Biomedical subjects

A Heath

Publications and source records attributed to A Heath.

At least 19 recordsLinked to original sources

PubMed2005

World Health Organization collaborative study to establish a replacement WHO international standard for hepatitis C virus RNA nucleic acid amplification technology assays.

BACKGROUND AND OBJECTIVES: A collaborative study was undertaken to establish a replacement for the current (1st) World Health Organization (WHO) hepatitis C virus (HCV) International Standard, 96/790. MATERIALS AND METHODS: Both the 1(st) International Standard and the replacement standard were prepared from the same starting material by diluting a high titre genotype 1a HCV isolate in pooled, human plasma. The only difference was that each standard was lyophilized in two, separate lyophilisation runs but under the same conditions. RESULTS: In the study to establish the 1st International Standard, no significant difference in potency was found between the material eventually designated as the 1st International Standard and that now selected as the 2nd International Standard. The present study also showed no significant differences between the materials stored at -20 degrees C and no evidence of degradation over 5 years. CONCLUSIONS: Material 96/798 was established as the 2nd HCV International Standard and assigned the same unitage as the 1st International Standard, i.e. 10(5) IU/ml (50,000 IU/vial).

DNA Primers↗

PubMed2005

International collaborative study to evaluate a candidate reference preparation to define an appropriate specified limit of anti-D in intravenous immunoglobulin products.

BACKGROUND AND OBJECTIVES: The aim of the study was to evaluate a lyophilized intravenous immunoglobulin (IVIG) preparation containing anti-D (02/228; nominal reciprocal titre of 8) for its suitability to define the maximum limit of anti-D in IVIG products when used in a proposed reference method of direct haemagglutination of papain-treated erythrocytes, in an international collaborative study. MATERIALS AND METHODS: Twenty laboratories tested 02/228 along with a negative control IVIG preparation and four IVIG samples containing different levels of anti-D. Nineteen laboratories performed direct haemagglutination methodology using papain-treated erythrocytes; five of these laboratories and one additional laboratory performed their in-house haemagglutination methodology (all indirect antiglobulin tests). RESULTS: The mode titre of 02/228, obtained by using the proposed reference method, was 8 (62.5% of tests). However, there was wide variation in haemagglutination titres between laboratories for three of the four samples. Correcting the titres of the samples relative to those of the proposed reference preparation reduced the interlaboratory variability and increased the frequency of the mode titres in three out of four samples. The indirect antiglobulin tests also showed wide interlaboratory variability and were less sensitive than the direct method in four laboratories. Eleven of the 14 laboratories that expressed an opinion considered that the level of anti-D in 02/228 was appropriate to define a specified limit. CONCLUSIONS: Our results demonstrate the necessity of using a reference preparation to define the maximum level of anti-D in IVIG products and ensure sufficient sensitivity in haemagglutination testing methodology. On the basis of these results, members of the European Pharmacopoeia Expert Group 6B recommended revision of the appropriate monograph to include this new specification and test. The Food and Drug Administration in the USA intends to adopt the same maximal specification defined by the reference preparation and to recommend the same test for the safety of IVIG products. Preparations 02/228 and 02/226 were also established by the World Health Organization as International Reference Reagents to standardize haemagglutination testing for anti-D in normal IVIG products.

Cooperative Behavior↗

PubMed2005

A World Health Organization International Standard for hepatitis A virus RNA nucleic acid amplification technology assays.

BACKGROUND AND OBJECTIVES: Sixteen laboratories from 10 different countries participated in an international collaborative study to evaluate candidate materials as the first World Health Organization (WHO) International Standard for hepatitis A virus (HAV) RNA nucleic acid amplification technology (NAT) assays. MATERIALS AND METHODS: Five candidate materials were analysed in this study: materials AA and BB were lyophilized, while materials CC, DD and EE were liquid preparations. Samples were diluted in pooled plasma or in pooled cryo-poor plasma (sample EE). Serial dilutions of the candidate materials were tested by each laboratory in four independent assays and the results were analysed statistically. RESULTS: The mean log(10)'equivalents' per ml were 5.29 for sample AA, 5.07 for sample BB, 4.99 for sample CC, 5.40 for sample DD and 4.08 for sample EE. CONCLUSIONS: Based on the results of this study, sample AA was established as the first International Standard for HAV RNA NAT assays at the WHO Expert Committee on Biological Standardizaton (ECBS) meeting held in February 2003. The code number of this preparation is 00/560 and the potency, based on the study, is 100 000 International Units (IU)/ml.

Cooperative Behavior↗

PubMed2003

Clonal analysis of a human antimouse antibody (HAMA) response.

Circulating human antimouse antibodies (HAMAs) directed to mouse immunoglobulin G (IgG) are clinically significant, compromising mouse antibody therapy and imaging, and interfering in immunological assays. To investigate the HAMA response, 20 stable cell lines secreting human monoclonal antibodies reactive with mouse IgG were established from a donor with a history of exposure to mice. Their subclass and domain specificities were established by solid-phase binding, indirect haemagglutination assays and immunoblotting, using Igs of known subclass and Ig fragments. The heavy-chain variable region gene usage was determined for 12 HAMAs. Eight HAMAs were IgM, 11 HAMAs were IgG4 and one HAMA was IgG1, indicating an IgG4-dominated response. All of the IgG HAMAs reacted with epitopes present on the Fc portion; one was subclass-specific, nine were subclass-restricted and two were pan-IgG-reactive. Measurement of their affinities gave dissociation constants typically in the nanomolar range. Seven and five HAMAs were derived from variable heavy-chain 3 (VH3) and VH1 gene segments, respectively. The IgG HAMAs used different VH segments to the IgM HAMAs. JH regions were coded by JH4 in eight HAMAs. DH segment usage appeared to be restricted in the IgM HAMAs. Two IgG HAMAs were clonally related. These monoclonal HAMAs are potentially useful as reagents for detecting mouse IgG and as reference reagents for the investigation of the HAMA response in patients undergoing mouse monoclonal antibody therapy and for the investigation of the influence of HAMAs on immunodiagnostic tests.

Amino Acid Sequence↗

PubMed2003

Collaborative study to calibrate hepatitis C virus genotypes 2-6 against the HCV International Standard, 96/790 (genotype 1).

BACKGROUND AND OBJECTIVES: A major requirement of a hepatitis C virus (HCV) RNA nucleic acid amplification technology (NAT) assay validation is the ability of the assay to detect the six major genotypes of HCV with equivalent sensitivities. The aim of this study was to characterize and calibrate an HCV genotype panel for use in such studies. MATERIALS AND METHODS: Panels consisting of the first International Standard (IS) for HCV RNA NAT assays (96/790; HCV genotype 1a) and isolates of genotypes 2-6 were sent to 17 laboratories worldwide which use a variety of NAT tests, both qualitative and quantitative. The HCV RNA content of each panel member was determined and the mean titre calculated in International Units/ml (IU/ml). RESULTS: The calculated mean titres (calibrated against the HCV International Standard), in log10 IU/ml, of the genotype 2-6 samples were 3.99, 3.81, 4.14, 4.18 and 4.61, respectively. CONCLUSIONS: An HCV genotype panel, calibrated in IU/ml, has been established and should be valuable for assay validation. All the genotypes were detected by all the assays used, but it was not possible to demonstrate that the genotypes were detected with equal efficiencies.

Calibration↗

PubMed2002

Establishment of the first World Health Organization International Standard for human parvovirus B19 DNA nucleic acid amplification techniques.

BACKGROUND AND OBJECTIVES: A collaborative study, involving 26 laboratories from 14 countries, was carried out in order to establish a World Health Organization (WHO) International Standard for human parvovirus B19 (B19) DNA nucleic acid amplification techniques (NAT). MATERIALS AND METHODS: Four samples: AA, BB (which were lyophilized), CC and DD (which were liquid preparations) were analysed using several different NAT assays. The mean B19 DNA content of each sample was determined for each laboratory using an end-point dilution method. RESULTS: There was good agreement between the overall mean 'equivalents'/ml obtained by the different assays. The mean log(10) 'equivalents'/ml were 5.76 for sample AA, 5.73 for sample BB, 5.82 for sample CC and 7.70 for sample DD. The differences in titre among samples AA, BB and CC were not statistically significant, but the titre of DD was significantly higher. CONCLUSIONS: Despite the range of NAT assays used in the study, it was possible to calculate the mean B19 DNA concentrations in the four preparations. Lyophilized preparation AA was established as the first International Standard for B19 DNA NAT assays and was assigned a concentration of 10(6) international units (IU)/ml.

