Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein.

The uptake of low density lipoprotein (LDL) by cultured mouse macrophages was markedly promoted by isolated rat mast cell granules present in the culture medium. The granule-mediated uptake of LDL enhanced the rate of cholesteryl ester synthesis in the macrophages, the result being accumulation of cholesteryl esters in these cells. Binding of LDL to the granules was essential for the granule-mediated uptake of LDL by macrophages, for the uptake process was prevented by treating the granules with avidin or protamine chloride or by treating LDL with 1,2-cyclohexanedione, all of which inhibit the binding of LDL to the granules. Inhibition of granule phagocytosis by the macrophages with cytochalasin B also abolished the granule-mediated uptake of LDL. Finally, mouse macrophage monolayers and LDL were incubated in the presence of isolated rat serosal mast cells. Stimulation of the mast cells with compound 48/80, a degranulating agent, resulted in dose-dependent release of secretory granules from the mast cells and a parallel increase in cholesteryl ester synthesis in the macrophages. The results show that, in this in vitro model, the sequence of events leading to accumulation of cholesteryl esters in macrophages involves initial stimulation of mast cells, subsequent release of their secretory granules, binding of LDL to the exocytosed granules, and, finally, phagocytosis of the LDL-containing granules by macrophages.     

A similar high level of immunoglobulin A and immunoglobulin G class milk antibodies and increment of local lymphoid tissue on the duodenal mucosa in subjects with cow's milk allergy and recurrent abdominal pains

In previous studies, we have reported endoscopic and histological alterations locally on the gastrointestinal (GI) tract associated with a gastrointestinal type of cow's milk allergy. In this study, we sought to further characterize endoscopic, and immunological findings in these children. We also hypothesized that the same type of immune responses might also be found in children with unexplained and recurrent abdominal pains. We did a gastroduodenoscopy for persistent GI symptoms, examined the mucosal histology of the small intestine and measured the antibodies to whole cow's milk and its fractions with an enzyme‐linked immunosorbent assay (ELISA) in a consecutive series of 22 subjects with untreated and 14 with treated cow's milk allergy (CMA) and 44 with recurrent abdominal pains (RAP). The immunological findings of the study subjects were compared with 54 controls. Lymphonodular hyperplasia (LNH) of the duodenum was the main endoscopic finding in 11 subjects (50%) with untreated and 5 (36%) with treated CMA. It was also found in 6 of 44 subjects with RAP. Compared with the controls, the patients with CMA showed significantly higher levels of IgA class antibodies to whole milk (p = 0.003) and βLG (p < 0.0001). Of the IgG class antibodies to βLG (p = 0.032), BSA (p < 0.0001) and αCAS (p < 0.0001) were significantly higher. The patients with LNH of the duodenal bulb as the main endoscopic finding showed significantly higher values of IgG class antibodies to βLG (p = 0.01) and αCAS (p = 0.005). Interestingly, the patients examined for RAP showed a similar increment in the pattern of whole milk and specific milk protein antibodies as the CMA children. In conclusion this study showed that gastrointestinal CMA beyond infancy is significantly associated with high levels of IgG and IgA class antibodies to milk and its fractions. As high levels of these antibodies and LNH of the duodenal bulb were also found in subjects with RAP, the study further suggests that gastrointestinal CMA might be one major reason for RAP.     

Macronutrient and energy contents of human milk fractions during the first six months of lactation

Aim: To study the macronutrient and energy contents of human milk fractions during the first 6 mo of lactation. Study design: A total of 483 milk samples, including 52 pairs of fore- and hindmilk samples from 20 mothers, 253 samples from 53 donor mothers and 126 samples from 36 mothers of preterm infants, were collected longitudinally, starting at 1 wk postpartum and continuing monthly up to 6 mo. Protein, lactose and fat contents were measured and energy density estimated. Results: The protein content was significantly lower in fore- and hindmilk than in donor or preterm milk during the first months of lactation. In donor and preterm milk, the protein content declined consistently from 2.0 g/100 ml at 1 wk to half of that at 6 mo, and a similar trend was observed in fore- and hindmilk. Lactose content showed no significant changes between the groups or in the course of lactation. The fat content was highest in hindmilk, being approximately two- to threefold that of foremilk. Accordingly, hindmilk included 25-35 kcal/100 ml more energy on average than foremilk.

Conclusions: The fat content of human milk increases in relation to breast emptying, while the other macronutritients of milk show only slight changes. When enteral feeding with high-energy human milk is preferred, as in the case of very preterm infants, hind milk, with its higher fat content, would be a natural choice.     

The associations of emotion regulation and dysregulation with the metabolic syndrome factor

OBJECTIVE: Emotion regulation has been associated with good, and dysregulation with poor subjective health; but it is unclear if emotion regulation is related to metabolic syndrome. METHODS: Associations between the metabolic syndrome factor (systolic and diastolic blood pressure, waist circumference, high-density lipoprotein, triglycerides, and glucose), emotion regulation (the strategies of repair and maintenance, self-perceived emotion regulation) and dysregulation (emotional ambivalence); and subjective health (self-rated health and psychosomatic symptoms) were studied using a structural equation modelling (SEM) approach. The participants (96 women, 85 men) were drawn from the Jyv?skyl? Longitudinal Study of Personality and Social Development (JYLS). RESULTS: High repair was associated directly to the low metabolic syndrome factor, while high maintenance, high self-perceived emotion regulation, and low emotional ambivalence were related indirectly to the low metabolic syndrome factor through good subjective health. CONCLUSIONS: Successful emotion regulation may have an association not only with the subjective experience of health, but also with physiological regulation systems, leading to a reduced risk for metabolic syndrome.     

