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At least 469 records · Page 26Linked to original sources
PubMed2003

High throughput detection of microsatellite instability by denaturing high-performance liquid chromatography.

Microsatellite instability (MSI) is a hallmark of the DNA replication error phenotype, due to the inactivation of mismatch repair genes. MSI has been implicated in colon and many other gastrointestinal cancers. MSI usually can be analyzed by PCR amplification of microsatellite markers followed by electrophoresis and detected using autoradiography or fluorescence techniques. We report here a novel method for high-throughput detection of MSI using denaturing high performance liquid chromatography (DHPLC). Amplification of two mononucleotide markers (BAT25 and BAT26) by polymerase chain reaction (PCR) is followed by DHPLC analysis to display alteration in the length of repetitive sequences. These two markers were tested in 84 colorectal cancer samples confirmed to be 44 MSI-H and 40 MSI-L or MSS, previously defined by multiple microsatellite markers and/or by immunohistochemical analyses of MLH1 and MSH2 proteins. Among 44 MSI-H samples, sequence variations in BAT26 and BAT25 were detected in 44 (100%) and 43 (98%), respectively, while no sequence variation in the two markers was detected in 40 MSI-L or MSS samples. A total of 96 gastric cancers and their matched normal tissues were then analyzed for MSI-H using this method. Sequence variations in BAT26 and BAT25 were detected in nine (9.4%) samples. Seven of the nine cases were shown unstable at both BAT26 and BAT25; one each was unstable at BAT26 or BAT25. These results were confirmed by autoradiography analyses. Together, our results demonstrate high sensitivity and specificity of DHPLC in the analysis of sequence variations in BAT25 and BAT26 to determine MSI status. This simple, efficient, and high-throughput approach will facilitate analysis of MSI in large sample sets of any cancers.

Chromatography, High Pressure Liquid↗
PubMed2002

Conservation and variation in human and common chimpanzee CD94 and NKG2 genes.

To assess polymorphism and variation in human and chimpanzee NK complex genes, we determined the coding-region sequences for CD94 and NKG2A, C, D, E, and F from several human (Homo sapiens) donors and common chimpanzees (Pan troglodytes). CD94 is highly conserved, while the NKG2 genes exhibit some polymorphism. For all the genes, alternative mRNA splicing variants were frequent among the clones obtained by RT-PCR. Alternative splicing acts similarly in human and chimpanzee to produce the CD94B variant from the CD94 gene and the NKG2B variant from the NKG2A gene. Whereas single chimpanzee orthologs for CD94, NKG2A, NKG2E, and NKG2F were identified, two chimpanzee paralogs of the human NKG2C gene were defined. The chimpanzee Pt-NKG2CI gene encodes a protein similar to human NKG2C, whereas in the chimpanzee Pt-NKG2CII gene the translation frame changes near the beginning of the carbohydrate recognition domain, causing premature termination. Analysis of a panel of chimpanzee NK cell clones showed that Pt-NKG2CI and Pt-NKG2CII are independently and clonally expressed. Pt-NKG2CI and Pt-NKG2CII are equally diverged from human NKG2C, indicating that they arose by gene duplication subsequent to the divergence of chimpanzee and human ancestors. Genomic DNA from 80 individuals representing six primate species were typed for the presence of CD94 and NKG2. Each species gave distinctive typing patterns, with NKG2A and CD94 being most conserved. Seven different NK complex genotypes within the panel of 48 common chimpanzees were due to differences in Pt-NKG2C and Pt-NKG2D genes.

Alleles↗
PubMed2000

The interaction between research and practice: a pan-European approach to managing H.pylori infection in primary care.

The transposition of evidence into clinical care presents many challenges. New knowledge may be immediately translatable to the practice setting, with barriers to be overcome before implementation. The early guidelines on Helicobacter pylori management presented an overview but were not able to take into account local factors and health care traditions, such as the non-availability of tests and established primary-secondary care relationships. Primary care is a specific specialty across most of Europe, existing within different health care systems and clinical traditions. The creation of H. pylori management guidelines, aimed at European primary care but adaptable to local national circumstances, presented a challenge in methodology and formulation. The process exposed similarities but also tensions between differing health care systems, as well as variations in the conditions in which GPs practise. Clinical differences, such as varying ulcer prevalence and drug resistance rates, highlighted the importance of guidelines being adaptable. This paper analyses the European Society for Primary Care Gastroenterology process of pan-European primary care agreement towards H.pylori management and how diverse views, traditions and national settings were reconciled through an evidence-based approach.