DNA, Viral↗

PubMed2001

A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen in primary care practice. The symptoms of IBS, including abdominal pain, discomfort, and abnormal bowel function, may be modulated by activity of the serotonin type 3 receptor (5-HT(3)). The efficacy and tolerability of the 5-HT(3) receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind, randomized, placebo-controlled trial. METHODS: Patients received either 1 mg of alosetron hydrochloride (n = 309) or placebo (n = 317) twice daily for 12 weeks, followed by a 4-week posttreatment period. Adequate relief of IBS pain and discomfort was the primary end point. Secondary end points included improvements in urgency, stool frequency, stool consistency, incomplete evacuation, and bloating. RESULTS: Seventy-one percent of patients were classified as having diarrhea-predominant IBS. Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS reported adequate relief for all 3 months compared with 26% of placebo-treated patients (P<.001; percentage point difference = 17; 95% confidence interval, 8.0-25.4). Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment. Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment. Effects were sustained throughout treatment and symptoms returned following treatment cessation. No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment. Constipation was the most commonly reported adverse event. CONCLUSION: Alosetron hydrochloride, 1 mg twice daily for 12 weeks, is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS.

Administration, Oral↗

PubMed2001

Spontaneous mutations in the CsrRS two-component regulatory system of Streptococcus pyogenes result in enhanced virulence in a murine model of skin and soft tissue infection.

CsrS/CsrR is a 2-component system in Streptococcus pyogenes that negatively regulates hyaluronic capsule and several exotoxins. To detect spontaneous mutations in csrRS, mucoid and large colony variants of M1 strain MGAS166 were isolated from experimental murine skin infections. By use of complementation with a csrRS(+) plasmid, relevant mutations were also detected in 7 of 12 human clinical isolates. The presence of spontaneous mutants in mouse infection was associated with larger, more necrotic lesions. Most spontaneous changes in CsrR resulted from single amino acid substitutions, whereas most csrS mutations were frameshift or nonsense mutations. In 2 instances, IS1548 insertions were found in csrS. Experimental inoculation of mixtures of wild-type (wt) and csrRS(-) bacteria yielded larger, more necrotic lesions than did either strain at twice the inoculum, which suggests that these variants may exhibit pathogenic synergy. Spontaneous emergence of csrRS(-) mutants in vivo enhances the virulence of wt bacteria and increases severity of murine skin infection.

Amino Acid Substitution↗

PubMed2001

Identification of a major, CsrRS-regulated secreted protein of Group A streptococcus.

CsrR/CsrS (CovR/CovS) is a two-component regulator of extracellular virulence factors in Group A streptococcus, but the full range of regulated exoproteins is unknown. Since CsrR represses expression of regulated factors, culture supernates of wild-type and CsrR(-)mutant strains were compared by two-dimensional gel electrophoresis (2DGE) to identify regulated exoproteins. Supernates of DeltacsrRS(-)mutant, but not wild-type, bacteria contained an abundant 23 kDa protein. The N-terminal sequence of this spot corresponded to a putative open reading frame (ORF) in the streptococcal genome. In a mobility shift assay, phosphorylated CsrR bound to a PCR amplicon that included sequences upstream of this ORF. By primer extension analysis, the ORF (designated mspA, for Mucoidy-associated Secreted Protein) was expressed in mid- and late-exponential phase in a DeltacsrRS(-)mutant. The presence of an in-frame deletion in mspA did not affect colony appearance, mucoidy or in vitro growth, and there was no difference between DeltamspA and wild-type strains in a mouse model of skin infection. MspA is co-regulated with other factors required for dermonecrosis (e.g. capsule, streptolysin S and purogenic exotoxin B); however, deletion of this gene does not affect expression of hyaluronic acid capsule or severity of skin infection in mice.

