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Biomedical subjects

A M Jensen

Publications and source records attributed to A M Jensen.

At least 19 recordsLinked to original sources

mosaic eyes: a zebrafish gene required in pigmented epithelium for apical localization of retinal cell division and lamination.

For proper function of the retina, the correct proportions of retinal cell types must be generated, they must be organized into cell-specific laminae, and appropriate synaptic connections must be made. To understand the genetic regulation of retinal development, we have analyzed mutations in the mosaic eyes gene that disrupt retinal lamination, the localization of retinal cell divisions to the retinal pigmented epithelial surface and retinal pigmented epithelial development. Although retinal organization is severely disrupted in mosaic eyes mutants, surprisingly, retinal cell differentiation occurs. The positions of dividing cells and neurons in the brain appear normal in mosaic eyes mutants, suggesting that wild-type mosaic eyes function is specifically required for normal retinal development. We demonstrate that mosaic eyes function is required within the retinal pigmented epithelium, rather than in dividing retinal cells. This analysis reveals an interaction between the retinal pigmented epithelium and the retina that is required for retinal patterning. We suggest that wild-type mosaic eyes function is required for the retinal pigmented epithelium to signal properly to the retina.

Animals↗

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2.

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.

Adolescent↗

Associations of Neospora caninum seropositivity with gestation number and pregnancy outcome in Danish dairy herds.

The prevalence and distribution of seropositivity towards the protozoan parasite Neospora caninum were studied in single blood samples from 1561 cows from 31 Danish dairy herds. Blood samples were analysed by an indirect enzyme-linked immunoassay and an indirect fluorescent-antibody test. Seroprevalence in 15 herds with previous abortions assigned to neosporosis ranged from 1% to 58%, with a mean frequency of 22%. In eight out of 16 herds without a history of N.caninum related abortions, no seroreactors were found. In the remaining eight herds, the seroprevalence ranged from 6% to 59%. The prevalence and distribution of seropositivity, gestation number prior to sampling, and breed were related to abortions and perinatal deaths using a random-effects logistic-regression model. Abortion risk was significantly increased in seropositive animals (OR = 3) and in > or = 2nd-gestation cows (OR = 3). Perinatal death was significantly influenced by gestation number and breed, but not by serostatus. Reproductive performance and culling risk of cows were not affected by serostatus. Seropositivity increased with "age" (i.e. gestation number) (P = 0.02). In open cows, seropositivity tended to decrease with distance from calving (P = 0.05). The proportion of seropositive pregnant cows increased with trimester (P = 0.02).

Abortion, Veterinary↗

[Von Hippel-Lindau disease and molecular genetic diagnosis].

Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited disorder, characterized by cysts and neoplastic formations mainly in the cerebellum, retina, pancreas, kidneys and adrenal glands. The disease is subdivided into two groups depending on absence or presence of phaeochromocytomas. VHL is caused by changes in a tumour suppressor gene, which was cloned in 1993 after having been mapped to chromosome 3p25-26 in 1988. We present two cases with VHL type 1. The first patient belonged to a family with 24 verified affected members, the second was the descendent of a patient carrying a presumed de novo mutation. By direct sequencing of the VHL gene, the mutation was identified in both families, thus enabling preclinical diagnosis of persons at risk in the families.

Adolescent↗

IBMX, taurine and 9-cis retinoic acid all act to accelerate rhodopsin expression in postmitotic cells.

Birth dating studies in the rodent retina have shown that rod photoreceptors are generated throughout most of retinal development, yet the majority do not begin to express rhodopsin until the first postnatal week. We show that treatment with 3-isobutyl-1-methylxanthine (IBMX) enhances rod development in reaggregate, explant, and monolayer cultures of embryonic and newborn rat neural retina and is more potent than another rod-promoting factor, taurine, but less potent than 9-cis retinoic acid (RA). The effect of IBMX on rod development is not associated with an increase in precursor cell proliferation, rod survival, or a reduction in the development of other retinal cell types. We provide evidence that IBMX, as well as the rod promoting molecules taurine and RA, all act on postmitotic rhodopsin(-)cells to accelerate their differentiation into rhodopsin(+)cells.

1-Methyl-3-isobutylxanthine↗

Clinical study of a digital vs an analogue hearing aid.

