Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isola... more Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isolated Synaptosomes from Rat Cerebral Cortex. Heterogeneity of Binding and Desensitization of Receptors "Pod Staun-Olsen ...
: Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the... more : Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the brain cortex. VIP receptors were studied in subcellular fractions isolated from rat cerebral cortex. The receptor binding of 125I‐VIP was greatest in the synaptosomal fraction at membrane protein concentrations of 50–100 μg/ml, a temperature of 37°C, and a pH from 7.4 to 7.7. Under these conditions the concomitant proteolytic degradation of 125I‐VIP was approximately 10% after 60 min of incubation. The binding of 60 pmoI/L 125I‐VIP reached steady‐state after 60 min and was maintained up to 240 min. At steady‐state, the receptor‐bound 125I‐VIP was displaced by unlabelled VIP with half‐maximal inhibition (IC50) at a concentration of approximately 3 nmol/L. The binding of 125I‐VIP in the concentration range of 10 pmol/L to 6 nmol/L was superimposable on the VIP displacement curve. The Scatchard plot was curvilinear with upward concavity, which can be interpreted to represent two classes of receptors with KD of 2.5 and 125 nmol/L, one class of receptors with negative cooperative interactions, or heterogeneity of the 125I‐ VIP preparation. The total amount of receptors was 9.5 pmol/mg of membrane protein. Secretin displaced receptor‐bound 125I‐VIP with an IC50 of 0.3 μmol/L, whereas glucagon snowed no inhibition up to 1 μmol/L. The dissociation of receptor‐bound 125I‐VIP was biexponential with rate constants (k2) of 4.1 – 10−3 and 0.18 min−1 corresponding to half‐times of approximately 170 and 4 min, respectively. The size of the two components was dependent on the duration of the 125I‐VIP association period. Initially, both components increased; at steady‐state, the rapid component declined, whereas the slow component increased to approximately 70% after 120 min. The association rate constants (k1) were estimated from the initial velocities as 106 and 4. 106 L. mol−1. min−1, and a calculation of the KD as k2/k1 gave values of 4.1 and 45 nmol/L, respectively. In conclusion, the presence of receptors for VIP on synaptosomes from the cerebral cortex supports the role of VIP as a neurotransmitter in the brain. The receptor binding was heterogeneous, suggesting the presence of two classes of receptors. The binding kinetics showed a time‐dependent transition of VIP receptors from a low‐ to a high‐affinity state, which may be interpreted as desensitisation of synapses to the action of VIP.
Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are... more Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are performed by laparotomy, although the use of laparoscopically assisted techniques is increasing. Laparoscopic surgery seems to lead to a reduction in the need for postoperative hospitalization and convalescence, which is confirmed in the few available randomised and to our knowledge all retrospective studies. The length of stay seems to be reduced from four to two days if the patient is hysterectomised by the laparoscopically assisted or vaginal techniques. The introduction of endoscopic techniques has caused a change in routines and recommendations, but not for women operated by the classical open procedures. In this article we question the relevance of comparing different types of operations given the fact that the routines and recommendations are different.
Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and femal... more Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and female genitourinary tract, appearing to innervate vascular and nonvascular smooth and epithelial cells. In the present study the concentration of VIP in tissue extracts of different parts of the male genitourinary tract from cat and man was determined by radioimmunoassay. In addition, the effect of VIP on the contractility of the smooth muscle from the cat genitourinary tract was investigated in vitro. The tissue concentrations of VIP were generally higher in cat than in man. In both species high concentrations were found in the vas deferens, bladder, urethra and prostate, In concentration from 3 x 10(-8) to 6 x 10(-7) mol x 1-1, VIP inhibited in a concentration-dependent manner the muscle contractions in specimens from all regions examined, i.e., the vas deferens, ureter, corpus of the bladder, and urethra. The data indicate that VIP might play a physiologic role in the local nervous control of the smooth muscle activity in the male genitourinary tract.
Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in diseas... more Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in disease activity during pregnancy, and a predictable flare in the months after they give birth. The cause of these changes is unknown. We hypothesized that understanding biological changes (through gene expression) that occur from pre-pregnancy through the pregnancy and post-partum periods will contribute important evidence to our knowledge of the drivers of disease activity in RA during and after pregnancy. Methods: We have established a prospective RA pregnancy cohort, with clinical data and blood samples collected at pre-pregnancy (T0), each trimester of pregnancy and every 3 months up to a year post-partum (up to 8 time points). Disease activity at each time point was assessed using disease activity scores (DAS28CRP4); women who showed an improvement during pregnancy were selected for analysis (n=9). Global gene expression profiles for each sample were generated using RNA-sequencing (RNA-seq). Raw reads were pseudo-aligned and quantified using kallisto. Random effects regression models were used to estimate the effects of changes in gene expression on disease activity (a) from T0 through the pregnancy period (P1), and (b) in the post-partum period (P2). The models were adjusted for age, medication status at baseline and batch effects. Significance was assessed using a threshold of q<0.05 (FDR-adjusted). Functional enrichment analysis was performed using WebGestalt. Results: During pregnancy, 1,174 genes had expression patterns significantly associated with disease activity. While these were not significantly enriched in specific pathways, the genes whose increased expression was associated with the largest decrease (improvement) in disease activity during pregnancy were immune-related, and included ERAP1, CSNK2A1 and FAM175B. ERAP1 is involved in trimming peptides for presentation on MHC class I molecules; CSNK2A1 regulates cellular processes including cellular response to viral infection; FAM175B is involved in interferon-signaling. In the post-partum period, 4,693 genes had expression patterns significantly associated with disease activity. These were enriched (p<1x10^(-6)) in numerous immune-related pathways including MAPK signaling, T cell receptor signaling, osteoclast differentiation, hematopoietic cell lineage, B cell receptor signaling, Toll-like receptor signaling and leukocyte trans-endothelial migration, in addition to several pathways related to cancer. The genes whose increased expression were associated with larger increases in disease activity included EI24, CMTM7, PPP2CB and BFAR which are related to tumor suppression and/or regulation of apoptosis. Conclusion: In this pilot RA pregnancy cohort study with longitudinal RNA-seq data, several candidate genes were identified as significantly associated with improvement in disease activity during pregnancy, and others were associated with post-partum flares. These results warrant further investigations into possible roles of these genes in modulating RA disease activity in a larger cohort.
Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memoria... more Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memorial lecture. The role of obstetricians and gynecologists in primary healthcare for women. Frontline lectures: Fetal cells or genetic diagnosis. Genetics of gynecological cancer. Fetal therapy. Reproductive impact of sexually transmitted infections. Updates: Environment and reproductive health. Obstetric imaging. Screening for gynecological cancer. Minimally invasive surgery. Electronic fetal monitoring. Plenary sessions: Advances in prenatal diagnosis. Women's right and women's health. Changing concepts in antenatal care. Ovarian cancer. Optimizing the infertility evaluation. Advances in perinatal medicine. Evidence-based practice in gynecology. Induced abortion. Violence against women. Emergency contraception: the casualty department of family planning. Debates: Is there a normal Cesarean rate and can it be achieved? Hormone replacement therapy for all? Can cervical cancer screening b e cost-effective? There is no place for electronic fetal monitoring in the low-risk patient. Does continuing medical education improve professional performance? New technology: Human genome project. Three-dimensional ultrasound. Microfertilization procedures. Gynecological endoscopy. Electronic journalism. New developments: Cloning perspectives in veterinarian and human medicine. Telemedicine. Are some diseases in adult life caused by factors before birth? Index.
The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mec... more The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mechanical activity in non‐pregnant estradiol‐treated rabbits was investigated using in vivo and in vitro methods. The studies were performed on spontaneous, oxytocin‐, car‐bachol‐, and prostaglandin‐F2α‐induced activity. VIP had a dose‐related inhbitory effect on both myoelectrical and mechanical activity. The concentration needed for 50% inhibition (ID50) was 2xl0−10mol VIP 1−1(in vivo), and 6xl0−8mol VIP‐ l−1(in vitro). This inhibition was unaffected by the presence of atropine (10−5mol‐ I−1), propranolol (10−5), phentolamine (10−5), naloxone (10−5), apamin (10−4), and tetrodotoxin (10−5). These findings indicate that VIP may act via a specific receptor on the smooth muscle and supports the hypothesis that VIP may be a neurotransmitter involved in the local nervous control of uterine smooth muscle activity.
Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isola... more Page 1. 0022-304218211 101-12421$02.7510 Receptors for Vasoactive Intestinal Polypeptide on Isolated Synaptosomes from Rat Cerebral Cortex. Heterogeneity of Binding and Desensitization of Receptors &quot;Pod Staun-Olsen ...
: Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the... more : Vasoactive intestinal polypeptide (VIP) is a neuropeptide that causes neurone excitation in the brain cortex. VIP receptors were studied in subcellular fractions isolated from rat cerebral cortex. The receptor binding of 125I‐VIP was greatest in the synaptosomal fraction at membrane protein concentrations of 50–100 μg/ml, a temperature of 37°C, and a pH from 7.4 to 7.7. Under these conditions the concomitant proteolytic degradation of 125I‐VIP was approximately 10% after 60 min of incubation. The binding of 60 pmoI/L 125I‐VIP reached steady‐state after 60 min and was maintained up to 240 min. At steady‐state, the receptor‐bound 125I‐VIP was displaced by unlabelled VIP with half‐maximal inhibition (IC50) at a concentration of approximately 3 nmol/L. The binding of 125I‐VIP in the concentration range of 10 pmol/L to 6 nmol/L was superimposable on the VIP displacement curve. The Scatchard plot was curvilinear with upward concavity, which can be interpreted to represent two classes of receptors with KD of 2.5 and 125 nmol/L, one class of receptors with negative cooperative interactions, or heterogeneity of the 125I‐ VIP preparation. The total amount of receptors was 9.5 pmol/mg of membrane protein. Secretin displaced receptor‐bound 125I‐VIP with an IC50 of 0.3 μmol/L, whereas glucagon snowed no inhibition up to 1 μmol/L. The dissociation of receptor‐bound 125I‐VIP was biexponential with rate constants (k2) of 4.1 – 10−3 and 0.18 min−1 corresponding to half‐times of approximately 170 and 4 min, respectively. The size of the two components was dependent on the duration of the 125I‐VIP association period. Initially, both components increased; at steady‐state, the rapid component declined, whereas the slow component increased to approximately 70% after 120 min. The association rate constants (k1) were estimated from the initial velocities as 106 and 4. 106 L. mol−1. min−1, and a calculation of the KD as k2/k1 gave values of 4.1 and 45 nmol/L, respectively. In conclusion, the presence of receptors for VIP on synaptosomes from the cerebral cortex supports the role of VIP as a neurotransmitter in the brain. The receptor binding was heterogeneous, suggesting the presence of two classes of receptors. The binding kinetics showed a time‐dependent transition of VIP receptors from a low‐ to a high‐affinity state, which may be interpreted as desensitisation of synapses to the action of VIP.
Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are... more Approximately 6,000 hysterectomies are performed per year in Denmark. The major part of these are performed by laparotomy, although the use of laparoscopically assisted techniques is increasing. Laparoscopic surgery seems to lead to a reduction in the need for postoperative hospitalization and convalescence, which is confirmed in the few available randomised and to our knowledge all retrospective studies. The length of stay seems to be reduced from four to two days if the patient is hysterectomised by the laparoscopically assisted or vaginal techniques. The introduction of endoscopic techniques has caused a change in routines and recommendations, but not for women operated by the classical open procedures. In this article we question the relevance of comparing different types of operations given the fact that the routines and recommendations are different.
Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and femal... more Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and female genitourinary tract, appearing to innervate vascular and nonvascular smooth and epithelial cells. In the present study the concentration of VIP in tissue extracts of different parts of the male genitourinary tract from cat and man was determined by radioimmunoassay. In addition, the effect of VIP on the contractility of the smooth muscle from the cat genitourinary tract was investigated in vitro. The tissue concentrations of VIP were generally higher in cat than in man. In both species high concentrations were found in the vas deferens, bladder, urethra and prostate, In concentration from 3 x 10(-8) to 6 x 10(-7) mol x 1-1, VIP inhibited in a concentration-dependent manner the muscle contractions in specimens from all regions examined, i.e., the vas deferens, ureter, corpus of the bladder, and urethra. The data indicate that VIP might play a physiologic role in the local nervous control of the smooth muscle activity in the male genitourinary tract.
Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in diseas... more Background/Purpose: Many women with rheumatoid arthritis (RA) experience an improvement in disease activity during pregnancy, and a predictable flare in the months after they give birth. The cause of these changes is unknown. We hypothesized that understanding biological changes (through gene expression) that occur from pre-pregnancy through the pregnancy and post-partum periods will contribute important evidence to our knowledge of the drivers of disease activity in RA during and after pregnancy. Methods: We have established a prospective RA pregnancy cohort, with clinical data and blood samples collected at pre-pregnancy (T0), each trimester of pregnancy and every 3 months up to a year post-partum (up to 8 time points). Disease activity at each time point was assessed using disease activity scores (DAS28CRP4); women who showed an improvement during pregnancy were selected for analysis (n=9). Global gene expression profiles for each sample were generated using RNA-sequencing (RNA-seq). Raw reads were pseudo-aligned and quantified using kallisto. Random effects regression models were used to estimate the effects of changes in gene expression on disease activity (a) from T0 through the pregnancy period (P1), and (b) in the post-partum period (P2). The models were adjusted for age, medication status at baseline and batch effects. Significance was assessed using a threshold of q<0.05 (FDR-adjusted). Functional enrichment analysis was performed using WebGestalt. Results: During pregnancy, 1,174 genes had expression patterns significantly associated with disease activity. While these were not significantly enriched in specific pathways, the genes whose increased expression was associated with the largest decrease (improvement) in disease activity during pregnancy were immune-related, and included ERAP1, CSNK2A1 and FAM175B. ERAP1 is involved in trimming peptides for presentation on MHC class I molecules; CSNK2A1 regulates cellular processes including cellular response to viral infection; FAM175B is involved in interferon-signaling. In the post-partum period, 4,693 genes had expression patterns significantly associated with disease activity. These were enriched (p<1x10^(-6)) in numerous immune-related pathways including MAPK signaling, T cell receptor signaling, osteoclast differentiation, hematopoietic cell lineage, B cell receptor signaling, Toll-like receptor signaling and leukocyte trans-endothelial migration, in addition to several pathways related to cancer. The genes whose increased expression were associated with larger increases in disease activity included EI24, CMTM7, PPP2CB and BFAR which are related to tumor suppression and/or regulation of apoptosis. Conclusion: In this pilot RA pregnancy cohort study with longitudinal RNA-seq data, several candidate genes were identified as significantly associated with improvement in disease activity during pregnancy, and others were associated with post-partum flares. These results warrant further investigations into possible roles of these genes in modulating RA disease activity in a larger cohort.
Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memoria... more Keynote addresses: What happens to health care in crisis situations? Hubert de Watteville Memorial lecture. The role of obstetricians and gynecologists in primary healthcare for women. Frontline lectures: Fetal cells or genetic diagnosis. Genetics of gynecological cancer. Fetal therapy. Reproductive impact of sexually transmitted infections. Updates: Environment and reproductive health. Obstetric imaging. Screening for gynecological cancer. Minimally invasive surgery. Electronic fetal monitoring. Plenary sessions: Advances in prenatal diagnosis. Women's right and women's health. Changing concepts in antenatal care. Ovarian cancer. Optimizing the infertility evaluation. Advances in perinatal medicine. Evidence-based practice in gynecology. Induced abortion. Violence against women. Emergency contraception: the casualty department of family planning. Debates: Is there a normal Cesarean rate and can it be achieved? Hormone replacement therapy for all? Can cervical cancer screening b e cost-effective? There is no place for electronic fetal monitoring in the low-risk patient. Does continuing medical education improve professional performance? New technology: Human genome project. Three-dimensional ultrasound. Microfertilization procedures. Gynecological endoscopy. Electronic journalism. New developments: Cloning perspectives in veterinarian and human medicine. Telemedicine. Are some diseases in adult life caused by factors before birth? Index.
The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mec... more The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mechanical activity in non‐pregnant estradiol‐treated rabbits was investigated using in vivo and in vitro methods. The studies were performed on spontaneous, oxytocin‐, car‐bachol‐, and prostaglandin‐F2α‐induced activity. VIP had a dose‐related inhbitory effect on both myoelectrical and mechanical activity. The concentration needed for 50% inhibition (ID50) was 2xl0−10mol VIP 1−1(in vivo), and 6xl0−8mol VIP‐ l−1(in vitro). This inhibition was unaffected by the presence of atropine (10−5mol‐ I−1), propranolol (10−5), phentolamine (10−5), naloxone (10−5), apamin (10−4), and tetrodotoxin (10−5). These findings indicate that VIP may act via a specific receptor on the smooth muscle and supports the hypothesis that VIP may be a neurotransmitter involved in the local nervous control of uterine smooth muscle activity.
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