Staphylococcal Culture Supernates Stimulate Human Phagocytes

Phagocytes play a major role in host defense against staphylococci as well as in the pathophysiology of Gram-positive septic shock. In Gram negative sepsis, the main mediator, LPS exerts its effects as easily suspendable mediator. In Gram positive sepsis the main mediator is still not found, therefore we studied the interaction of soluble staphylococcal products with phagocytes. Staphylococcus aureus supernates (SaS) were harvested from several laboratory and clinical strains that were grown to late-log phase. These supernates upregulated CD11b/CD18 expression on human neutrophils even in a 100-fold dilution. SaS also induced the release of TNF- and IL-1 by human monocytes. Control experiments excluded peptidoglycan, lipoteichoic acid, and toxin, leucocidin, TSST-1 and all enterotoxins as sole mediators. Endotoxin contamination was also excluded. SaS was heat-stable; incubation for 45 minutes at 100°C did not affect its activity. Compared to purified peptidoglycan and intact bacteria per bacterium, SaS had a higher potency in stimulating phagocytes. We hypothesize that there are more—yet unknown—soluble staphylococcal products which are very important in phagocyte stimulation.     

Isolation and Purification of Treponema pallidum from Syphilitic Lesions in Rabbits

Treponema pallidum were extracted from testicular syphilomas of corticosteroid-treated rabbits and purified by differential centrifugation. The steroid therapy allowed a longer holding time for infected rabbits, which produced greater treponeme yields, averaging 1.58 × 10¹⁰ treponemes per rabbit. The treatment, which also diminished cellular infiltration and increased the extracellular mucoid material in lesions, produced much cleaner suspensions than preparations from nontreated animals. Most of the treponemes in the purified suspensions were still motile, and none carried demonstrable host immunoglobulin. The preparations were free of recognizable host tissue debris and they contained, on the average, 1.9 × 10⁻⁷ μg of protein per treponeme.     

Autoimmunity in chronic bullous skin diseases. Immunofluorescent demonstration of three types of antibodies to skin in sera of patients with pemphigus, bullous pemphigoid and in other human sera

Antibodies to an intercellular substance of epidermis and other stratified squamous epithelia demonstrable by immunofluorescent staining have been reported to occur in the sera of patients with pemphigus vulgaris. Using sera of patients with bullous pemphigoid, antibodies to a component of the basement zone of skin had been found by the same technique. In the present study these observations have been confirmed and extended. In addition to the above mentioned immunofluorescent staining reactions, another type of antibody directed to a cytoplasmic or perinuclear component of epidermal cells was found in a variety of pathologic sera. This observation points to the need for differentiating other skin-reactive antibodies from those found only in pemphigus. Guinea-pig lip sections appeared to be satisfactory for these studies. Mixed immunofluorescence was found to yield staining reactions identical to those observed by the indirect staining method, and gave titres the same as or lower than those obtained by the indirect staining procedure. Using the indirect method with guinea-pig lip sections it was found that eight of ten sera of patients with pemphigus contained intercellular antibodies while 102 control sera failed to yield reactions of this type. The titres of antibodies appeared to be proportional to the severity of the disease process. Sera of two out of three patients suffering from bullous pemphigoid yielded immunofluorescence staining of the basement zone while 109 controls were negative for this antibody.     

Composition of TCR-CD3 complex in human intestinal intraepithelial lymphocytes: lack of Fc{varepsilon}Rl{gamma} chain

Human intestinal intraepithelial lymphocytes (DEL) are a uniquepopulation of predominantly CD8ß⁺ TCRß⁺lymphocytes and, to a lesser extent, TCR⁺ lymphocytes that proliferatepoorly to anti-CD3 mitogenic signals but display significantcytolytic activity. Studies in mouse model systems have shownthat the chain of the high-CD3 affinity receptor for IgE (FcRl)may substitute for the chain in the TCR-CD3 complex of iIEL.This has suggested that the functional properties of these cellsmay be associated with an altered composition of the TCR-CD3complex. We therefore analyzed the TCR-CD3 complex of normalhuman iIEL. One-and two-dimensional non-reducing/reducing SDS-PAGEanalysis of CD3, CD3, CD3, and FcRr chain immunopreclpitatesof cell surface radiolabeled proteins with subunit-specificantibodies revealed a TCR-CD3 complex without associated FcRrchains. Thus, normal human NEL contain a TCR-CD3 complex thatconsists predominantly of , homodimers in association with theß TCR and CD3, and , similar to the majority of peripherallymphocytes. This indicates that the distinct properties ofhuman DEL are not associated with substitutions of the FcRlchain in the TCR-CD3 complex.     

