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Biomedical subjects

U Bengtsson

Publications and source records attributed to U Bengtsson.

At least 19 recordsLinked to original sources
PubMed2000

A functional investigation of tumor suppressor gene activities in a nasopharyngeal carcinoma cell line HONE1 using a monochromosome transfer approach.

Monochromosome transfers of selected chromosomes into a nasopharyngeal carcinoma (NPC) cell line were performed to determine if tumor suppressing activity for NPC mapped to chromosomes 9, 11, and 17. Current information from cytogenetic and molecular allelotyping studies indicate that these chromosomes may harbor potential tumor suppressor genes vital to NPC. The present results show the importance of CDKN2A on chromosome 9 in NPC development. There was no functional suppression of tumor development in nude mice with microcell hybrids harboring the newly transferred chromosome 9 containing an interstitial deletion at 9p21, whereas transfection of CDKN2A into the NPC HONE1 cells resulted in obvious growth suppression. Whereas intact chromosome 17 transfers into HONE1 cells showed no functional suppression of tumor formation, chromosome 11 was able to do so. Molecular analysis of chromosome 11 tumor segregants indicated that at least two tumor suppressive regions mapping to 11q13 and 11q22-23 may be critical for the development of NPC.

Animals↗
PubMed1999

Analysis of aberrant methylation of the VHL gene by transgenes, monochromosome transfer, and cell fusion.

Several tumor suppressor genes were shown to be inactivated by a process involving aberrant de novo methylation of their GC-rich promoters which is usually associated with transcriptional repression. The mechanisms underlying this process are poorly understood. In particular this abnormal methylation may be caused and/or maintained by either deficiency of some trans-acting factor(s) or by various malfunctions acting in cis. Here we studied the nature of aberrant methylation of the von Hippel-Lindau (VHL) disease tumor suppressor gene in a human clear cell renal carcinoma cell line, UOK 121, that contains a silent hypermethylated endogenous VHL allele. First, we transfected unmethylated VHL transgenes, driven by the VHL promoter, into UOK 121 cells. Next, to exclude possible position effects that may influence methylation of the introduced VHL genes, we transferred a single chromosome 3, carrying an apparently normal hypomethylated VHL allele into the UOK 121 cells. Finally, we created somatic cell hybrids between UOK 121 and UMRC 6 cells containing a mutant VHL-expressing hypomethylated allele. In these three experiments both the methylation of the VHL promoter and the transcriptional status of the introduced and endogenous VHL alleles remained unchanged. Our results demonstrate that the putative trans-acting factors present in the UOK 121 and UMRC 6 cells are unable to induce changes in methylation pattern of the VHL alleles in all cell lines and hybrids studied. Taken together, the results indicate that cis-specific local features are pivotal in maintaining and perpetuating aberrant methylation of the VHL CpG island. Contribution of some putative trans-acting factors cannot be excluded during a period when the aberrant VHL methylation pattern was first generated.

Adenocarcinoma, Clear Cell↗
PubMed1999

Malignant transformation of human diploid fibroblasts and suppression of their anchorage independence by introduction of chromosome 13.

Isolation of cell lines that display various degrees of transformed phenotypes may be very useful to clarify multistep mechanisms of oncogenesis, but malignant transformation of human diploid fibroblasts in culture is a very rare event. We attempted to isolate variously transformed cell lines from human diploid fibroblasts (RB) of a patient with hereditary retinoblastoma. The RB cells exhibited normal karyotypes with the exception of one copy of chromosome 13, which contained a large deletion at the q14-22 region, where the RB1 gene is located. By transfection with SV40 early genes and repeated passage, we succeeded in obtaining SV40-transfected mortal, immortalized, anchorage-independent, and tumorigenic RB cell lines. DNA fingerprinting showed that these cell lines were not contaminants, but derivatives of the original RB cells. The remaining RB1 allele may be wild-type even in the malignant cell lines, because the expression and the LT-binding ability were normal. Furthermore, we did not find any homozygous loss in 16 polymorphic markers located in the 13q14-22 region in the transformed cell lines. However, introduction of a copy of a normal chromosome 13 into the anchorage-independent cell line suppressed its anchorage-independent growth ability. All these data, together with the fact that the RB cells containing the deletion progressed to a tumorigenic state spontaneously, but normal fibroblasts did not, raise the possibility that a new tumor suppressor gene, located at 13q14-22, may play a critical role in neoplastic transformation. We conclude that these RB cell lines provide an excellent system for identification of genes involved in malignant transformation of human cells. Genes Chromosomes Cancer 26:47-53, 1999.

