Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C.

The heat-stable enterotoxin of Escherichia coli (STa) stimulates membrane-bound guanylate cyclase in intestinal epithelium and induces fluid and ion secretion. Using the T84 human colon carcinoma cell line as a model, we observed that phorbol esters markedly enhanced STa-stimulated cyclic GMP accumulation in T84 cells (C. S. Weikel, C. L. Spann, C. P. Chambers, J. K. Crane, J. Linden, and E. L. Hewlett, Infect. Immun. 58:1402-1407, 1990). In this study we document that the phorbol ester treatment increases 125I-STa-binding sites as well as membrane-bound guanylate cyclase activity in T84 cells and provide evidence that both effects are mediated by phosphorylation. Guanylate cyclase activity was increased approximately 50% in membranes prepared from intact T84 cells treated with phorbol-12,13-dibutyrate (beta-PDB) and after treatment of homogenates with beta-PDB in a manner dependent on ATP, MgCl2, and cytosol. Similarly, treatment of membranes with purified bovine brain protein kinase C in the presence of appropriate cofactors and beta-PDB resulted in an increase in STa-stimulated guanylate cyclase activity of about 70%. Likewise, the number of 125I-STa-binding sites was increased by about 25 to 40% in membranes prepared from intact cells or homogenates treated with beta-PDB; no effect on binding affinity (Kd = 0.15 nM) was noted. These experiments suggest that protein kinase C may phosphorylate the STa receptor-guanylate cyclase or a closely related protein and increase guanylate cyclase activity. The stimulatory effects of protein kinase C on STa-sensitive guanylate cyclase are opposite in direction to the profound inhibitory effects of the kinase on atrial natriuretic peptide-stimulated guanylate cyclase, demonstrating differential regulation by protein kinases within the guanylate cyclase-receptor family.     

Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase

BACKGROUND: Commercially available assays for IgE antibody provide results in international units per milliliter for many allergen extracts, but this is not easily achieved with purified or novel allergens. OBJECTIVE: To develop assays for IgE antibody suitable for purified or novel allergens by using a commercially available immunosorbent. METHODS: Streptavidin coupled to a high-capacity immunosorbent (CAP) was used to bind biotinylated purified allergens from mite (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody to these allergens were performed on sera from children (asthma and control) as well as adults with atopic dermatitis. RESULTS: The results were validated by serial dilution of sera with high and low levels of IgE antibody and were quantitated in international units per milliliter by using a standard curve. Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P < .001 in each case). Furthermore, the values for IgE antibody in sera from children with high exposure to mite and cat allergens demonstrated 10-fold higher levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001). CONCLUSION: The streptavidin immunosorbent technique provides a new method for quantifying IgE antibody to purified proteins. The results provide evidence about the high quantities of IgE antibody to purified inhalant allergens in patients with atopic dermatitis. In addition, the results demonstrate major differences in IgE antibodies specific for mite and cat allergens among children with high exposure to both allergens.     

The relationship between epithelial Ia expression and the inflammatory cell infiltrate during experimental oral carcinogenesis

Summary The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r⁺ (CD25⁺) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2–9 months) expression was present in only 20–40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25⁺ cells. Overall there were significantly more CD25⁺ cells in tissue specimens containing Ia⁺ epithelium compared with Ia^– epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25⁺ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25⁺ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN- by locally activated T cells.     

Double-blind, controlled study of clemastine fumarate, chlorpheniramine and placebo in patients with seasonal allergic rhinitis.

A whole body plethysmograph (body box) equipped with a flow meter (see Figure 1) was used for objective quantification of the effects of single doses of clemastine fumarate 2.68 mg, chlorpheniramine 4 mg and placebo in a double-blind study of 48 patients with seasonal allergic rhinitis. This technique offers an objective means of assessing drug effects on nasal congestion and obstruction. Before the development of whole body plethysmography, only subjective assessments of antihistamines' effects on nasal blockage or congestion were available. These subjective reports usually noted that nasal blockage or congestion was refractory to antihistamines or minimally relieved by them. However, in this study, nasal and oral airway resistances, each measured by whole body plethysmography, were lowered by clemastine fumarate and chlorpheniramine. These results were corroborated by the patients' and physician's assessments of changes in symptom severity and the physician's evaluation of intranasal photographs taken for each patient. Oral airway resistance of patients treated with clemastine fumarate was improved to a significantly greater extent than in patients receiving placebo. At two hours post-drug, patients receiving clemastine fumarate usually showed a greater response in most assessments than those receiving chlorpheniramine, and the trend of most comparisons was clearly in favor of clemastine fumarate. Patients in all three treatment groups experienced drowsiness but both incidence and severity were lower with clemastine fumarate.     

Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation

Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference <10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A “triangular” face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45, X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS. © 1992 Wiley-Liss, Inc.     

