Technical limits of sensitivity for EIT magnetometry.

Optical magnetometers based on electromagnetically induced transparency (EIT) in atomic vapor can in principle achieve outstanding sensitivity and accuracy in a small volume. Up until now, however, the predicted fundamental quantum-noise-limited sensitivity has not been achieved in practice due to various technical limitations associated with the measurement apparatus. Here we analyze these restrictions and propose viable mitigation strategies for performance optimization. As an example, we show that an EIT magnetometer can theoretically achieve sensitivity better than 100 fT at 1 s measurement time under realistic conditions.

Compact laser modulation system for a transportable atomic gravimeter.

Nowadays, atom-based quantum sensors are leaving the laboratory towards field applications requiring compact and robust laser systems. Here we describe the realization of a compact laser system for atomic gravimetry. Starting with a single diode laser operating at 780 nm and adding only one fiber electro-optical modulator, one acousto-optical modulator and one laser amplifier we produce laser beams at all the frequencies required for a Rb-87 atomic gravimeter. Furthermore, we demonstrate that an atomic fountain configuration can also be implemented with our laser system. The modulated system reported here represents a substantial advance in the simplification of the laser source for transportable atom-based quantum sensors that can be adapted to other sensors such as atomic clocks, accelerometers, gyroscopes or magnetometers with minor modifications.

Training the "less-affected" forelimb after unilateral cortical infarcts interferes with functional recovery of the impaired forelimb in rats.

PURPOSE: Unilateral lesions of the sensorimotor cortex (SMC) in adult rats cause major behavioral changes in the ipsilesional, "less-affected" forelimb. An increase in function and reliance on this forelimb can aid compensation for contralesional impairments, but may also promote disuse and reduced functionality of the impaired forelimb. We hypothesized that training focused on the ipsilesional forelimb following a unilateral SMC lesion would reduce the efficacy of later motor rehabilitative training of the impaired forelimb. METHODS: Rats with ischemic SMC lesions were trained on a skilled reaching task with the ipsilesional forelimb (PriorT) or received control procedures (Cont) for 10 days. Both groups were then trained with the impaired forelimb on the same reaching task for 10 days. RESULTS: In comparison with Cont, PriorT rats had little improvement on the reaching task with the impaired forelimb and had a more enduring disuse of the impaired forelimb for postural support behaviors. Lesion sizes were similar between groups. CONCLUSIONS: Behavioral experience with the less-affected forelimb early after unilateral SMC lesions has the potential to increase disuse and dysfunction of the impaired forelimb, consistent with a training-induced exacerbation of learned non-use. These findings are suggestive of competitive processes in experience-dependent neural restructuring after brain damage.

Differential control of autoantibodies and lymphoproliferation by Fas ligand expression on CD4+ and CD8+ T cells in vivo.

We have previously shown that the gld autoimmune syndrome is suppressed in lethally irradiated gld mice reconstituted with a mixture of normal and gld bone marrow (BM). Furthermore, in vivo depletion of normal Thy-1+ cells restores lymphoproliferation and autoantibody production in such chimeras, suggesting that T cells bearing Fas ligand are responsible for correcting the gld defect. In this study, mixed-BM chimeras lacking either normal CD4+ (B6CD4KO-B6gld) or normal CD8+ T cells (B6CD8KO-B6gld) were generated to determine the contribution of the normal T cell subsets to disease suppression. Lymphoproliferation was completely suppressed in B6CD4KO-B6gld chimeras but only modestly in B6CD8KO-B6gld chimeras. On the other hand, both types of mixed-BM chimeras had incomplete effects on the suppression of serum autoantibodies when compared with B6gld reconstituted with isologous BM. These results suggest that both T cell subsets provide Fas ligand to suppress immune cells responsible for autoantibody production; however, CD8+ T cells are mainly responsible for preventing lymphoproliferation.

The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice.