Cell Adhesion↗
PubMed1999

Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity.

BACKGROUND: In earlier studies, we have shown that patients with a history of sensory hyperreactivity develop asthma-like symptoms when exposed to strong scents, even if they cannot smell any scent. METHODS: For study of possible pathophysiologic mechanisms behind sensory hyperreactivity, the patients' airways and eyes were separately exposed to a common inducing factor, perfume. Eleven patients with a history of hyperreactivity to chemical trigger factors, such as perfume, were provoked single-blindly in a placebo-controlled, randomized study. During airway exposure, the eyes were covered and, during the eye exposure, the patients inhaled fresh air. A special face mask or a nose clip was used to avoid any smell. RESULTS: During the 30-min exposure to perfume, there was a gradual increase in three main symptoms; i.e., eye irritation, cough, and dyspnea, after both the airway and eye exposures. The increases were significant compared with placebo. CONCLUSIONS: Asthma-like and other symptoms, such as irritation of the eyes, may be induced by exposure of both the airways and the eyes in patients with sensory hyperreactivity. This points to the importance of studying the sensory nervous system, not only in the airways, but also in other organs.

Adult↗
PubMed1998

Bacteriuria in a population sample of women: 24-year follow-up study. Results from the prospective population-based study of women in Gothenburg, Sweden.

The aims of the study were to estimate the prevalence of bacteriuria in a female urban population, to follow up the same population over the years, and to relate bacteriuria to long-term prognosis with respect to mortality and kidney disease. The study was based on a randomly selected population sample comprising 1462 women aged 38-60 years at entrance to the study in 1968-69 with an initial participation rate of 90.1%. Bacteriuria was observed in 3-5%, increasing with age, and most often asymptomatic. Bacteriuria on one occasion meant increased risk of having bacteriuria 6 and 12 years later. The percentages of different types of bacteria and the resistance pattern were similar initially and at follow-up studies after 6 and 12 years. There were no differences in mortality or incidence of severe kidney disease during a 24-year follow-up between those with and those without bacteriuria in the baseline study.

Adult↗
PubMed1997

Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance.

BACKGROUND: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. METHODS: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. CONCLUSION: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease.

Adult↗
PubMed1996

Effects of luminal antigen on intestinal albumin and hyaluronan permeability and ion transport in atopic patients.

BACKGROUND: Increased luminal transport of proteins and fluid is part of the inflammatory reaction in inflammatory disease of the bowel and of the airways in allergic diseases and asthma. The objective of this study was to determine intestinal appearance rates of albumin and hyaluronan in vivo in atopic patients allergic to birch, as well as changes in net jejunal transport of monovalent ions and water induced by the antigen. METHODS: Secretion studies were performed with the use of a segmental jejunal perfusion system with a small two-balloon, six-channel tube. The intestinal mucosa was challenged with birch allergen in patients allergic to birch and in matched control subjects (n = 12 in both groups). RESULTS: In patients, but not in control subjects, the luminal antigen induced a net increase in albumin of 2689 +/- 567 micrograms/cm/hr and in hyaluronan of 2609 +/- 737 ng/cm/hr (p < 0.01 vs control subjects in both cases). Furthermore, basal net absorption of Cl- ions, Na+ ions, and water was converted to a net secretion after antigen challenge. CONCLUSION: Exposure to antigen normally acting on the respiratory tract induced increased permeability of the gastrointestinal mucosa. This would suggest less organ specificity and more general allergic recognition shared by several immunocompetent tissues in the body, probably mediated by circulating IgE antibodies.

