A Nice development: The first joint meeting of the British and French Societies for Developmental Biology, 13-16th September, 2003, Nice, France.

Held this autumn on the beautiful Cote d'Azur, the first joint meeting of the BSDB and SFBD provided delegates with the perfect informal setting for discussion spanning a broad cross-section of Developmental Biology. Participants' interests were diverse, ranging from the implementation of genome-wide approaches aimed at identifying all the molecular components of cell proliferation, signalling, patterning, and morphogenesis, to those engaged in capturing mesmerising glimpses of the minute and intricate workings of the cell. The meeting considered a wide spectrum of model organisms, including the simple plant Arabidopsis, the invertebrates Dictyostelium, Caenorhabditis elegans, and Drosophila melanogaster, the ascidian Ciona intestinalis, and the vertebrates Xenopus, zebrafish, chick, and mouse. Such a diverse approach served to highlight both similarities and differences in the molecular mechanisms that govern embryonic development among different species. Here, we highlight a few aspects of the meeting that illustrate this point.     

Self-criticism and social phobia in the US national comorbidity survey

BACKGROUND: This study sought to extend findings from a preliminary clinical investigation [J. Affect. Disord. 57 (2000) 223] by examining relations between the personality dimension of self-criticism and diagnostic prevalence of social phobia in a large nationally representative sample. METHODS: Participants were from the national comorbidity survey Part II [n=5877; Arch. Gen. Psychiatry 51 (1994) 8]. Psychiatric diagnoses were made using a modified version of the composite international psychiatric interview. Personality dimensions and distress were assessed using brief self-report measures with strong psychometric properties. RESULTS: Self-criticism was elevated in NCS respondents with a diagnosis of social phobia, even in cases of only past history of social phobia (i.e. >1 year ago), compared to individuals with no psychiatric disorder. The highest levels of self-criticism were reported by people with the complex subtype of social phobia, both with and without comorbid major depression. These levels were significantly greater compared to those observed in another anxiety disorder (panic disorder), the pure speaking subtype of social phobia, and cases of major depression alone. In a regression analysis that controlled for current emotional distress, the broad personality trait of neuroticism, and lifetime histories of mood, anxiety, and substance use disorders, self-criticism remained significantly associated with lifetime prevalence of social phobia. LIMITATIONS: The cross-sectional design of the study does not permit causal inferences. CONCLUSIONS: Findings from this general population mental health survey demonstrated that self-criticism is robustly associated with social phobia. It may represent an important core psychological process in the complex subtype of this anxiety disorder.     

Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56Ick in human CD4 T lymphocytes

Human immunodeficiency virus binds to CD4 T lymphocytes by interaction between its envelope glycoprotein gpl20 and the CD4 molecule. The latter is non-covalently associated with a src-related tyrosine kinase, p56^lck. CD4 cross-linking increases the activity of p56^lck, leading to phosphorylation of several cellular substrates. We report here that gpl60/120 increases both the autophos-phorylation of p56^lck and its enzymatic activity (reflected by phosphorylation of an exogeneous substrate) in normal T cells and the HUT78 CD4⁺ T cell line. This effect was detectable 5 min after activation and persisted for 40 min in normal T cells. It did not require gpl20 cross-linking and was associated with phosphorylation of tyrosine residue on several proteins, as shown by phosphotyrosine Western blot analysis. The pattern of proteins phosphorylated on tyrosine residues in response to gpl20 activation was distinct from that induced by anti-CD4 antibodies. p56^lck activation required its association with CD4, since p56^lck activity was not modified in HUT78 T cell lines expressing a truncated or mutated form of CD4 unable to associate with p56^lck. Peptides mimicking residues 418 to 434 and 449 to 464 of HIV-1 Bru gpl20, regions known to participate in gpl20 binding to CD4, also increased p56^lck activity and triggered phosphorylation of similar substrates. Taken together, these results show that gpl60/120 and derived peptides can transiently increase p56^lck activity without the need for CD4 cross-linking. This activation led to a specific pattern of tyrosine phosphorylation on cellular proteins that may be of significance in the biological effects of the gpl20/CD4 interaction, e.g. syncytium formation and inhibition of T cell activation.     