Digital signal processing in hearing instruments has brought new perspectives to the compensation of hearing impairment and may result in alleviation of the adverse effects of hearing problems. This study compares a commercially available digital signal processing hearing aid (HA) (Senso) with a modern analogue HA with programmable fitting (Logo). The HAs tested are identical in appearance and, in spite of a different mode of operation, the study design ensured blinding of the test subjects. Outcome parameters were: improvements in speech recognition score in noise (deltaSRSN) with the HAs; overall preference for HA; overall satisfaction; and various measures of HA performance evaluated by a self-assessment questionnaire. A total of 28 experienced HA users with sensorineural hearing impairment were included and 25 completed the trial. No significant differences were found in deltaSRSN between the two HAs. Eleven subjects indicated an overall preference for the digital HA, 10 preferred the analogue HA and 4 had no preference. Concerning overall satisfaction, 8 subjects rated the digital HA superior to the analogue one, whereas 7 indicated a superior rating for the analogue HA and 10 rated the HAs equal. Acceptability of noise from traffic was the only outcome parameter which gave a significant difference between the HAs in favour of the digital HA. It is concluded that there are no significant differences in outcome between the digital and analogue signal processing HAs tested by these experienced HA-users.

Acoustic Impedance Tests↗

Central precocious puberty in girls: internal genitalia before, during, and after treatment with long-acting gonadotropin-releasing hormone analogues.

Pelvic ultrasonography was systematically performed on 33 girls with idiopathic central precocious puberty to investigate the impact of treatment with gonadotropin-releasing hormone analogues on female internal genitalia. All girls were treated with a long-acting gonadotropin-releasing hormone analogue (Decapeptyl Depot; Ferring Co., Copenhagen, Denmark) 75 micrograms/kg every 4 weeks. Before, during, and after treatment, pelvic ultrasonography was performed and ovarian and uterine volumes were calculated. The size of follicles > 5 mm were accurately measured. The results were related to a normative study of healthy Danish schoolgirls. Our data demonstrated that ovaries and uterus are enlarged in a significant number of girls (50%) with the diagnosis of central precocious puberty at the time of diagnosis. Median ovarian volume at time of diagnosis was 1.1 standard deviation scores (range -0.6 to 3.2 SD), median uterine volume was 1.8 standard deviation scores (range 0.0 to 3.5 SD). Within 3 months of treatment, both ovarian and uterine volumes decreased significantly (p < 0.01) to normal values appropriate for age. Median ovarian volume after 3 months of treatment was 0.0 SD (range -2.4 to 1.5 SD); median uterine volume was 0.7 SD (range -0.6 to 4.1 SD). Ovarian and uterine volume remained within normal range (< 2 standard deviation scores) after discontinuation of treatment. Follicles and macrocysts regressed during treatment. None of the girls' ovaries had a polycystic appearance during or after treatment with the gonadotropin-releasing hormone analogue. Our results confirmed pelvic ultrasonography as a reliable tool for investigation of internal genitalia in girls with precocious puberty and as a valid method for evaluation of the efficacy of treatment with gonadotropin-releasing hormone analogues. We suggest that repeated investigations be performed when evaluating treatment because the morphologic changes, including follicular maturation or regression, reflect ovarian stimulation or suppression. We found no evidence that girls with precocious puberty treated with long-acting gonadotropin-releasing hormone analogues have enlarged polycystic ovaries develop.

Adnexa Uteri↗

Partnership and parenthood in contemporary Europe: a review of recent findings.

"In this article I will give a cross-sectional presentation of differences by region and sex in the propensity of men and women [in Europe] to live with adults and to live with children. It is expected that an East-West divide, apparent at least until the end of the 1980s, will be reflected in the European Fertility and Family Surveys (FFS) data, since some surveys from Eastern European countries were carried out only a couple of years after the transition. First a review of the changes in fertility and family patterns over the last decades is given, and then we turn to findings from FFS."

Adolescent↗

Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells.

