Expression of ɛBP, a β-galactoside-binding soluble lectin, in normal and neoplastic epidermis

Abstract The study of animal lectins and glycoconjugates has become an important area of research in biomedical sciences, as these molecules are believed to play important roles in a variety of biological processes. This report describes a study of the expression of an animal lectin, IgE-binding protein (?BP), also known as Mac-2 and CBP35, in human skin. We have analyzed cultured human keratinocytes as well as normal human skin and a number of epidermal neoplasms, by immunoblotting. immuno-fluorescence and immunohistochemistry. We showed that ?BP is expressed in human keratinocytes, hair follicles, sebaceous and sweat glands. We found that cBP expression retains in various epidermal neoplasms, including basal cell carcinoma, squamous cell carcinoma and keratoacan-thoma, although the level of expression appears to be reduced as compared to normal epidermis. The immunohistochemical analysis also suggests that the level of ?BP expression appears to be dependent on the degree of cellular differentiation of keratinocytes.     

Human serum IgE-mediated mast cell degranulation shows poor correlation to allergen-specific IgE content

BACKGROUND: Although allergen-specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering. OBJECTIVES: Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti-IgE or allergen using a rat mast cell line (RBL) transfected with the alpha-chain of the human high-affinity IgE receptor (FcepsilonRI). METHODS: Purified IgE specific for 4-hydroxy-3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a beta-hexosaminidase release assay after anti-IgE or allergen-specific challenge. RESULTS: For purified monoclonal IgE a significant correlation (r = 0.97) was found between the proportion of bound allergen-specific IgE and the strength of the degranulation response. In contrast, no correlation (r = 0.27) was detected after sensitization with serum IgE. CONCLUSION: Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen-specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation.     

Identification of N<Superscript>ɛ</Superscript>-(carboxymethyl)lysine-positive cells in astroglia-rich primary cultures

Summary. Astroglia-rich primary cultures from rat brain were used to investigate the presence in glial cells of N^{603.gif" alt="epsiv" align="BASELINE" BORDER="0">}-(carboxymethyl)lysine (CML), an advanced glycation endproduct. Westernblot analysis of homogenates of rat brain as well as of astroglia-rich cultures demonstrated the presence of CML-modified proteins in these samples. Immunocytochemical staining of astroglia-rich cultures revealed that only a minority of the cells in these cultures were intensively stained for CML. The staining intensity of CML-positive cells was strongly reduced, if the cells were not permeabilized, indicating that intracellular proteins were CML-modified. The CML-positive cells were identified as astrocytes and oligodendrocytes by double-labelling immunocytochemical staining for CML and the cellular markers galactocerobroside, myelin basic protein and glial fibrillary acidic protein. In contrast to other glial cells, microglial cells in astroglia-rich cultures were CML-negative. The finding that only a minority of cells in astroglia-rich cultures contains high amounts of intracellular CML-modified proteins indicates that specific properties of these CML-positive cells are responsible for the CML-formation in these cells.Received January 28, 2003; accepted April 22, 2003 Published online June 30, 2003     

Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue

Significantly increased up-regulation of HLA DR (major histocompatibility complex class II antigen) was seen using immunohistochemistry in postmortem brain tissue from demented patients with Alzheimer’s disease (AD) (73 cases, 61 females/12 males, mean age 84 ± 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 ± 9 years). The counts of HLA DR-expressing activated microglia were significantly higher in female AD patients compared to males, significantly higher in AD patients with the age at death greater than 75 years compared to those dying younger and higher, although not statistically significantly, in AD patients with the apolipoprotein E (ApoE) &#603;4 allele compared to those patients not carrying this allele. In contrast to the situation in AD patients, in the control cases the HLA DR expression was higher in males compared to females. Furthermore, in the very old non-demented patients (age at death > 80 years), a decrease in the up-regulation of HLA DR expression was observed. A significant correlation between activated microglia and neurofibrillary tangles was seen in female AD patients compared to males, in AD cases without ApoE &#603;4 allele compared to those with this allele, in sporadic cases compared to familial and in cases with senile rather than presenile onset of the disease. Our results indicate that there is an age- and/or sex-related variability in up-regulation of HLA DR expression of microglia and that the linkage between this up-regulation and AD lesions is significantly influenced by the ApoE &#603;4 allele, gender of subjects, age at onset and familiality of the disease. Received: 20 May 1998 / Revised: 5 August 1998, 4 October 1998 / Accepted: 21 October 1998     

