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Biomedical subjects

U Bengtsson

Publications and source records attributed to U Bengtsson.

At least 19 recordsLinked to original sources
PubMed2006

Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity.

BACKGROUND: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. METHODS: Eleven patients (4 with IgE-mediated allergy and 7 without) with food hypersensitivity and positive double-blind, placebo-controlled food challenge were subjected to food challenge in a single-blinded fashion. Four subjects with no known food hypersensitivity were recruited as controls. Placebo was given after a 1-week washout period followed by an active dose. Stool, urinary and serum samples were collected and symptoms were recorded in a diary. Fecal samples were analyzed for eosinophil protein X (F-EPX) and tryptase; urinary samples for EPX (U-EPX) and leukotriene E4 (U-LTE4) and serum samples were analyzed for eotaxin and food-specific IgE antibodies. RESULTS: Patients with IgE-mediated food allergy had increased levels of F-EPX compared to controls and tended to have lower serum levels of eotaxin compared to non-allergic patients and controls. U-LTE4 was significantly higher in allergic patients compared to non-allergic patients after challenge. Moreover, F-EPX correlated to U-LTE4 (p = 0.011). Reported symptoms, abdominal pain, distension, flatulence and nausea were similar in the allergic and non-allergic patients. CONCLUSION: The results strongly indicate that eosinophils are activated in the gastrointestinal tract of food-allergic patients but not in patients with non-allergic food hypersensitivity. Due to the inconsistent pattern of symptoms after placebo and active food challenge, it was not possible to relate the levels of inflammation markers to the recorded symptoms.

Abdominal Pain↗
PubMed2006

IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in cow's milk allergic patients.

BACKGROUND: Allergic reactions to cow's milk are common in small children. One of the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg). Reindeer and bovine milk both contain related beta-Lg proteins, but the allergenicity of reindeer beta-Lg has not previously been studied. The purpose of this study was to analyze the immunological cross-reactivity of IgE antibodies from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS: Sera from 17 children and a serum pool of 4 patients with elevated cow's milk-specific IgE were investigated. Beta-Lg from bovine and reindeer milk was isolated in native form and an enzyme-linked immunosorbent inhibition assay was developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS: Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg varied among patients. In general, reindeer beta-Lg showed significantly lower inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta-Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests that it lacks important bovine epitopes and those that are recognized are only weakly bound.

Animals↗
PubMed2005

Double-blind placebo-controlled challenges for peanut allergy the efficiency of blinding procedures and the allergenic activity of peanut availability in the recipes.

BACKGROUND: A firm diagnosis of double-blind placebo-controlled food challenge (DBPCFC) would facilitate the diagnosis in patients with uncertain history of reaction. Guidelines are lacking for an upper provoking dose and how to hide high concentrations of peanuts. AIM: To develop and evaluate a double-blind recipe with minimum 10% of peanut. To compare the recipe with published recipes regarding blindness, taste, texture and immunoglobulin (Ig)E antibody binding to peanut. METHODS: A recipe (I) with 10% of peanut was developed evaluated and used in DBPCFC. The challenges were followed by development of a concentrated recipe (II) (15% peanut, 25% fat). Recipe II was compared with the only published recipe (III) (11% peanut, 7% fat) regarding taste, texture and availability of peanut. Recipe IV (12% peanut, 10% fat) was developed using the same methods. The binding of IgE in the recipes was measured using an inhibition method. RESULTS: During challenges, one patient reacted after 4 g, emphasizing the need for blinding recipes containing high doses of peanut. Evaluation between recipes II and III, only recipe II was regarded as blind by the taste panels. A tenfold lower availability of peanut protein in the recipe II was found at 50% of inhibition. Recipe IV had a better IgE binding that did not differ from the original peanut extract. CONCLUSION: The peanut taste and texture can be hidden in a challenge medium. The fat content was important for the availability of the allergenic protein in challenges. The availability of allergens must be taken into consideration when used for DBPCFC.

Allergens↗
PubMed2004

Interpretation of subjective symptoms in double-blind placebo-controlled food challenges - interobserver reliability.

