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Biomedical subjects

H S Nielsen

Publications and source records attributed to H S Nielsen.

At least 19 recordsLinked to original sources

Impact of the sex of first child on the prognosis in secondary recurrent miscarriage.

BACKGROUND: The carriage of a male fetus often initiates maternal immunological reactions against male-specific minor histocompatibility (HY) antigens, which, in theory, could result in subsequent recurrent miscarriage (RM). METHODS: Information about subsequent pregnancy outcome was procured among 182 women with RM after a birth (secondary RM) referred since 1986 using questionnaires, telephone interviews and registers. RESULTS: Significantly more of the women had had a male first-born as compared with a female first-born (110 versus 72; P < 0.02). By January 2002, 58% of those who had a male first-born had given birth to a second live infant compared with 76% of those who previously had had a female first-born (P = 0.01). Women in the former group had a significantly lower chance of having a second child than those in the latter (adjusted hazard ratio 0.59; 95% confidence interval 0.41-0.86). The number of miscarriages after admission and the risk of secondary infertility were significantly greater in women with a male first-born than among those with a female first-born (P < 0.001 and P = 0.02; respectively). CONCLUSIONS: A male first-born seems to be associated with a less favourable reproductive potential among women with secondary RM. Maternal immunization against HY antigens may be responsible for these findings.

Abortion, Habitual↗

Generation of an infectious clone of VR-2332, a highly virulent North American-type isolate of porcine reproductive and respiratory syndrome virus.

A full-length cDNA clone of the prototypical North American porcine reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332 was assembled in the plasmid vector pOK(12). To rescue infectious virus, capped RNA was transcribed in vitro from the pOK(12) clone and transfected into BHK-21C cells. The supernatant from transfected monolayers were serially passaged on Marc-145 cells and porcine pulmonary alveolar macrophages. Infectious PRRSV was recovered on Marc-145 cells as well as porcine pulmonary macrophages; thus, the cloned virus exhibited the same cell tropism as the parental VR-2332 strain. However, the cloned virus was clearly distinguishable from the parental VR-2332 strain by an engineered marker, a BstZ17I restriction site. The full-length cDNA clone had 11 nucleotide changes, 2 of which affected coding, compared to the parental VR-2332 strain. Additionally, the transcribed RNA had an extra G at the 5' end. To examine whether these changes influenced viral replication, we examined the growth kinetics of the cloned virus in vitro. In Marc-145 cells, the growth kinetics of the cloned virus reflected those of the parental isolate, even though the titers of the cloned virus were consistently slightly lower. In experimentally infected 5.5-week-old pigs, the cloned virus produced blue discoloration of the ears, a classical clinical symptom of PRRSV. Also, the seroconversion kinetics of pigs infected with the cloned virus and VR-2332 were very similar. Hence, virus derived from the full-length cDNA clone appeared to recapitulate the biological properties of the highly virulent parental VR-2332 strain. This is the first report of an infectious cDNA clone based on American-type PRRSV. The availability of this cDNA clone will allow examination of the molecular mechanisms behind PRRSV virulence and attenuation, which might in turn allow the production of second-generation, genetically engineered PRRSV vaccines.

Animals↗

Dissociation between light-induced phase shift of the circadian rhythm and clock gene expression in mice lacking the pituitary adenylate cyclase activating polypeptide type 1 receptor.

The circadian clock located in the suprachiasmatic nucleus (SCN) organizes autonomic and behavioral rhythms into a near 24 hr time that is adjusted daily to the solar cycle via a direct projection from the retina, the retinohypothalamic tract (RHT). This neuronal pathway costores the neurotransmitters PACAP and glutamate, which seem to be important for light-induced resetting of the clock. At the molecular level the clock genes mPer1 and mPer2 are believed to be target for the light signaling to the clock. In this study, we investigated the possible role of PACAP-type 1 receptor signaling in light-induced resetting of the behavioral rhythm and light-induced clock gene expression in the SCN. Light stimulation at early night resulted in larger phase delays in PACAP-type 1 receptor-deficient mice (PAC1(-)/-) compared with wild-type mice accompanied by a marked reduction in light-induced mPer1, mPer2, and c-fos gene expression. Light stimulation at late night induced mPer1 and c-fos gene expression in the SCN to the same levels in both wild type and PAC1(-)/- mice. However, in contrast to the phase advance seen in wild-type mice, PAC1(-)/- mice responded with phase delays after photic stimulation. These data indicate that PAC1 receptor signaling participates in the gating control of photic sensitivity of the clock and suggest that mPer1, mPer2, and c-fos are of less importance for light-induced phase shifts at night.

