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Biomedical subjects

P Svendsen

Publications and source records attributed to P Svendsen.

At least 19 recordsLinked to original sources

Protein-binding elements in the proximal parotid secretory protein gene enhancer essential for salivary-gland-specific expression.

The murine parotid secretory protein (PSP) gene is expressed at high levels in the parotid gland and at lower levels in the sublingual gland. A proximal enhancer core necessary for tissue-specific expression was identified previously, and it was demonstrated that one element, parotid gland element I (PGE I), exhibited specific binding of parotid gland nuclear proteins. In the present study, we demonstrate that a related adjacent element, PGE II, which binds nuclear proteins in a much less tissue-restricted manner, is able to compete with PGE I for binding of parotid-gland-specific factors. The functional significance of PGE I and PGE II was examined in transgenic mice. Deletion of PGE II reduced transgene expression only in the parotid gland, whereas deletion of PGE I appeared to reduce expression in both of the PSP-expressing salivary glands. Combined deletion of PGE I and PGE II reduced expression below the limit of detection. Thus PGE I and PGE II are functionally important salivary-gland-specific binding elements that are necessary for the salivary-gland-specific expression of a PSP minigene in transgenic mice.

Animals↗

The Göteborg cohort of embolized cerebral arteriovenous malformations: a 6-year follow-up.

OBJECTIVE: To present a follow-up of the results after endovascular treatment of cerebral arteriovenous malformations (AVMs) with acrylic glue. An initial follow-up was published in 1996. METHODS: A cohort of 150 patients with cerebral AVMs underwent embolization between 1987 and 1993. Fifty-seven patients had supplemental stereotactic irradiation, and 13 had subsequent surgery. The follow-up was carried out clinically and radiologically. RESULTS: The mean follow-up time was 6.2 years. Only four patients were lost to follow-up. If at least 90% of the AVM had been obliterated, the clinical course was stable and there were no new manifestations from the AVM. No recanalization occurred in any AVM that had been totally obliterated with glue. For patients in whom it was not possible to totally obliterate the AVM either with glue alone or glue supplemented with stereotactic irradiation or surgery, the long-term outcome was discouraging. CONCLUSION: Obliteration of an AVM with acrylic glue seems to offer stability. If the AVM is totally obliterated, the patient had a stable clinical course. Patients with large AVMs with minor occlusion after embolization may have a worse clinical outcome than expected.

Adolescent↗

A molecule basis for the HLA association in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease that primarily affects the joints. The etiology of RA is unknown, and the pathogenesis is only poorly defined. One of the few clues to the understanding of the pathogenesis of RA is the observation that the disease is associated with genes in the major histocompatibility complex (MHC). Recent structural and functional studies provide molecular insight into the role of MHC genes in RA susceptibility. This insight provides an important basis for further understanding of the disease mechanism, generation of humanized animal models for RA, and the development of new immunomodulatory drugs with a minimum of unwanted side effects.

Animals↗

The effects of feeding and housing on the behaviour of the laboratory rabbit.

The effects of housing, feeding time and diet composition on the behaviour of the laboratory rabbit were examined. The animals were caged individually in single or double metal cages with perforated metal floors, metal walls, and bars in the front, or kept as a group in floor pens. The light/dark cycle was 12/12 h with light from 04:00 to 16:00 h and 30 min twilight. One experiment compared feeding equal energy levels of a high energy diet (10.1 MJ/kg) and with a low energy diet (7.0 MJ/kg) at 08:00 h. The second experiment compared feeding the high energy diet at 08:00 h and at 14:00 h. In both studies the behaviour of the rabbits was recorded between 08:00 and 14:00 h and between 16:00 and 22:00 h. Feeding the animals at 14:00 h reduced abnormal behaviour during the dark period compared to feeding at 08:00 h, whereas no difference in behaviour could be detected between feeding a high-energy and a low-energy diet at 08:00 h. Animals in floor pens generally showed less abnormal behaviour than caged animals. The results indicate that the welfare for caged rabbits can be improved by feeding the animals in the afternoon rather than in the morning.

Animal Feed↗

[Thrombolysis changes the care of stroke].

