we extracted RNA from serum samples taken every 6 months. All samples were amplified in parallel for 20 and 30 PCR cycles. Analysis of HDV cDNA after ethidium bromide/agarose gel electrophoresis and after molecular hybridization (100 times more sensitive than gel analysis), enabled us to grade the signals observed from negative to positive as 1+, 2+, 3+ and 4+, with all results being positive. Three types of evolution of HDV viraemia were evidenced among the 8 treated patients. HDV replication continued to occur at a high level at the 6th and 12th month in 2 patient sera. For 2 other patients, an HDV RNA decrease or disappearance was evidenced in the serum at the 6th month; however, viral replication recurred at a higher level at the 12th month.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