Animals↗

PubMed2001

An international collaborative study to establish the 1st international standard for HIV-1 RNA for use in nucleic acid-based techniques.

Twenty-six laboratories from 10 different countries participated in a collaborative study to establish the 1st International Standard for HIV-1 RNA for use in nucleic acid-based techniques (NAT). Three candidate preparations were tested all based on genotype B viruses. The candidates were tested by each laboratory at a range of dilutions in four independent assays and the results collated and analysed statistically. All three candidates gave results that were tightly grouped, with little difference between the results from different laboratories or from the use of different assays. Studies of relative potency showed good agreement between laboratories. There were no significant differences between five commercial assay types, except that candidate XX showed a slightly lower potency compared to YY and ZZ with a single commercial assay. The reason for this was not established. Degradation studies showed that the freeze-dried preparations were stable at -20,4 and 20 degrees C for 26 weeks, the longest period studied, but that they became difficult to reconstitute after 3 weeks at 45 degrees C and 9 weeks at 37 degrees C. As a result of the study, the World Health Organisation (WHO) Expert Committee on Biological Standardisation (ECBS) established the preparation referred to as candidate YY (NIBSC Code No. 97/656) as the 1st International Standard for HIV-1 RNA for use with NAT with an assigned potency of 100000 International Units per vial.

HIV Infections↗

PubMed2001

Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: the dominant role of DHI.

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Biopsy↗

PubMed2001

An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques.

BACKGROUND AND OBJECTIVES: Twenty-two laboratories from nine countries participated in an international collaborative study to establish a World Health Organization (WHO) international standard for hepatitis B virus (HBV) DNA nucleic acid amplification techniques (NAT). MATERIALS AND METHODS: Three samples, AA, BB (both of which were lyophilized) and CC (which was a liquid preparation), were analysed using several different NAT assays. The mean HBV DNA content of each sample was determined from the study. RESULTS: Despite the range of assays (commercial and in-house) used by participants, there was good agreement among the overall mean 'equivalents'/ml obtained by the different assays, except for one laboratory (laboratory 4). The variation in estimates of log10 'equivalents'/ml was 1.75-1.25 for the three samples if results from laboratory 4 were excluded. The mean log10 'equivalents'/ml for all laboratories were 6.42 for sample AA, 6.30 for sample BB and 5.03 for sample CC (exclusion of results from laboratory 4 made little difference). The difference in titres between the two lyophilized samples (AA and BB) was not statistically significant but the titre of the frozen sample (CC) was significantly lower. Material AA (code 97/746) was accepted as the first WHO international standard for HBV DNA NAT assays and assigned a potency of 10(6) international units (IU)/ml. CONCLUSIONS: The titres (genome equivalents/ml) of three HBV preparations were determined by several laboratories using different NAT assays. This study enabled the establishment of an international standard, 97/746, for HBV DNA NAT assays.

DNA, Viral↗

PubMed2001

Latent class analysis of ADHD and comorbid symptoms in a population sample of adolescent female twins.

Attention-deficit/hyperactivity disorder (ADHD) is a phenotypically heterogeneous and highly heritable syndrome. which commonly co-occurs with other psychiatry disorders. To assess the role of genetic influences in ADHD, we used latent class analysis (LCA) to identify subtypes of ADHD taking into account its comorbidity with separation anxiety, oppositional defiant disorder (ODD), and three major depression symptoms. A structured interview was used to collect diagnostic data from a population sample of 2,904 adolescent female twins and their parents. LCA was applied to ADHD. separation anxiety. ODD symptom profiles obtained from the twins' parents, and major depression symptom profiles obtained from the twins' self-report. Odds ratios were used to test for familiality of class membership by examining the effect of zygosity on twin concordance within and between latent classes. Structural equation modeling was used to compute heritabilities for latent class membership. LCA revealed three ADHD categories of clinical interest: an inattentive subtype without comorbidity, a second inattentive subtype with increased number of ODD symptoms. and a combined inattentive/hyperactive-impulsive type with elevated levels of ODD, separation anxiety, and depressive symptoms. LCA also distinguished an ODD class and a separation anxiety class, each without increased levels of other comorbid symptoms; a second ODD class co-occurring with increased separation anxiety and depression symptoms; and a pure depression class. Odds ratios for MZ contrasted with DZ twin concordance for individual latent class membership ranged from 2.5 to 19.4. Overall, 66% of MZ pairs, but only 36% of DZ pairs, were assigned to the same latent class, consistent with a genetic hypothesis for latent class membership. Individual class membership was shown to have high heritability ranging from .34-.85. The pattern of latent classes suggested that in the general female adolescent population, there are three highly heritable ADHD subtypes, two of which are comorbid with other disorders. These classes were consistent with a genetic hypothesis for ADHD, with each class potentially reflecting a unique genetic subtype.

