Search PubMed⌕ Search

Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 91 records · Page 5Linked to original sources
PubMed2000

A European study on the genetics of mite sensitization.

BACKGROUND: Sensitization to mite allergens represents a prominent feature of atopy and an important predictor of bronchial asthma. OBJECTIVE: It was the intention of this study to define genetic loci linked to mite sensitization because these could represent the genetic basis of the important atopic component of asthma. METHODS: We studied a multiethnic white population of 99 families, including 224 sib pairs sensitized to Dermatophagoides pteronyssinus. A genome-wide candidate-region search was performed that covered potential asthma and atopy regions. RESULTS: As for nonparametric linkage (NPL) analysis, 14 of the candidate regions showed evidence for linkage (NPL > 2.0), and 4 of them showed prominent linkage (NPL > 3.0). However, there were substantial ethnic differences. Maximizing the LOD score analysis identified candidate regions with suspected dominant and recessive mode of inheritance. Furthermore, genetic imprinting models provided significant evidence for linkage in the 8p23 region and revealed potential maternal imprinting. The regions found are distinct to those in asthma searches that have been found to be linked to asthma, as well to other inflammatory diseases. In addition, we could not find linkage to the HLA region. By different cutoff points of the phenotype definition, the IL cluster showed evidence of being linked to the degree of sensitization rather than to sensitization per se. CONCLUSION: The results indicate that the genetic basis of the atopic component of asthma is different from that of the inflammatory component. Furthermore, it seems reasonable to assume that specific sensitizations are influenced by distinct genetic variants leading to their initiation versus those leading to their enhancement.

Allergens↗
PubMed2000

Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.

Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.

Adolescent↗
PubMed2000

Recent studies on natural products as anti-HIV agents.

The discovery of medicinal agents capable of specifically inhibiting human immunodeficiency virus (HIV) is urgently needed due to its globally widespread infection. Most of clinically useful anti-HIV agents are nucleosides but their use is limited due to their severe toxicity and emerging drug resistance. More than 50% of world marketed drugs have their origin of the nature. Natural products, of which structural diversity is so broad, are good sources for the effective discovery of anti-HIV agents with decreased toxicity. Over the past decade, substantial progress has been made in research on the natural products for the anti-HIV agents. New natural products that have potent anti-HIV activities with novel structures were reviewed in this article. These compounds, isolated mainly from medicinal plants, in this review have been classified as secondary metabolites such as terpenes, phenolics, and naturally scarce peptides and sugars. Especially, terpenes and phenol substances have gained much interest due to their significant anti-HIV activities along with their structural diversity. Recent studies also showed that several polysaccharides are effective inhibitors of HIV replication. Most of chemotherapeutic targets reviewed in this article are found to be HIV reverse transcriptase (RT).

Alkaloids↗
PubMed2000

First non-radioactive assay for in vitro screening of histone deacetylase inhibitors.

Inhibitors of histone deacetylase (HD) are of great potential as new drugs due to their ability to influence transcriptional regulation and to induce apoptosis or differentiation in cancer cells. So far only radioactive enzyme activity assays or in-vivo assays with subsequent electrophoresis and immunoblotting existed to study the activity of HD and potential inhibitors. To aid in the search of new inhibitors, a non-radioactive screening assay was sought and we have previously succeeded in establishing this for the first time. The assay uses an aminocoumarin derivative of an omega-acetylated lysine as substrate for the enzyme. Here we report full experimental details, the evaluation of other potential substrates, and comparative analysis of various inhibitors. This advantageous method should have an impact on further developments in the field.

Aminocaproic Acid↗
PubMed1999

Mutation in the betaA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse.