The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients and healthy volunteers with calcipotriol and placebo ointment for 4 and 7 days, and obtained epidermal cell suspensions from treated areas. Epidermal cells were cocultured with autologous T cells, isolated from peripheral blood, in the absence or the presence of a classical antigen or a superantigen. In both psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen-presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen-presenting cells in psoriatic epidermis. In contrast, we found that calcipotriol significantly inhibited the proliferation of epidermal cells isolated from psoriatic skin after in vivo treatment, as determined by propidium iodide staining and flow cytometry. More specifically, we stained for CD29+ keratinocytes and found an even more significant reduction in proliferative capacity. This cell type contains the population of hyperproliferative keratinocytes in psoriatic epidermis. In conclusion, calcipotriol seems to act via an inhibitory effect on hyperproliferative basal keratinocytes of psoriatic epidermis, rather than via an effect on infiltrating leucocytes, including antigen-presenting cells.

Calcitriol↗

Epidemiology of respiratory syncytial virus infection requiring hospitalization in East Denmark.

BACKGROUND: Prophylaxis against infection caused by respiratory syncytial virus (RSV) with high titered RSV immunoglobulin or humanized antibody may soon be available in Europe. OBJECTIVE: To study the epidemiology of RSV infections requiring hospitalization in infants <6 months in East Denmark to provide a rational basis for decisions concerning prophylaxis against RSV. METHOD: Populat ion-based retrospective review of case records of infants <6 months admitted to pediatric departments with RSV infection in East Denmark from November 1, 1995, to April 30, 1996. RESULTS: Data were obtained from 459 infants. Seventy-three had predisposing conditions: prematurity, 49; pulmonary disease, 2; congenital heart disease, 7; neurologic disease, 6; others, 9. One preterm infant had bronchopulmonary dysplasia. The incidence of RSV infection requiring hospitalization in East Denmark among infants <6 months was estimated to be 34/1000/season. It was 32/1000/season among term infants and 66/ 1000/season among preterm infants (P<0.001). Infants with predisposing conditions and/or nosocomial infection (n = 24) had significantly more severe courses than otherwise healthy infants (P<0.01). One-hundred thirty infants received respiratory support by nasal continuous positive airway pressure, but only six required mechanical ventilation. No infants died. CONCLUSION: The course of RSV disease in East Denmark was milder than reported elsewhere, possibly as a result of the low prevalence of bronchopulmonary dysplasia in Denmark. However, RSV constitutes a considerable burden to the Danish pediatric health care system, and therefore prophylaxis against RSV is desirable.

Denmark↗

Continuous observation of multipotential retinal progenitor cells in clonal density culture.

All neural cell types in the vertebrate retina, except astrocytes, have been shown to develop from multipotential progenitor cells. It is not known, however, to what extent the progenitor cells are heterogeneous in their developmental potential or to what extent cell-cell interactions versus cell-autonomous factors influence the types of cells they become. To address these issues we developed a clonal-density cell culture system where mouse retinal progenitor cells can survive, divide, and differentiate. We followed the development of clones both by continuous time-lapse video microscopy and by daily microscopic observation. We show that even when cultured at clonal density in a homogeneous general environment, where they cannot contact cells outside their own clone, the retinal progenitor cells vary in proliferative capacity, cell cycle time, and in the cell types that they generate. In addition, we show that under these conditions single progenitor cells can generate both neurons and glia, in which case the neurons almost always develop before glial cells, as is the case in vivo.

Animals↗

Regulation of lactase-phlorizin hydrolase gene expression by the caudal-related homoeodomain protein Cdx-2.

Lactase-phlorizin hydrolase is exclusively expressed in the small intestine and is often used as a marker for the differentiation of enterocytes. The cis-element CE-LPH1 found in the lactase-phlorizin hydrolase promoter has previously been shown to bind an intestinal-specific nuclear factor. By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1. A mutation in CE-LPH1, which does not affect Cdx-2 binding, results in a higher transcriptional activity, indicating that the CE-LPH1 site contains other binding site(s) in addition to the Cdx-2-binding site.

Base Sequence↗

Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina.

We show that Sonic hedgehog and patched are expressed in adjacent domains in the developing mouse retina. Treatment of cultures of perinatal mouse retinal cells with the amino-terminal fragment of Sonic hedgehog protein results in an increase in the proportion of cells that incorporate bromodeoxuridine, in total cell numbers, and in rod photoreceptors, amacrine cells and Muller glial cells, suggesting that Sonic hedgehog promotes the proliferation of retinal precursor cells. These findings suggest that hedgehog and patched are part of a conserved signalling pathway in retinal development in mammals and insects.

