Citizen minds,citizen bodies: the citizenship experience and the government of mentally ill persons

The concept of citizenship is becoming more and more prominent in specific fields, such as psychiatry/mental health, where it is constituted as a solution to the issues of exclusion, discrimination, and poverty often endured by the mentally ill. We argue that such discourse of citizenship represents a break in the history of psychiatry and constitutes a powerful strategy to counter the effects of equally powerful psychiatric labelling. However, we call into question the emancipatory promise of a citizenship agenda. Foucault's concept of governmentality is helpful in understanding the production of the citizen subject, its location within the ‘art of government’, as well as the ethical and political implications of citizenship in the context of mental health.     

Occupational disease surveillance data sources, 1985.

Health department epidemiologists in 50 states, New York City, and the District of Columbia were surveyed in 1985 about seven potential data sources for occupational disease surveillance. Reported sources of occupational disease data were: automated workers' compensation claims (63 per cent of the 52 respondents); provider reports (62 per cent); death certificates with occupation or industry (60 per cent); cancer registries with occupational histories (35 per cent); birth certificates with parent's occupation (27 per cent); non-cancer disease registries (13 per cent); and hospital or insurance records (8 per cent).     

A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia

The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy.     

B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation

The SH2 domain-containing transforming Shc protein has been implicated in mitogenic signaling via several surface receptors through p21^ras. Following tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine nucleotide exchange factor for human ras. Ligation of the antigen receptor complex on B cells (BCR) is known to activate various intracellular signaling pathways, which may accumulate in mitogenic responses. With respect to the initial steps, the activation of BCR-associated non-receptor tyrosine kinases appears to be indispensible. In this report we show that Shc proteins become tyrosine phosphorylated after BCR ligation on both transformed and normal human B cells. This is accompanied by the association of Shc with Grb2 proteins and a yet unidentified 145-kDa tyrosine phosphorylated protein. Subcellular fractionation revealed that this activation-induced multimeric Shc complex rapidly translocates towards the plasma membrane. Co-ligation of the BCR with the CD19 molecule results in a marked increase of these events, whereas CD19 cross-linking alone does not induce Shc tyrosine phosphorylation or translocation. Thus, in B cells the Shc complex may represent a molecular junction between the BCR and the mitogenic p21^ras cascade.     

Influence of CD28 co-stimulation on cytokine production is mainly regulated via interleukin-2.

Interaction of CD28 with its ligand B7 plays an important role in the initiation of immune responses. The co-stimulatory signal generated by cross-linking of CD28 molecules results in enhanced T-cell proliferation and augmentation of cytokine production. In particular, mRNA levels of T-helper 1 (Th1)-type cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are reported to be strongly increased. We investigated the effect of CD28 co-stimulation on the production of Th2-type cytokines. CD28 mAb induced a strong augmentation of IL-2 secretion in activated T-cell clones. Production of IFN-gamma was also enhanced, but the increase in IL-4 secretion was generally moderate. Augmentation of IL-4 production by CD28 was most pronounced in clones that produced low amounts of IL-2, compared to clones producing high levels of IL-2. It was found that the up-regulation of IL-4 by CD28 co-stimulation was mainly controlled indirectly via an increase of IL-2. Some clones could produce IL-4 in an IL-2-independent manner; in these situations CD28 co-stimulation had no augmenting effect on the production of IL-4. The secretion of IL-4 by peripheral blood CD4+ T cells, that were activated with B7-expressing transfectants, was also found to be dependent on IL-2. Finally, Northern blot analysis confirmed that co-stimulation of CD28 primarily affected IL-2 production, and that inhibition of IL-2/IL-2 receptor interaction abolished the augmenting action of CD28 monoclonal antibody on the production of the Th2-type cytokines IL-4, IL-5 and IL-10 and of the Th1 cytokine IFN-gamma.     

Gemins modulate the expression and activity of the SMN complex

Reduction in the expression of the survival of motor neurons (SMN) protein results in spinal muscular atrophy (SMA), a common motor neuron degenerative disease. SMN is part of a large macromolecular complex (the SMN complex) that includes at least six additional proteins called Gemins (Gemin2-7). The SMN complex is expressed in all cells and is present throughout the cytoplasm and in the nucleus where it is concentrated in Gems. The SMN complex plays an essential role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs. To study the roles of the individual proteins, we systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA interference. We show that the reduction of SMN leads to a decrease in snRNP assembly, the disappearance of Gems, and to a drastic reduction in the amounts of several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the activity of the SMN complex. These findings demonstrate that other components of the SMN complex, in addition to SMN, are critical for the activity of the complex and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as well as potential disease genes for non-SMN motor neuron diseases.     

Induction of T cell proliferation with anti-CD3 switch-variant monoclonal antibodies: effects of heavy chain isotype in monocyte-dependent systems

Monoclonal antibodies (mAb) directed against the CD3 (T3), antigen are able to induce proliferation in resting human T lymphocytes. T cell proliferation only occurs in the presence of monocytes that carry the proper Fc receptor for the mAb used. To further analyze the role of the Fc portion of anti-CD3 mAb in proliferation induction, we isolated, starting from a gamma 1 anti-CD3-producing hybridoma, four heavy-chain isotype switch-variant antibody-secreting clones, producing gamma 2b, gamma 2a, epsilon and alpha, respectively. All variant antibodies recognize the CD3 antigen as determined by immunoprecipitation and cross-blocking experiments. With this series of isotype variant antibodies we were able, in proliferation induction experiments, to confirm the Fc receptor polymorphism for murine IgG2a, IgG2b and IgG1 on human monocytes. Moreover, we found that all 30 donors tested responded to the IgE anti-CD3 antibody, while no IgA responders could be identified. The induction of proliferation by the IgE variant antibody does not require the 72-kDa Fc receptor which is responsible for the interaction with mouse IgG2a. Nonresponsiveness to the IgG1 antibody, but not to the IgG2b or IgA variant antibodies, could be overcome by the addition of exogenous interleukin 2 to the cultures. When the switch-variant antibodies were used to induce IgM synthesis in peripheral blood mononuclear cells only low IgM synthesis was found, with the exception of the IgE variant, which induced excellent T cell help for IgM production.