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At least 883 records · Page 49Linked to original sources
PubMed1998

Comparison of amino acid sequences in hypervariable region-1 of hepatitis C virus clones between human inocula and the infected chimpanzee sera.

We analyzed nucleic and amino acid sequences of the hypervariable region (HVR)-1 of the hepatitis C virus (HCV) from inocula and the infected chimpanzee sera. One milliliter each of 10(-5), 10(-3) and 10(-2) dilutions of serum no. 4, and those of 10(-4), 10(-5) and 10(-6) dilutions of serum no. 6 were inoculated to six different chimpanzees. Both inocula nos. 4 and 6 contained 10(7) copies of HCV RNA/ml. The two chimpanzees inoculated with 10(-4) and 10(-5) dilutions of no. 6 were infective, while none of the dilutions from inoculum no. 4 were infective. Our results indicated that HCV RNA titer in sera did not correlate with in vivo infectivity. RNA from both inocula and the infected chimpanzee sera were extracted and transcribed to cDNA. The PCR products amplifying the HCV HVR-1 were incorporated into a vector, followed by transformation. Twenty colonies were picked up randomly from each sample. DNA was extracted and the DNA and amino acid sequences were determined. Genetic variations of 20 clones from inoculum no. 6 were divided into six groups, whereas, 40 clones from infected chimpanzees were completely identical to the major quasispecies of inoculum no. 6 in amino acid sequences. The study suggested that the major quasispecies in the diluted inocula were transmitted and replicated.

Amino Acid Sequence↗
PubMed2000

The g factor in non-human animals.

Animals possess the attributes we label as 'intelligent' in humans. 'Insight' and 'reasoning' have been demonstrated in chimpanzees, monkeys, racoons, rats, mice, ravens and pigeons. In the rat, the animal species best characterized psychologically and neuroanatomically, reasoning ability correlates with other cognitive capacities and brain size. Other learning task paradigms tested on mice and rats have confirmed consistent individual differences, indicated a neuroanatomical network for learning, and shown the presence of genetic influences for cognitive ability. Animals offer an opportunity to test ideas about intelligence that cannot be performed on humans. Methylazoxymethanol (MAM) administered prenatally can arrest cortical cell division and produce a 'mentally retarded' microcephalic rat. This intellectual deficiency can be ameliorated by postnatal induction of dendritic arborization and synapse formation with naltrexone, suggesting the relevance of neuronal and synapse number for behavioural variation in rat g. Inbred mice lines differ in brain size and behaviour, permitting, through the use of recombinant inbred strains, the determination of genetic loci with quantitative effects on structure and function. Lastly, genetic contributions to g can be directly tested by modifying gene expression and determining the anatomical, physiological, and behavioural benefits.

Animals↗
PubMed2006

[Study on content variation of chemical constituents during combination of rhizoma coptidis alkaloids with fructus evodiae flavonoids by high performance liquid chromatography].

In order to study the compatibility of Chinese herbal drugs, a method was proposed by investigating chemical reactions with combination of chemical constituents or major groups of chemical compounds of Chinese herbal drugs. The content variation of chemical constituents during combination of rhizoma coptidis alkaloids with fructus evodiae flavonoids was analyzed by high performance liquid chromatography (HPLC). The experimental results showed that only small changes of the relative peak areas of different chemical constituents were observed and no new peaks were detected. No chemical reactions were observed during the compatibility test of rhizoma coptidis alkaloids with fructus evodiae flavonoids.

Chromatography, High Pressure Liquid↗
PubMed2004

Identification of variable amino acids in the SRS1 region of CYP6B1 modulating furanocoumarin metabolism.

The homology model of Papilio polyxenes CYP6B1 places Ile115, one of two variable amino acids, in the SRS1 of various CYP6B subfamily proteins in close proximity to the heme and Ala113, another variable amino acid, in a more distal position. We have constructed mutant CYP6B1 proteins altered at either of these positions and homology models of each based on multiple alignments with crystallized P450 proteins. The homology models suggest the existence of significant structural diversity in the hydrogen bond network surrounding the heme as a result of single point mutations in SRS1. Mutagenesis of Ile115 or Ala113 to other residues present in the insect CYP6B subfamily indicates that these amino acids control the spin state of the heme and, as a result, the catalytic activity of this monooxygenase. In particular, the I115L mutation significantly increases the spin state of the heme coordinately with 2- to 4-fold increases in its turnover of linear furanocoumarins. Other A113V, A113L, A113Q, and A113E mutations display more variation in their effects but, in each case, strong correlations exist between furanocoumarin turnover and heme spin state. These data demonstrate that variable amino acids in SRS1 of the insect CYP6B subfamily exert dramatic effects on the range of furanocoumarins metabolized, even when they occur in positions potentially distal from the substrate. These effects are possibly mediated through rearrangement of the local hydrogen bond network.