Cultural Diversity↗
PubMed2005

Grip preference, dermatoglyphics, and hand use in captive chimpanzees (Pan troglodytes).

This paper examined the association between grip type, hand use, and fingerprint patterns in a sample of captive chimpanzees. Grip type for simple reaching was assessed for the left and right hand and classified as thumb-index, middle-index, or single-digit responses. Fingerprint patterns were characterized as whorls, loops, or arches on each finger. The results indicated that chimpanzees exhibit significantly more thumb-index responses for the right compared to the left hand. In addition, thumb-index responses were more prevalent for subjects that had a whorl compared to a loop or arch on their thumb. The results suggest that fingerprint patterns are associated with individual differences in grasping type in chimpanzees as well as some variation in hand use.

Animals↗
PubMed2004

Functional analysis of MOR-1 splice variants of the mouse mu opioid receptor gene Oprm.

A series of mu opioid receptor gene Oprm splice variants have been reported that differ only at their C-terminus. These variants all contain exons 1, 2, and 3 of the gene, the exons responsible for coding all seven transmembrane domains. Whereas MOR-1 also has exon 4 that encodes for an additional 12 amino acids at the tip of the C-terminus, the other MOR-1 variants have unique amino acid sequences distinct from those in MOR-1 due to alternative splicing. All these variants are mu-selective in binding assays. The current study explored the ability of these variants to stimulate [35S]GTPgammaS binding to assess them functionally. Only mu opioids stimulated [35S]GTPgammaS binding. Among the mu opioids we noted marked differences in their maximal stimulation among the clones. This was most prominent with beta-endorphin, which stimulated [35S]GTPgammaS binding in the MOR-1E expressing cells to a greater degree than [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 130%) and was far less effective than DAMGO in MOR-1C cells (44%). The rank order of maximal stimulation of the drugs varied among the clones as well. Dynorphin A, beta-endorphin and morphine were most effective in stimulating [35S]GTPgammaS binding in MOR-1E, while M6G and fentanyl were most effective in MOR-1 expressing cells. The potency (EC50) of some of the drugs also varied extensively among the clones, with a poor correlation between the potency of the drugs to stimulate [35S]GTPgammaS binding and their binding affinity. Together, these findings reveal marked functional differences among the variants that only can be explained by their structural differences at the tip of their C-terminus.

Alternative Splicing↗
PubMed1991

In vitro and in vivo replication capacity of the precore region defective hepatitis B virus variants.

Although the precore region defective hepatitis B virus variants have been implicated in chronic liver disease and fulminant hepatitis, our knowledge on the molecular biology of these variants is still limited. Using an in vitro transfection assay, we confirmed the replication competent but HBeAg-negative nature of the major variants containing a TAG stop codon in the distal precore region associated with one or two point mutations. Transfection of the two-point-mutated variant into a chimpanzee induced serological responses including anti-HBc and anti-HBs. Interestingly, anti-HBe response was found in the absence of HBeAg antigenemia, suggesting that anti-HBe can be stimulated by degraded HBc. Using the rabbit reticulocyte system the possible effect of the different precore region mutations on the expression of HBcAg from precore- and core-mRNAs was also studied.

Animals↗
PubMed2002

Incorporating soil structure and root distribution into plant uptake models for radionuclides: toward a more physically based transfer model.

Most biosphere and contamination assessment models are based on uniform soil conditions, since single coefficients are used to describe the transfer of contaminants to the plant. Indeed, physical and chemical characteristics and root distribution are highly variable in the soil profile. These parameters have to be considered in the formulation of a more realistic soil-plant transfer model for naturally structured soils. The impact of monolith soil structure (repacked and structured) on Zn and Mn uptake by wheat was studied in a controlled tracer application (dye and radioactive) experiment. We used Brilliant Blue and Sulforhodamine B to dye flow lines and 65Zn and 54Mn to trace soil distribution and plant uptake of surface-applied particle-reactive contaminants. Spatial variation of the soil water content during irrigation and plant growth informs indirectly about tracer and root location in the soil profile. In the structured monolith, a till pan at a depth of 30 cm limited vertical water flow and root penetration into deeper soil layers and restricted tracers to the upper third of the monolith. In the repacked monolith, roots were observed at all depths and fingering flow allowed for the fast appearance of all tracers in the outflow. These differences between the two monoliths are reflected by significantly higher 54Mn and 65Zn uptake in wheat grown on the structured monolith. The higher uptake of Mn can be modelled on the basis of radionuclide and root distribution as a function of depth and using a combination of preferential flow and rooting. The considerably higher uptake of Zn requires transfer factors which account for variable biochemical uptake as a function of location.

