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Biomedical subjects

B Andersen

Publications and source records attributed to B Andersen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation.

Here we report on investigation of the role of the POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from the cell cycle, migrate suprabasally, and terminally differentiate to form a multilayered, stratified epithelium. The expression of the Skn-1a/i and Tst-1 genes is linked to keratinocyte differentiation in vivo and in vitro, whereas the ubiquitous POU domain factor Oct-1 is expressed highly in both proliferating and post-mitotic keratinocytes. Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i gene modulates the pattern of expression of the terminal differentiation marker loricrin and inhibits expression of genes encoding markers of the epidermal keratinocyte wounding response. Although epidermis from Tst-1 gene-deleted mice develops normally, epidermis from mice deleted for both Skn-1a/i and Tst-1 is hyperplastic and fails to suppress expression of K14 and Spr-1 in suprabasal cells when transplanted onto athymic mice. This suggests that Skn-1a/i and Tst-1 serve redundant functions in epidermis. Therefore, at least two POU domain genes, Skn-1a/i and Tst-1, serve both distinct and overlapping functions to regulate differentiation of epidermal keratinocytes during normal development and wound healing.

Animals↗
PubMed1997

Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression.

Tissue-restricted POU domain transcription factors, which bind octamer or octamer-like gene sequences, play roles in cellular differentiation and the development of several organs. We have previously identified a POU domain gene, Skn-1a/i, expressed primarily in epidermis, that encodes at least two products through alternative splicing. One of these, Skn-1a, acts as a transcriptional activator, and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which prevents DNA-binding in vitro and transcriptional activation in vivo. We now demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an octamer site, suggesting that in vivo cellular factors modulate the activity of the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not allow transactivation by Skn-1i or by a heterologous transactivator containing this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are the major octamer-binding proteins in epidermis. Since Skn-1a is primarily expressed in suprabasal cells of the epidermis, we have tested its possible role in the regulation of epidermal papillomaviruses. In transient transfection assays, Skn-1a and Tst-1 can activate the long control region of the epidermis-specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo transcription data, in vitro DNA binding studies identify three octamer-like sites, which are capable of binding Skn-1a, in the HPV-1A long control region. Mutations of all three octamer-like sites prevent transactivation by Skn-1a in transient transfection assays. Taken together, these results provide evidence that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression and epidermal differentiation.

Base Sequence↗
PubMed1997

Expression and purification of the Saccharomyces cerevisiae alpha-factor receptor (Ste2p), a 7-transmembrane-segment G protein-coupled receptor.

A plasmid vector was developed that permitted high-level expression of a functional form of the Saccharomyces cerevisiae alpha-factor receptor (the STE2 gene product) tagged at its C-terminal end with an epitope (FLAG) and a His6 tract. When expressed in yeast from this plasmid, Ste2p was produced at a level at least 3-fold higher than that reported previously for any other 7-transmembrane-segment receptor expressed in the same cells. For purification, isolated cell membranes containing the overexpressed receptor were solubilized with detergent under specific conditions and subjected to immobilized metal affinity chromatography. Yields as high as 1 mg of nearly homogeneous (95%) receptor were routinely obtained even from relatively small scale preparations (60 g of frozen cell paste). The purified receptor was reconstituted into artificial phospholipid vesicles. Radioligand binding studies demonstrated that the purified receptor, in the reconstituted vesicles, bound its tridecapeptide ligand (alpha-factor) with a KD (155 nM) consistent with the affinity expected for this receptor in the absence of its associated G protein. Efficient restoration of ligand binding activity upon reconstitution required the addition of solubilized membranes prepared from a yeast strain lacking the receptor. Sufficient amounts of active material can be obtained by this procedure to allow physical studies of this receptor and other 7-transmembrane-segment receptors expressed in this system.

Amino Acid Sequence↗
PubMed1997

A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins.