Thrombolysis using tissue plasminogen activator (tPA) is not the leading strategy in the development of pharmacological treatments for acute ischaemic stroke. The prospect of tPA becoming routine treatment in ischaemic stroke raises several issues the magnitude of the treatment load, the requisite neurological and neuroradiological diagnostic qualifications, identification of local reperfusion effects in the brain, and the pre-hospital and hospital management of acute stroke patients. The results of large randomised trials of intravenous tPA treatment are reviewed in the article, and the current state of our knowledge about interventional thrombolysis is reported. Recruitment for the second European intravenous tPA trail, ECASS II, has recently been completed, and the study findings will be available during the latter half of 1988. In the USA, tPA is already recommended treatment for acute ischaemic stroke within three hours after the onset of symptoms. In Europe, the formulation of guidelines awaits the results of ECASS II.

Cerebral Infarction↗

Novel salivary gland specific binding elements located in the PSP proximal enhancer core.

The murine parotid secretory protein (PSP) gene is expressed selectively at high levels in parotid and sublingual salivary glands. Previously, the transcriptional activity of a PSP mini-gene, called Lama, was shown to be dependent on a 1.5 kb region located 3 kb upstream of the transcription start site. Here, functional studies in transgenic mice demonstrate that this proximal regulatory region has properties of a parotid and sublingual gland specific enhancer. Protein-binding experiments identify multiple sequence-specific binding complexes spanning the entire 1.5 kb enhancer region. Several sequence elements bound specifically by parotid and/or sublingual gland nuclear extracts, including consensus binding elements for previously described transcription factors as well as novel binding elements are located in the proximal enhancer region. A deletion analysis of the enhancer region in transgenic mice identified a core sequence of 700 bp. This region contains five elements bound specifically by nuclear proteins isolated from the PSP-expressing parotid and sublingual glands. Two of these elements, denoted parotid gland element I (PGE I) and sublingual gland element I (SLE I), are novel salivary gland specific binding elements, bound uniquely by parotid and sublingual gland nuclear extracts, respectively.

Amino Acid Sequence↗

[Two cases of Still disease in adults].

We describe two cases of adult onset Stills disease. Both patients presented with typical features of adult Stills disease: high spiking fever, arthralgia, oligo- and polyarticular arthritis, transient rash, sore throat, lymphadenopathy and leukocytosis. Both patients failed to improve when treated with nonsteroidal antiinflammatory drugs (NSAIDs) and azathioprine, but responded adequately when sulfasalazine was added to the medication. It is suggested that sulfasalazine is a useful adjunct if the clinical response to NSAIDs is not sufficient.

Adult↗

Vasodilator response to exogenous adrenocorticotropic hormone in fetal adrenal cortex precedes increased steroidogenesis in sheep at 105-112 days gestation.

OBJECTIVE: To examine whether the increase in adrenal cortical blood flow induced by adrenocorticotropic hormone (ACTH) is linked to steroidogenesis, or if these effects can be separated. STUDY DESIGN: Adrenal cortical responses to ACTH were measured in ovine fetuses at 105-112 days gestation, when the adrenal is hyporesponsive. Fetuses were given an intravenous infusion of ACTH(1-24) or of vehicle. We measured regional adrenal blood flows by the microsphere technique and plasma ACTH and cortisol levels by radioimmunoassay. RESULTS: After 3 and 24 h of ACTH infusion, plasma cortisol concentrations had risen from 2.8+/-0.8 ng/ml to 8.4+/-0.3 and 78.0+/-15.8 ng/ml (means+/-S.E.M.). Adrenal cortical blood flow increased from 108+/-25 ml/min/100 g to 319+/-33 and 518+/-51 ml/min/100 g. Plasma cortisol levels and adrenal blood flow did not change in control fetuses. CONCLUSION: Since there was a rapid blood flow response to ACTH, despite the expected delay in the rise of plasma cortisol, we suggest that vascular responses to ACTH are not tightly linked to adrenal metabolic activity in the ovine fetus at 0.7 gestation.

Adrenal Cortex↗

Regulation of porcine biliary secretion by secretin.

The importance of physiological plasma levels of secretin in biliary bicarbonate secretion is not known. However, in anaesthetized pigs the substantial hepatic output of bicarbonate into the duodenum in response to low doses of secretin exceeds pancreatic bicarbonate output. The aim was therefore to study the relationship between duodenal acidification, secretin and hepatic biliary bicarbonate output in the conscious pig. Göttingen minipigs (n = 22) were cholecystectomized and the common bile duct catheterized. The biliary bicarbonate secretion in response to intraduodenal HCl, secretin or pentagastrin given intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and pentagastrin given intravenously augmented hepatic bicarbonate output and plasma secretin concentrations significantly. The secretin response to acidification was sufficient to explain the subsequent increase in biliary bicarbonate secretion. Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma increased postprandially. Exclusion of bile salts from the duodenum abolished postprandial increase in bile volume and increased release of CCK in fasting and fed pigs whereas secretin release was diminished. The results demonstrate that hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore may have a physiological role in duodenal neutralization.

