Biomedical subjects

B Andersen

Publications and source records attributed to B Andersen.

At least 19 recordsLinked to original sources

PubMed2006

LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells.

LIM-only protein 4 (LMO4) plays critical roles in mammalian development, and has been proposed to play roles in epithelial oncogenesis, including breast cancer. As LMO4 is highly expressed in the epithelial compartments at locations of active mesenchymal-epithelial interactions, we reasoned that LMO4 might act by modulating signaling pathways involved in mesenchymal-epithelial signaling. One such candidate signal is the transforming growth factor-beta (TGFbeta) cytokine pathway, which plays important roles both in development and cancer. We show here that the transcriptional response to TGFbeta in epithelial cells is sensitive to LMO4 levels; both up- and downregulation of LMO4 can enhance TGFbeta signaling as assessed by a TGFbeta-responsive reporter gene. Furthermore, LMO4 can interact with the MH1 and linker domains of receptor-mediated Smad proteins, and associate with the endogenous TGFbeta-responsive Plasminogen Activator Inhibitor-1 gene promoter in a TGFbeta-dependent manner, suggesting that such interactions may mediate the effects of LMO4 on TGFbeta signaling. When introduced into mammary epithelial cells, LMO4 potentiated the growth-inhibitory effects of TGFbeta in those cells. These results define a new function for LMO4 as a coactivator in TGFbeta signaling, and provide a potential novel mechanism for LMO4-mediated regulation in development and oncogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Catabolism of pyrimidines in yeast: a tool to understand degradation of anticancer drugs.

The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides/antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway was present in the ancient yeasts but was lost approximately 100 million years ago in the S. cerevisiae lineage.

Antineoplastic Agents↗

PubMed2004

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Adult↗

PubMed2003

Reasons for Chlamydia trachomatis testing and the associated age-specific prevalences.

OBJECTIVE: to assess the age- and sex-specific prevalence of Chlamydia trachomatis infection according to the indications for testing. This was done as part of a health technology assessment to identify the populations that would benefit most from universal screening, and to identify ongoing potential superfluous testing that could liberate resources to be used for targeted screening programs. METHODS: In Aarhus County, Denmark, population of 630,000, data were collected on 11,423 persons who were being tested for C. trachomatis (10,351 females and 1072 males). Indicated on the request slip were: the sex, the age and the reasons for testing (infected partner; planned transcervical procedure; symptoms consistent with C. trachomatis infection; or routine testing). All samples were analyzed by the Ligase Chain Reaction. RESULTS: More than 90% of all the tests were conducted in women. The majority of tests were performed in the 21-25 years age group but the prevalence was highest in the 16-20 years age group (7.2%; 95% CI: 5.4%-9.3%). A total of 25% of all tests were carried out in asymptomatic women above the age of 30 in whom the prevalence was only 1.3% (95% CI: 0.8%-1.9%). More than three times as many women (5.8%) than men (1.7%) were tested as sexual partners to C. trachomatis-infected index patients but the risk of infection was highest among men. In women who were tested prior to a transcervical procedure, the prevalence was highest (5.5%; 95% CI: 1.8%-12.4%) in the 16-20 years age group, whereas most samples were obtained in women aged 31-35 years in whom the prevalence was only 0.8% (0.2%-2.3%). CONCLUSIONS: The prevalence of C. trachomatis infection justifies the screening of asymptomatic individuals below 30 years of age. At present, however, 25% of all tests are requested in asymptomatic women above the age of 30. It might be advisable to use the resources for systematic universal screening of younger individuals rather than to continue the current opportunistic screening of older women.

Adolescent↗

PubMed2003

Managing partners of people diagnosed with Chlamydia trachomatis: a comparison of two partner testing methods.