Adult↗
PubMed1996

The evolutionary distribution and structural organization of the homeobox-containing repeat D4Z4 indicates a functional role for the ancestral copy in the FSHD region.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disease that has been linked to deletions within a tandem array of 3.2 kb repeats adjacent to the telomere of 4q. These repeats are also present in other locations in the human genome, including the short arms of all the acrocentric chromosomes. Here, we examine two models for the role of this repeat in FSHD. First, because of the extensive similarity between the 3.2 kb repeats on 4q and those adjacent to rDNA on the acrocentric chromosomes, we investigated whether the FSHD region on 4q is involved in sub-nuclear localization, specifically to the nucleolus. The results likely exclude any involvement of nucleolar localization in the development of FSHD. Second, we investigated a model that suggests that a functional gene may be buried within the tandem array of 3.2 kb repeats. Toward this end, we evaluated the evolutionary conservation of the repeat and a double homeodomain sequence within the repeat in a variety of primate species. The genomic organization of the 3.2 kb repeat in humans, great apes and lower primates identified the FSHD-associated repeat on chromosome 4q as the likely ancestral copy. The sequence of the rhesus monkey double homeodomain reveals significant sequence identity with the human 4q sequence. These results strongly suggest a functional role for a component of the FSHD-associated repeat.

Amino Acid Sequence↗
PubMed1996

Increased levels of hyaluronan and albumin after intestinal challenge in adult patients with cow's milk intolerance.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. Presently, only limited possibilities are available for identification of adverse immunological reactions to different foods. OBJECTIVE: The intestinal inflammatory reactions in adult patients with a history of milk-related gastrointestinal symptoms were studied after intestinal challenges by a jejunal perfusion technique and compared with the reactions in a control group. METHODS: Five skin-prick test and radioallergosorbent test negative and lactose tolerant patients with a history of milk-related gastrointestinal symptoms, verified by double-blind placebo-controlled challenge, and eight healthy controls were investigated. Perfusions were performed allowing analyses of a well-defined 'closed' jejunal segment. Milk perfusions were performed in patients and controls after an overnight fast. Ten millilitres of milk were administered to the segment at 3 mL/min. The jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin were measured. RESULTS: In the five patients the milk challenges induced as a mean fivefold increased levels of hyaluronan compared with prestimulation values, whereas no such increases were seen in the control subjects. Albumin, as a marker of plasma leakage, was also increased in the patients but not in the control subjects. CONCLUSION: The underlying mechanisms for locally increased levels of hyaluronan and also albumin in the intestinal lumen may be secretion of lymph rich in hyaluronan and reflect the mucosal oedema. This capacity of the intestinal mucosa to react with lymph leakage towards a locally infused allergen may be a possible way to delineate gastrointestinal reactions in food-related disorders.

Adult↗
PubMed1996

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. There is conflicting evidence in the literature on the role for IgE mediated allergy in gastrointestinal reactions to staple foods. AIM: The aim was therefore to study the role of IgE mediated allergy in a group of patients with a history of gastrointestinal symptoms related to staple foods (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC, identified by screening of 96 consecutive patients referred to our allergy clinic for investigation of suspected gastrointestinal symptoms due to staple foods. METHODS: The screening included diaries as well as elimination diets and open and blinded food challenges. The frequency of atopy were compared between the double blind positive and double blind negative patients. RESULTS: The positive DBPCFC in the 15 patients included eight patients with milk intolerance, four with wheat flour, two with egg, and one with rye flour. There was no indications of an allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick test and radioallergosorbent test were negative for the relevant allergens. The frequency of atopy was four of 21 (19%) in the double blind negative group and three of 15 (20%) in the double blind positive group. CONCLUSION: In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods suggesting other mechanisms in adults than in children. Future studies may include measures of local events in the shock organs in relation to food intake, for instance utilising inflammatory markers in jejunal fluids.

Adolescent↗
PubMed1996

Survey of gastrointestinal reactions to foods in adults in relation to atopy, presence of mucus in the stools, swelling of joints and arthralgia in patients with gastrointestinal reactions to foods.