Discriminating adaptive attributions: Agreement between self-report and objective ratings

According to the reformulated learned helplessness model of depression, causal attributions are an important mediator of the effects on mood of positive and negative experiences. Adaptive attributions for negative events are assumed to be external, unstable, and specific. In the present study, subjects exposed to one of two attribution training procedures or a control condition made attributions for hypothetical events under neutral and adaptive instructional sets. Attributions were rated by subjects and coders blind to the purpose of the study. Results indicated that subjects' views of adaptive causal attributions were congruent with predictions from the learned helplessness model. The ratings of the objective coders indicated that subjects' attributions really did change in response to the adaptive instructions in the predicted direction. Implications of these results for the reformulated learned helplessness model and depression therapies that include an attribution retraining component are discussed.The authors would like to thank Dan Russell for his very helpful comments on earlier drafts of this paper.     

Effect of verapamil on daunorubicin accumulation in Ehrlich ascites tumor cells

Summary Previous studies have demonstrated that verapamil may overcome resistance to anthracyclines. In vitro and in vivo experiments were performed on wild-type and resistant Ehrlich ascites tumor cells.Verapamil in concentrations of 25–50 M enhances the accumulation of daunorubicin (DNR) in resistant cells to the same level as in wild-type cells. No significant effect of verapamil on influx or nuclear binding could be demonstrated, indicating that verapamil enhances DNR uptake by blocking active drug extrusion. Exposure of cells to a high concentration of Ca²⁺ did not influence the effect of verapamil on DNR accumulation, suggesting a different mode of verapamil action apart from the Ca²⁺-blocking effect. Attempts to circumvent acquired resistance to DNR in vivo with verapamil showed that the combination of the two drugs was more toxic than DNR given alone. The LD₁₀ of DNR was determined as 3 mg/kg and the LD₁₀ of the combination, as 2.5 mg/kg. The therapeutic effect of verapamil at a dose of 50 mg/kg and DNR of 2.5 mg/kg increased the life span of the mice by 50%. No difference was seen in the wild-type tumor in vivo.These data lead us to conclude that verapamil can reverse DNR resistance completely, but that verapamil at non-toxic dosage only reduces DNR resistance by 50% in vivo.The Danish Cancer Society, Copenhagen, Denmark, the Kathrine and Vigo Skovgaard Foundation, Holbæk, Denmark and the Anders Hasselbalch Foundation, Copenhagen, Denmark, kindly supported this work.     

Care-Seeking Behavior for Newborns in Rural Zambia

Maternal and Child Health Journal - Mothers in resource-limited areas face barriers in initiating care for ill newborns, leading to delays that may contribute to newborn mortality. This qualitative...     

A Pilot Trial of a Health Promotion and Illness Prevention Paradigm in the Perinatal Period

Maternal and Child Health Journal - This is a pilot study of the Vermont Family Based Approach, an innovative health promotion program designed to address behavioral health prevention in primary...     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO₃⁻) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m²) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO₃⁻ (HN: 2 × 70 mL BJ/day) (2) medium-NO₃⁻ (MN: 70 mL BJ/day), (3) low-NO₃⁻ (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO₃⁻-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO₃⁻ intake, and by measuring NO₃⁻ and NO₂⁻ concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO₃⁻ dose and the increase in plasma and urinary NO₃⁻ concentration (R² = 0.71, p < 0.001 and R² = 0.46 p < 0.001, respectively), but relationships between NO₃⁻ dose and changes in salivary NO₃⁻ and NO₂⁻ were non-linear (R² = 0.35, p = 0.002 and R² = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.