The human force:velocity relationship; activity in the knee flexor and extensor muscles before and after eccentric practice

The human voluntary force:velocity relationship frequently fails to demonstrate the expected high eccentric forces. Possible explanations include unique activation strategies which might be affected by neural learning mechanisms. We investigated the effect of practicing eccentric contractions on (1) the force: velocity relationship of the human knee extensor muscles and (2) the extent of agonist and antagonist muscle activity. Eight healthy adults [seven women, group mean age 31 (SEM 5) years ± ] practised twice a week for 4 weeks using their non-dominant legs. Each session comprised three isokinetic concentric and eccentric maximal voluntary contractions (MVC) at randomised angular velocities of 100, 200 and 300° · s⁻¹. Before and after, the force:velocity relationship was determined bilaterally (angular velocities 0–300° · s⁻¹). There were no significant differences in the forces generated or relative electromyogram (EMG) activity after practice, although there was a trend for dynamic forces to increase. Beforehand, the bilateral eccentric MVC forces were lower than isometric (P < 0.0025); afterwards they were broadly similar. The agonist EMG was similar during isometric and eccentric contractions, but lower during concentric (P < 0.03). Antagonist EMG activity showed considerable individual variation, was similar during all contraction types and tended to be greater during dynamic contractions. These data indicate that neither central learning mechanisms nor total muscle activation strategies underlie the human failure to produce the expected high eccentric voluntary forces in humans. Accepted: 19 September 2000     

Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.     

Effect of beta2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice

beta(2)-Glycoprotein I (beta(2)GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted beta(2)GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional beta(2)GPI in pregnancy was investigated by evaluating reproductive outcomes in beta(2)GPI null mutant (beta(2)GPI-/-) mice. beta(2)GPI-/- mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in beta(2)GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in beta(2)GPI-/- implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of beta(2)GPI. The effect of beta(2)GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with beta(2)GPI was also explored. Two of five anti-beta(2)GPI antibodies induced pregnancy loss in beta(2)GPI+/+ mice but beta(2)GPI-/- mice were refractory to antibody-induced pregnancy failure. We conclude that functional beta(2)GPI is not essential for successful pregnancy in mice, but optimal placental development and fetal growth require this molecule. Together these data are consistent with pathogenic mechanisms in antiphospholipid syndrome involving both neutralization of beta(2)GPI function and beta(2)GPI-immunoglobulin complex formation.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains a major opportunistic agent among transplant recipients. While detection of CMV pp65-lower matrix protein (pp65Ag) is still widely used for monitoring CMV infection, real-time PCR assays have been recently developed for routine quantitation of CMV DNA. However, correlations are lacking between results of pp65Ag and quantitative PCR assays and there is no consensus yet as to the more appropriate blood compartment (whole blood (WB), leukocytes, plasma) to be tested with PCR assays. OBJECTIVES: The aims of the study were to determine, in a population of transplant recipients: (i) the correlation between pp65Ag and CMV quantitative real-time PCR in our setting and (ii) the utility of plasma CMV DNA quantitation in comparison to WB quantitation. METHODS: In 170 blood samples (from 61 solid organ or bone marrow transplant recipients) with pp65Ag results, CMV quantitation was performed in WB and plasma using an in-house real-time quantitative PCR. RESULTS: Real-time PCR and pp65Ag results in WB were correlated: thresholds of 10 and 50(+) cells/200,000 cells were equivalent to 3.3 log(10)copies/mL (2,000 copies/mL) and 3.8 log(10)copies/mL (6,300 copies/mL), respectively. When WB viral load was >or=3.6 log(10)copies/mL, the risk to have a negative plasma CMV DNA result was 相似文献   

Taste and olfaction: Independence vs interaction

Twenty persons sipped and judged overall perceived magnitude, odor magnitude, and taste magnitude of various concentrations of the odorant citral, the tastants sodium chloride and sucrose, and odorant-tastant combinations. In a second experiment, the same twenty persons sniffed and judged perceived odor magnitude for the same set of stimuli. The investigation probed two primary questions: Does the apparent harmony of an olfactory-taste mixture dictate the degree of additivity in that mixture? Does harmony of the components influence the production of any taste-smell confusion? The data from both the harmonious mixture (citral and sucrose) and the dissonant mixture (citral and NaCl) imply absence of sensory inhibition or facilitation between taste and olfaction. Nevertheless, both types of mixtures led to substantial taste-smell confusion whereby olfactory stimulation evoked sensations of taste.     

ASC:SIL ratio following implementation of the 2001 Bethesda System

The 2001 Bethesda system (TBS 2001) eliminated the "satisfactory but limited by" category, benign cellular changes (BCC), and the designations "favor benign" (ASC-B) and "favor low grade" (ASC-L) for atypical squamous cells. We compared the unsatisfactory rate and atypical squamous cells:squamous intraepithelial lesions (ASC:SIL) ratio pre- and postimplementation of TBS 2001 to see if there was an increase in unsatisfactory specimens, ASC rate, and altered ASC:SIL ratio. Pap Tests (569,726) reviewed at the Cytopathology Laboratory of Women and Infants Hospital from 1998-2002 were included. TBS 1991 terminology was used through December 31, 2001. Conversion to TBS 2001 took place on January 1, 2002. The average ASC:SIL ratios pre- and postimplementation of TBS 2001 were 1.52:1 and 1.42:1, respectively. The rates of unsatisfactory specimens and ASC remained unchanged. Conversion to TBS 2001 did not adversely affect the ASC:SIL ratio or the detection rates of abnormalities of Pap tests.