Adolescent↗

PubMed2001

Familiality and heritability of subtypes of attention deficit hyperactivity disorder in a population sample of adolescent female twins.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a highly heritable but clinically heterogeneous syndrome. The study examined the familiality and heritability of ADHD subtypes as defined by DSM-IV and by latent-class analysis in a population sample of adolescent female twins. METHOD: To determine which elements of ADHD cluster together, latent-class analysis was applied to data obtained from parents on the 18 DSM-IV ADHD symptoms in 4,036 female twins age 13-23 years in a population sample identified from the registry of all births in Missouri for the years 1968-1996. Relative risk and odds ratios were used to assess within-subtype and between-subtype familiality and heritability of both DSM-IV and latent-class ADHD subtypes. RESULTS: Latent-class analysis was most compatible with the existence of three mild and three severe classes of ADHD symptoms in the general population. The three severe classes showed moderate overlap with DSM-IV ADHD subtypes. The primarily inattentive and combined subtypes of DSM-IV ADHD co-clustered within families. The primarily hyperactive/impulsive DSM-IV subtype and the individual latent-class analysis subtypes did not co-cluster. Subtypes defined by both approaches were highly heritable. CONCLUSIONS: Unlike DSM-IV subtypes of ADHD, latent-class ADHD subtypes appear to be independently transmitted in families. These classes may be more appropriate targets for molecular genetic studies of ADHD.

Adolescent↗

PubMed2001

An exploration of the value of the personal doctor-patient relationship in general practice.

BACKGROUND: Within the context of general practice, continuity of care creates an opportunity for a personal doctor-patient relationship to develop which has been associated with significant benefits for patients and general practitioners (GPs). Continuity of care is, however, threatened by trends in the organisational development of primary health care in the United Kingdom and its intrinsic role within general practice is currently the subject of debate. AIMS: To determine how many patients report having a personal doctor and when this is most valued, to compare the value of a personal doctor-patient relationship with that of convenience, and to relate these findings to a range of patient, GP, and practice variables. DESIGN OF STUDY: Cross sectional postal questionnaire study. SETTING: Nine hundred and ninety-six randomly selected adult patients from a stratified random sample of 18 practices and 284 GP principals in Oxfordshire. METHOD: Qualitative interviews with patients and GPs were conducted and used to derive a parallel patient and GP questionnaire. Each patient (100 from each practice) was invited to complete a questionnaire to evaluate their experience and views concerning personal care. All GP principals currently practising in Oxfordshire were sent a similar questionnaire, which also included demographic variables. RESULTS: Overall, 75% of patients reported having at least one personal GP. The number of patients reporting a personal GP in each practice varied from 53% to 92%. Having a personal doctor-patient relationship was highly valued by patients and GPs, in particular for more serious, psychological and family issues when 77-88% of patients and 80-98% of GPs valued a personal relationship more than a convenient appointment. For minor illness it had much less value. CONCLUSIONS: Patients and GPs particularly value a personal doctor-patient relationship for more serious or for psychological problems. Whether a patient has a personal GP is associated with their perception of its importance and with factors which create an opportunity for a relationship to evolve.

Adolescent↗

PubMed2000

Virulence gene regulation inside and outside.

