Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane.

BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. METHOD: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-na?ve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD.     

CD4-positive/heat-stable antigen-positive thymocytes cause graft-versus-host disease across non-major histocompatibility complex incompatibilities

Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral “self” antigens. Since RTE are difficult to analyze, precursor CD4⁺/8⁻ thymocytes were assessed in a model in vivo to determine their functional capability and their susceptibility to tolerance induction. The ability of both heat-stable antigen-positive (HSA⁺) (immature) and HSA⁻ (mature) single-positive thymocytes to cause graft-versus-host disease (GVHD) across non-major histocompatibility complex differences was examined. Both HSA⁻ and HSA⁺ CD4⁺/8⁻ thymocytes from C3H mice caused lethal GVHD in AKR recipients as did CD4⁺ peripheral T cells in controls. Further, neonatal C3H thymocytes also caused lethal GVHD in AKR recipients. Since CD4⁺/8⁻ thymocytes are the precursors of RTE, these results suggest that RTE are not susceptible to tolerance induction to “minor” antigens and may have a normal immune function in vivo. This would suggest that peripheral tolerance may be dependent upon the manner of antigen presentation rather than T cell maturity.     

SAS amplification in soft tissue sarcomas.

Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated SAS (sarcoma amplified sequence). In the present study, a series of soft tissue sarcomas was studied to characterize further the phenomenon of SAS amplification. Seven of 22 (32%) malignant fibrous histiocytomas and three liposarcomas contained SAS amplification. Strikingly, all of the tumors with SAS amplification occurred in central sites (i.e., in the abdominal or inguinal regions) rather than in the extremities (i.e., in the arms of legs). These observations demonstrate that SAS amplification occurs with a significant frequency in mesenchymal tumors and is particularly associated with abdominal disease.     

Platelet MAO activity and the cortisol response to dexamethasone in major depression

Previous studies have sometimes found a positive relationship between platelet monoamine oxidase (MAO) activity and dexamethasone nonsuppression in depressed patients. To assess this relationship in more detail, we examined the association between these two biological variables in unmedicated depressed patients. A positive correlation between platelet MAO activity and 8:00 AM serum cortisol levels following an overnight dexamethasone test (1 mg) was observed. The relationship between high and low platelet MAO activity (median split) and suppression of serum cortisol levels was also significant. These relationships were stronger in bipolar patients. Multiple regression revealed that postdexamethasone 8:00 AM dexamethasone levels and platelet MAO activity were independent predictors of the 8:00 AM cortisol levels following dexamethasone. The possibility that platelet MAO activity may be a peripheral marker of brain serotonergic activity which in turn may affect various aspects of the hypothalamo-pituitary-adrenal axis activity, is discussed. We also found that all nine depressed patients studied greater than or equal to 15 days after admission were suppressors. Platelet MAO activity, but not 8:00 AM pre- or postdexamethasone serum cortisol, was related to the severity of depression.     

The symmetry of hip bone mineral density. A dual photon absorptiometry approach

Dual photon absorptiometry studies were performed on the hips of 23 patients to determine whether bone mineral density values obtained from one hip were indicative of the values in the contralateral hip of the ambulatory patient. The femoral neck, trochanteric, and Ward's triangle areas of both hips were analyzed. There were no significant differences between the right and left hip bone mineral density measurements in any of these three areas. Since the right and left hip readings were highly correlated, either hip may be used to evaluate osseous status.     

T-cell-mediated activation of macrophages

Functionally diverse subpopulations of macrophages and lymphocytes, a wide array of stimulatory signals, and an enormous effector repertoire of activated macrophages keeps this field dynamically active. We review new advances in the identification of cytokines that interact to activate macrophages, and in the discovery of effector molecules used by activated macrophages to destroy their targets.