Activity Cycles↗

Pituitary adenylate cyclase-activating polypeptide induces period1 and period2 gene expression in the rat suprachiasmatic nucleus during late night.

The suprachiasmatic nucleus generates circadian rhythms which are synchronized to the environmental light-dark cycle via the retinohypothalamic tract. Pituitary adenylate cyclase-activating polypeptide and glutamate, two neurotransmitters co-stored in the retinohypothalamic tract of the rat, are able to phase shift the endogenous rhythm similar to light. The "clock genes" period1 (per1) and per2, which show circadian oscillation within the suprachiasmatic nucleus, have been attributed a role in light-induced resetting of the mammalian circadian clock due to rapid induction of the period (per) genes after light stimulation at night. Using a rat in vitro brain slice model, we demonstrate by quantitative in situ hybridization histochemistry that the diurnal alteration in expression of both per genes in the suprachiasmatic nucleus was retained in vitro. In the model, we examined the effects of pituitary adenylate cyclase-activating polypeptide and glutamate alone and in combination on per1 and per2 gene expression at late subjective night (circadian time 19). Glutamate administration (10(-3)M) induced both per1 and per2 gene expression in the suprachiasmatic nucleus of the brain slice within 1h. The per gene responses were similar to the induction of gene expression observed after light stimulation in vivo at late night. Pituitary adenylate cyclase-activating polypeptide (10(-6)M) administered alone had no effect on the per gene expression, but when pituitary adenylate cyclase-activating polypeptide in micromolar concentration was applied before glutamate, the neuropeptide blocked the glutamate-induced per1 and per2 gene expression in the suprachiasmatic nucleus. In contrast to the lack of effect of pituitary adenylate cyclase-activating polypeptide itself in micromolar concentration, pituitary adenylate cyclase-activating polypeptide (10(-9)M) induced both per1 and per2 gene expression, an effect which was not augmented by co-application of glutamate. Our results provide the molecular substrate for the previous electrophysiological findings that pituitary adenylate cyclase-activating polypeptide in high concentration is able to block glutamate-induced phase advance at late night, and that the peptide in low concentration can induce a phase advance similar to light and glutamate.

Animals↗

Analysis of ORF 1 in European porcine reproductive and respiratory syndrome virus by long RT-PCR and restriction fragment length polymorphism (RFLP) analysis.

A rapid method was developed for partial characterization of the replicase-encoding open reading frame 1 (ORF 1) of porcine reproductive and respiratory syndrome virus (PRRSV). It comprised long RT-PCR amplification of 11.1 kb (94%) of ORF 1, followed by restriction fragment length polymorphism analysis. The method was used to compare ORF 1 sequences of two divergent European-type PRRSV strains. Our results indicated that the structural and replicase parts of these two strains had evolved at overall similar rates.

Blotting, Southern↗

A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis.

OBJECTIVE: To assess the efficacy of oral high-dose methylprednisolone in acute optic neuritis (ON). BACKGROUND: It has been determined that oral high-dose methylprednisolone is efficacious in attacks of MS. METHODS: A total of 60 patients with symptoms and signs of ON with a duration of less than 4 weeks and a visual acuity of 0.7 or less were randomized to treatment with placebo (n = 30) or oral methylprednisolone (n = 30; 500 mg daily for 5 days, with a 10-day tapering period). Visual function was measured and symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks. Primary efficacy measures were spatial vision and VAS scores the first 3 weeks (analysis of variance with baseline values as the covariate), and changes in spatial vision and VAS scores after 8 weeks. A significance level of p < 0.0125 was employed. RESULTS: The VAS score (p = 0.008) but not the spatial visual function (p = 0.03) differed in methylprednisolone- and placebo-treated patients during the first 3 weeks. After 8 weeks the improvement in VAS scores (p = 0.8) and spatial visual function (p = 0.5) was comparable with methylprednisolone- and placebo-treated patients. A post hoc subgroup analysis suggested that patients with more severe baseline visual deficit and patients treated early after onset of symptoms had a more pronounced response to treatment. The risk of a new demyelinating attack within 1 year was unaffected by treatment. No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone treatment improves recovery from ON at 1 and 3 weeks, but no effect could be demonstrated at 8 weeks or on subsequent attack frequency.

