Costimulation mediated by the CD28 receptor has been shown to play an important role in the development of a vigorous T cell immune response. Nevertheless, CD28-deficient mice can mount effective T ...cell-dependent immune responses. These data suggest that other costimulatory molecules may play a role in T cell activation. In a search for other costimulatory receptors on T cells, we have characterized a monoclonal antibody (mAb) that can costimulate T cells in the absence of accessory cells. Similar to CD28 antibodies, this mAb, R2/60, was found to synergize with T cell receptor engagement in inducing proliferation. Independent ligation of CD3 and the ligand recognized by R2/60 results in T cell proliferation, suggesting that the two molecules do not have to colocalize to activate the R2/60 costimulatory pathway. R2/60 does not react with CD28, and furthermore, R2/60 costimulates in a CD28-independent fashion since the mAb costimulates T cells from the CD28-deficient mice as well as wild-type mice. Expression cloning of the R2/60 antigen identified the ligand as murine CD43. Together, these data demonstrate that CD43 can serve as a receptor on T cells that can provide CD28-independent costimulation.
Numerous studies have documented high rates of co-morbidity between major depressive disorder (MDD) and the anxiety disorders (ANX). However, the reason for this is unclear. Family studies provide ...one potentially useful approach for addressing this issue.
We explored six explanations of the co-morbidity between MDD and ANX using a family study of a large community sample of young adults and their first-degree relatives. Participants included 112 probands with a lifetime history of both MDD and one or more ANX, 290 probands with a history of MDD but no ANX, 43 probands with a history of one or more ANX but no MDD. 352 probands with no lifetime history of either MDD or ANX, and the probands' 2608 first-degree relatives. Probands were assessed using semi-structured diagnostic interviews on two occasions in adolescence and a third time at age 24. Diagnostic data on relatives were collected using both direct and family history interviews.
Compared with controls, MDD aggregated in the families of probands with MDD, whether or not they had co-morbid ANX; ANX aggregated in the families of probands with ANX, regardless of whether they had co-morbid MDD; and co-morbid MDD/ANX aggregated only in the families of probands with both MDD and ANX. The relatives of probands with ANX alone had a significantly higher rate of ANX than the relatives of probands with MDD alone, although none of the other comparisons between the depressed and anxious groups were significant.
This pattern of findings is largely, although not completely, consistent with the view that MDD and ANX are transmitted independently within families, and suggests that the comorbidity between MDD and ANX is caused by non-familial aetiological factors.
Beam-target double spin asymmetries and target single-spin asymmetries in exclusive $\pi^+$ and $\pi^-$ electroproduction were obtained from scattering of 1.6 to 5.7 GeV longitudinally polarized ...electrons from longitudinally polarized protons (for $\pi^+$) and deuterons (for $\pi^-$) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic range covered is $1.1<W<2.6$ GeV and $0.05<Q^2<5$ GeV$^2$, with good anglular coverage in the forward hemisphere. The asymmetry results were divided into approximately 40,000 kinematic bins for $\pi^+$ from free protons and 15,000 bins for $\pi^-$ production from bound nucleons in the deuteron. The present results are found to be in reasonable agreement with fits to previous world data for $W<1.7$ GeV and $Q^2<0.5$ GeV$^2$, with discrepancies increasing at higher values of $Q^2$, especially for $W>1.5$ GeV. Very large target-spin asymmetries are observed for $W>1.6$ GeV. When combined with cross section measurements, the present results will provide powerful constraints on nucleon resonance amplitudes at moderate and large values of $Q^2$, for resonances with masses as high as 2.3 GeV.
We have measured the moment (ProQuest: Formulae and/or non-USASCII text omitted) corresponding to the polarized electron beam-spin asymmetry in semi-inclusive deep inelastic scattering. (ProQuest: ...Formulae and/or non-USASCII text omitted) is a twist-3 quantity providing information about quark-gluon correlations. Data were taken with the CLAS Spectrometer at Jefferson Lab using a 5.498 GeV longitudinally polarized electron beam and an unpolarized liquid hydrogen target. All three pion channels (pi super(+), pi super(0) and pi super(-)) were measured simultaneously over a large range of kinematics within the virtuality range Q super(2) approximate 1.0-4.5 GeV super(2). The observable was measured with better than 1% statistical precision over a large range of z, PT, xB, and Q super(2), which permits comparison with several reaction models. The discussed measurements provide an upgrade in statistics over previous measurements, and serve as the first evidence for the negative sign of the pi super(-) sin varphi moment.
Numerous studies have focused on characterizing personality differences between individuals with and without psychopathology. For drawing valid conclusions for these comparisons, the personality ...instruments used must demonstrate psychometric equivalence. However, we are unaware of any studies that examine measurement invariance in personality across individuals with and without psychopathology. This study conducted tests of measurement invariance for positive emotionality, negative emotionality, and disinhibition across individuals with and without histories of depressive, anxiety, and substance use disorders. We found consistent evidence that positive emotionality, negative emotionality, and disinhibition were assessed equivalently across all comparisons with each demonstrating strict invariance. Overall, results suggest that comparisons of personality measures between diagnostic groups satisfy the assumption of measurement invariance and these scales represent the same psychological constructs. Thus, mean-level comparisons across these groups are valid tests.
Pertussis toxin is an exotoxin of the A-B class produced by Bordetella pertussis. The holotoxin comprises 952 residues forming six subunits (five different sequences, S1-S5). It plays an important ...role in the development of protective immunity to whooping cough, and is an essential component of new acellular vaccines. It is also widely used as a biochemical tool to ADP-ribosylate GTP-binding proteins in the study of signal transduction.
The crystal structure of pertussis toxin has been determined at 2.9 A resolution. The catalytic A-subunit (S1) shares structural homology with other ADP-ribosylating bacterial toxins, although differences in the carboxy-terminal portion explain its unique activation mechanism. Despite its heterogeneous subunit composition, the structure of the cell-binding B-oligomer (S2, S3, two copies of S4, and S5) resembles the symmetrical B-pentamers of the cholera toxin and Shiga toxin families, but it interacts differently with the A-subunit. The structural similarity is all the more surprising given that there is almost no sequence homology between B-subunits of the different toxins. Two peripheral domains that are unique to the pertussis toxin B-oligomer show unexpected structural homology with a calcium-dependent eukaryotic lectin, and reveal possible receptor-binding sites.
The structure provides insight into the pathogenic mechanisms of pertussis toxin and the evolution of bacterial toxins. Knowledge of the tertiary structure of the active site forms a rational basis for elimination of catalytic activity in recombinant molecules for vaccine use.
OBJECTIVES
The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of ...decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof.
DESIGN
Cross‐sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2‐ and 4‐week blood specimens from VLBW infants.
PATIENTS
Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing 2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995–96 in 19 VLBW infants and 21 full term infants (Cohort B).
MEASUREMENTS
T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2‐ and 4‐week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated.
RESULTS
(1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 ± 111 vs 680 ± 172 nmol/l (P < 0.0005). T4 concentrations were 76 ± 22 vs 139 ± 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37–113 pmol/l and T4 concentrations of 13–48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested.
CONCLUSIONS
Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the ‘sick euthyroid syndrome’.
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