Autoimmune hemolytic anemias and IgG antierythrocyte autoantibodies in Waldenström's macroglobulinemia: association with FcgammaRIIa polymorphism.
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Aged↗
Biomedical subjects
J Fernandes
Publications and source records attributed to J Fernandes.
Determination of acrylamide in coffee and coffee products by GC-MS using an improved SPE clean-up.
An improved gas chromatography-mass spectrometry (GC-MS) method to determine acrylamide (AA) in coffee and coffee products was developed. The method was based on two main purification steps: the first with ethanol and Carrez solutions in order to precipitate polysaccharides and proteins, respectively; and the second with a layered solid-phase extraction (SPE) column which proved to be efficient in the elimination of the main chromatographic interferences. The method is applicable to a wide range of coffee products. Twenty-six samples of different coffee products were analysed. The levels of AA were in the range 11.4-36.2 microg l-1 for 'espresso coffee' and 200.8-229.4 microg l-1 for coffee blends with cereals. The results indicate that the presence of cereals significantly increased the levels of AA.
Acrylamide↗
Synthesis of some new biologically active 1,3,4-oxadiazolyl nitroindoles and a modified Fischer indole synthesis of ethyl nitro indole-2-carboxylates.
An efficient and modified synthesis of ethyl-4-nitro/5-nitro/6-nitro and 7-nitroindole-2-carboxylates is described. Carbohydrazides of corresponding ethyl nitroindole-2-carboxylates underwent smooth one-step transformation to 1,3,4-oxadiazolyl nitroindoles (4a-l) on reaction with aromatic carboxylic acids in the presence of phosphorus oxychloride. An alternate method to synthesize 1,3,4-oxadiazolyl nitroindoles is also described. Among the newly synthesized 1,3,4-oxadiazolyl nitroindoles, a few compounds are studied for anti-inflammatory activity.
Animals↗
Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a COX-2 selective inhibitor, in dogs.
This study assessed the gastroduodenal safety profile of licofelone, a new nonsteroidal anti-inflammatory drug with dual inhibitory activity against 5-lipoxygenase and cyclo-oxygenase (COX), by using endoscopic evaluations and by comparing licofelone to rofecoxib, a selective COX-2 inhibitor. Twenty-one dogs underwent blinded gastroduodenoscopies, during which the mucosa of the gastroduodenal tract was assessed and scored. Blood analyses were monitored on days 0 (baseline), 14, 28, 42, and 56. Examinations to detect fecal occult blood were performed daily. Dogs were randomly assigned to three groups that received either a placebo, licofelone at a dose of 2.5 mg/kg twice daily, or rofecoxib at a dose of 0.5 mg/kg daily, respectively. Significant differences between the groups in gastric (P = 0.003), duodenal (P = 0.009), and gastroduodenal (P = 0.002) endoscopic lesion scores were observed at day 56. Rofecoxib-treated dogs had more lesions in all areas when compared with placebo-treated dogs, more duodenal lesions when compared with licofelone-treated dogs and more lesions than they had at baseline. In contrast to licofelone, rofecoxib was found to induce significant gastric and gastroduodenal lesions in dogs that lacked pre-existing lesions at baseline. Blood analyses and fecal examinations did not reveal abnormalities in any of the experimental groups. Treatment with licofelone was well tolerated and was shown to be safer than rofecoxib in terms of upper gastrointestinal damage. In this way, this study demonstrates the gastroduodenal safety profile of licofelone for chronic treatment.
Acetates↗
Detection and identification of mycobacteria in the Lisbon water distribution system.
Mycobacteria have emerged as a major cause of opportunistic infections. Until the present, only a few studies have characterized mycobacteria present in the water distribution system of urban areas. In this study, we characterize these microorganisms in the Lisbon water distribution system. Our results indicate a high rate of positivities (90.5%) with mainly saprophytic mycobacteria. Around 63% of these results belong to strains of Mycobacterium gordonae indicating a generalized proliferation of this species in the Lisbon water distribution system. A total of 21.05% of the isolates are from M. kansasii, M. intracellulare and M. chelonae.