BACKGROUND: Food intolerance in adults is mostly associated with vague symptoms and not clearly related to atopy and food allergy. A combination of different pathogenetic mechanisms may be responsible for the symptoms. OBJECTIVE: The aim of this study was to describe patients with a history of food-related gastrointestinal symptoms in relation to the presence of mucus in the stools, joint swelling and arthralgia and to determine whether or not there is an association between the presence of these parameters, atopic disease and the presence of immune complexes in serum. METHODS: Fifty-eight patients consecutively referred to our clinic with food-related gastrointestinal symptoms were investigated. RESULTS: Thirty-five patients (60%) had mucus in their stools, 24 patients (41%) complained about joint swelling and 41 patients (71%) had arthralgia. There were no correlations between these parameters and atopy according to Phadiatope test or skin prick test (SPT). No correlations were found between the occurrence of mucus in the stools, arthralgia and joint swelling. There were significantly higher levels of circulating immune complexes in patients with a history of arthralgia compared with patients with no such history (P < 0.03) and the number of individuals with the presence of such immune complexes was higher among the patients with arthralgia than among the patients without. In general the patients did not relate the exposure to certain foods to symptoms like joint swelling, arthralgia and presence of mucus in the stools. However, there were significant positive correlations between food-related gastrointestinal symptoms in the following instances: chocolate-induced gastrointestinal symptoms and mucus in the stools (P = 0.006), vegetable-induced gastrointestinal symptoms and mucus in the stools (P = 0.002) and meat-induced gastrointestinal symptoms and mucus in the stools (P = 0.003). In a group of individuals without food-related symptoms investigated separately, a very low frequency of mucus in the stools, joint swelling and arthralgia was seen (none, two and three individuals of the 20 subjects, respectively). Of 41 patients with immediate onset of gastrointestinal symptoms, 20 were atopic according to Phadiatope and SPT. Of 11 patients with late onset of symptoms 10 were negative in Phadiatope and SPT (P < 0.05). The most frequently involved foods were fruits, vegetables, milk, fish and meat. CONCLUSION: The results suggest the involvement of different inflammatogenic mechanisms in food-related gastrointestinal symptoms.

Adolescent↗
PubMed1995

Prevention of asthma induced by cold air by cellulose-fabric face mask.

We have tested the effect of a porous cellulose fabric face mask. Nine asthmatic patients, anamnestically sensitive to cold, took part in exercise tests on an ergometer bicycle at a temperature of approximately -10 degrees C, with and without a face mask. For comparison, exercise tests were also performed with breathing taking place through a woolen scarf. Three minutes after finishing the exercise test, there was an average fall in FEV1 of 32% in the group without a face mask. The corresponding fall in FEV1 was 6% with a face mask and 17% with a scarf. In order to get some idea of the patients' attitudes to the face mask, it was used by 25 asthma patients during a period of 2 weeks in winter, after which they were asked to answer a simple questionnaire. Eighty-eight percent of the patients stated that the face mask had provided satisfactory protection against asthma complaints induced by cold air, and 72% reported that they had been able to spend more time out-of-doors. The results show that porous cellulose fabric designed as a face mask offers effective protection against asthma complaints induced by cold air and exercise, and that the patients appear to appreciate this protective aid highly despite the cosmetic disadvantages.

Adult↗
PubMed1995

A breathing filter exchanging heat and moisture prevents asthma induced by cold air.

In order to devise a protective aid against bronchial obstruction induced by cold air, we have tested a breathing filter with heat and moisture exchanging properties. Nine asthma patients, who all had a history of cold-induced asthma, took part in exercise tests on an ergometer bicycle at a temperature of approximately -10 degrees C, without and with a breathing filter. Without a breathing filter, the maximum reduction in FEV1 was, on average, 36%. With the breathing filter, the maximum reduction in FEV1 was, on average, 11%. The difference was clearly significant (P < 0.001). A further five cold-sensitive asthmatics performed similar exercise tests at -10 degrees C on three occasions: 1) without and 2) with a breathing filter as above, and 3) with two breathing filters connected in parallel: one for inspiration and the other for expiration. Thus, no heat-moisture exchange could take place. The fall in FEV1 after provocation without a breathing filter and with parallel breathing filters was similar but attenuated when rebreathing took place through the breathing filter. The results confirm the theory that in cold/exercise-induced asthma, it is indeed the heat and/or water loss from the airways that triggers airway narrowing, and that a heat and moisture exchanging filter has a considerable protective effect and can be of value in the treatment of asthma.

Adult↗