Somatization and alexithymia in young adult Finnish population

BACKGROUND: We assessed alexithymia and alexithymic features among young adult subjects with and without somatization symptoms in an epidemiological setting with a sample of young adults. METHODS: The sample consisted of urban 31-year-old subjects (N=1002). Data on somatization were gathered from a review of all public health outpatient records. Subjects with four or more somatization symptoms according to the DSM-III-R criteria were considered somatizers. The 20-item version of the Toronto Alexithymia Scale (TAS-20) was used to measure alexithymia. Subjects with a total TAS score over 60 were considered as being alexithymic, and those with a score under 52 were considered nonalexithymic. Subjects with a total TAS score from 52 to 60 were considered as having alexithymic features. RESULTS: The prevalence of alexithymia was 6.0% among somatizers and 4.8% among subjects without somatization symptoms, and the prevalence of alexithymic features was 7.5% and 12.6%, respectively. CONCLUSIONS: No association was found between alexithymia and somatization in young adult general population. The earlier theory of the association between alexithymia and somatization may be questionable.     

Histopathological features of breast tumours in <Emphasis Type="Italic">BRCA1</Emphasis>, <Emphasis Type="Italic">BRCA2</Emphasis> and mutation-negative breast cancer families

Introduction

Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families.

Methods

Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases.

Results

BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups.

Conclusions

BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker.

     

Cytokines and adhesion molecules in duodenal mucosa of children with delayed-type food allergy

OBJECTIVES: The aim was to investigate the expression of cytokines, adhesion molecules, and activation and proliferation markers in duodenal biopsies from children with delayed-type food allergy (FA). METHODS: Seven children with untreated FA (uFA), seven children with treated FA (tFA) to cow milk and/or cereals, and five normal controls furnished duodenal biopsy specimens. Additionally, five pediatric patients with celiac disease were included, serving exclusively as positive controls for in situ hybridization. Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), adhesion molecules, and activation markers were detected by immunohistochemistry, and expression of IFN-gamma and IL-4 messenger RNA was revealed by in situ hybridization. RESULTS: uFA patients had a higher density of IFN-gamma positive cells in the lamina propria than did tFA patients and controls (P = 0.053 and P = 0.018). Moreover, the uFA patients exhibited a higher proportion of crypt cells in mitosis than did tFA patients (P = 0.026), and stronger staining of HLA-DR in the crypts and increased density of gammadelta-T cell receptor-positive intraepithelial lymphocytes than did controls (P = 0.048 and P = 0.010). The densities of alpha(4)beta(7) positive cells in the lamina propria tended to be higher in controls than in uFA or tFA patients (P = 0.106, P = 0.073). Expression of IL-4 mRNA was significantly higher in celiac patients than in the other study groups (uFA P = 0.006, tFA P = 0.010; controls P = 0.029), and celiac patients showed higher expression of IFN-gamma mRNA than did tFA patients or controls (P = 0.017 and P = 0.016). CONCLUSIONS: As expected, Th1 dominance was present in the lamina propria of children with delayed-type FA. It may cause activation of epithelial cells and increase their turnover.     

Mucosal pathology of the foregut associated with food allergy and recurrent abdominal pains in children

To determine whether children with recurrent abdominal pain (RAP) include an excess of children with food allergy (FA), this study examined a consecutive series of 84 children (43M, 41F, mean age 7.9 y, range 1.6-15 y) referred during 1 y to 2 university hospitals. In addition to a clinical examination, the patients underwent gastroduodenoscopy with three biopsy specimens, skin-prick and patch tests, and comprehensive laboratory tests for atopic allergy. Based on an open elimination-challenge test, a total of 28 (33%) subjects were diagnosed for FA. In the whole material, specific endoscopic abnormalities were found in 38 (45%) subjects: oesophagitis in 17, gastric erosions in 8, lymphonodular duodenitis in 12 and erosive duodenitis in 5. FA showed a close relationship with duodenal lesions, but no significant association with oesophagitis and gastritis. The histological findings were mild, although some alterations could be observed in up to 66 (79%) subjects, equally often in patients with and without FA. None showed villous atrophy or severe infiltration of eosinophilic or mononuclear cells. Slightly increased densities of eosinophilic cells were significantly associated with endoscopic findings, especially oesophagitis. At least one positive skin-prick test with food allergens was found in 11 subjects and a positive patch test in 21 subjects, but neither showed an association with the endoscopic or histological findings, or even with clinical FA. Conclusion: Since the children with FA showed significantly more often concomitant mucosal pathology of the foregut than those without FA, FA may be considered one of the major factors underlying RAP. The report suggests the trial of an elimination diet in cases with RAP if lymphonodular hyperplasia or duodenitis is seen on gastroduodenoscopy.