Amino Acid Sequence↗
PubMed1993

In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees.

Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4-cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murine anti-CD4. Moreover, the anti-cM-T412 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after either the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions.

Animals↗
PubMed2005

Biochemical fingerprints of prion diseases: scrapie prion protein in human prion diseases that share prion genotype and type.

The phenotype of human prion diseases is influenced by the prion protein (PrP) genotype as determined by the methionine (M)/valine (V) polymorphism at codon 129, the scrapie PrP (PrPSc) type and the etiology. To gain further insight into the mechanisms of phenotype determination, we compared two-dimensional immunoblot profiles of detergent insoluble and proteinase K-resistant PrP species in a type of sporadic Creutzfeldt-Jakob disease (sCJDMM2), variant CJD (vCJD) and sporadic fatal insomnia (sFI). Full-length and truncated PrP forms present in the insoluble fractions were also separately analyzed. These three diseases were selected because they have the same M/M PrP genotype at codon 129 and the same type 2 PrPSc, but different etiologies, also sCJDMM2 and sFI are sporadic, whereas vCJD is acquired by infection. We observed minor differences in the PrP detergent-insoluble fractions between sCJDMM2 and vCJD, although both differ in the corresponding fractions from sFI. We detected more substantial heterogeneity between sCJDMM2 and vCJD in the two-dimensional blots of the proteinase K-resistant PrP fraction suggesting that different PrP species are selected for conversion to proteinase K-resistant PrP in sCJDMM2 and vCJD. These differences are mostly, but not exclusively, due to variations in the type of the N-linked glycans. We also show that the over-representation of the highly glycosylated forms distinctive of the proteinase K-resistant PrPSc of vCJD in one-dimensional blots is due to differences in both the amount and the natures of the glycans. Overall, these findings underline the complexity of phenotypic determination in human prion diseases.

Biomarkers↗
PubMed2001

Heterogeneity of host immunological risk factors in patients with aggressive periodontitis.

BACKGROUND: The pathogenesis of early-onset periodontitis (EOP) can be explained by various host risk factors. Previous studies have focused on a single (among many possible) immunological risk factor and the association among the factors has not been assessed. We comprehensively investigated the associations among multiple host immunological risk factors in EOP patients to further elucidate their role in the pathogenesis of EOP. METHODS: Sixty-eight EOP patients (50 generalized EOP, 18 localized EOP), 51 EOP-suspected patients (S-EOP), 43 adult periodontitis (AP) patients, and 36 periodontally healthy subjects (HS) participated in this cross-sectional study. We examined peripheral neutrophil functions, phenotypic and functional characterization of peripheral lymphocytes (lymphocyte subsets, T-cell proliferative activity), cytokine productivity (interleukin [IL]-1, IL-2, tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, IL-4 and IL-6), serum immunoglobulin G (IgG) antibody titers against 12 periodontal bacteria, and HLA class II genotypes. RESULTS: G-EOP, S-EOP, and AP patient groups showed significantly lower percentages of pan T cells and CD8-positive cells (P < 0.02) compared with the HS group. L-EOP patients showed depressed IL-4 and TNF-alpha productivity compared with the HS group (P < 0.02). The EOP group showed significantly elevated antibody levels against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum compared with the HS group (P < 0.05). The frequency with DQB1*0503 was significantly higher in the EOP patient group than the HS group (P = 0.045) due to the higher frequency in L-EOP patients than the HS group (P = 0.035). There were wide interindividual variations in each of the tests among patient and HS groups; however, EOP patients showed wider intradiagnostic group variations in certain host defensive cell functions than the other groups. There were some EOP patients who showed extremely low or high values in some tests; the EOP patients could be further divided into subgroups according to their host defensive and immunological profiles. However, there was heterogeneity in some of the other host immunological tests even in the subgroups. CONCLUSIONS: The association of host immunological risk factors in EOP patients is widely varied and more complex than previously thought. These results indicate the difficulty of explaining the pathogenesis of EOP based on a single host risk factor and also emphasize the importance of critical assessment of not only EOP patient groups, but also individual patients.