OBJECTIVE: To compare the effectiveness of "home sampling" with that of "office sampling" for testing partners to men and women infected with Chlamydia trachomatis. METHOD: A randomised controlled effectiveness trial took place in the general community in Denmark. 1300 index women and 526 index men (>/=18 years) with a positive test result for C trachomatis were identified. Of these, 414 index women and 148 index men gave implied consent. Index patients were randomly assigned to provide their partner(s) through the past 12 months with either (1) a kit by which partner(s) could be tested by home sampling, or (2) a kit by which partner(s) could only be tested by seeing a healthcare professional (office sampling). The mainoutcome measure was the proportion of index patients who had at least one partner tested for C trachomatis. RESULTS: The proportion of index women with at least one partner tested was higher in the home sampling group (0.26) than in the office group (0.12) (difference 0.14; 95% CI 0.10 to 0.19; p<0.0001) and so it was for index men (0.15 v 0.03; difference 0.12; 95% CI 0.07 to 0.16; p<0.0001). Also the proportion of index women for whom at least one partner was identified as infected was higher in the home sampling group compared with the office group (0.11 v 0.07, p=0.01). The corresponding figures for index men were 0.06 v 0.01, p=0.02. CONCLUSION: The effectiveness of partner testing is higher when partners of C trachomatis infected patients are offered home sampling than when they are offered office sampling.

Adult↗

PubMed2003

Cellular determination in the anterior pituitary gland: PIT-1 and PROP-1 mutations as causes of human combined pituitary hormone deficiency.

In the anterior pituitary gland, five distinct hormone producing cell types are generated from common epithelial progenitor cells. This process of cellular determination is controlled by signaling molecules acting on transcription factors, which in turn regulate genes critical for the appearance of hormone producing cells. Two pituitary specific transcription factors, Pit-1 and Prop-1, which are required for generation of hormone producing cells in the anterior pituitary gland, have proved to be important in the cause of hypopituitarism in humans. Mutations in the human PIT-1 gene lead to a combined pituitary hormone deficiency characterized by lack of GH, PRL and TSH. Mutations in the PROP-1 gene, which are a more common cause of hypopituitarism, lead to a clinical phenotype characterized by GH, PRL, TSH, LH and FSH deficiency, and sometimes ACTH deficiency as well.

DNA-Binding Proteins↗

PubMed2002

Identification of two novel and potent competitive inhibitors of the glucose-6-phosphatase catalytic protein.

AIM: In this study, we show that inhibitors of the glucose-6-phosphatase (G-6-Pase) catalytic protein could be an alternative approach to the recent G-6-Pase T1-translocase inhibitors to target this enzyme for the treatment of type 2 diabetes. METHOD: The active enantiomers of 4-methoxyphenyl-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone (Compound A-1) and 4-methoxyphenyl-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone (Compound B-1) were characterized as inhibitors of the G-6-Pase catalytic protein using pig and rat liver microsomes and cultured rat hepatocytes. RESULTS: Both compounds were found to be potent competitive inhibitors of the G-6-Pase catalytic protein obtained from pig and rat liver microsomes. The K(i) values (microM) were calculated to be 0.61 +/- 0.02 and 0.63 +/- 0.08 for compound A-1 and B-1 on intact pig microsomes, and 0.27 +/- 0.02 and 0.29 +/- 0.06 on disrupted pig microsomes. The corresponding values for rat liver microsomes were found to be 3.3 +/- 0.6 and 4.0 +/- 1.2 for compound A-1 and B-1 on intact microsomes, and 1.54 +/- 0.1 and 1.21 +/- 0.1 on disrupted microsomes. Compound A-1 was also able to inhibit pyrophosphatase activities from both intact and disrupted microsomes with equal potency (IC50; 0.43-0.55 microm). Using cultured rat hepatocytes and glycerol as the substrate, these compounds were able to prevent glucose production up to 60% with a concomitant increase in the G-6-P content (2.3-fold) using compound A-1. No increase in glycogen levels was seen. CONCLUSION: These data demonstrated that these compounds were more potent inhibitors on G-6-Pase obtained from pig microsomes and were able to penetrate the microsomal membrane. The hepatocyte data further support the kinetic data, and are also consistent with the evoked mechanism of action.

Animals↗

PubMed2002

Toxigenic diversity of two different RAPD groups of Stachybotrys chartarum isolates analyzed by potential for trichothecene production and for boar sperm cell motility inhibition.