Forecasting↗
PubMed2001

Comparison of Vif sequences from diverse geographical isolates of HIV type 1 and SIV(cpz) identifies substitutions common to subtype C isolates and extensive variation in a proposed nuclear transport inhibition signal.

We compared the Vif sequences from more than 100 group M and O strains of HIV-1 isolated from diverse geographical regions and various subtypes, in order to identify regions of high variability and those amino acid residues that were highly conserved or invariant. Our analysis found that there were 10 highly conserved domains with additional invariant residues located throughout the protein. Our analysis revealed that in the highly conserved amino-terminal domain, all subtype C isolates examined had a methionine-to-leucine substitution at position 8 and most subtype C isolates had an arginine-to-lysine substitution at position 17 of the protein. Our analysis revealed that the MAP kinase phosphorylation sites, and the cysteine residues at positions 114 and 133, were conserved in Vif sequences from group M, group O, and SIV cpz isolates. Our analysis also shows that the RKKR motif at positions 90--93, proposed as a nuclear transport inhibition signal (NTIS), was conserved neither in different geographical group M and O HIV-1 isolates nor in SIVcpz.

Amino Acid Sequence↗
PubMed2003

Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees.

We have investigated the pattern and extent of nucleotide diversity in 10 X-chromosomal genes where mutations are known to cause mental retardation in humans. For each gene, we sequenced the entire coding region from cDNA in humans, chimpanzees, and orangutans, as well as about 3 kb of genomic DNA in 20 humans sampled worldwide and in 10 chimpanzees representing two "subspecies." Overall nucleotide diversity in these genes is about twofold lower in humans than in chimpanzees, and nucleotide diversity within and between species is low, suggesting that a high level of functional constraint acts on these genes. Strikingly, we find that a summary of the allele frequency spectrum is significantly correlated in humans and chimpanzees, perhaps reflecting very similar levels of constraint at these genes in the two species. A possible exception is FMR2, which shows a higher number of nonsynonymous than synonymous substitutions on the human lineage, suggesting the action of positive selection.

Animals↗
PubMed2006

Sepsis in European intensive care units: results of the SOAP study.

OBJECTIVE: To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight intensive care units in 24 European countries. PATIENTS: All new adult admissions to a participating intensive care unit between May 1 and 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries. CONCLUSIONS: This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

APACHE↗
PubMedDate not supplied

Tangle diseases and the tau haplotypes.

Neurofibrillary tangles are found in many neurologic diseases. Here we review the unusual characteristics of the MAPT locus, which shows genetic association with many of these diseases and in Caucasian populations, is the largest stretch of linkage disequilibrium in the genome. We discuss the reason for this disequilibrium, its evolutionary history, and the role of genetic variability at MAPT in the etiology of tauopathies.

Alzheimer Disease↗
PubMed2025

The Arms Race Between Actinobacillus pleuropneumoniae and Its Genetic Environment: A Comprehensive Analysis of Its Defensome and Mobile Genetic Elements.

Actinobacillus pleuropneumoniae is the causative agent of pleuropneumonia in swine, a highly contagious and economically significant disease. The genetic variability of A. pleuropneumoniae complicates disease control efforts, as it enables rapid adaptation to various stressors, including antimicrobial treatments. To better understand the molecular mechanisms underlying this adaptability, we investigated the role of the bacterial defensome and its relationship with mobile genetic elements (MGEs), such as prophages, plasmids, and integrative conjugative elements (ICEs). Using bioinformatic tools, we identified a diverse and rich defensome in A. pleuropneumoniae, with an average of 16 different defense systems per strain. We found that CRISPR-Cas systems, along with other defense mechanisms, are actively involved in restricting the entry of foreign genetic material, playing a crucial role in bacterial adaptation. Additionally, we characterized several novel prophages and examined their distribution across different strains, revealing their potential contribution to the bacterium's evolutionary success. Our findings underscore the complex interplay between the bacterium's defense systems and MGEs, shedding light on how A. pleuropneumoniae maintains genetic diversity while also safeguarding itself against external threats. These insights provide a better understanding of the genetic factors that influence the pathogen's adaptability and highlight potential avenues for more effective disease control strategies.

Actinobacillus pleuropneumoniae↗
PubMed2002

Differential selection of specific human immunodeficiency virus type 1/JC499 variants after mucosal and parenteral inoculation of chimpanzees.