Cities↗
Enhancement of murine IgE antibody detection by IgG removal.
RATIONALE: Although animal models for the study of allergic reactions are desirable, the use of mice has been hindered by the lack of sufficiently sensitive in vitro immunoglobulin epsilon (IgE) antibody assays. The aim of this study was to enhance IgE antibody measurements by immunoglobulin gamma (IgG) depletion. METHODS: Seven- to eight-week-old female mice of four strains (C3H/HeJ, CBA/J, C57Bl/6J, and Balb/c) were immunized (20 mice/group) with shrimp or peanut extracts using Al(OH)(3) as adjuvant. Following immunization, animals were sacrificed by exsanguination and the sera of each group pooled. Initial measurements of IgE antibody levels by enzyme-linked immunosorbent assay (ELISA) were relatively low; IgG and IgE reactivity patterns by immunoblot were similar. Thus, sera from shrimp or peanut immunized mice were depleted of IgG (absorbed 3-6 times with immobilized protein G) and then tested for IgE antibody to shrimp or peanut allergen. RESULTS: A 3- to 5-fold increase in IgE antibody reactivity as measured by ELISA was demonstrated when >80-90% of the IgG was removed. This increase in detection of allergen-specific IgE occurred in sera from all mouse strains and to all allergens tested. In addition, reactivity of IgE antibodies to peanut or shrimp allergens by immunoblot increased visually approximately 4- to 10-fold. CONCLUSIONS: These studies indicate that allergen-specific IgG antibodies, which may be in more than 100-fold excess to IgE antibodies, interferes with detection of allergen-specific IgE, probably by competitive binding to allergenic epitopes. Substantial depletion of IgG antibodies (>80%) result in a significant increase in the sensitivity of the antibody measurements.
Allergens↗
Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews.
BACKGROUND: Assessment of allergic (IgE antibody-mediated) reactions to foods may become complicated by cross-reactivity that can occur among certain food families and between foods and seemingly unrelated allergens. OBJECTIVE: The allergenic properties of tropomyosin (muscle-derived protein) have been recently demonstrated in invertebrates such as cockroaches, dust mites, and shrimp. In view of a possible cross-reactivity between food allergens and related allergens from animal sources, we designed a study to assess IgE antibody reactivity to the major shrimp allergen, Pen a 1, in an unexposed population of Orthodox Jews, who observe Kosher dietary laws that prohibit eating shellfish. METHODS: Nine subjects, who reacted positively by skin tests to shrimp (Penaeus setiferous), were selected for the study. Subjects (two females, seven males) ranged in age from 14 to 32 years (mean 20.4). All subjects were strictly observant of Jewish tradition and had no prior exposure to seafood (regarded as a non-Kosher food). Serum was obtained from all the subjects and tested for IgE antibody reactivity to shrimp and dust mite. RESULTS: All subjects reported symptoms of perennial allergic rhinitis, five had history of asthma, atopic dermatitis, and/or sinusitis. All had positive skin prick tests to shrimp and house dust mite (HDM) (Dermatophagoides farinae, D. pteronyssinus, or both); 2/7 subjects were positive to cockroach mix (Blattella germanica and Periplaneta americana). Sera of 4/9 subjects demonstrated specific IgE antibodies by RAST to shrimp (7.0-20.0%), 3/9 to Pen a 1 (6.3-24.1%), and 3/9 to shrimp or Pen a 1 by immunoblot. IgE binding to Pen a 1 was inhibited with either mite or cockroach extracts as demonstrated by RAST and/or immunoblot inhibition analysis. CONCLUSIONS: These studies indicate that IgE antibody reactivity to a major food allergen, shrimp, can occur in an unexposed population of individuals; some subjects allergic to HDM and/or cockroach show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1 (tropomyosin). Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross-reacting tropomyosins.
Allergens↗
CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx.