Thirty-one isolates of Stachybotrys chartarum from indoor and outdoor environments were analyzed for the presence of the trichodiene synthase (Tri5) gene, trichothecenes, boar sperm cell motility inhibition, and randomly amplified polymorphic DNA banding patterns (RAPDs). Twenty-two S. chartarum isolates tested positive for the Tri5 gene and nine were negative when tested using novel Tri5 gene-specific PCR primer pair. The Tri5 gene positive isolates contained satratoxins (five isolates) or the simple trichothecene, trichodermol (11 isolates). The Tri5 gene negative isolates did not produce satratoxins or trichodermol. Nineteen S. chartarum isolates, distributed among the Tri5 gene negative and positive groups, inhibited boar spermatozoan motility at concentrations of < or = 60 microg of crude cell extract/mL. The inhibition of motility was independent of satratoxins or atranones. Unweighted pair group method of arithmetic averages (UPGMA) cluster analysis of RAPD fragments clustered the 31 S. chartarum isolates in two distinct groups designated as RAPD groups 1 and 2. The grouping of S. chartarum isolates obtained by UPGMA cluster analysis of RAPD fragments was identical to the grouping obtained by Tri5 gene-specific PCR. This indicates that the S. chartarum isolates belonging to different groups were genetically distinct in a much wider area than just the Tri5 gene.

Animals↗

PubMed2001

The POU domain factor Skin-1a represses the keratin 14 promoter independent of DNA binding. A possible role for interactions between Skn-1a and CREB-binding protein/p300.

The genes encoding keratin 5 and 14 are highly expressed in the basal cell layer keratinocytes of the epidermis, but both genes are silenced when keratinocytes move into the suprabasal compartment. The POU homeodomain factors Skn-1a and Tst-1, which are expressed in epidermis, may play a role in the suprabasal repression of the keratin 5 and 14 genes because keratin 14 mRNA expression persists in suprabasal cells in Skn-1/Tst-1 double knockout mice. In transfection experiments, both Skn-1a and Tst-1 repress the keratin 14 promoter, with the POU domain being sufficient for repression. The region of the keratin 14 gene sufficient and required for repression by Skn-1a is a 100-base pair sequence lacking POU-binding sites adjacent to the transcription start site. DNA-binding defective mutants of Skn-1a and Tst-1 are as effective at mediating repression as the wild type proteins, suggesting that protein-protein interactions rather than direct DNA binding are important for repression. We also show that CREB-binding protein (CBP)/p300 co-activators are strong activators of keratin 14 gene expression, acting through sequences close to the keratin 14 promoter. Further, CBP interacts directly with the POU domain of Skn-1a, and increasing concentrations of CBP can overcome Skn-1a-mediated repression, suggesting that POU domain factors may repress keratin 14 gene expression by interfering with the activity of co-activators such as CBP/p300.

Animals↗

PubMed2001

Large scale expression, purification and 2D crystallization of recombinant plant plasma membrane H+-ATPase.

P-type ATPases convert chemical energy into electrochemical gradients that are used to energize secondary active transport. Analysis of the structure and function of P-type ATPases has been limited by the lack of active recombinant ATPases in quantities suitable for crystallographic studies aiming at solving their three-dimensional structure. We have expressed Arabidopsis thaliana plasma membrane H+-ATPase isoform AHA2, equipped with a His(6)-tag, in the yeast Saccharomyces cerevisiae. The H+-ATPase could be purified both in the presence and in the absence of regulatory 14-3-3 protein depending on the presence of the diterpene fusicoccin which specifically induces formation of the H+-ATPase/14-3-3 protein complex. Amino acid analysis of the purified complex suggested a stoichiometry of two 14-3-3 proteins per H+-ATPase polypeptide. The purified H(+)-ATPase readily formed two-dimensional crystals following reconstitution into lipid vesicles. Electron cryo-microscopy of the crystals yielded a projection map at approximately 8 A resolution, the p22(1)2(1) symmetry of which suggests a dimeric protein complex. Three distinct regions of density of approximately equal size are apparent and may reflect different domains in individual molecules of AHA2.