It has been proposed that the "normal" stimulation of the immune system that occurs from interactions with environmental stimuli, whether infectious or dietary, is necessary for the initiation and/or continuation of autoimmunity. We tested this hypothesis by deriving a group of MRL-lpr mice into a germfree (GF) environment. At 5 mo of age, no differences between GF and conventional MRL-lpr mice were noted in lymphoproliferation, flow cytometric analysis of lymph node cells (LN), or histologic analysis of the kidneys. Autoantibody levels were comparably elevated in both groups. A second experiment tested the role of residual environmental stimuli by contrasting GF mice fed either a low m.w., ultrafiltered Ag-free (GF-AF) diet or an autoclaved natural ingredient diet (GF-NI). At 4 mo of age, both groups showed extensive lymphoproliferation and aberrant T cell formation, although the GF-AF mice had approximately 50% smaller LNs compared with sex-matched GF-NI controls. Autoantibody formation was present in both groups. Histologic analysis of the kidneys revealed that GF-AF mice had much lower levels of nephritis, while immunofluorescence analysis demonstrated no difference in Ig deposits but did reveal a paucity of C3 deposition in the kidneys of GF-AF mice. These data do not support a role for infectious agents in the induction of lymphoproliferation and B cell autoimmunity in MRL-lpr mice. Furthermore, they suggest that autoantibodies do not originate from B cells that were initially committed to exogenous Ags. They do suggest a possible contributory role for dietary exposure in the extent of lymphoproliferation and development of nephritis in this strain.

CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo.

Activation of T cells requires both TCR-specific ligation by direct contact with peptide Ag-MHC complexes and coligation of the B7 family of ligands through CD28/CTLA-4 on the T cell surface. We recently reported that coadministration of CD86 cDNA along with DNA encoding HIV-1 Ags i.m. dramatically increased Ag-specific CTL responses. We investigated whether the bone marrow-derived professional APCs or muscle cells were responsible for the enhancement of CTL responses following CD86 coadministration. Accordingly, we analyzed CTL induction in bone marrow chimeras. These chimeras are capable of generating functional viral-specific CTLs against vaccinia virus and therefore represent a useful model system to study APC/T cell function in vivo. In vaccinated chimeras, we observed that only CD86 + Ag + MHC class I results in 1) detectable CTLs following in vitro restimulation, 2) detectable direct CTLs, 3) enhanced IFN-gamma production in an Ag-specific manner, and 4) dramatic tissue invasion of T cells. These results support that CD86 plays a central role in CTL induction in vivo, enabling non-bone marrow-derived cells to prime CTLs, a property previously associated solely with bone marrow-derived APCs.

The role of host (endogenous) T cells in chronic graft-versus-host autoimmune disease.

Chronic graft-vs-host (cGVH) disease induced by the transfer of Ia-incompatible spleen cells from one normal mouse strain (such as B6.C-H2(bm12)/KhEg (bm12)) to another (such as C57BL/6) causes an autoimmune syndrome resembling systemic lupus erythematosus (SLE). The role of host-derived T cells in this response is not obvious. Previous reports suggested that host T cells might serve to down-regulate the autoimmune syndrome. To address this issue more definitively, we used CD4 knockout (KO) or CD8KO C57BL/6 (B6) mice as recipients in the bm12-->C57B6 cGVH model. CD4KO B6 mice injected with allogeneic bm12 spleen cells (bm12-->CD4KO group) showed no evidence of cGVH disease. They made no detectable autoantibodies, including anti-chromatin, anti-dsDNA, anti-ssDNA, and rheumatoid factor. They survived at least 20 wks after induction of cGVH disease; and they did not develop nephritis, based on the absence of detectable levels of proteinuria and normal renal histology at the time of sacrifice. By contrast, CD8KO B6 mice (bm12-->CD8KO group) and normal B6 mice (bm12-->B6 group) injected with bm12 spleen cells generally showed similar levels of mortality, nephritis, and autoantibodies, although the autoantibody titers declined somewhat after week 8 in the bm12-->CD8KO group. Control groups of recipients injected with B6 spleen cells showed no induction of autoantibodies. A surprising finding, however, was that the B6-->CD8KO group developed severe histologic glomerulonephritis in the absence of autoantibodies and with decreased immune deposits. These results indicate that endogenous (host) CD4+ T cells play an essential role in the cGVH autoimmune syndrome.