Much knowledge about microbial gene regulation and virulence is derived from genetic and biochemical studies done outside of hosts. The aim of this review is to correlate observations made in vitro and in vivo with two different bacterial pathogens in which the nature of regulated gene expression leading to virulence is quite different. The first is Vibrio cholerae, in which the concerted action of a complicated regulatory cascade involving several transcription activators leads ultimately to expression of cholera toxin and the toxin-coregulated pilus. The regulatory cascade is active in vivo and is also required for maintenance of V. cholerae in the intestinal tract during experimental infection. Nevertheless, specific signals predicted to be generated in vivo, such as bile and a temperature of 37 degrees C, have a severe down-modulating effect on activation of toxin and pilus expression. Another unusual aspect of gene regulation in this system is the role played by inner membrane proteins that activate transcription. Although the topology of these proteins suggests an appealing model for signal transduction leading to virulence gene expression, experimental evidence suggests that such a model may be simplistic. In Streptococcus pyogenes, capsule production is critical for virulence in an animal model of necrotizing skin infection. Yet capsule is apparently produced to high levels only from mutation in a two-component regulatory system, CsrR and CsrS. Thus it seems that in V. cholerae a complex regulatory pathway has evolved to control virulence by induction of gene expression in vivo, whereas in S. pyogenes at least one mode of pathogenicity is potentiated by the absence of regulation.

Animals↗

PubMed2000

Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-gamma stimulation through a mechanism dependent on endogenous TNF-alpha and IL-1alpha.

Bone marrow contains nonadherent low-density wheat germ agglutinin-positive (Fr3-WGA(+)) cells that release large amounts of NO and show natural suppressor activity if stimulated with activated T cells. We have assessed the involvement of CD40-derived signals in NO production and their cytokine requirements. Production of NO by Fr3-WGA(+) cells in co-culture with activated T cells is inhibited by a competing CD40 soluble fusion protein. Fr3-WGA(+) cells express the inducible NO synthase (iNOS) and release NO following CD40 plus IFN-gamma activation. Production of NO through CD40 is strictly dependent on endogenous TNF-alpha and / or IL-1alpha, since it is inhibited by neutralizing these cytokines or blocking the TNF receptor (p55). Both cytokines are transcribed when Fr3-WGA(+) cells are stimulated by CD40 signaling plus IFN-gamma, although TNF-alpha remains below detection limits in stimulated Fr3-WGA(+) cell cultures. Phenotypic studies combined with data on intracellular iNOS expression and cell sorting indicate that NO-producing cells are CD40, CD31 (ER-MP12), CD11b (Mac-1)low, ER-MP20 (Ly-6C) and Gr-1 (Ly-6G) positive, consistent with myeloid progenitors. The results point to early myeloid cells as an important cell source of NO once triggered by activated T cells through CD40 and IFN-gamma-derived signals, in a mechanism involving the production of TNF-alpha and / or IL-1alpha.

Animals↗

PubMed2000

Phylogeny and life history evolution of the genus Chrysoritis within the Aphnaeini (Lepidoptera: Lycaenidae), inferred from mitochondrial cytochrome oxidase I sequences.

Phylogenetic relationships among 26 South African species in the tribe Aphnaeini (Lepidoptera: Lycaenidae) were inferred from DNA characters of the mitochondrial gene cytochrome oxidase I (COI), using maximum-parsimony methods. The resulting phylogenetic estimate supports the systematic hypothesis made by Heath (1997, Metamorphosis, supplement 2), based on morphological characters, that at least three preexisting genera (Chrysoritis, Poecilmitis, and Oxychaeta) should be collapsed into the single monophyletic genus Chrysoritis. Two of the species groups described by Heath within Chrysoritis are also monophyletic, while one is paraphyletic and thus unsupported by the molecular data. Strong node support and skewed transition/transversion ratios suggest that two Chrysoritis clades contain synonymous species. Aphytophagy appears as a derived feeding strategy. Evolutionary patterns of ant association indicate lability at the level of ant genus, while association with different ant subfamilies may have played an ancestral and chemically mediated role in the diversification of South African aphnaeines.

Animals↗