The present study was undertaken to examine CYP1A1 and XRCC1 polymorphisms as potential genetic susceptibility markers for laryngeal squamous cell carcinoma (SCC). Eighty-eight patients with laryngeal SCC and 178 randomly selected healthy blood donors from the same Caucasian population (Porto, Northern Portugal) were analysed for CYP1A1 (MspI and NcoI) and XRCC1 (Arg194Trp and Arg399Gln) polymorphisms, using PCR-RFLP techniques. CYP1A1 MspI MH (mutant homozygous) and CYP1A1 NcoI HT (heterozygous) genotypes were more frequent in patients than in controls, with those carrying a CYP1A1 NcoI HT genotype having a 2.3-fold higher risk for tumour development. On the other hand, polymorphisms in XRCC1 codon 399 and codon 194 do not seem to play a role in the aetiology of smoking-related laryngeal SCC, once its distribution was similar in both analysed groups. All the significant associations observed were exclusively due to differences between controls and larynx glottic cancer patient subgroup. Furthermore, lower lifetime tobacco consumption was observed in laryngeal SCC patients carrying the MspI and NcoI polymorphisms, than in those who did not show the polymorphic variants. This investigation seems to support the importance of CYP1A1 gene polymorphism as a potential genetic marker of laryngeal cancer development, specially concerning smokers who have inherited the at-risk genotypes CYP1A1 MspI MH or CYP1A1 NcoI HT, who do appear to be more susceptible to the development of SCC of the glottic larynx.
Adult↗
Is the routine use of antibiotics justified in adult tonsillectomy?
Pain and secondary haemorrhage are the commonest complications of adult tonsillectomy, occurring mostly in the community. This is a randomized, double-blind, placebo-controlled, prospective trial of the effect of perioperative amoxycillin on these complications. The incidence and severity of post-operative haemorrhage was measured. For the first 10 post-operative days patients provided a linear pain score, a record of GP visits, and their use of additional antibiotics and analgesics. Of 95 patients considered: 23 suffered a secondary haemorrhage; 54 consulted their general practitioner (GP) because of pain; additional antibiotics were used by at least 31 and additional analgesics by at least 41. No significant differences were demonstrated between the active and placebo groups for any of these measures. This study demonstrates that secondary haemorrhage is common after adult tonsillectomy. Post-operative pain remains a major problem requiring frequent GP consultations. There appears to be no justification for the routine use of perioperative antibiotics.
Adolescent↗
[Nutrition and health].
In this issue the journal publishes the first of a series of articles on nutrition and health. Dutch investigators have contributed to food research since the work of Eijkman and co-workers on vitamins at the end of the nineteenth century. During the last forty years, food research has moved towards investigating the role of nutrients in the prevention of diseases with a long latency and in specific population groups, e.g. the elderly and people with hypertension or obesity. More recent research has focused on enriched food products and biotechnologically manufactured nutritional elements. The series will discuss subjects such as dietary reference intakes, dietary infections, dietary requirements of the elderly and patients in hospitals and rehabilitation institutions, and the beneficial and detrimental effects of alcohol consumption. This will enable the clinician to provide answers to patients' questions regarding their diet and to recommend a healthy diet.
Diet↗
[Nutrition and health--recommendations of the Health Council of the Netherlands regarding energy, proteins, fats and carbohydrates].
The present report of the Health Council of the Netherlands, entitled 'Dietary reference intakes: energy, proteins, fats and digestible carbohydrates' is the second of a series of updated and revised recommendations in which the emphasis has shifted from nutritional deficiencies to the risks for some chronic diseases caused by the affluent nutrition of the 'developed' Western countries. The recommendation for total fat differs between people with an optimum weight and those who are overweight. The range for normal intake, from 20 to 40 energy per cent, has been enlarged due to a higher upper threshold. For persons who are already overweight, the narrower range from 20 to 30/35 energy percent has been maintained. Due attention should be given to the fatty acid composition of the fat and the favourable effects of unsaturated fatty acids on some chronic diseases, particularly coronary heart disease. The adequate intake of alpha-linolenic acid has been raised to 1 energy per cent while maintaining linoleic acid at 2 energy per cent. The benefits of the n-3-polyunsaturated fatty acids from fish are emphasised. Trans fatty acids should be limited to 1 energy per cent. The recommendation of 50 to 40 energy per cent for digestible carbohydrates from birth to old age is lower than in foreign recommendations. The estimate is derived from the production of endogenous glucose. No specific effects on chronic diseases are known. The recommended dietary allowances for protein are lower than those in the previous Dutch recommendation. They are now in line with most recommendations in other countries. With respect to the energy requirement, an abnormal level of physical activity should be reflected in a correction factor on the normal energy consumption.
