Biomedical subjects

Henriette S Nielsen

Publications and source records attributed to Henriette S Nielsen.

11 recordsLinked to original sources

PubMed2006

Inflammation and miscarriage.

Most relevant studies in animals and humans indicate that some degree of systemic or uterine inflammation is necessary both for normal implantation and pregnancy. However, if inflammation becomes too excessive it might cause pregnancy complications such as fetal resorption/miscarriage. The main regulator of the correct level of inflammation at the feto-maternal interface seems to be the uterine CD16(-) CD56(bright) natural killer (NK) cells. Trophoblast debris, apoptotic cells and progesterone probably stimulate/regulate the production of inflammatory cytokines from these cells. Miscarriage of karyotypically normal embryos may occur when the level of inflammation at the feto-maternal interface falls outside the optimal range. This may be caused by an insufficient influx of CD56(bright) NK cells into the decidua, too little soluble histocompatibility leukocyte antigen (HLA)-G secretion from the trophoblast, hypersecretion of inflammatory cytokines due to the presence of high-production polymorphisms, presence of maternal HLA-DR alleles associated with high tumor necrosis factor (TNF)-alpha production, or maternal mannose-binding lectin deficiency.

Abortion, Habitual↗

PubMed2006

Future directions of failed implantation and recurrent miscarriage research.

Recurrent implantation failure is today the major reason for women completing several IVF/intracytoplasmic sperm injection attempts without having achieved a child, and is probably also the explanation for many cases of unexplained infertility. Most causes of recurrent miscarriage are still poorly elucidated, but from a theoretical point of view recurrent implantation failure and recurrent miscarriage are suggested to have partly overlapping causes. Recent research has indeed documented that both syndromes can be caused by the same embryonic chromosomal abnormalities and the same maternal endocrine, thrombophilic and immunological disturbances. Consequently, many treatments attempting to normalize these abnormalities have been tested or are currently used in women with both recurrent implantation failure and recurrent miscarriage. However, no treatment for the two syndromes is at the moment sufficiently documented to justify its routine use. In this review, an overview is given regarding present knowledge about causes that may be common for recurrent implantation failure and recurrent miscarriage, and suggestions are put forward for future research that may significantly improve understanding and treatment options for the syndromes.

Abortion, Habitual↗

PubMed2006

Research methodology and epidemiology of relevance in recurrent pregnancy loss.

With respect to recurrent pregnancy loss (RPL), unfortunately there is very little consensus about which investigations are useful for identifying causes and evaluating the prognosis, and also about which treatments are effective. In this review, arguments are given for the claim that this lack of consensus may mainly be because studies in the field of RPL have yielded very heterogeneous results. This heterogeneity, in the authors' belief, is caused by the scientists' lack of appreciation, when they do research, of important epidemiological knowledge about RPL (e.g., about the multifactorial background for most of the RPL cases and the importance of matching/adjusting for a series of prognostic variables when groups are mutually compared). Furthermore, many studies in RPL contain methodological flaws that are sometimes severe. A series of important epidemiological features of RPL is highlighted in the review and the most important methodological pitfalls, many of them specific for RPL research, are discussed. Advice is given about to how to avoid the pitfalls in order that the validity of the studies can improve for the benefit of the patients.

Abortion, Habitual↗

PubMed2005

Generalized cellular hypertrophy is induced by a dual-acting PPAR agonist in rat urinary bladder urothelium in vivo.