Aging↗

[Prognostic value of interleukin-8 in AIDS-related Pneumocystis carinii pneumonia].

UNLABELLED: We evaluated the significance of interleukin-8 (IL-8) in Pneumocystis carinii pneumonia (PCP). Bronchoalveolar lavage (BAL) fluid and serum was prospectively collected in 76 consecutive HIV-infected patients with a primary episode of PCP, as well as in ten healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared to control subjects (p < 0.01). Nine patients died during the course of PCP. Non-survivors had significantly higher IL-8 levels in BAL fluid than survivors (p < 0.05). Furthermore patients with levels of IL-8 in BAL greater then 90 pg/ml (i.e. greater than control subjects) had significantly worse vital prognosis (log rank test, p < 0.05). Thirteen patients required mechanical ventilation (MV), and these patients had significantly elevated levels of IL-8 compared with patients not requiring MV (p < 0.05). IN CONCLUSION: i) IL-8 in BAL fluid correlates to the clinical severity of the pneumonia, and ii) is a predictor of mortality and severe respiratory compromise.

AIDS-Related Opportunistic Infections↗

[Prevalence of Chlamydia trachomatis among conscripts. A comparative study of urine samples and urethral swabs].

The purpose of the investigation was 1) to determine the prevalence of C. trachomatis among young men and women enrolled in military service, 2) to compare enzyme-immunoassay (EIA) of a urethral swab with a sample of first voided morning urine, 3) to determine frequency of earlier venereal diseases (VD) and actual symptoms of urethritis and cervicitis. EIA positive specimens were confirmed by immunofluorescent microscopy. The investigation comprised 831 men and 80 women (17-26 years). The prevalence was 5.7% (95% confidence limits 4.2-7.4%) and 15% (8-25%) for men and women, respectively (p < 0.005, chi 2). The agreement between the results of the urethral swab and the urine sample was low. Sensitivity and positive predictive value for urethral swab was better than for urine. The handling of urine specimens was more laborious and confirmation more difficult. The percentage of actual symptoms among Chlamydia positive men was 6. The frequency of earlier VD was 7.5% and 10% among men and women, respectively. Treatment with tetracycline was effective, which makes control of eradication unnecessary. We conclude that genital chlamydial infection among young asymptomatic people is common and screening would be desirable. We still recommend urethral swabbing as the routine method until simpler and/or more reliable assays for urine specimens are developed.

Adolescent↗

Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study.

The aim of the study was to examine the role of peak bone mass and rate of postmenopausal bone loss for the subsequent risk of osteoporotic fracture. 182 women within 3 years of menopause were followed longitudinally for 15 years. Over the first 2 years, forearm bone mass (single photon absorptiometry) was measured nine times, the rate of bone loss was calculated, and the women were stratified into a group of "fast bone losers" (n = 49) and a group of "normal bone losers" (n = 133). Later, bone mass was also measured in the lumbar spine and hip with dual energy X-ray absorptiometry. At 15 years, the fast losers had significantly lower body weight (4.4 kG; p < 0.05) than the normal losers. Furthermore, the fast losers had significantly increased values of bone turnover (osteocalcin and C-terminal type I collagen breakdown products). In both the forearm, spine, and hip, the fast bone losers had at all sites significantly less bone mass than the normal bone losers (p < 0.001). 23 women had experienced a peripheral (Colles') fracture and 25 a spinal fracture. The fracture groups had generally significantly (p < 0.05) less bone mass than the group without fracture, both in the forearm, spine, and hip and they also had the highest rate of bone loss after menopause (p < 0.05). Baseline bone mass and rate of loss predisposed to the same extent to fractures with ODD's ratios of about 2. If both low bone mass and rate of loss were present, the ODD's ratio increased to about 3. We conclude that fast rate of bone loss and low bone mass are equally important for the risk of fracture. The identification of women at risk of osteoporosis should therefore consider both a measurement of bone mass status, and a determination of the postmenopausal rate of loss.

Bone Density↗