An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcɛRI with FcγRIIb

Background IgE binds to mast cells and basophils via its high‐affinity receptor, Fc?RI, and cross‐linking of Fc?RI‐bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross‐linking of Fc?RI with FcγRIIb, an ITIM‐containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti‐idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to Fc?RI‐bound IgE, via its Fab regions, and the negative regulatory receptor, FcγRIIb, via its Fc region. Objective To assess the ability of human 2G10 to inhibit anti‐IgE and allergen‐driven basophil degranulation through cross‐linking of Fc?RI‐bound IgE with FcγRIIb. Methods 2G10 was assessed for its ability to bind to FcγRIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti‐IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL‐4 expression intracellularly, using flow cytometery. Results Human 2G10 was able to bind to FcγRIIb on transfected cells and on purified basophils, and induce a dose‐dependent inhibition of both anti‐IgE and Der p 1‐driven degranulation of basophils. Conclusion The inhibition of basophil degranulation by the human IgG1 anti‐idiotype 2G10 highlights the therapeutic potential of IgE‐reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor FcγRIIb.     

Impact of a Pilot School-Based Nutrition Intervention on Fruit and Vegetable Waste at School Lunches

ObjectiveTo determine the preliminary impact of the Brighter Bites nutrition intervention on decreasing fruit and vegetable (F&V) waste at school lunches among fourth- and fifth-grade children.MethodThis was a nonrandomized pre–post-controlled study in Houston and Dallas, TX. Two schools received the Brighter Bites intervention (n = 76), and 1 comparison school (n = 39), during the 2017-2018 school year. Brighter Bites is a 16-week school-based nutrition intervention providing weekly distribution of fresh F&V plus nutrition education. Main outcome measures were direct observation and weights to measure the number of F&V dishes selected at school lunches, amount of F&V wasted (gm), and related nutrient waste (4 time points/child). Mixed-effects linear regression analysis was used to determine change in F&V selection and waste over time.ResultsThere was a significant decrease over time in proportion of F&V selected among those in the comparison school, but not the intervention schools (P < .001). Compared with children in the comparison group, those receiving Brighter Bites showed a significant decrease in the amount of F&V wasted at each meal (P < .001) and per item (P < .05) at the end of both 8 and 16 weeks of intervention. There were significant decreases in waste of energy (kcal); dietary fiber (gm); vitamins B₁, B₃, and B₆ (mg); total folate (µg); and B₁₂ (µg) among those receiving Brighter Bites (P < .05).Conclusions and ImplicationsAlthough absolute food or nutrient changes were small even when significant, programs such as Brighter Bites may contribute to a healthy intake. Future studies are warranted that include a larger sample size with a stringent, cluster-randomized control trial design and consideration for other covariates.     

Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury

Objectives –  Severe head injury (HI) and the apolipoprotein E (ApoE) &#603;4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE &#603;4 is not known.
Materials and methods –  Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored ≥26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable.
Results –  Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE &#603;4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE &#603;4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02–7.16).
Conclusions –  According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE &#603;4 allele is associated with subsequent dementia among older adults.     

Systemic markers of inflammation and cognitive decline in old age

OBJECTIVES: To investigate whether higher circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and alpha1-antichymotrypsin (ACT) are associated with worse cognitive function and decline in old age. DESIGN: Two independent population-based cohort studies. SETTING: The Rotterdam Study (mean follow-up 4.6 years) and the Leiden 85-plus Study (maximal follow-up 5 years). PARTICIPANTS: Three thousand eight hundred seventy-four individuals, mean age 72, from the Rotterdam Study, and 491 individuals, all aged 85, from the Leiden 85-plus Study. MEASUREMENTS: Both studies assessed global cognition, executive function, and memory. Linear regression analyses were used in the current study to investigate the associations between inflammatory markers and cognitive function and decline. RESULTS: In the Rotterdam Study, higher levels of CRP and IL-6 were cross-sectionally associated with worse global cognition and executive function (P<.05). ACT was not associated with cognitive function. In the Leiden 85-plus Study, estimates were similar for CRP, although not statistically significant. Higher IL-6 levels were related to a steeper annual decline in memory function in the longitudinal analysis in the Leiden 85-plus Study (P<.05). The effect of higher IL-6 levels on global and memory function decline was stronger in apolipoprotein E (APOE) epsilon4 carriers (P-interaction=.01) than in those who were not (P-interaction=.05). In the Rotterdam Study, higher IL-6 levels were related to a steeper annual decline in global cognition in APOE epsilon4 carriers only. CONCLUSION: Systemic markers of inflammation are only moderately associated with cognitive function and decline and tend to be stronger in carriers of the APOE epsilon4 allele. Systemic markers of inflammation are not suitable for risk stratification.