During the mouse ENU mutagenesis screen, mice were tested for the occurrence of dominant cataracts. One particular mutant was discovered as a progressive opacity (Po). Heterozygotes show opacification of a superficial layer of the fetal nucleus, which progresses and finally forms a nuclear opacity. Since the homozygotes have already developed the total cataract at eye opening, the mode of inheritance is semidominant. Linkage analysis was performed using a set of genome-wide microsatellite markers. The mutation was mapped to chromosome 11 distal of the marker D11Mit242 (9.3 +/- 4.4 cM) and proximal to D11Mit36 (2.3 +/- 2.3 cM). This position makes the betaA3/A1-crystallin encoding gene Cryba1 an excellent candidate gene. Mouse Cryba1 was amplified from lens mRNA. Sequence analysis revealed a mutation of a T to an A at the second base of exon 6, leading to an exchange of Trp by Arg. Computer analysis predicts that the fourth Greek key motif of the affected betaA3/A1-crystallin will not be formed. Moreover, the mutation leads also to an additional splicing signal, to the skipping of the first 3 bp of exon 6, and finally to the deletion of the Trp residue. Both types of mRNA are present in the homozygous mutant lenses. The mutation will be referred to as Cryba1(po1). This particular mouse mutation provides an excellent animal model for a human congenital zonular cataract with suture opacities, which is caused by a mutation in the homologous gene.

Amino Acid Sequence↗
PubMed1999

Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.

Animals↗
PubMed1999

Sensing of ionizing radiation-induced DNA damage by ATM through interaction with histone deacetylase.

The ATM gene is mutated in individuals with ataxia telangiectasia, a human genetic disease characterized by extreme sensitivity to radiation. The ATM protein acts as a sensor of radiation-induced cellular damage and contributes to cell cycle regulation, signal transduction, and DNA repair; however, the mechanisms underlying these functions of ATM remain largely unknown. Binding and immunoprecipitation assays have now shown that ATM interacts with the histone deacetylase HDAC1 both in vitro and in vivo, and that the extent of this association is increased after exposure of MRC5CV1 human fibroblasts to ionizing radiation. Histone deacetylase activity was also detected in immunoprecipitates prepared from these cells with antibodies to ATM, and this activity was blocked by the histone deacetylase inhibitor trichostatin A. These results suggest a previously unanticipated role for ATM in the modification of chromatin components in response to ionizing radiation.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1999

Chemistry in Supercritical Water.

Water is a special liquid-and not only under "normal" conditions. Water in the supercritical state (shaded area in the phase diagram) is distinguished by special properties which are wholly at variance with those of normal water. So far these have usually been exploited for the purification of waste water, for example for the complete oxidation of poorly degradable substances. But what is the potential of supercritical water for synthesis? Answers are provided here on the basis of thermodynamic and kinetic studies as well as with reference to measurements of corrosion.

Journal Article↗
PubMed1999

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

Asthma↗
PubMed1999

A non-isotopic assay for histone deacetylase activity.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. To study the activity of HD and the effect of potential inhibitors in vitro so far only radio-active assays have existed. For the search of new inhibitors and for the use in HD identification and purification we established a simple, non-radioactive assay that allows screening of large numbers of compounds. The assay is based on an aminocoumarin derivative of an Omega-acetylated lysine as enzyme substrate.

Acetylation↗
PubMed1999

Triptolide is more effective in preventing T cell proliferation and interferon-gamma production than is FK506.

The Chinese traditional herb Tripterygium wilfordii Hook. F (TWHF) has been reported to be effective in the treatment of a variety of autoimmune disorders. The major active component of this herb is triptolide and most of the efficacy of this herb immunosuppression is attributed to triptolide. FK506 is also a potent immunosuppressive agent and is currently being used clinically. The present studies compare the effectiveness of triptolide and FK506 to suppress certain human T cell functions. Specifically human T cell proliferation, IL-2 and IFNgamma were compared. The results show that, overall, triptolide is more effective at inhibiting T cell proliferation and IFNgamma production than FK506 and the two compounds inhibit IL-2 production in an equivalent manner.

Cells, Cultured↗
PubMed1999

Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient.

We observed severe late effects in a patient treated with radiation therapy for breast cancer. Radiation survival studies of patient fibroblasts show an enhanced cellular radiation sensitivity (Do = 0.95 Gy). Genetic analysis reveals that the patient is heterozygous for a mutated ATM gene. Protein truncation test (PTT) and sequence analysis identified a truncation within the leucine zipper domain, corresponding to a fragment previously reported to exhibit dominant negative function. These findings demonstrate that ATM heterozygosity may be associated with enhanced clinical radiation sensitivity and suggest a clinical relevance to this truncation that results in a dominant negative-acting protein.