BACKGROUND: Subjective symptoms after food challenges are difficult to interpret and no standard is available. We discuss a strategy for how to interpret a diary. Furthermore, the interobserver reliability is evaluated. METHODS: Diaries for 32 patients with subjective symptoms were used. The diaries were re-evaluated with a predefined strategy by three independent observers. RESULTS: The proportion of positives was 21.9% among the old diagnoses, according to the new approach 34.4% (observers I and II) and 37.5% (observer III) were positive. The new approach had high interobserver reliability (97 and 100%). CONCLUSIONS: The proportion of positives depends on how subjective symptoms are interpreted. Interpretations of subjective symptoms in diaries could be made with high interobserver reliability.

Adolescent↗
PubMed2004

Bet v 1 homologues in strawberry identified as IgE-binding proteins and presumptive allergens.

BACKGROUND: No strawberry allergen has so far been identified and characterized. METHODS: Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. RESULTS: Several IgE-binding proteins could be detected. In more than half of the patient sera, a 20/18-kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18-kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. CONCLUSIONS: We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.

Adult↗
PubMed2004

Specific immunoglobulin E antibodies to peanut over time in relation to peanut intake, symptoms and age.

The clinical outcome of peanut allergy and some factors associated with development of peanut allergy remain unsolved. It has not been clarified to what extent peanut intake affects immunoglobulin (IgE) antibody formation in peanut sensitized individuals. The aim of the study was to investigate the development of peanut hypersensitivity in children and adolescents with specific IgE antibodies to peanut, using questionnaires and current serum tests and comparing it to information obtained 5-6 yr earlier, to investigate how peanut intake during this period related to subject age, IgE antibody levels and symptoms and to investigate what information this patient group was given at the time of diagnosis regarding avoidance of peanut related food. All patients with detectable peanut-specific IgE antibodies investigated during 1994-1996 deriving from two allergy laboratories in the western region of Sweden were traced and reinvestigated (n=132). A total of 111 subjects (63 with peanut allergy and 48 peanut sensitized) participated in the questionnaire. Eighty-six of them consented to be enrolled in a further interview and renewed testing of specific IgE antibody to peanut 5 yr later. All tests were done using the Pharmacia CAP system. Increased IgE antibody levels during follow-up was related to age; subjects 0-6 yr at initial test occasion were more likely to have higher IgE antibody class than the older individuals (p=0.018). Exposure to peanut during the study, i.e. 5-6 yr since diagnosis, did not seem to affect the result. During the follow-up period, 29 out of 86 (34%) increased their IgE antibody class. At the second test occasion the remaining subjects had similar (28%) or lowered (38%) levels of IgE antibodies. Exposure to peanut during follow-up was more common in subjects with IgE antibody class 1-3 compared to subjects with high value (> 3) at the initial test (p=0.003). Reported symptoms during follow-up were also more common in subjects with initially high IgE antibody value. Individuals with initially high IgE antibodies to peanut had been given more information about peanut allergy and cross-reacting allergens than other individuals. The subjects over 6 yr of age showed a decrease in peanut-specific IgE class over a 5-yr period. Together with the literature, our result suggest that follow-up and renewed testing is recommended, since there may be a change in IgE antibody classes and clinical sensitivity over time. Even in Sweden, with a low consumption of peanuts, the youngest individuals with peanut sensitization experienced a similar course of events that has been reported in other countries.

Age Factors↗
PubMed2004

Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and Russia.

AIM: The main aim of the study was to describe the differences between some Northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms. METHODS: At the participating clinics, patients with a history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire in which 86 different foodstuffs were listed. Skin-prick tests (SPT) were performed with common inhalant allergens. RESULTS: The foods that were reported as eliciting symptoms differed between countries. In Russia, Estonia, and Lithuania; citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, egg, and milk were most often reported as causes of hypersensitivity. In Sweden and Denmark; birch pollen (BP) related foods, such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common causes. In all countries, children, more often than adults, had symptoms of allergic reaction to citrus fruits, tomato, strawberry, milk, egg, and fish. Most patients (95%) reported hypersensitivity to several foodstuffs (median: eight foods). The most common symptoms were oral allergy syndrome and urticaria. Severe symptoms were most common with fish, shellfish, nuts, and milk. Slight symptoms were most common with rice, coriander, poppy seed, lingonberry, corn, caraway red currant, and fig. Earlier well-known correlations, such as that between BP sensitization and some fruits and vegetables, as well as that between mugwort and some spices, were conoborated. Positive correlations were found between self-reported hypersensitivity to crustaceans and SPT with horse. A negative correlation was seen between hypersensitivity to crustaceans and SPT with BP. CONCLUSIONS: The foodstuffs that often are reported to cause food hypersensitivity, differ between Sweden/Denmark on one side and the Baltic States and Russia on the other. BP-related foods dominate in Scandinavia, whereas some mugwort-related foods are of more importance in Russia and the Baltic States.