Adult↗
PubMed2006

Reproducibility and validity of a Chinese food frequency questionnaire used in Taiwan.

A 64-item Chinese food frequency questionnaire (FFQ) combined with open questions on types of staples and cooking oil most frequently consumed was designed for a prospective study in Taiwan to appraise participants' usual intake. We examined its reproducibility and validity. The form was administered three times at three-month intervals by face-to-face interview to 83 senior college students majoring in nutrition, in order to recall their usual dietary intake over the past six months. They also completed five-day (includes both weekends) diet records (DR) after each interview. Averaged intake levels of most nutrients assessed by the three FFQs were slightly higher than those of 15-day DR. Intraclass correlation coefficients for nutrient intakes assessed by three FFQs three months apart ranged from 0.37 for saturated fat to 0.82 for alcohol (average: 0.52). Averaged Pearson correlation coefficients between the unadjusted and energy-adjusted nutrient intakes measured by DR and by the third FFQ (which asked about diet during the six months encompassing the diet records) were 0.40 and 0.35, respectively, not including vitamins A and C. These correlations were higher (average: 0.47) after adjusting for the daily variation of the diet records. On average, 50% subjects were correctly classified into the same tertiles by both methods; 11% of the subjects were misclassified to extreme categories. These data indicate that this FFQ for Chinese-speaking people in Taiwan is reproducible and provides a useful measure of intake for many nutrients over a six-month period.

Adult↗
PubMed2006

A pan-Canadian perspective on institutional long-term care.

We aggregate long-term care (LTC) facility-level data collected by Statistics Canada to National and regional levels to make observations relating to environmental characteristics--including the age distribution by region, and market share by type of ownership--and organizational characteristics--including ownership, facility size, resident age distribution, and the types of care provided in facilities by ownership. We observe significant differences in ownership by region, in facility size by ownership, and in levels of resident care provided by ownership. Further, we examine some of the classic proxies for quality of care for the LTC sector in this paper, including a variety of staffing intensity levels, observing significant differences in staffing intensities by region. We hope that our observations prompt researchers and policy makers to question the desirability and implications of this variation in the Canadian LTC industry.

Aged↗
PubMed2003

Assertive outreach teams in London: models of operation. Pan-London Assertive Outreach Study, part 1.

BACKGROUND: Assertive outreach teams have been introduced in the UK, based on the assertive community treatment (ACT) model. It is unclear how models of community care translate from one culture to another or the degree of adaptation that may result. AIMS: To characterise London assertive outreach teams and determine whether there are distinct groups within them. METHOD: Semi-structured interviews with team managers plus one month's prospective process of care data collection were used to test for 'model fidelity' to ACT and, by cluster analysis, to identify groupings. RESULTS: Fidelity varied widely, with four teams (out of 24 studied) rated 'high fidelity' and three teams rated 'low fidelity' by US standards and 17 rated 'ACT-like'. Three clusters were identified, with voluntary sector teams being the most distinct group. CONCLUSIONS: There is wide variation in the practice of assertive outreach in London. The role of the voluntary sector requires increased attention. Heterogeneity in practice is a clinical challenge but a research opportunity in distinguishing effective from redundant components of the approach.

Adult↗
PubMed2004

Activity of plasma sprayed yttria stabilized zirconia reinforced hydroxyapatite/Ti-6Al-4V composite coatings in simulated body fluid.

Hydroxyapatite (HA)/yttria stabilized zirconia/Ti-6Al-4V bio-composite coatings deposited onto Ti-6Al-4V substrate through a plasma spray technique were immersed in simulated body fluid (SBF) to investigate their behavior in vitro. Surface morphologies and structural changes in the coatings were analyzed by scanning electron microscopy, thin-film X-ray diffractometer, and X-ray photoelectron spectroscopy. The tensile bond strength of the coatings after immersion was also conducted through the ASTM C-633 standard for thermal sprayed coatings. Results showed that carbonate-containing hydroxyapatite (CHA) layer formed on the surface of composite coatings after 4 weeks immersion in SBF solution, indicating the composite coating possessed excellent bioactivity. The mechanical properties were found to decrease with immersion duration of maximum 56 days. However, minimal variation in mechanical properties was found subsequent to achieving supersaturation of the calcium ions, which was attained with the precipitation of the calcium phosphate layers. The mechanical properties of the composite coating were found to be significantly higher than those of pure HA coatings even after immersion in the SBF solution, indicating the enhanced mechanical properties of the composite coatings.