Animals↗

Transarterial embolization of the uterine arteries: patient reactions and effects on uterine vasculature.

BACKGROUND: Therapeutic embolization of the uterine arteries has been successfully used to manage profuse gynecological hemorrhage. In the present study we aimed to investigate whether embolization of uterine arteries may serve as a safe and effective alternative treatment in cases of menorrhagia in fertile and perimenopausal women. As a first step, we have evaluated the methodology, patient reactions and effects on the uterine vasculature. METHODS: The distal part of the uterine artery was embolized with polyvinyl alcohol particles via catheterization of the right femoral artery. Total abdominal hysterectomy was performed the next day. RESULTS: Bilateral embolization in two patients resulted in considerable pain that required morphine analgesic medication and epidural analgesia. One patient was embolized unilaterally and experienced only slight discomfort with no need for analgesic medication at all, indicating that unilateral embolization is a well-tolerated method. After embolization, angiography showed stagnant flow in embolized vessels without contrast filling of distal branches. Angiography of the specimen showed normal vascular architecture in non-treated vessels. In treated vessels the main arterial trunks were patent but all smaller branches were occluded. Histology showed that most of the particles lodged in small arteries and that arterioles never showed injected material. CONCLUSION: The study indicates that the procedure involves an efficient occlusion of uterine vessels and that unilateral embolization of uterine arteries is well tolerated.

Adult↗

Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice.

BACKGROUND & AIMS: Duodenal bicarbonate secretion is an important factor in epithelial protection. The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in acid-induced bicarbonate secretion is unknown. The aim of this study was to determine whether CFTR mediates acid-stimulated duodenal epithelial bicarbonate secretion. METHODS: Basal and stimulated bicarbonate secretion was examined in the cystic fibrosis murine model cftrm1UNC, which displays defective CFTR in various organs including chloride transport abnormalities in epithelia. After anesthesia, the proximal duodenum was cannulated and perfused with isotonic saline, and [HCO3-] was determined. RESULTS: Basal bicarbonate secretion was diminished in cystic fibrosis vs. normal mice, 2.8 +/- 0.7 vs. 4.7 +/- 1.7 mumol.cm-1.h-1, respectively (P < 0.001). Luminal acidification failed to elicit a bicarbonate secretory response in cystic fibrosis compared with normal littermates (peak response, 2.3 +/- 0.2 vs. 9.9 +/- 1.5 mumol.cm-1.h-1, respectively; P < 0.01). Prostaglandin E2- and vasoactive intestinal peptide-stimulated bicarbonate secretion were also significantly impaired in cystic fibrosis. Defective bicarbonate secretion in cystic fibrosis genotypes was due to decreased net fluid secretion and [HCO3-]. CONCLUSIONS: Basal and stimulated proximal duodenal bicarbonate secretion may involve a CFTR-mediated transport pathway. It is likely that CFTR, directly or indirectly, has a major functional role in mediating bicarbonate transport in the proximal duodenum.

Animals↗

Hidden compartments in AVMs--a new concept.

PURPOSE: The concept of hidden compartments in cerebral arteriovenous malformations (AVMs), which is hereby launched, offers a new explanation for the neurosurgical and neuroradiological controversies concerning patients with AVMs. MATERIAL AND METHODS: Three patients who were considered completely cured of their AVMs, subsequently developed new areas of malformed vessels as revealed by later angiograms. RESULTS: These 3 cases support our hidden compartment hypothesis and are reported on here, illustrated with relevant angiograms. The clinical implications of the hidden compartment concept refer to phenomena such as AVM growth, AVM recurrence after surgical excision, irradiation or embolization as well as per- or postoperative hemorrhage and swelling. CONCLUSION: The incidence of hidden compartments in the AVM population is unknown but further studies, particularly in the realm of superselective embolization, could reveal their presence.

Adult↗

Anaesthesia and basic experimental surgery of minipigs. A practical exercise.

Minipigs tolerate anaesthesia very well. The only disadvantages are the difficulties in performing venous puncture and endotracheal intubation. To overcome these the animals should be well sedated prior to induction by intravenous injection, and deeply anaesthetized prior to the introduction of the endotracheal tube. Anaesthetic regimen and several basic experimental surgical techniques will be practised.

Adjuvants, Anesthesia↗