Regardless of the route of transmission, it is generally accepted that the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted from an infected individual to an uninfected individual is genetically homogeneous. This finding and the observation that HIV-1 genotypes in recipients are minor variants in the donors suggest strongly that selection for specific variants occurs. However, most analyses have been limited to the V3 region of env. In addition, the exact time at which most new infections occurred was not known, making it almost impossible to analyze virus populations present in donor-recipient pairs at the time of HIV-1 transmission. To circumvent this problem, three chimpanzees were inoculated with a genetically defined stock of cell-free HIV-1/JC499 by one of three routes: intravenously or via the cervical or penile mucosa. PCR products of the C2-to-V5 region of env were amplified from both proviral DNA and virion RNA in blood samples collected soon after infection and were screened by heteroduplex analysis (HDA). Those PCR products with distinct HDA banding patterns were cloned and sequenced. In all three animals, transmitted variants encoded one of two V3-loop populations identified in the inoculum, indicating relative homogeneity in this region. However, different virus populations, defined by combinations of specific V4 and V5 sequences, were found when variants in the animal inoculated intravenously (at least 13 V4-plus-V5 combinations) were compared with those in the two animals inoculated by the mucosal routes (limited to only four V4-plus-V5 combinations). The only V4-plus-V5 population in variants found in all three chimpanzees was the major population in the inoculum, which contained viruses with more than 30 different V4-plus-V5 combinations. That the majority of the V4-plus-V5 genotypes in variants transmitted to all three animals were minor populations in the inoculum indicated that selective transmission defined by the V4-plus-V5 regions had occurred but that distinct populations were transmitted by parenteral versus mucosal routes. These results indicate that the putative homogeneity of HIV-1 variants in a newly infected individual might be an artifact of the region of the env gene evaluated and that regions other than V3 might play a major role in selective transmission.

Amino Acid Sequence↗
PubMed1990

The NT 1311 polymorphism of G6PD: G6PD Mediterranean mutation may have originated independently in Europe and Asia.

A polymorphic site exists in exon 11 of G6PD: in the wild-type enzyme, nucleotide (NT) 1311 is a C, but is some individuals from diverse populations a T is present instead. Nine of 54 X chromosomes from Europeans of mixed origins, nine of 41 X chromosomes of Ashkenazi Jewish subjects, three of 18 X chromosomes of Sicilians, five of 20 African X chromosomes, and nine of 20 Asian Indian X chromosomes had the mutant genotype. In contrast, the mutation was found in only three of 59 Oriental X chromosomes and in three of 30 Central/South American X chromosomes. The mutation was absent from four samples of chimpanzee DNA. Twenty-one of 22 male subjects from Mediterranean countries who had the G6PD Mediterranean 563T genotype investigated in the present study or reported previously had a T at NT 1311. Only one had the normal C at NT 1311. In contrast, both G6PD Mediterranean563T males from the Indian subcontinent had the normal C at NT 1311. These findings suggest that the same mutation at nucleotide 563 giving rise to G6PD Mediterranean may have arisen independently in Europe and in Asia.

Animals↗
PubMed1985

Diversity of African swine fever virus.

An African swine fever virus is an heterogeneous population, consisting of clones having different biological characteristics in respect to hemadsorption, virulence, infectivity, plaque size, and antigenic determinants. The following observations were made: Nonhemadsorbing virus (NHV) have been segregated from field isolates from Haiti (HT-1) and a bone marrow- and buffy coat-passaged Portuguese isolate (L'60BM89BC1) and appear as a major, minor, or equal mixture with hemadsorbing viruses in the virus population. Biological characteristics of the virus inoculated into pigs often differed from viruses isolated later from the same pigs. Virulence and nonhemadsorbing characteristics of isolated clones were genetically stable. The lethal effect of 2 NHV clones of L'60BM89BC1 virus was dose-dependent; small doses of virus induced immunologic deaths or recoveries from the clinical disease in pigs, and large doses induced acute deaths. The NHV of Lisbon isolate of 1960 (L'60) and HT-1 isolate share the same antigenic determinants for inducing protection. Tengani isolate contained clones of distinctly different antigenic determinants, not shared by L'60 or HT-1 isolate that enabled it to overcome the protection induced by the other clones. Passaging of an African swine fever virus isolate in pigs or cell cultures may readily alter the proportions of the different clones in the population and thereby change its overall characteristics. A new virus population with atypical hemadsorption was found in HT-1 field isolate and L'60BM89BC1 virus.

African Swine Fever↗