The essential roles of LIM homeodomain proteins in cell fate determination during development have been demonstrated in organisms as divergent as Drosophila and higher mammals. We have isolated murine cDNAs encoding two highly homologous proteins that specifically interact with the LIM domains of P-Lim/Lhx3 and several other LIM homeodomain factors. Transcripts encoding these factors can be detected as early as mouse E8.5, with maximal expression observed in regions of the embryo in which the LIM homeodomain factors P-Lim/Lhx3, Isl-1, and LH-2 are selectively expressed. These proteins can potentiate transactivation by P-Lim/Lhx-3 and are required for a synergistic activation of the glycoprotein hormone alpha-subunit promoter by P-Lim/Lhx3 and a pituitary Otx class homeodomain transcription factor, with which they also specifically associate. Our results link LIM homeodomain proteins and members of the Otx class of transcription factors in gene activation events during embryogenesis via the actions of specific cofactors.

Amino Acid Sequence↗
PubMed1996

Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism.

The gene apparently responsible for a heritable form of murine pituitary-dependent dwarfism (Ames dwarf, df) has been positionally cloned, identifying a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (Prop-1). The df phenotype results from an apparent failure of initial determination of the Pit-1 lineage required for production of growth hormone, prolactin or thyroid-stimulating hormone, resulting in dysmorphogenesis and failure to activate Pit-1 gene expression. These results imply that a cascade of tissue-specific regulators is responsible for the determination and differentiation of specific cell lineages in pituitary organogenesis.

Alleles↗
PubMed1996

Diagnosis of urogenital Chlamydia trachomatis infection in women based on mailed samples obtained at home: multipractice comparative study.

OBJECTIVE: To compare urine and vaginal flush samples collected by women at home with endocervical and urethral swabs obtained by general practitioners for their efficacy in the diagnosis of urogenital Chlamydia trachomatis infection. DESIGN: Multipractice comparative study. SETTING: 33 general practices and a central department of clinical microbiology in Aarhus County, Denmark. SUBJECTS: 222 women aged 18-25 years who for any reason had a gynaecological examination. INTERVENTIONS: Endocervical and urethral swabs were obtained by the women's general practitioners. The same women when at home then collected a first void urine sample, a midstream urine sample, and a vaginal flush sample (using a vaginal pipette) and mailed them to the laboratory. MAIN OUTCOME MEASURES: C trachomatis defected by the polymerase chain reaction and the ligase chain reaction. Eight tests for C trachomatis were performed for every woman. When two of the eight yielded positive results the patient was considered infected. RESULTS: The overall prevalence of C trachomatis infection was 11.2% (23/205 women). Test sensitivities in samples obtained by general practitioners, samples obtained at home subjected to polymerase chain reaction, and samples obtained at home subjected to ligase chain reaction were 91%, 96%, and 100% respectively. The corresponding specificities were 100%, 92.9%, and 99.5%. CONCLUSIONS: The diagnostic efficacy of samples obtained by women at home and mailed to the laboratory was as good as for samples obtained by a general practitioner when using the ligase chain reaction. This may have important implications for the practicability of screening for this common, often asymptomatic, and treatable infection.

Adolescent↗
PubMed1996

[Induced abortions in relation to the use of contraceptive agents].

The aim of the study was to investigate the use of contraceptive methods among women referred to an induced abortion. The design was a prospective study of women seeking abortion, 854 were included consecutively. All were asked about the contraceptive methods used preceding their actual pregnancy. Was the contraceptive method used in a regular way, and what was the motive for her voluntary abortion? Of the 854 women, 831 chose to participate and answered the questions (97.3%). We found that 35% had used their contraceptive method in a regular way but became pregnant nevertheless. Another group of 33% had forgotten to use their contraceptives for a few days and became pregnant by accident. In the last group of 32% the women had not used any contraceptive methods. It is concluded that more information is necessary to get women and men to use contraceptive methods regularly with better precision and more seriousness.

Abortion Applicants↗
PubMed1996

["The withered arm". A multifocal motor neuropathy and considerations in differential diagnosis].

Multifocal motor neuropathy (MMN) is a newly recognized disorder with a characteristic clinical picture. The diagnosis of MMN is established by the presence of a specific electrodiagnostic abnormality, conduction block confined to motor axons, and in some instances by the associated high titers of anti-GM1 antibodies. Clinical improvement may be achieved by treatment with intravenous immunoglobulin or cyclophosphamide, which underlines the importance of recognizing these patients. We present two patients with slowly progressive predominantly distal weakness and muscle wasting of an upper extremity characteristic of MMN. Extensive electrophysiological examinations are necessary to demonstrate conduction block of motor axons, which distinguishes patients with MMN from patients with motor neuron disease. Other diagnostic possibilities are discussed.