Some developmental dual-acting PPARalpha/gamma agonists, such as ragaglitazar, have shown carcinogenic effects in the rodent urinary bladder urothelium after months-years of dosing. We examined early (precancerous) changes in the bladder urothelium of rats orally dosed with ragaglitazar, using a newly developed flow cytometric method. Following 3 weeks of oral ragaglitazar dosing, increases in physical size occurred in a generalized fashion in rat bladder urothelial cells, determined by flow cytometry. Protein/DNA measurements confirmed increased protein content of urothelial cells in the bladder, and hypertrophy was observed in the kidney pelvis urothelium by histopathology. In animals exhibiting urothelial hypertrophy, no cell cycle changes were detected in parallel samples of bladder urothelium. Interestingly, urothelial cells from normal rats were found to constitute a unique type of noncycling population, with high G2/M fractions. In summary, our findings showed that in the urothelium of ragaglitazar-treated animals, hypertrophy (increased size and protein content per cell) was an early change, that affected the whole bladder urothelial cell population. The urothelial hypertrophy was primary, i.e., occurred in the absence of similarly pronounced changes in cell cycle distributions. To our knowledge, this is the first report of a direct hypertrophic effect of a PPAR agonist. Urothelial hypertrophy might be a relevant early biological endpoint in mechanistic studies regarding the bladder-carcinogenic effect of PPAR agonists.

Animals↗

PubMed2005

Intravenous immunoglobulin in the prevention of recurrent miscarriage: does it work?

Immunological disturbances play a role in the majority of patients with recurrent miscarriage (RM) and therefore treatment with intravenous immunoglobulin (IvIg) has been tested in patients with RM in several trials. Seven placebo-controlled trials that were extremely heterogeneous with respect to patient characteristics and treatment procedures were carried out. One trial found that IvIg significantly improved pregnancy outcome in all patients whereas the remaining trials could either detect no treatment effect at all or only an effect in subsets of patients. In a meta-analysis, the pooled odds ratio for a new live birth in IvIg- versus placebo-treated patients with RM after a birth (secondary RM) was 1.60 (95% CI = 0.70-3.66). IvIg seems to be efficacious in patients with repeated second trimester intrauterine fetal deaths since it significantly (p < 0.01) increased the live birth rate in this subset compared with placebo. In most trials the design was suboptimal with regard to detecting any treatment effect of IvIg in RM due to low doses or starting the treatment late. A new large placebo-controlled trial should be conducted in RM patients with secondary RM or repeated second trimester fetal deaths and sufficient IvIg doses should be given with optimal timing.

Abortion, Habitual↗

PubMed2004

Expression of melanopsin during development of the rat retina.

There is accumulating evidence that the new opsin-like protein, melanopsin, in adult rodents functions as non-visual photoreceptor. Here we report using immunohistochemistry and in situ hybridisation that melanopsin during rat retinal development is expressed already at prenatal day 18 in cells of the inner neuroblast layer. Perinatally the melanopsin positive cells increase in number and migrate towards the ganglion cell layer. During early postnatal development a melanopsin immunoreactive dendritic network is formed in the inner plexiform layer. Melanopsin is exclusively expressed in PACAP-containing cells which in adults become the retinal ganglion cells constituting the retinohypothalamic tract. The early expression of melanopsin argues for a photoreceptor role in the developing retinohypothalamic tract which is functional as early as the first day after birth.

Animals↗

PubMed2004

Active or passive immunization in unexplained recurrent miscarriage.

Controversy exists as to whether active immunotherapy with allogeneic lymphocyte transfusions (ALT) or passive immunotherapy with intravenous immunoglobulin (IvIg) improve the chance of live birth in women with unexplained recurrent miscarriages (RM). Meta-analyses of the placebo-controlled trials carried out as Cochrane reviews have concluded than none of the different forms of immunotherapy has proved effective in the total RM population. However, the included trials have generally been small and very heterogenous with respect to the clinical histories of patients and the immunization protocols. Thus, other meta-analyses which have looked at the efficacy in subgroups of RM patients have reported that ALT and IvIg may be effective in women with primary RM and secondary RM, respectively. In RM clinics in Denmark, ALT with donor lymphocytes or IvIg immunotherapy have been tested in several placebo-controlled trials since 1986 in which greater doses than used in other trials have been administered, and both treatments are now used for routine therapy. Our results have convinced us that using the correct immunization protocols on the right subsets of RM patients is effective, but we admit that new placebo-controlled trials focusing on subsets of RM patients are now urgently needed. Furthermore, treated patients should be extensively monitored for changes in a series of immune parameters that may predict pregnancy success and be of importance for our understanding of the mechanisms of action of immunotherapy in RM.