Alloys↗
PubMed2002

A strong signature of balancing selection in the 5' cis-regulatory region of CCR5.

CCR5 encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for HIV-type 1 (HIV-1). Varied HIV-1 susceptibility and time to progression to AIDS have been associated with polymorphisms in CCR5. Many of these polymorphisms are located in the 5' cis-regulatory region of CCR5, suggesting that it may have been a target of natural selection. We characterized CCR5 sequence variation in this region in 400 chromosomes from worldwide populations and compared it to a genome-wide analysis of 100 Alu polymorphisms typed in the same populations. Variation was substantially higher than expected and characterized by an excess of intermediate-frequency alleles. A genealogy of CCR5 haplotypes had deep branch lengths despite markedly little differentiation among populations. This finding suggested a deviation from neutrality not accounted for by population structure, which was confirmed by tests for natural selection. These results are strong evidence that balancing selection has shaped the pattern of variation in CCR5 and suggest that HIV-1 resistance afforded by CCR5 5' cis-regulatory region haplotypes may be the consequence of adaptive changes to older pathogens.

Alleles↗
PubMed2006

Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees.

This study determined whether selective transmission of hepatitis C virus (HCV) species occurred among human and chimpanzee recipients of contaminated blood products or plasma containing multiple genotypes, subgenotypes and quasispecies. Commercially prepared factor VIII concentrate (lot DO56), produced prior to HCV testing and inactivation, was subsequently found by direct cloning to contain the following subgenotypes: 1a and 1b (73 % of clones), 2a (13 % of clones), 2b (11 % of clones) and 3a (4 % of clones). A patient transfused with factor VIII concentrate DO56 was diagnosed with clinical non-A, non-B hepatitis and subsequently found to be infected with HCV subgenotype 1b. Among five chimpanzees inoculated experimentally with the same factor VIII concentrate, two were infected only with HCV subgenotype 1a and three were infected with approximately equivalent clonal proportions of subgenotypes 1a and 1b. HCV hypervariable region 1 (HVR1) quasispecies analysis of the DO56 factor VIII concentrate and a serum specimen from the single chimpanzee that developed a chronic HCV infection following inoculation with DO56 showed 0-56 % nucleotide variation. However, specimens from chimpanzees infected in the second to fourth passages of the DO56 inoculum had 0-8 % HVR1 quasispecies nucleotide variation. The high HVR1 quasispecies variation in the factor VIII concentrate and its first passage in chimpanzees indicates the presence of multiple HCV isolates, whereas the low variation in the second to fourth chimpanzee passages suggests transmission of a single HCV isolate. These findings strongly suggest selective transmission of HCV isolates during experimental chimpanzee infection and among humans exposed to multiple HCV species.

Animals↗
PubMed1995

The feline lymphoid cell line MBM and its use for feline immunodeficiency virus isolation and quantitation.

We report on the development of a feline T lymphoblastoid cell line obtained from the peripheral blood mononuclear cells (PBMC) of a specific pathogen free cat and designated MBM. The cells are pan-T+, CD4- and CD8- and remained interleukin-2-dependent and concanavalin A-dependent throughout the period of observation. MBM cells have proved at least as sensitive as fresh blasts to infection with cell-free stocks of three feline immunodeficiency virus (FIV) isolates. Upon infection, they exhibit a lytic cytopathic effect. Repeated attempts to establish a chronic infection have failed. Using a limiting cell dilution method, it has been shown that MBM cells may be more sensitive than fresh blasts as substrate for isolating FIV from the PBMC of infected cats. These studies have also shown that considerable individual variations exist in the virus loads present in the PBMC of naturally infected cats, and that load size does not appear to correlate with cat age, clinical status, CD4/CD8 ratio and titer of serum neutralizing antibody.

Animals↗
PubMed2002

Brain size and the human cranial base: a prenatal perspective.