Arm↗
PubMed1996

Analogues of carbacholine: synthesis and relationship between structure and affinity for muscarinic and nicotinic acetylcholine receptors.

A series of acyclic and heterocyclic analogues of carbacholine (1) was synthesized using N-methylcarbacholine (MCC, 2), N,N-dimethylcarbacholine (DMCC, 3), and the corresponding tertiary amine (4) as leads. Whereas nicotinic acetylcholine receptor affinity was determined using [3H]nicotine as the radioactive ligand, [3H]oxotremorine-M ([3H]Oxo-M) and [3H]quinuclidinyl benzilate ([3H]QNB), in some cases supplemented with [3H]pirenzepine ([3H]PZ), were used as radioligands for muscarinic acetyicholine receptors on rat brain membranes. On the basis of receptor binding data, nicotinic/muscarinic (N/M) selectivity factors were determined, and muscarinic receptor efficacy (M agonist index) and M1 selectivity (M2/M1 index) estimated. In most cases, quaternized analogues showed higher affinity than the corresponding tertiary amines for muscarinic and, in particular, nicotinic receptor sites. Among the new compounds, N,N-diethylcarbacholine (9e) (IC50 = 0.046 microM), (S)-1-methyl-2-(N,N- dimethyl-aminocarbonyloxymethyl)pyrrolidine (17k) (IC50 = 0.068 microM), and the corresponding quaternized analogue, 18k (IC50 = 0.018 microM) showed the highest nicotinic receptor affinity. The tertiary amine, 17k showed much higher nicotinic receptor affinity than the acyclic analogue, 4 (IC50 = 5.7 microM), and the N/M selectivity factor determined for 17k (150) is an order of magnitude lower than that of nicotine (1400). THe N/M selectivity factors for MCC (2) and DMCC (3), previously reported to be highly selective nicotinic receptor ligands, were shown to be 6.5 and 60, respectively, the latter value being comparable with that of 18k (89).

Animals↗
PubMed1996

Corpus callosotomy: seizure and psychosocial outcome. A 39-month follow-up of 20 patients.

The aim of the present study was to investigate the effect of corpus callosotomy on seizures, with emphasis on the psychosocial outcome. Data were retrospectively obtained from 20 patients (mean age 20.8 years, range 6-46). Sixteen of the operated patients took part in the 39-month (range 19-62) follow-up. Outcome measures were post-operative seizures, changes in the antiepileptic drug treatment, surgical complications including disconnection syndrome, degree of dependency according to the Barthel index, quality of life, burden on caretakers and satisfaction with the treatment. Half of the patients had a favorable seizure outcome, and of these 50% noticed an improved quality of life and were satisfied with the treatment. Four patients suffered from symptoms of cerebral disconnection syndrome which interfered with the activities of daily life. One patient died of complications 3 months after the operation. There were no significant changes in antiepileptic drug treatment, the patients' social lives or the burden of the patients on the caretakers. The conclusion is that prospective studies are needed to clarify the criteria for optimal patient selection to increase the likelihood of a positive psychosocial outcome.

Adolescent↗
PubMed1996

Peyronie curvature treated by plication of the penile fasciae.

OBJECTIVE: To evaluate the results of plication of the penile fascia in patients with penile curvature secondary to Peyronie's disease. PATIENTS AND METHODS: Twenty-eight men with Peyronie curvature underwent plication of the penile fascia. Before operation, the deviation of the penis was so severe (median 60 degrees) in 24 men that they were unable to perform sexual intercourse. Follow-up was based on hospital records, one postal questionnaire sent to all patients and a clinical evaluation of the men in the out-patient clinic. RESULTS: After an uncomplicated operation and a median follow-up of 34 months, 20 of the 28 men were able to perform sexual intercourse and 23 were satisfied with the result of the operation. The most frequent reasons for dissatisfaction with the outcome of the operation were insufficient straightening, pain from sutures and uncharacteristic pain related to the penis and/or scrotum. CONCLUSION: The technique is simple to perform and the method gives functional and cosmetic results equal to those of more invasive procedures. The provision of adequate information to patients before the operation is important to ensure their satisfaction with the outcome.