Adolescent↗
PubMed2003

A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples.

BACKGROUND: Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking. OBJECTIVES: To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO). METHODS: Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples. RESULTS: A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms. CONCLUSIONS: An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.

Adult↗
PubMed2003

The hazards of kissing when you are food allergic. A survey on the occurrence of kiss-induced allergic reactions among 1139 patients with self-reported food hypersensitivity.

BACKGROUND: According to a few case reports, kissing can induce symptoms due to food allergy. OBJECTIVE: We wanted to investigate the occurrence of kiss-induced allergic symptoms and other social inconveniences among patients with self-reported food hypersensitivity. METHODS: A questionnaire was answered by 1139 patients (1-84 years old, mean age 29 years, 393 males and 746 females) who considered themselves to be food allergic. RESULTS: 12% of the patients experienced allergic symptoms when in close contact with (e.g., kissing) a person who had eaten a nontolerated food prior to the contact. Some case histories suggested that the symptoms only appeared if the food intake had occurred immediately before the kiss. In addition, the questionnaires showed that 55% had problems in daily life finding tolerable food, 44% were afraid of a severe reaction from eating nontolerated food, 13% could experience symptoms when sitting beside a person who was eating such a food, and 17% could experience symptoms in the kitchen when someone else was preparing such food. CONCLUSIONS: What other people eat can influence the quality of life of food-allergic patients.

Adolescent↗
PubMed2001

Specific IgE antibodies to peanut in western Sweden--has the occurrence of peanut allergy increased without an increase in consumption?

BACKGROUND: Sensitization to peanut has seldom been investigated in Sweden. Therefore, all IgE-specific tests for peanut during a 5-year period were reviewed to study the relation between the levels of specific IgE antibody to peanut and age, sex, symptoms, and other atopic manifestations. METHODS: All serum samples were analyzed for IgE antibodies to peanut in relation to sex, age, clinical reactions, and other food allergens. A subgroup was asked to answer a questionnaire about symptoms and atopic manifestations in relation to IgE antibody levels. RESULTS: During the study period, 2417 tests were made for peanut. There was an increased prevalence of detectable IgE antibodies during the years studied. More than 80 individuals under 2 years of age were sensitized to peanut. In the subgroup, individuals with detectable IgE antibodies reported a shorter reaction time after eating peanuts than individuals with normal IgE antibody levels (P < 0.05). CONCLUSION: The reaction pattern to peanuts in Sweden is similar to that in many other countries despite a reported steady and low consumption. The severity of symptoms was connected to age and IgE antibody level. Patients with normal or low IgE antibody levels were not always free of symptoms even though their risk of allergic symptoms was reduced.

Adolescent↗
PubMed2001

Food-related gastrointestinal symptoms in the irritable bowel syndrome.

BACKGROUND/AIMS: Postprandial symptoms are common in patients with irritable bowel syndrome (IBS). However, existing studies have come to different conclusions about the role of food in the pathophysiology of IBS. We explored the prevalence of subjective food-related gastrointestinal (GI) symptoms and its relationship to clinical characteristics and psychological factors in IBS. METHODS: 330 patients with IBS and 80 healthy volunteers completed a food questionnaire developed for this study. The subjects graded their subjective symptoms after 35 different foods and a food score was obtained by adding the item scores. The relationship between subjective food-related GI symptoms and referral status, IBS subgroup (predominant bowel pattern), sex, anxiety, depression and body mass index (BMI) was estimated. RESULTS: In 209 (63%) of the patients the GI symptoms were related to meals. Gas problems and abdominal pain were the most frequently reported symptoms. Foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices were most frequently reported to cause symptoms. The food score was higher in patients than in controls (p < 0.0001). In the IBS group higher scores were observed in patients with anxiety (p = 0.005), and females (p < 0.001), but the results were unrelated to IBS subgroup, referral status or BMI. The BMI did not differ between groups. CONCLUSION: A majority of IBS patients consider their symptoms to be related to meals. Especially foods rich in carbohydrates and fat cause problems. Nevertheless, the majority of IBS patients are normal or overweight. Female sex and anxiety predict a high degree of food-related symptoms in IBS.