Animals↗
Sodium channel currents in maturing acutely isolated rat hippocampal CA1 neurones.
Sodium channel currents were recorded in excised inside-out patches from immature (P(4-10)) and older (P(20-46)) rat CA1 neurones. Channel conductance was 16.6+/-0.013 pS (P(20-46)) and 19.0+/-0.031 pS (P(4-10)). Opening patterns varied with step voltage and with age. In some patches bursting was apparent at voltages positive to -30 mV. Non-bursting behaviour was more dominant in patches from younger animals. In older animals mean open time (m.o.t.) was best described by two exponentials especially in the older cells; in the immature, there were fewer cases with two exponentials. The time constant of inactivation (tau(h)) estimated in ensemble averages was best described by two exponentials (tau(hf) and tau(hs)) in most patches from older cells. tau(hf) decreased with depolarization; tau(hs) increased in the range -30 to 0 mV. The voltage dependence of tau(hf) in the older cells is identical to that of the single tau(h) found in the younger; the results indicate a dominance of tau(hf) in the younger. Patches from younger cells more often showed one apparent active channel; in such cases, m.o.t. was described by a single exponential. However, in two cases, channels showed bursting behaviour with one of these channels showing a shift between bursting and non-bursting modes. Our findings are consistent with a heterogeneous channel population and with changes in the population in the course of maturation.
Animals↗
[Unfounded recommendations for vitamin D supplementation in pregnant and breastfeeding women].
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Breast Feeding↗
Manipulating the vascular biology of coronary atherosclerosis in diabetes: new opportunities.
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Angiotensin-Converting Enzyme Inhibitors↗
Protein phosphatase 1beta is required for the maintenance of muscle attachments.
Type 1 serine/threonine protein phosphatases (PP1) are important regulators of many cellular and developmental processes, including glycogen metabolism, muscle contraction, and the cell cycle [1] [2] [3] [4] [5]. Drosophila and humans both have multiple genes encoding PP1 isoforms [3] [6] [7]; each has one beta and several alpha isoform genes (alpha(1), alpha(2), alpha(3) in flies, alpha and gamma in humans; mammalian PP1beta is also known as PP1delta). The alpha/beta subtype differences are highly conserved between flies and mammals [6]. Though all these proteins are >85% identical to each other and have indistinguishable activities in vitro, we show here that the Drosophila beta isoform has a distinct biological role. We show that PP1beta9C corresponds to flapwing (flw), previously identified mutants of which are viable but flightless because of defects in indirect flight muscles (IFMs) [8]. We have isolated a new, semi-lethal flw allele that shows a range of defects, especially in muscles, which break away from their attachment sites and degenerate.
Alleles↗
Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I.
OBJECTIVE: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. METHOD: As part of a collaborative European Study on GSD type I, a retrospective registry was established in 12 European countries that included all patients with GSD-I who were known at the centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I, 57 who had GSD-Ib form the basis of this study. RESULTS: Neutropenia (defined as an absolute neutrophil count <1 x 10(9)/L) was found in 54 patients. In 64% of the patients neutropenia was documented before the age of 1 year, but in 18% of the patients neutropenia was first noted between the ages of 6 and 9 years. Neutropenia was persistent in 5 patients and intermittent without any clear cyclical course in 45. Neutrophil function was investigated in 18 patients with neutropenia and was abnormal in all. Perioral infections were reported in 37 patients, perianal infections in 27 patients, and protracted diarrhea in 23 patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients suspected to have IBD were abnormal in all. All patients with IBD, perioral infections, and perianal infections had neutropenia. CONCLUSIONS: Intermittent severe neutropenia is frequently found in patients with GSD-Ib. The study also indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied had evidence of IBD, all of whom had neutropenia. IBD was not detected in those with normal neutrophil counts. These findings support the notion that neutropenia and/or neutrophil dysfunction in GSD-Ib and IBD are causally related.