Adult↗
PubMed1996

Nearest-neighbor analysis of higher-plant photosystem I holocomplex.

Photosystem 1 (PSI) preparations from barley (Hordeum vulgare) and spinach (Spinacia oleracea) were subjected to chemical cross-linking using the cleavable homobifunctional cross-linkers dithiobis(succinimidylpropionate) and 3,3'-dithiobis(sulfosuccinimidyl-propionate). The overall pattern of cross-linked products was analyzed by the simple but powerful technique of diagonal electrophoresis, in which the disulfide bond in the cross-linker was cleaved between the first and second dimensions of the gel, and immunoblotting. A large number of cross-linked products were identified. Together with preexisting data on the structure of PSI, it was deduced that the subunits PSI-D, PSI-H, PSI-I, and PSI-L occupy one side of the complex, whereas PSI-E, PSI-F, and PSI-J occupy the other. PSI-K and PSI-G appear to be adjacent to Lhca3 and Lhca2, respectively, and not close to the other small subunits. Experiments with isolated light-harvesting complex I preparations indicate that the subunits are organized as dimers, which seem to associate to the PSI-A/PSI-B proteins independent of each other. We suggest which PSI subunit corresponds to each membrane-spanning helix in the cyanobacterial PSI structure, and present a model for higher-plant PSI.

Amino Acid Sequence↗
PubMed1995

The Ames dwarf gene is required for Pit-1 gene activation.

The tissue-specific POU domain transcription factor Pit-1 is required for phenotypic specification of three cell types in the anterior pituitary gland of mammals: somatotropes, thyrotropes, and lactotropes. Mutations in the Pit-1 gene, as first described in Snell and Jackson dwarf (dw) mice, led to pituitary hypoplasia due to lack of these three cell types, as well as hypothyroidism and dwarfism because of deficiency of thyroid-stimulating hormone and growth hormone, respectively. The Ames dwarf (df) exhibits a phenotype identical to that of Pit-1 mutated mice but the defective gene has been mapped to a locus on mouse chromosome 11, distinct from the Pit-1 gene located on mouse chromosome 6. Our studies indicate that initial activation of the Pit-1 gene is deficient in the Ames dwarf. This suggests that the df gene is required for activation of the Pit-1 gene and provides evidence for a hierarchy of tissue-specific factors required for cellular commitment in the anterior pituitary gland.

Animals↗
PubMed1995

A stereologic study of postmature placentas fixed by dual perfusion.

OBJECTIVE: Placental insufficiency has been considered the cause of increased morbidity in infants delivered postmaturely. Former quantitative studies have indicated a decrease in some placental structures just before term. In this study we describe a method of dual perfusion fixation to provide tissue for stereologic examination. Postmature placentas were examined with this method. STUDY DESIGN: Eleven postmature placentas and 14 placentas delivered at term were fixed by dual perfusion. The volume and the surface area of villi, the trophoblast volume, and the volume, surface area, and length of villous capillaries were estimated by stereologic examination. The Mann-Whitney test (p < or = 0.05) was used for statistical analysis. RESULTS: Morphologic features were normal in all placentas. No significant differences were disclosed in the stereologic estimates of placentas delivered at term and postmature placentas. CONCLUSION: No morphologic or significant quantitative changes were found in postmature placentas.

Female↗
PubMed1995

Acute admissions to medical departments. A comparison between an urban and a rural district.

To compare hospitalization into medical departments, acute admissions into a city hospital and into a district hospital were compared prospectively over a two-week period. Patients referred to the city hospital were on average older, were more frequently living alone and they had a greater amount of social care attendance in their homes. On the other hand, distribution of referral diagnoses, overall patient activity, occupational status and contact with relatives were similar in the two areas. Sub-acute or acute illness was considered the main cause of admission in both areas; the amount of admissions for social reasons was 13 percent to the city hospital versus 3 percent to the district hospital. Relevant alternatives to hospitalization seemed to exist in 50 percent of the admissions to the city hospital versus only 3 percent to the district hospital. Since patients admitted for social reasons block hospital beds for a longer time period than those admitted for other reasons, these differences may to some extent explain why length of hospital stay is longer in city hospitals than in rural ones.

Acute Disease↗