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Biomedical subjects

M Lindstedt

Publications and source records attributed to M Lindstedt.

15 recordsLinked to original sources
PubMed2005

Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response.

BACKGROUND: In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme-exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen-specific T cells. OBJECTIVE: This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild-type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells. METHODS: Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis. RESULTS: Lipase-specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co-cultured with DCs pulsed with either hypoallergenic or wild-type lipase, as demonstrated by high IL-4 and IL-13, and low IFN-gamma production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non-responders. CONCLUSIONS: DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild-type lipase in vitro. Only allergen-pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase-specific T cells displayed a T-helper type 2 phenotype, which was not altered by hypoallergenic lipase-pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response.

Animals↗
PubMed2004

Cognitive training in home environment.

PRIMARY OBJECTIVE: To examine the efficacy of cognitive rehabilitation in the patient's home or vocational environment. RESEARCH DESIGN: Pre-post-follow-up design. METHODS AND PROCEDURES: Ten outpatients with acquired attention and memory problems received cognitive training three times weekly, for 3 weeks. They received individual attention training with Attention Process Training, training for generalization for everyday activities and education in compensatory strategies for self-selected cognitive problems. Treatment effects were evaluated with neuropsychological and occupational therapy instruments before and after the training and after 3 months on impairment, activity and participation levels. MAIN OUTCOMES AND RESULTS: The results indicated a positive effect on some measures on impairment level, but no differences on activity or participation levels at follow-up. CONCLUSIONS: The study indicates that home-based cognitive training improves some attentional and memory functions and facilitates learning of strategies. Future controlled studies are needed to confirm the results and analyse the efficacy of different aspects of home-based training.

Activities of Daily Living↗
PubMed2003

Expression of CD137 (4-1BB) on human follicular dendritic cells.

Follicular dendritic cells (FDCs) are the antigen (Ag)-trapping accessory cells of the germinal centres (GCs), essential for the development of humoral immune responses and memory. FDCs reside in the microenvironment of secondary lymphoid tissue where Ag-activated B cells expand, and undergo isotype switching and affinity maturation prior to becoming memory B cells. In addition to delivering Ag, FDCs also provide potent nonspecific accessory signals to the B cells, which are important for the GC reaction. In this report, we show that human tonsilar FDCs express the costimulatory molecule CD137. Surface expression of CD137 on FDCs was confirmed by immunofluorescent labelling and fluorescence-activated cell sorter analysis. CD137 was also highly expressed by the human cell line HK, which displays many characteristics of in vivo FDCs. The interaction between B cells and FDCs is essential for the GC reactions, and our finding suggests that CD137 plays a role in FDC-regulated B-cell responses.

Antigens, CD↗
PubMed1995

Effects of the mutant von Willebrand factor gene in von Willebrand disease.

Von Willebrand disease (vWD) is a common inherited bleeding disorder in humans, and can be divided into a mild (type 1) and severe (type 3) form. Previous linkage studies identified one subject with vWD type 1 who transmitted different alleles of the von Willebrand factor (vWF) gene to his two affected children, one having vWD type 3 and the other having type 1. By screening the promoter and coding sequence (52 exons) of the vWF gene, three missense mutations were detected in this family. The type 1 individual who transmitted different alleles of the gene to his two sick children carries two substitutions, one in exon 5 and the other in exon 18 on the respective alleles. The relationship between the genotype (mutations) and the phenotype in this family is complex. In order further to correlate the relationship in vWD type 1 individuals, fifty-five subjects who carry one null allele of the vWF gene were collected. All these subjects are from vWD type 3 families with known mutations. Biochemical data of these 55 subjects indicate that gene dosage and other factors, such as blood group, age, and environment factors, play a critical role in the development of the phenotype of the disease.

Adult↗
PubMed1993

Hemophilia B in a 46,XX female probably caused by non-random X inactivation.

A female whose father had severe hemophilia B was found to have a factor IX activity of about 1%. No chromosomal abnormality could be detected and DNA analysis gave no indications of deletions or mutations of Taq I cleavage sites in the factor IX gene. Analysis of the methylation pattern of locus DXS255 indicates that the expression of hemophilia B in this patient is caused by non-random X inactivation.