Pivotally positioned as the interface between the neurocranium and the face, the cranial base has long been recognized as a key area to our understanding of the origins of modern human skull form. Compared with other primates, modern humans have more coronally orientated petrous bones and a higher degree of basicranial flexion, resulting in a deeper and wider posterior cranial fossa. It has been argued that this derived condition results from a phylogenetic increase in the size of the brain and its subcomponents (infra- and supratentorial volumes) relative to corresponding lengths of the cranial base (posterior and anterior, respectively). The purpose of this study was to test such evolutionary hypotheses in a prenatal ontogenetic context. We measured the degree of basicranial flexion, petrous reorientation, base lengths, and endocranial volumes from high-resolution magnetic resonance images (hrMRI) of 46 human fetuses ranging from 10-29 weeks of gestation. Bivariate comparisons with age revealed a number of temporal trends during the period investigated, most notable of which were coronal rotation of the petrous bones and basicranial retroflexion (flattening). Importantly, the results reveal significant increases of relative endocranial sizes across the sample, and the hypotheses therefore predict correlated variations of cranial base flexion and petrous orientation in accordance with these increases. Statistical analyses did not yield results as predicted by the hypotheses. Thus, the propositions that base flexion and petrous reorientation are due to increases of relative endocranial sizes were not corroborated by the findings of this study, at least for the period investigated.

Animals↗
PubMed1993

Immunocytochemical expression of protein gene product (PGP) 9.5 in the cat bronchopulmonary neuroendocrine cells and nerves.

Variously fixed, wax-embedded lung and gastrointestinal serial tissue sections from newborn to adult cats were stained with hematoxylin-eosin (H&E), Grimelius' silver, and immunohistochemical techniques using antisera to protein gene product (PGP) 9.5, a neuron-specific protein under strong evolutionary constraints. PGP 9.5 is revealed as a pan-neuroendocrine marker useful for tracing the pulmonary diffuse neuroendocrine system (PDNES) and studying the relationships between neuronal and neuroendocrine elements at various stages of life. Its occurrence is also compared in the pulmonary and the gastrointestinal tract. In spite of a close resemblance to already described neuroepithelial bodies (NEB) of other mammals, cat NEB feature typical constitutional and distributional difference, illustrating interspecies differences. The number of PGP 9.5 immunopositive pulmonary neuroendocrine cells declines gradually after 3 weeks and throughout adult life. Immunoreactivity in neuronal elements is lost after 1 week of age. In gastrointestinal tissues, only neuronal elements immunostain, suggesting functional variations or a separate embryological origin for enteroendocrine cells.

Animals↗
PubMed2000

Interaction between the hepatitis C virus and the immune system.

The hepatitis C virus (HCV) causes a wide spectrum of liver diseases ranging from symptomatic or asymptomatic acute infection with self-limited disease to persistent infection with chronic active hepatitis and an increased risk of liver cirrhosis and hepatocellular carcinoma. The outcome of HCV infection (i.e., viral clearance or persistence) and the manifestation and degree of liver disease is the result of complicated interactions between the virus and the immune response of the host. Remarkably, most de novo HCV infections are clinically inapparent and characterized by a high incidence (70%) of chronically evolving hepatitis, which suggests that HCV may have evolved strategies to not induce, overcome, or evade efficient immune responses of the host. This may be a multifactorial process, influenced by viral tissue tropism, replication, sequence variation and by functional alteration of infected cells. The interaction between HCV and the specific humoral and cellular immune response of the host, the role of the liver as the primary site of viral replication, the target of the host's immune response, and potential mechanisms of viral escape are discussed.

Animals↗
PubMed2004

Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape.

Escape mutations are believed to be important contributors to immune evasion by rapidly evolving viruses such as hepatitis C virus (HCV). We show that the majority of HCV-specific cytotoxic T lymphocyte (CTL) responses directed against viral epitopes that escaped immune recognition in HCV-infected chimpanzees displayed a reduced CDR3 amino acid diversity when compared with responses in which no CTL epitope variation was detected during chronic infection or with those associated with protective immunity. Decreased T cell receptor (TCR) CDR3 amino acid diversity in chronic infection could be detected long before the appearance of viral escape mutations in the plasma. In both chronic and resolved infection, identical T cell receptor clonotypes were present in liver and peripheral blood. These findings provide a deeper understanding of the evolution of CTL epitope variations in chronic viral infections and highlight the importance of the generation and maintenance of a diverse TCR repertoire directed against individual epitopes.

Amino Acid Sequence↗