Abortion, Habitual↗

PubMed2002

Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm.

The suprachiasmatic nucleus (SCN) generates circadian rhythms which are synchronised to the environmental light/dark cycle via the retinohypothalamic tract (RHT). Pituitary adenylate cyclase activating polypeptide (PACAP) and glutamate, two transmitters co-stored in the rat retinohypothalamic tract, are involved in photic entrainment of the circadian pacemaker, but their functional interplay is poorly understood. Homer proteins are involved in glutamatergic receptor function and signalling. By quantitative in situ hybridisation histochemistry we found that light stimulation of rats at early and late night induced Homer-1 gene expression in the SCN at time points where light induces phase-delay or phase-advance, respectively. Using a rat brain slice model Homer-1 mRNA levels in the SCN displayed a modest diurnal variation similar to that in vivo. The changes in Homer-1 gene expression after in vitro stimulation with PACAP and/or glutamate differed at early and late night. Nanomolar PACAP induced Homer-1 gene expression at both early and late night while glutamate was only able to increase Homer-1 mRNA level at early night. PACAP in micromolar concentration had no effect per se, but inhibited the glutamate induced Homer-1 response at early night, while at late night co-administration of PACAP and glutamate mediated a slight induction of Homer-1 gene expression. In conclusion, the RHT transmitters PACAP and glutamate could be responsible for the light-induced expression of Homer-1 in the SCN, and Homer-1 seems to be differentially regulated by the two transmitters at early and late night.

Animals↗

PubMed2002

The genetic diversity of European type PRRSV is similar to that of the North American type but is geographically skewed within Europe.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a recently emerged pathogen. Two PRRSV genotypes exist, North American and European, which are only 55-70% identical at the nucleotide level. Previous studies have shown high nucleotide diversity in the North American genotype and low nucleotide diversity in the European genotype. Here, we analyzed the ORF5 and ORF7 genes for a large number of new European type PRRSV isolates in conjunction with existing database sequences. This new analysis showed that contrary to previous assumptions, genetic diversity is at least as high in the European genotype as in the North American genotype. Furthermore, we showed that genetic diversity of European type PRRSV has a marked geographical pattern, with exceptionally high genetic diversity among Italian sequences. The geographical pattern of diversity in relation to the epidemiology of PRRSV in Europe is discussed. Discrepancies between ORF5- and ORF7-based genealogies were observed, and further analysis of the data set confirmed the presence of recombination. We were therefore able to report the first observation of recombination in wild-type isolates of European genotype PRRSV.

Animals↗

PubMed2002

Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night.

Circadian rhythms in behaviour and physiology generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via the retinohypothalamic tract. How light is able to adjust the endogenous rhythm is not fully understood, but induction of the two clock genes per1 and per2 in the SCN is believed to be important for the adjustment. Recently, it was shown that vasoactive intestinal polypeptide (VIP), a neurotransmitter found in light-responsive cells of the SCN, is able to phase shift the circadian rhythm similar to light. In the present study we show by means of an in vitro brain slice model and quantitative in situ hybridization histochemistry that VIP induces both per1 and per2 gene expression in the SCN during late subjective night (CT19). The signalling pathways responsible for the VIP signalling to the clock were investigated using inhibitors of protein kinase A and phospholipase C mediated signalling. Our results demonstrate that both pathways are involved in VIP induced per gene expression and suggest that VIP is important for light-induced phase shift late at night.

Animals↗

PubMed2001

Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations.

A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequenced and compared with the parental strain of the vaccine virus (VR2332). This revealed five mutations that had occurred independently in all three vaccine-derived field isolates, indicating strong parallel selective pressure on these positions in the vaccine virus when used in swine herds. Two of these parallel mutations were direct reversions to the parental VR2332 sequence and were situated in a papain-like cysteine protease domain and in the helicase domain. The remaining parallel mutations might be seen as second-site compensatory mutations for one or more of the mutations that accumulated in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change during the time period studied. The implications of these findings for PRRS vaccine attenuation and reversion are discussed.

Amino Acid Sequence↗