14-3-3 Proteins↗

PubMed2001

Recent advances in hypospadias: current surgical technique and research in incidence and etiology.

Surgical techniques to repair hypospadias have undergone remarkable advances in recent years with the development and widespread use of dorsal urethral plate incision to facilitate urethroplasty. Clinical studies of the technique have shown excellent cosmesis and low complication rates for dorsal plate incision (DPI) in distal hypospadias repair, and have demonstrated the efficacy of expanding the use of the DPI in conjunction with other surgical techniques in more proximal repairs. There have been reports of increasing overall incidence of hypospadias in Scandinavian and US populations, but this might not be a uniform trend. There is, in fact, wide variation in the reported incidence of hypospadias among different countries. Many countries have not shown increased rates of hypospadias; furthermore, in countries noted previously to have an increased incidence of hypospadias, rates have leveled off since 1985. Investigations into the etiology of hypospadias have shown potential links to estrogen effects in utero from increased phytoestrogen intake in maternal vegetarian diets, and rare cases of genetic mutations in 5-alpha reductase type II.

Humans↗

PubMed2001

Iminosugars: potential inhibitors of liver glycogen phosphorylase.

The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S): (3R,4R,5S) and (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well as of a series of N-substituted derivatives of the (3R,4R,5R)-isomer and selected hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at submicromolar concentration. The results also showed that all three hydroxy groups should be present and could not be substituted, nor were extra OH groups allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect was retained for N-substituted derivatives of Isofagomine; however, N-substitution always resulted in a loss of activity compared to the parent compound, IC50 values ranging from 1 to 100 microM were obtained for simple alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it was not enough to assure inhibitory effect to have the (R,R,R) configuration. Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an IC50 value of 200 microM compared to 0.7 microM for Isofagomine. In addition, Isofagomine was able to prevent basal and glucagon stimulated glycogen degradation in cultured hepatocytes with IC50 values of 2-3 microM.

Animals↗

PubMed2001

A community needs assessment for a SANE program using Neuman's model.

PURPOSE: To present guidelines for a community needs assessment for a Sexual Assault Nurse Examiner (SANE) program using Neuman's Systems Model. The guidelines provide advanced practice nurses with a holistic, systematic means to conduct an assessment prior to the implementation of a SANE program and facilitate collaborative work with other disciplines and agencies. DATA SOURCES: Selected research-based articles on sexual assault, classic texts and writings on Neuman's Systems Model, and community assessment models and programs. CONCLUSIONS: Sexual assault is a problem faced by almost every community. A thorough community assessment is an important first step in establishing programs that adequately meet a community's needs. Guidelines for conducting such an assessment related to implementation of a SANE program are rare, and guidelines using a nursing model were not found in the literature. IMPLICATIONS FOR PRACTICE: One program that has been successful in meeting community needs is the SANE program. A concise and organized assessment guide can reduce the necessary time and money allocated for a community assessment and can provide a basis for evaluation and research.

Community Health Services↗

PubMed2001

The pyrimidine operon pyrRPB-carA from Lactococcus lactis.

The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in Lactococcus lactis subsp. lactis MG1363. The functions of the different genes were established by mutational analysis. The first gene in the operon is the pyrimidine regulatory gene, pyrR, which is responsible for the regulation of the expression of the pyrimidine biosynthetic genes leading to UMP formation. The second gene encodes a membrane-bound high-affinity uracil permease, required for utilization of exogenous uracil. The last two genes in the operon, pyrB and carA, encode pyrimidine biosynthetic enzymes; aspartate transcarbamoylase (pyrB) is the second enzyme in the pathway, whereas carbamoyl-phosphate synthetase subunit A (carA) is the small subunit of a heterodimeric enzyme, catalyzing the formation of carbamoyl phosphate. The carA gene product is shown to be required for both pyrimidine and arginine biosynthesis. The expression of the pyrimidine biosynthetic genes including the pyrRPB-carA operon is subject to control at the transcriptional level, most probably by an attenuator mechanism in which PyrR acts as the regulatory protein.