Acute Disease↗

Expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the postnatal and adult rat cerebellar cortex.

In adult rat, immunostaining for pituitary adenylate cyclase activating polypeptide (PACAP) was demonstrated in the soma and dendrites of Purkinje cells and in nerve fibres around granule cells. PACAP in the Purkinje cells was confirmed by the presence of mRNA. The concentration of PACAP-38 was high after birth and declined to adult levels within a few weeks. At birth PACAP-immunoreactive nerve fibres and a few cells were present in the Purkinje cell layer, but already at postnatal day 7 an adult PACAP immunostaining pattern was found. The findings suggest that PACAP could be a neurotransmitter in the adult cerebellum and provide a morphological correlate for the reported in vitro anti-apoptotic PACAP effects on cerebellar granule cells from 1-week-old rats.

Animals↗

Embryonic expression of pituitary adenylate cyclase-activating polypeptide in sensory and autonomic ganglia and in spinal cord of the rat.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that is related structurally to vasoactive intestinal polypeptide (VIP), has been shown to stimulate neuronal growth and differentiation, indicating a possible function in the development of the nervous system. Studies have indicated that the PACAP receptor is expressed during development, but data on PACAP expression are limited mainly to postnatal development. In the present study, we used immunohistochemistry and in situ hybridization histochemistry to examine the expression of PACAP in autonomic and sensory ganglia and spinal cord of rat fetuses at embryonic days 12-21 (E12-E21). PACAP immunoreactivity was visualized by using a specific monoclonal anti-PACAP antibody to detect both PACAP-38 and PACAP-27, and PACAP mRNA was visualized by using a [33P]-labeled cRNA-probe. PACAP- nerve fibers were observed in the spinal cord as early as E13. At E14, PACAP-immunoreactive nerve fibers projected to the sympathetic trunk, where few PACAP- nerve cell bodies were seen from E15. On the same embryonic day, PACAP-immunoreactive nerve cell bodies appeared in the intermediolateral column of the spinal cord. From E15 to E16, PACAP-immunoreactive nerve cell bodies were visible within sensory and autonomic ganglia, such as the dorsal root, the trigeminal, the sphenopalatine, the otic, the submandibular, and the nodose ganglia. At E16, PACAP+ nerve fibers were innervating the adrenal medulla, and immunoreactive fibers could also be observed in the superior cervical ganglion, in which PACAP-immunoreactive cell bodies were detected occasionally from E18. The synthesis of PACAP in neuronal cell bodies was confirmed by the demonstration of PACAP mRNA with in situ hybridization histochemistry. Thus, in all of the structures examined, PACAP appeared at roughly the same embryonic stage and, thereafter, increased to the adult level before birth. Because PACAP occurred with the same distribution pattern as that described in the adult rat, there is no evidence for transient expression. The early expression of PACAP suggests a possible role for the peptide in the developing nervous system.

Adrenal Glands↗

Child labour or school attendance? Evidence from Zambia.

"In this paper we investigate what affects school attendance and child labour in an LDC, using data for Zambia.... The empirical analysis suggests that both economic and sociological variables are important determinants for the choice between school attendance and child labour. In particular, we find some support for the hypothesis that poverty forces households to keep their children away from school."

Africa↗

[The new ambulatory non-invasive 24-hour blood pressure monitoring system, Takeda Medical TM 2420. Reliability and practical experiences].

Takeda TM 2420 is an automatic ambulant device for measuring blood pressure which functions by auscultation of the Korokoff sounds. During static conditions, the apparatus was investigated by means of a double stetoscope and a connecting branch with the Hawksley random zero manometer. Where 69 persons were concerned (ages 13-89 years, systolic blood pressures 85-212 mmHg, diastolic blood pressure 44-110 mmHg) a difference in the systolic blood pressure of 1.5 +/- 9.2 mm Hg were found (average +/- standard deviation) and where the diastolic blood pressure was concerned 2.8 +/- 6.3 mm Hg. Statistical comparison with the Hawksley manometer on the contralateral arm in 51 volunteers produced corresponding results. In 24-hour monitoring of 80 persons, useful results were obtained in 74. The proportion of erroneous measurements was acceptable but the apparatus was unsuitable for exercise testing on an ergometer bicycle. The quality of the cuff, the connecting tubing, the carrying strap and computer programmel should be improved but the apparatus was otherwise found to be useful for daily clinical use.

Adolescent↗