Intravenous colchicine use in crystal-induced arthropathies: a retrospective analysis of hospitalized patients.

OBJECTIVES: To assess current prescribing patterns, and adherence to recommended practice guidelines, for the use of intravenous colchicine in the treatments of crystal-induced arthropathies. METHODS: Medical records of patients at an urban academic medical center who received intravenous colchicine were reviewed. Information about colchicine dosing and clinical outcomes, with particular attention to interventions by Rheumatologists, was obtained. All hospitalized patients with confirmed or suspected crystal-induced arthropathies treated with intravenous colchicine during a 48-month period were included in this retrospective study. The demographic profile, medical history and clinical data were reviewed. RESULTS: Intravenous colchicine dosing schedules generally followed recommended guidelines. There was no significant difference between patients evaluated by a Rheumatologist, and those that were not, in the cumulative colchicine dose received, clinical response, or length of hospitalization. Relative contraindications to intravenous colchicine were present frequently, but no morbidity or mortality directly attributable to intravenous colchicine was recorded. Patients evaluated by a Rheumatologist prior to receiving intravenous colchicine were significantly more likely to have the diagnosis of a crystal-induced arthropathy confirmed by the identification of crystals from synovial fluid, and less likely to have received oral colchicine prior to intravenous colchicine, than patients who were not evaluated by a Rheumatologist. CONCLUSIONS: Increased involvement of Rheumatologists, and increased awareness of the appropriate indications and guidelines for the safe administration of intravenous colchicine are recommended.

Greatly reduced lymphoproliferation in lpr mice lacking major histocompatibility complex class I.

Mice homozygous for the lpr gene have a defect in fas (CD95), a cell surface receptor that belongs to the tumor necrosis factor receptor family and that mediates apoptosis. This genetic abnormality results in lymphoproliferation characterized by the accumulation of CD4-CD8- (double negative [DN]) T cells, autoantibody production, and background strain-dependent, end-organ disease. Our previous results suggested that major histocompatibility complex (MHC) class I may be involved in the development of DN cells. To test this hypothesis, we derived C57BL/6-lpr/lpr (B6/lpr) mice that were deficient for the beta 2-microglobulin gene (beta 2m lpr) and had no detectable class I expression. At 6 mo of age, compared with B6/lpr littermates with normal class I genes, these mice showed greatly reduced lymphadenopathy, mostly due to a dramatic decrease in the number of DN cells. Significant changes in the percentage of other T cell subsets were noted, but only gamma/delta+ T cells showed a marked increase in both percentage and absolute numbers. Analysis of T cell receptor V beta expression of the remaining DN T cells in beta 2m -lpr mice showed a shift to a CD4-like repertoire from a CD8-like repertoire in control B6/lpr mice, indicating that a small MHC class II selected DN population was unmasked in lpr mice lacking class I. We also found that the production of immunoglobulin G (IgG) autoantibodies (antichromatin and anti-single stranded DNA), total IgG and IgG2a, but not total IgM or IgM rheumatoid factor, was significantly reduced in the beta 2m -lpr mice. This work suggests that >90% of DN T cells in lpr mice are derived from the CD8 lineage and are selected on class I. However, a T cell subset selected on class II and T cells expressing gamma/delta are also affected by the lpr defect and become minor components of the aberrant DN population.

[Violence against women because of their being women. Myths and stereotypes perpetuated in "El Vocero"]. / Violencia contra la mujer por ser mujer. Mitos y estereotipos perpetuados en El Vocero.

A model is presented for examining the myths, sterotypes, and prejudices about women that are presented daily to our society through the popular press, specifically The Vocero. The journalistic vocabulary and style, the interpretation of the information offered and the significance of the information omitted in the Vocero articles are examined. The myths and stereotypes of women that are repeated consistently in these articles are correlated with the clinical experience of the Puerto Rico Rape Crisis Center and Casa Julia Battered Woman's Shelter. Finally, this process of popular education is presented as an important determinant for violence against women in Puerto Rico and for the prevalence of a high degree of social apathy and indifference to the problem in our community.