Adolescent↗
Different substrates and methane producing status affect short-chain fatty acid profiles produced by In vitro fermentation of human feces.
Five different substrates, i.e., lactulose, rhamnose, cornstarch, guar and ileostomy effluent, were used to determine whether methane producing status alters the production of short-chain fatty acids (SCFA) in methane producers (MP; n = 6) and nonproducers (MNP; n = 5). Fecal samples from MP and MNP were fermented with the five substrates using an in vitro fermentation method. Subjects with a mean breath methane concentration > 0.045 micromol/L above ambient air were classified as MP. Fermentation was stopped and samples were obtained at 3, 5 and 24 h. An HPLC method was used to measure the SCFA, acetate, propionate, isobutyrate, butyrate, valerate and isocaproate. A significant interaction between methane producing status and time for acetate production from lactulose was observed. There were no differences in fermentation of the four remaining substrates between MP and MNP, but there were significant differences among substrates in the two groups combined. Acetate production from lactulose was significantly greater than from the four other substrates, whereas that from ileostomy effluent was significantly less than the four other substrates. The amount of propionate produced from rhamnose was significantly higher than from the other substrates. The amount of butyrate produced from lactulose and cornstarch was significantly higher than from the other substrates. We conclude that differences exist in the fermentation patterns of lactulose, rhamnose, cornstarch, guar and ileostomy effluent. Methane producing status may influence fermentation patterns only of substrates that are largely fermented to acetate and not others.
Adult↗
Enhancement of phosphorylation and transcriptional activity of the glucocorticoid receptor in human synovial fibroblasts by nimesulide, a preferential cyclooxygenase 2 inhibitor.
OBJECTIVE: To examine the effect of 2 nonsteroidal antiinflammatory drugs (NSAIDs), nimesulide (NIM), a preferential cyclooxygenase 2 (COX-2) inhibitor, and naproxen (NAP), on the functional parameters and transcriptional activity of the glucocorticoid receptor (GR) system in cultured human synovial fibroblasts (HSF). METHODS: HSF were incubated with NIM (0.3, 3, and 30 microg/ml), NAP (15, 30, and 90 microg/ml), and dexamethasone (DEX; 0.01, 0.1, and 1 microM) on a time- and dose-dependent basis. The numbers of GR binding sites per cell were determined by radioligand receptor assay. Total cellular, cytoplasmic, or nuclear GR protein was measured by Western analysis using a specific anti-human GR antibody. Phosphorylation of GR was determined by specific immunoprecipitation of protein extracts from 32P-orthophosphate-labeled HSF. Mitogen-activated protein kinase p44/42 (MAPK) phosphorylation was followed by Western analysis using a specific anti-phosphoMAPK antibody. Levels of activated nuclear GR capable of binding specifically to a 32P-labeled oligonucleotide harboring the glucocorticoid/hormone response element (GRE) were evaluated by gel electrophoretic mobility shift analysis. The effects of NIM and DEX on transcriptional activation of the mouse mammary tumor virus (MMTV) promoter was determined by transfecting HSF with MMTV-luciferase (reporter gene) constructs. RESULTS: NIM had no effect on the number of GR binding sites, in contrast to NAP and DEX. NIM and NAP did not influence cellular GR protein levels or nucleocytoplasmic shuttling, although DEX lowered GR messenger RNA and protein levels after 48 hours. NIM, but not NAP, markedly increased MAPK phosphorylation (suggesting an increase in MAPK cascade activity), GR phosphorylation, GR binding to GRE, and transcriptional activation of MMTV promoter through the GRE site in the promoter. CONCLUSION: This study is the first to report that the antiinflammatory effects of NIM, an NSAID, may be partly related to its activation of the GR system.
Blotting, Western↗