Adult↗
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↗
PubMed2000

Interstitial deletion of 11q13 sequences in HeLa cells.

Previous cytogenetic and molecular genetic studies have shown that the HeLa (cervical carcinoma) cell line D98/AH-2 contains two apparently normal copies of chromosome 11 and additional 11q13-25 material translocated onto a chromosome 3 marker. To determine the 11q13 breakpoint, we performed fluorescence in situ hybridization (FISH) using 18 different 11q13 specific BAC (bacterial artificial chromosome) and cosmid probes spanning a 5.6 Mb interval. Markers localized to the multiple endocrine neoplasia type 1 (MEN1) gene (menin) were also included in the analysis. The FISH study identified an interstitial deletion between markers D11S449 and GSTP1, an interval of 2.3 Mb, in the marker chromosome. This deletion did not include the MEN1 gene. Because point mutations and methylations can inactivate the MEN1 gene, single stranded conformational polymorphism (SSCP) and Northern and Western blot analyses were performed with MEN1 specific probes and antibody. SSCP did not reveal mutations of the MEN1 gene in HeLa or in seven other cervical cancer cell lines. Northern and Western blot studies revealed normal levels of expression of this gene in the cervical cancer cell lines as well as in HeLa cell derived tumorigenic hybrids. Because deletions of tumor suppressor genes often occur in cancer progression, we hypothesize that the inactivation of a tumor suppressor gene other than MEN1, localized to the 2.3 Mb interval on 11q13, might play a role in the abnormal growth behavior of HeLa cells in vitro or in vivo.

Cell Transformation, Neoplastic↗
PubMed2000

Characterization of the murine homolog of C1qR(P): identical cellular expression pattern, chromosomal location and functional activity of the human and murine C1qR(P).

Human C1qR(P) is a highly glycosylated transmembrane protein that is the human C1q receptor/receptor component that in vitro mediates enhancement of Fc- and C3b-mediated phagocytosis. A human genomic clone and a murine genomic clone that is 73% identical in sequence with the coding region for human C1qR(P) cDNA have been isolated. Chromosomal localization of the human and murine gene demonstrates that these genes are syntenic. Murine cell lines of diverse myeloid origins are shown to respond to interaction of C1q with the enhancement of phagocytosis similar to that seen previously in human peripheral blood monocytes. Northern blot, RT-PCR, Western blot and FACS analyses demonstrated that mC1qR(P) is expressed in these murine myeloid cell lines, but not in a mouse epithelial cell line, similar to the cell type expression of the human gene product. A polyclonal antibody to a peptide sequence common to the deduced sequence from the both murine and human C1qR(P) inhibited the enhancement of phagocytosis response to C1q when cells were permeabilized to permit access of the antibody to the intracellular milieu. These data support the postulate that the identified murine and human genes are homologs, confirm the previously predicted intracellular location of the C-terminus of the molecule, and indicates the necessary role of this intracellular domain in transducing the signal that leads to enhancement of phagocytic function.

Amino Acid Sequence↗
PubMed2000

Combining a beta2-agonist with a face mask to prevent exercise-induced bronchoconstriction.

BACKGROUND: In this study, we aimed to test the effect of combining a P2-agonist with a heat- and moisture-exchanging cellulose face mask in patients with bronchoconstriction induced by exercise in cold air. METHODS: Nine allergic, asthmatic patients with a history of adverse reaction to exercise were tested on an ergometric bicycle at a temperature of approximately -10 degrees C. They were in turn given no treatment, given premedication with a beta2-agonist, allowed to breathe through a heat- and moisture-exchanging cellulose face mask, and given both premedication and the face mask. After each treatment regimen, they were subjected to provocation with exercise and cold air. RESULTS: The decrease in FEV, was greatest with no therapy (mean maximal change: 27%), and this diminished when the face mask was used (mean maximal change: 12%,) or premedication with a 32-agonist was given (mean maximal change: 7%); no decrease in FEV1 occurred with the combination of agonist and face mask. CONCLUSIONS: The results suggest that different mechanisms are involved in the pathophysiology of exercise-induced bronchoconstriction (EIB). This finding may be of importance for asthmatic athletes who train and compete in a cold climate and are affected by small changes in their lung function.

Adrenergic beta-2 Receptor Agonists↗
PubMed2000

Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity.

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.

Adult↗
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↗