Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.     

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson’s disease focusing on correlations with motor symptoms

GeroScience - The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD)...     

Alterations during medical interpretation of ICU family conferences that interfere with or enhance communication

RATIONALE: Many conferences in the ICU occur with the families of patients with limited English proficiency, requiring a medical interpreter. Despite the importance of medical interpretation, little is known about the alterations that occur and their effect on communication. OBJECTIVES: This study characterizes the types, prevalence, and potential effects of alterations in interpretation during ICU family conferences involving end-of-life discussions. METHODS: We identified ICU family conferences in two hospitals in which a medical interpreter was used. Ten conferences were audiotaped; 9 physicians led these conferences, and 70 family members participated. Research interpreters different from those attending the conference translated the non-English language portions of the audiotaped conferences. We identified interpretation alterations, grouped them into four types, and categorized their potential effects on communication. RESULTS: For each interpreted exchange between clinicians and family, there was a 55% chance that an alteration would occur. These alterations included additions, omissions, substitutions, and editorializations. Over three quarters of alterations were judged to have potentially clinically significant consequences on the goals of the conference. Of the potentially significant alterations, 93% were likely to have a negative effect on communication; the remainder, a positive effect. The alterations with potentially negative effects included interference with the transfer of information, reduced emotional support, and reduced rapport. Those with potential positive effects included improvements in conveying information and emotional support. CONCLUSIONS: Alterations in medical interpretation seem to occur frequently and often have the potential for negative consequences on the common goals of the family conference. Further studies examining and addressing these alterations may help clinicians and interpreters to improve communication with family members during ICU family conferences.     

Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting.

The inability to detect insulin-like growth factor binding protein-3 (IGFBP-3) in some circumstances by Western ligand blot analysis has emphasized the need to characterize IGFBPs by both ligand binding and immunological techniques. In this study, we have: 1) characterized and quantified IGFBP-3 in nonpregnancy, pregnancy, and fetal cord serum, follicular, peritoneal, and amniotic fluid, seminal plasma, cerebrospinal fluid (CSF), and urine; 2) established a new IGFBP-3 RIA that detects both intact and fragments of IGFBP-3; 3) identified both intact and fragments of IGFBP-3 by Western immunoblot techniques; and 4) addressed the discordance between Western ligand blot analysis and RIA by assessing fluids for IGFBP proteolytic activity. All fluids examined, except pregnancy serum, CSF, and amniotic fluid, displayed a 44-34-kilodalton (kDa) IGFBP-3 doublet by Western ligand blot analysis. Western immunoblot analysis using specific IGFBP-3 antiserum showed a 44-34-kDa IGFBP-3 doublet and a 28-kDa fragment in nonpregnancy serum, fetal cord serum, follicular fluid, and peritoneal fluid. The immunoreactive 42-38-kDa doublet was faint in urine and seminal plasma. IGFBPs in CSF did not cross-react with IGFBP-3 antiserum. Pregnancy serum and amniotic fluid contained only the 28-kDa fragment when compared against equal volumes of nonpregnancy serum. With the development of an IGFBP-3 RIA, IGFBP-3 could be accurately measured; urine, CSF, and seminal plasma contained the lowest levels of IGFBP-3 at 27 +/- 3 ng/ml (mean +/- SEM), 110 +/- 26 ng/ml, and 209 +/- 56 ng/ml, respectively. In increasing concentration: fetal cord serum contained 753 +/- 101 ng/ml; peritoneal fluid, 1124 +/- 130 ng/ml; follicular fluid, 2356 +/- 211 ng/ml; nonpregnancy serum, 3556 +/- 508 ng/ml; pregnancy serum, 3718 +/- 842 ng/ml; and amniotic fluid, 5150 +/- 688 ng/ml. The measurable concentrations of IGFBP-3 in CSF and the high concentrations measured in pregnancy serum and amniotic fluid conflicted with Western blot analysis. Thus, fluids were assessed for IGFBP proteolytic activity by incubation with a source of IGFBP-3, either nonpregnancy serum or purified IGFBP-3. All fluids displayed some proteolytic activity with either assay. Fluids with little protease activity (nonpregnancy serum, follicular fluid, and urine) showed a close relationship between immunoassayable IGFBP-3 by RIA and IGFBP-3 band intensity by Western ligand blot. Fluids with high proteolytic activity (pregnancy serum, CSF, seminal plasma, peritoneal fluid, and amniotic fluid) gave discrepant IGFBP-3 values between RIA and Western ligand blot.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bronchial Hyperresponsiveness in Farmers: Relation to Respiratory Symptoms, Lung Function, and Atopy

There is only limited information on the factors associated with nonspecific bronchial hyperresponsiveness (BHR) in farmers. Our purpose was to examine the relationship between BHR and respiratory symptoms, atopy, and abnormalities of lung function in a sample of French farmers. Farmers scheduled for a preventive medicine check-up in northeastern France were examined. Occupational exposure, respiratory symptoms, and work-related symptoms were assessed by questionnaire, sensitization to 34 common and agricultural allergens by skin prick tests, and BHR by the single-dose (1,200 μg) acetylcholine (ACh) challenge test. Data were obtained from 741 farmers (95% of those invited). Seventy-seven subjects (10.3%) had BHR defined as a fall in forced expiratory volume in 1 s (FEV₁) ≥ 10% after the inhalation of ACh or, for those with a poor lung function, an increase in FEV₁ > 10% and > 200 ml after the inhalation of 200 μg of salbutamol. The proportion of asthmalike symptoms, especially wheeze during work, positive skin tests to acarian (storage mites) and cereal dust allergens, and low levels of lung function was significantly greater among reactors than among nonreactors. Stepwise logistic regression analysis showed a significant and independent association between BHR and wheezing during work (OR = 4.99; 95% CI = 2.29–10.89; p= 0.0001) and baseline FEV₁ (OR = 1.49; 95% CI = 1.05–2.20; p= 0.026). In conclusion, hyperreactive farmers had significantly more asthmalike symptoms, positive skin tests, and abnormal lung function than normoreactive farmers. Work-related wheeze and low baseline FEV₁ were significantly and independently associated with BHR. Accepted for publication: 26 January 1999