Amino Acid Sequence↗

PubMed2001

Effectiveness of a mass media campaign to recruit young adults for testing of Chlamydia trachomatis by use of home obtained and mailed samples.

OBJECTIVE: To evaluate the effectiveness of a structured information campaign aiming to recruit young adults for a Chlamydia trachomatis test by use of a non-invasive, home obtained and mailed sample. METHODS: All individuals aged 21-23 living in Aarhus county, Denmark (30 000 young adults) were offered a mailed home sampling test for C trachomatis as part of a structured 14 week information campaign on chlamydia. The kit for home sampling could be requested by leaving a message on an answering machine or through a website on the internet. RESULTS: During the campaign 119 of 15 000 women (0.8%) and 64 of 15 000 men (0.4%) were tested. Prevalence of infection was 8.4% (10/119) and 7.8% (5/64) in females and males, respectively. Four infections in women (4/10=40%) and three infections in men (3/5=60%) were asymptomatic. CONCLUSIONS: The mass media campaign had only a limited effect, and there is a need for more effective outreach programmes to recruit young asymptomatic individuals for C trachomatis testing.

Adult↗

PubMed2001

POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease.

POU domain factors are transcriptional regulators characterized by a highly conserved DNA-binding domain referred to as the POU domain. The structure of the POU domain has been solved, facilitating the understanding of how these proteins bind to DNA and regulate transcription via complex protein-protein interactions. Several members of the POU domain family have been implicated in the control of development and function of the neuroendocrine system. Such roles have been most clearly established for Pit-1, which is required for formation of somatotropes, lactotropes, and thyrotropes in the anterior pituitary gland, and for Brn-2, which is critical for formation of magnocellular and parvocellular neurons in the paraventricular and supraoptic nuclei of the hypothalamus. While genetic evidence is lacking, molecular biology experiments have implicated several other POU factors in the regulation of gene expression in the hypothalamus and pituitary gland. Pit-1 mutations in humans cause combined pituitary hormone deficiency similar to that found in mice deleted for the Pit-1 gene, providing a striking example of how basic developmental biology studies have provided important insights into human disease.

Animals↗

PubMed2000

Home sampling versus conventional swab sampling for screening of Chlamydia trachomatis in women: a cluster-randomized 1-year follow-up study.

We compared the efficacy of a screening program for urogenital Chlamydia trachomatis infections based on home sampling with that of a screening program based on conventional swab sampling performed at a physician's office. Female subjects, comprising students at 17 high schools in the county of Aarhus, Denmark, were divided into a study group (tested by home sampling) and a control group (tested in a physician's office). We assessed the number of new infections and the number of subjects who reported being treated for pelvic inflammatory disease (PID) at 1 year of follow-up; 443 (51.1%) of 867 women in the intervention group and 487 (58.5%) of 833 women in the control group were available for follow-up. Thirteen (2.9%) and 32 (6.6%) new infections were identified in the intervention group and the control group, respectively (Wilcoxon exact value, P=.026). Nine (2.1%) women in the intervention group and 20 (4.2%) in the control group reported being treated for PID (P=.045), indicating that a screening strategy involving home sampling is associated with a lower prevalence of C. trachomatis and a lower proportion of reported cases of PID.

Adolescent↗

PubMed2000

Defective terminal differentiation and hypoplasia of the epidermis in mice lacking the Fgf10 gene.

Here, we characterized the skin and hair phenotype of mice lacking the fibroblast growth factor 10 gene (Fgf10), a newly identified member of the fibroblast growth factor family. Histological examination of Fgf10(-/-) newborn mouse skin revealed abnormalities in epidermal morphogenesis. The number of proliferating cells in the basal layer was decreased, the granular layer was hypoplastic and lacked distinctive keratohyaline granules and tonofibrils. The expression of loricrin, a marker of epidermal differentiation, was dramatically reduced. Despite the presence of Fgf10 transcripts in normal hair follicles, abnormalities of hair development were not observed in Fgf10(-/-) skin. These data suggest that Fgf10 is required for embryonic epidermal morphogenesis but is not essential for hair follicle development.

Animals↗