Blotting, Southern↗
PubMed1992

Genetic and blood coagulation characterization of "Swedish" families with von Willebrand's disease types I and III: new aspects of heredity.

Twenty-five patients with von Willebrand's disease (vWD) type III were analysed with regard to blood coagulation variables and possible deletions. Nine of the probands and their families were further investigated with DNA linkage analyses. Different patterns of heredity can be suggested in our families with vWD type III, on the basis of blood coagulation analyses. The findings suggest homozygosity in five families and the possibility of compound heterozygosity or a new mutation in the proband in three families. The linkage analyses confirm the results of the coagulation analyses. The segregation of the von Willebrand factor (vWF) gene can be followed in the families, and carrier diagnosis can be made in several of the probands' relatives. The possibility of large deletions in the vWF gene of the probands and their parents was investigated with probes representing the whole vWF cDNA. No deletions were found.

Blood Coagulation↗
PubMed1992

Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.

von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA----TGA) were detected in exons 28, 32, and 45 by screening of all the 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicated that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I were found to be heterozygous for the mutation.

Adolescent↗
PubMed1991

Multiple sclerosis--is research on the wrong track?

The search for a MS virus, specific or otherwise, seems to be futile and I therefore contend that the activation mechanism of MS deserves much more attention than it has received. Could it be located in the pineal that transmits information by altering the secretion rate of melatonin, a hormone with noradrenaline or serotonin as precursor? The human pineal--and its major hormone, melatonin--is very likely to prove that it has a number of physiological roles involving the brain and perhaps other organs. There is also the possibility that a mycotoxin, ergotamine or a related alkaloid e.g. could be the triggering factor for the manifestation of MS. It is noteworthy that the geographical distribution of ergot corresponds to such an extent with the geographical distribution of MS as is shown in the present paper.

Ergotamine↗
PubMed1991

Evaluation of DNA-based diagnosis for haemophilia A.

Haemophilia A is an X-linked disorder affecting 1.7/10,000 males. Carrier detection in females and prenatal diagnosis of male foetuses is greatly improved by DNA-based diagnosis. This study describes the use of the polymerase chain reaction (PCR) and allele-specific oligonucleotides (ASO) in a clinical study comprising 190 individuals in 27 families. Prenatal diagnosis was performed in eight cases. Of three male fetuses, two were found to be affected and one unaffected. It is shown that 62% of women in the Swedish population are heterozygous for the intragenic BclI or XbaI polymorphisms and consequently a majority of them (53%) can be analysed in the PCR-based format. Using three intragenic polymorphisms, a combined heterozygosity of 64% was recorded in the females. If the extragenic loci DXS52 and DXS15 were used in addition, 97% of the women could be counselled by DNA-analysis. Our study demonstrates the usefulness of PCR-based analysis of the BclI- and the XbaI-polymorphisms in genetic counselling. The counselling of women with conflicting results between coagulation data and DNA-based linkage analysis is discussed.

Alleles↗
PubMed1990

Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components.

A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effect was comparable to that of the stable quaternary ammonium compound cetyltrimethylammonium bromide. At higher pH values, both the antimicrobial effect and the rate of hydrolysis of the esters increased. However, whereas at pH 6 greater than 99.99% killing of Salmonella typhimurium was achieved with 5 micrograms/ml in 3 min, the rate of hydrolysis was less than 20% in 18 h. At pH 7, a similar killing effect was achieved in 2 min and 50% hydrolysis occurred in ca. 5 h. Thus, it is possible to exploit the rapid microbicidal effect of the compounds before they hydrolyze. The rate of hydrolysis was reduced by the presence of salt. The bactericidal effect of the betaine esters increased with the length of the hydrocarbon chain of the fatty alcohol moiety up to 18 carbon atoms. Since the hydrolysis products are normal human metabolites, the hydrolysis property may extend the use of these quaternary ammonium compounds as disinfectants and antiseptics for food and body surfaces.

Bacteria↗