Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis.

Cytokines (IL-1 alpha and IL-2) and soluble interleukin 2 receptors (sIL-2r) were evaluated in patients with rheumatoid arthritis (RA) and controls. In RA, serum sIL-2r and IL-1 alpha were increased, and sIL-2r were significantly higher in synovial fluid than in serum. Serum levels of sIL-1r but not IL-1 alpha were increased in patients with acute infections, suggesting additional discriminatory specificity for IL-1 alpha. Both tender and swollen joint scores were higher for patients with RA with serum sIL-2r levels greater than or equal to 700 U/ml. Quantitation of immune mediators may be useful in the clinical assessment of RA in addition to their implication regarding the pathogenesis of the disease.     

Glucocorticoids Decrease Hippocampal and Prefrontal Activation during Declarative Memory Retrieval in Young Men

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dopamine neurons projecting to the medial prefrontal cortex possess release-modulating autoreceptors

The ability of dopamine (DA) agonists and antagonists to modulate the K+-evoked overflow of radioactivity from superfused slices of prefrontal cortex of the rat, preincubated with [3H]DA in the presence of 1 microM desipramine, was examined. Apomorphine and the putative autoreceptor-selective DA agonist EMD 23 448 inhibited the K+-evoked overflow of radioactivity, while the DA antagonist sulpiride enhanced the evoked overflow in a dose-dependent and stereoselective manner. The latter effect was partially reversed by EMD 23 448. More than 95% of the radioactivity retained by the slices chromatographed with DA, while deaminated metabolites represented the majority of both the basal efflux (84% metabolites, 4-5% DA) and evoked overflow (84% metabolites, 14% DA) of radioactivity. These findings indicate that mesoprefrontal DA neurons possess release-modulating nerve terminal autoreceptors. Previous studies have shown that these neurons lack synthesis-modulating autoreceptors. Thus, autoreceptors on prefrontal DA terminals appear to be coupled to regulation of the release but not the synthesis of DA.     

Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis

Because little is known about the mechanisms involved in local tumor-host immune reactions in squamous carcinoma of the head and neck, a study was undertaken to better characterize the types of immune cells present at the local tumor site and determine their relationship to tumor extent, systemic cellular immune parameters, and clinical outcome. In 40 untreated patients, lymphocyte subsets (LS) at the tumor-host interface were quantitated immunohistologically from serial sections of frozen tumor specimens and correlated with concurrently measured peripheral LS levels and in vitro lymphocyte reactivity to phytohemagglutinin (PHA). The majority of infiltrating lymphocytes were T cells with rare B or Leu 7 cells. Proportions of T4 and T8 were similar in peritumor stroma; however, T8 cells predominated tumor parenchyma. Stromal and parenchymal infiltration by LS were not related to peripheral blood LS levels, lymphocyte reactivity, or tumor site. However, parenchymal T11 and T4 cell infiltration was less in advanced primary tumors (T3, T4) than in early tumors (T1, T2) (P = 0.01, P = 0.067, respectively), as was peripheral lymphocyte reactivity to PHA (P = 0.013). Short-term disease-free interval and actuarial survival differed significantly--according to parenchymal T11 and T4 cell infiltration--and were not related to T8, Leu 7, and B-cell infiltration. The findings extend prior studies of lymphocytic infiltration in head and neck cancer and demonstrate the potential importance of differences in tumor stromal and parenchymal infiltration. Together with recent evidence that T4 cells are critical for lymphokine production and for the proliferation of cytotoxic effector cells, the current results suggest that T4 cells play a critical role in the local immune response in squamous carcinoma of the head and neck.     

Case-control study of colon cancer and drinking water trihalomethanes in Wisconsin

A case-control study was conducted to test the hypothesis that chronic ingestion of trihalomethanes (THMs), occurring as chlorination byproducts in drinking water, carries a risk of colon cancer. Lifetime residential and water source histories and information on water-drinking habits, diet, sociodemographics, medical and occupation histories, lifestyle and other factors were obtained by questionnaire from a statewide sample of newly-diagnosed colon cancer cases (N = 347), controls with cancer of other sites (N = 639) and general population controls (N = 611). Since no data on past THM levels exists, it was necessary to devise a scheme to generate THM estimates for all Wisconsin water sources. For this, a statistical model based on quantitative THM measures and routinely-recorded data taken at 81 municipal water facilities was used in conjunction with individual residential histories to estimate lifetime and period-specific THM exposure for each case and control. Logistic regression was used to estimate odds ratios adjusted for age, sex and urban living, for colon cancer and THM exposure. The study results indicate that THM in Wisconsin drinking water does not pose a significant colon cancer risk. Odds ratios for exposure to the middle and highest category of lifetime cumulative THM were 1.05 (95% Cl = 0.66-1.68) and 0.93(95%Cl = 0.55-1.57) respectively, relative to the cancer control group, and 1.10 (95%Cl = 0.68-1.78) and 0.73 (95% Cl = 0.44-1.21) respectively, relative to the general population controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safer, more expensive iodinated contrast agents: how do we decide?

The advantages of the new, safer, but more expensive iodinated contrast agents are discussed, and opinions on which patient groups should receive the agents are presented.     

Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.

Prior studies of alterations in tumor expression of normal blood group antigens and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested that these immunohistologic markers reflect the biologic aggressiveness of head and neck squamous carcinomas. To confirm these preliminary observations, prospective long-term follow-up of 82 previously untreated head and neck squamous carcinoma patients was performed. All patients were treated with conventional therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood group and A9/alpha 6 beta 4 integrin expression was performed and correlated with measures of host cellular immunity, disease-free survival, and overall survival. Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression were each directly related to an increased frequency of early tumor recurrence. The combination of both variables was significantly associated with both disease-free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha 6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss of blood group expression was associated with decreased peripheral blood levels of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic characteristics of antigen expression in head and neck squamous carcinomas are important markers of biologically aggressive cancers and impaired host immune response. The clinical use of these biologic staging parameters in the initial assessment of patients should allow selection of more aggressive primary treatment strategies for individual patients.