A pilot study of the effect of mechanical ventilation and heat exchange on house-dust mites and Der p 1 in New Zealand homes

We have examined the effect of reducing relative humidity (RH), with inbuilt mechanical ventilation and heat-exchange (MVHE) units, on house-dust- mite (HDM) counts and allergen levels, in a pilot study of 10 Wellington dwellings. Recent international prevalence studies in adults and children have confirmed a high prevalence of asthma in New Zealand, Sensitivity to HDM is common among the general population, and HDM is the major allergen associated with asthma. Recent studies of allergen levels have confirmed high concentrations of Der p 1 in the domestic environment. While humidity was significantly reduced in those dwellings fitted with ventilation units, no systematic effect on mites or Der p 1 was observed during the study period. When the reductions in humidity were examined in the context of the time spent below the critical equilibrium humidity (CEH), the intervention led to RH values below the CEH for only 39% of the total of 24-h periods for which measurements were made. Reducing RH by means of MVHE in New Zealand domestic dwellings does not lower humidity sufficiently, or long enough, to have any measurable effect on HDM populations.     

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...     

Pregnancy outcomes among visually impaired women in Washington State, 1987–2014

BackgroundWomen with visual impairment may have reduced ability to access standard care resources, however, information on their pregnancy and neonatal outcomes is limited.ObjectiveTo assess risk of adverse pregnancy and neonatal outcomes among visually impaired women in Washington State from 1987 to 2014.MethodsWe conducted a retrospective cohort study using linked Washington State birth/fetal death hospital discharge records to compare outcomes among women with and without visual impairment noted at their delivery hospitalization. Pregnancy conditions and outcomes evaluated included gestational diabetes, pre-eclampsia, labor induction and cesarean delivery. Neonatal outcomes included preterm delivery and birth weight <2500 g. We assessed length of maternal and infant delivery hospitalization. We performed Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CIs) for each outcome, adjusting for year of delivery, maternal age, and parity.ResultsMost adverse pregnancy and neonatal outcomes were similar for visually impaired (N = 232) and comparison women (N = 2362). However, visually impaired women had increased risks of severe pre-eclampsia (RR 3.77, 95% CI 1.69–8.43), labor induction (RR 1.33, 95% CI 1.10–1.61) and preterm delivery (RR 1.60, 95% CI 1.06–2.42). They were also more likely to have delivery hospitalizations of 3 or more days following a vaginal (RR 1.86, 95% CI 1.41–2.47). Among cesarean deliveries, infants of visually impaired women had increased risk (RR 1.24, 95% CI 1.02–1.51) of hospitalization for 3 or more days postpartum.ConclusionOur findings may be useful for obstetric providers in counseling their visually impaired patients.     

Assessment of Informal Caregiver Assistance and Strain With Total Hip and Knee Arthroplasty

BackgroundThe purpose of our study is to assess which patient-related and caregiver-related factors are predictive of caregiver strain and assistance when caring for total hip and knee arthroplasty (THA and TKA) patients within 2 weeks after surgery.MethodsWe conducted a prospective study of caregivers of participants enrolled in 2 randomized trials. Caregivers provided demographics and completed the Caregiver Strain Index and Caregiver Assistance Scale pre-surgery and post-surgery. We performed backwards stepwise regression with mixed-effects negative binomial models to investigate predictors of caregiver strain and assistance for THA and TKA caregivers.ResultsThree hundred six caregiver/patient pairs were included. Our models of caregiver strain found Caregiver Assistance Scale scores and patient age to be predictive for all caregivers. We also found caregiver gender and smoking status to be predictive for THA caregivers and caregiver age to be predictive for TKA caregivers. Our models of assistance provided by caregivers found time (post-surgery vs pre-surgery) was predictive for all caregivers. We also found patient body mass index, and patient and caregiver gender to be predictive for THA caregivers, and patient and caregiver employment status and caregiver education level to be predictive for TKA caregivers.ConclusionOur study identifies patient-related and caregiver-related factors which are associated with caregiver strain and assistance when caring for arthroplasty patients. As this is the first study to assess assistance provided by caregivers, it is important for future research to validate our results and to further explore whether patient-reported outcomes may also be related to assistance and strain.     

Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center

Tobacco use remains the leading cause of preventable disease and death in the US. The number of tobacco products has grown over the past decade. E-cigarette use has increased rapidly in recent years, but patterns and correlates of use have not been thoroughly assessed. We examined relationships among demographic factors, e-cigarette and conventional cigarette use in a large sample (N?=?12,409) of adult patients at a community health center in the Northeastern US. Overall, 13% (N?=?1675) of the sample reported ever using e-cigarettes. In logistic regression models, ever having used e-cigarettes was associated with younger age (ages 18–25; OR?=?3.5, p?<?0.001). Being transgender (OR?=?1.8, p?<?0.001), bisexual (OR?=?1.5, p?<?0.001), un-partnered (OR?=?1.5, p?<?0.001), having a lower income (OR?=?1.6, p?<?0.001) or a high BMI (OR?=?1.4, p?=?0.009) were associated with increased odds of use, whereas being a woman (OR?=?0.7, p?<?0.001) or Black/African American (OR?=?0.7, p?=?0.007) were associated with lower odds of use. Of the participants who reported e-cigarette use, a majority also endorsed current or former use of conventional cigarettes. Individuals who formerly used conventional cigarettes were nearly three times more likely to report daily e-cigarette use than current users. Among primary care patients at a community health center, e-cigarette use was reported by a sizeable portion of the sample. Overall, odds of use were higher in certain patient populations, and individuals who formally used cigarettes were more likely to report e-cigarette use than individuals who currently smoke, suggesting that e-cigarettes may be functioning as a cessation aid or a strategy to reduce conventional cigarette use.