Adenocarcinoma, Mucinous↗
PubMed1999

Inhibitors of histone deacetylase suppress the growth of MCF-7 breast cancer cells.

Inhibitors of histone deacetylase are attracting increasing interest due to their influence on transcription, differentiation, and apoptosis. We have investigated two synthetic inhibitors 3 and 4 of histone deacetylase and the natural product inhibitor trichostatin A for their ability to suppress the growth of MCF-7 breast cancer cells and here present complete and improved synthetic procedures. The compounds show a dose dependent inhibition of growth with activities in the low micromolar and nanomolar range. Trichostatin shows cytocidal effects at 100 nM and still has activity comparable to cisplatin (0.5 microM) at 10 nM. Whereas the synthetic inhibitor 3 has cytocidal activity at 10 microM compound 4 shows a maximum of 40% growth suppression at that concentration.

Antineoplastic Agents↗
PubMed1999

Surface roughness and bond strength of enamel to composite.

OBJECTIVES: The aim of the study was to assess the influence of pretreating enamel by different rotary instruments on shear-bond strength of composite to enamel after the acid etch technique. METHODS: Ninety human enamel specimens with transversely and longitudinally sectioned prisms were ground flat, and half of the enamel area of each specimen was prepared with one of the eight different rotary instruments: a 120 microns diamond bur, three finishing diamonds (30, 15 and 8 microns), two tungsten carbide finishing instruments (8- and 30-fluted) and two stones (Dura green and Dura white). The other half of the enamel area was left untreated. Enamel roughness was measured by laser-stylus profilometry. Two cylinders filled with the hybrid composite Pertac were adhesively fixed on each enamel surface, one on the prepared side and the other on the untreated side. After seven days of water storage, shear-bond strength was measured with a Universal testing machine. RESULTS: Rz values of the treated enamel surfaces were between 4.14 and 17.75 microns. The shear-bond strength data varied between 16.8 and 29.4 MPa and were similar for transversely and longitudinally orientated prisms. The different roughness data had no significant influence on shear-bond strength of composite to enamel. Additional SEM investigation showed that the surface geometry caused by the rotary instruments largely persisted after acid etching. SIGNIFICANCE: With regard to shear-bond strength, there was no advantage in using a special bur for finishing enamel surfaces prior to the acid etch technique. Burs causing extreme roughness should not be used for this purpose.

Acid Etching, Dental↗
PubMed1999

Increased risk of bullous pemphigoid in male and very old patients: A population-based study on incidence.

No data are available on gender- and age-specific incidences for bullous pemphigoid (BP). The aim of this study was to calculate incidences for different gender- and age-strata and to assess risk differences between these strata in BP. A retrospective population-based cohort was recruited from all patients diagnosed with BP in 2 well-defined regions of Germany. The average population number was 1.7 million, and the observation period was 9 years (1989-1997). Incidences were calculated as newly diagnosed cases for a population of 1 million per year. Confidence intervals (CI) were estimated based on a Poisson distribution. For evaluation of risk between different age and gender strata a Poisson regression analysis was used. The highest incidence was calculated for individuals older than 90 years, with 398 (CI: 360, 439) new cases of BP per 1 million residents for men, and 87 (CI: 70, 108) new cases per 1 million residents for women. Risk (95% CI) was 1.9 (1.3, 2.9) fold higher in men than in women. In addition, the risk for BP was increased for patients above the age of 60 years. The highest risk was found for patients older than 90 years. For this age group, the risk was 297 (CI: 107, 826) fold higher than in patients 60 years of age and younger. Men are affected by BP almost twice as often as women. The risk for BP increases rapidly beyond the age of 60 years. Because the structure of the European population is shifting towards the aged, more people are expected to suffer from BP in the coming decades.

Age Factors↗