Antigen-specific T-helper cells abrogate suppression in Trypanosoma cruzi-infected mice.

The ability of antigen-specific T-helper (Th) cells to enhance direct plaque-forming cell responses in spleen cells from Trypanosoma cruzi-infected C57BL/6 mice was investigated at various times during the course of infection from day 7 to day 230. The injection of antigen-specific Th cells in vivo or the addition of antigen-specific Th cells in vitro was effective in enhancing direct plaque-forming cell responses, except at the time of the most intense suppression during the acute phase of infection (i.e., day 28). The ability of antigen-specific Th cells to overcome nonspecific immunosuppression was due not only to the activity of antigen-specific Th cells added to Mishel-Dutton cultures but also to activation of resident T cells. Thus, antigen-specific Th cells and resident T cells act in concert to produce enhanced direct plaque-forming cell responses. The effect of plastic-adherent spleen cells from infected mice on the ability of antigen-specific Th cells to stimulate anti-sheep erythrocyte responses of normal spleen cells was examined because macrophages have been shown to have an immunoregulatory role during the course of experimental American trypanosomiasis. Increasing numbers of macrophages from infected mice caused increased immunosuppression of normal spleen cells that could not be overcome with the addition of primed Th cells. It can be concluded from these data that antigen-specific Th cells can potentiate immune responses in mice infected with T. cruzi but that highly active suppressor macrophages can inhibit the expression of these primed Th cells.     

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients

Summary Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 620 ng/kg bw·min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4 : 1.5 ± 0.11 vs. 2.19 ± 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4 : 109 ± 8 vs. 154.7 ± 8.94 mg/dl ; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls. The mean central venous pressure was significantly lower by about 50% (P = 0.02) during the administration of urodilatin in spite of reduced vasodilator medication with nitroglycerin. From this phase IIa study, we may conclude that urodilatin could be an important drug in intensive care treatment. For patients undergoing HTx, this peptide seems to be indicated for the improvement of renal function and cardiovascular status, especially in postoperative therapy using high-dose cyclosporin A treatment.Abbreviations ACE angiotensin converting enzyme - ANP atrial natriuretic polypeptide - ATG antithymocyte globulin - bpm beats per minute - bw body weight - CDD cardiodilatin - CDD/ANP-99-126 circulating form of vasorelaxant cardiac peptide - CHD coronary heart disease - CyA cyclosporin A - DCM dilated cardiomyopathy - GLM general linear model - hANP human atrial natriuretic polypeptide - HTx heart transplantation - NTG nitroglycerine - PC plasma creatinine - SU serum urea - SAS statistical analysing system     

Hemolysin supports survival but not entry of the intracellular bacterium Listeria monocytogenes.

The gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen. The only known property of L. monocytogenes which has been shown to be involved in virulence is a hemolysin, listeriolysin (J. L. Gaillard, P. Berche, and P. Sansonetti, Infect. Immun. 52:50-55, 1986; S. Kathariou, P. Metz, H. Hof, and W. Goebel, J. Bacteriol. 169:1291-1297, 1987). Using our previously obtained transposon Tn916-induced hemolysin-negative mutants of L. monocytogenes Sv1/2a (Mackaness strain), we demonstrated that the loss of hemolysin reduced significantly the rate of survival of the bacteria in mouse peritoneal macrophages but did not reduce their uptake. It was further shown that virulent L. monocytogenes strains could invade the mouse embryo fibroblast 3T6 cell line, i.e., mammalian cells which are nonprofessional phagocytes. This uptake was inhibited by cytochalasin B and hence seems to be accomplished by parasite-induced endocytosis. Hemolysin was not essential for this step. Strains of other Listeria species could not efficiently penetrate the 3T6 cells.     

Relative right versus left frontal EEG in neonates

Although infants have been noted to have greater relative right or left frontal EEG as early as the neonatal period, other ways in which these newborns differ have not been reported. In this study, 48 newborns were divided on the basis of greater relative right versus greater relative left frontal EEG to determine whether these groups differed in other ways at the neonatal period including behavior, physiology, and biochemistry. We also were interested in whether these EEG patterns were related to any prenatal maternal variables including mood states (depression, anxiety, anger) and biochemistry as well as fetal activity. The greater relative right frontal EEG newborns had mothers with lower prenatal and postnatal serotonin and higher postnatal cortisol levels. The mothers of the greater relative right frontal EEG newborns also had greater relative right frontal EEG activation and lower vagal tone. The greater relative right frontal EEG newborns themselves had elevated cortisol levels, showed a greater number of state changes during sleep/wake behavior observations, and performed less optimally on the Brazelton Neonatal Behavior Assessment (T. B. Brazelton, 1973) including the habituation, motor, range of state, excitability, and depressive symptoms scales. These data suggest that greater relative right frontal EEG newborns may be at greater risk for developmental problems than those with greater relative left frontal EEG activation. In addition, a discriminant function analysis correctly classified 67% of the newborns' EEGs by prenatal maternal variables, suggesting that these might be used to target pregnant women for prenatal intervention.     

Classically conditioned enhancement of hyperinsulinemia in the ob/ob mouse

The obese (C57BL/6J ob/ob) mouse is a commonly used animal model of non-insulin-dependent diabetes mellitus. Recent experiments have shown that stress hyperglycemia can be classically conditioned in the obese but not in the lean mouse. In the present study, classical conditioning of insulin secretion was attempted in C57BL/6J obese and lean animals. For 21 days, obese and lean mice were exposed to a conditioned olfactory stimulus prior to and during eating. On the 22nd day, blood was sampled for all animals following presentation of the conditioned stimulus; testing was repeated 2 weeks later following an additional 4 days of conditioning. Results indicated an effect of conditioning, with significantly greater plasma insulin for trained than for untrained obese mice. That insulin secretion can be more easily conditioned in the obese mouse suggests that a cholinergic mechanism may be involved in the hyperinsulinemia characteristic of this animal.     

Huntington's disease: biochemical prediction by determination of GABA synthesis of cultured fibroblasts

Summary GABA synthesis in skin fibroblasts from patients with Huntington's chorea was compared with that in a control group by means of the highly specific ³H-muscimol radioreceptor assay. A significantly increased rate of GABA synthesis was found in the group with Huntington's chorea in an early cell passage. The possible use of this method for early diagnosis of Huntington's chorea is considered.

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Zusammenfassung Die GABA-Synthese in Hautifbroblasten von Chorea Huntington-Patienten im Vergleich zu einer gesunden Kontrollgruppe wurde mittels des hochspezifischen ³H-Muscimol-Radiorezeptoren-Assays untersucht. Wir fanden eine signifikante 8fache Erhöhung der GABA-Synthese bei Chorea Huntington in einer frühen Zellpassage. Es wird erwogen, diese Methode zur Frühdiagnostik von Chorea Huntington einzusetzen.

     

Improving medical residents’ self-assessment of their diagnostic accuracy: does feedback help?

Advances in Health Sciences Education - When physicians do not estimate their diagnostic accuracy correctly, i.e. show inaccurate diagnostic calibration, diagnostic errors or overtesting can occur....     

Markers of Intestinal Permeability Are Rapidly Improved by Alcohol Withdrawal in Patients with Alcohol-Related Liver Disease

Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients.     

The Hunger Games: Homeostatic State-Dependent Fluctuations in Disinhibition Measured with a Novel Gamified Test Battery

Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours.