PubMed Health⌕ Search

Biomedical subjects

C J Dalsgaard

Publications and source records attributed to C J Dalsgaard.

At least 37 records · Page 2Linked to original sources
PubMed1990

Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.

Calcitonin↗
PubMed1990

The neuropeptide substance P stimulates production of interleukin 1 in human blood monocytes: activated cells are preferentially influenced by the neuropeptide.

Substance P (SP) has recently been reported to induce interleukin 1 (IL-1) production by human monocytes. This was confirmed in our experiments with human monocytes cultivated in the presence of SP or SP together with lipopolysaccharide (LPS). In addition, a wide variability of cell response to the neuropeptide was noticed. Three out of twelve cell cultures were directly stimulated by SP to release IL-1, while four additional cultures needed prestimulation with suboptimal doses of LPS, and no effect was seen in the five remaining experiments. The data may suggest that preferentially activated monocytes respond to SP. The production of IL-1 by SP-stimulated monocytes is of great interest considering the broad spectrum of activity of IL-1 and the increasing evidence of sensory neuron involvement in acute and chronic inflammatory responses.

Cells, Cultured↗
PubMed1990

The effect of calcitonin gene-related peptide (CGRP) on human forearm blood flow.

The effect of intravenous and intra-arterially administered calcitonin gene-related peptide (CGRP) on the human forearm blood flow and cutaneous blood flow were investigated by means of venous occlusion plethysmography and laser-Doppler flowmetry, respectively. Infusion of CGRP (11-216 pmol min-1) into the brachial artery resulted in a dose-dependent increase in forearm blood flow and cutaneous blood flow which persisted for up to 90 min after the infusion was stopped. Repeated infusions resulted in an identical response. Systemic intravenous infusion of CGRP (104-520 pmol min-1) resulted in a dose-dependent flush in the face, neck, upper trunck and upper arms, and an increase in the forearm blood flow. The cutaneous blood flow was dramatically increased on the forehead, whereas on the hand only a slight increase was noted. By intravenous infusions a significant drop in blood pressure and increase in heart rate were seen at 520 pmol min-1. Thus, it is possible to give CGRP in doses that increase the blood flow in muscle and skin without resulting in a fall in systemic arterial blood pressure and tachycardia, suggesting that CGRP may be used as a tool for the treatment of various conditions in man with compromised blood flow.

Adolescent↗
PubMed1989

[The Magendie law on spinal ventral and dorsal roots is still of current value].

The law of Magendie--that the spinal ventral roots are motor and the dorsal roots sensory--was recently questioned. It turned out that ventral roots contain a substantial proportion of unmyelinated sensory axons. This and other observations promoted theories that ventral roots might constitute an additional pain pathway. However, it has now become clear that sensory ventral root axons do not enter the CNS via the ventral roots. Instead, they either leave the ventral root at the PNS/CNS interface and either continue to the pia mater, or loop and return to the periphery. The law of Magendie seems still to be valid.

Animals↗
PubMed1989

Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies.

Using antibodies to the neuronal cytoplasmic protein, protein gene product 9.5 (PGP 9.5) the cutaneous innervation in man was investigated. The distribution of PGP 9.5 immunoreactive nerve fibers was compared with the distribution of nerve fibers immunoreactive to neuron specific enolase, neurofilament proteins, calcitonin gene related peptide, vasoactive intestinal polypeptide and neuropeptide Y. PGP 9.5 immunoreactive nerve fibers were found in the epidermis, dermis, in Meissner's corpuscles, innervating Merkel cells, around blood vessels, sweat glands and hair follicles. Merkel cells were also PGP 9.5 positive. The labelled nerve fibers included sensory and autonomic fibers, visualizing the whole innervation of the human skin. The number of positive fibers and the intensity of the fluorescence was greater with PGP 9.5 antibodies than with any of the other markers included. Thus, PGP 9.5 antibodies may serve as a tool for investigations of cutaneous innervation, reinnervation and nerve regeneration in different clinical conditions.

Antibodies↗
PubMed1989

Calcitonin gene-related peptide-like immunoreactivity in nerve fibers in the human skin. Relation to fibers containing substance P-, somatostatin- and vasocactive intestinalpolypeptide-like immunoreactivity.

Calcitonin gene-related peptide-like immunoreactivity was demonstrated in in sensory nerve fibers in the epidermis and dermis as free nerve endings and around blood vessels and hair follicles of the human finger pad and arm skin. The vast majority of the calcitonin gene-related immunoreactive fibers was shown to display also substance P-like immunoreactivity and a few fibers in the dermis were somatostatin positive. No fibers displaying both substance P and somatostatin-like immunoreactivity were found but a few substance P immunoreactive fibers in the dermis-epidermis region were found to contain also vasointestinal polypeptide-like immunoreactivity. In the sweat glands, abundant calcitonin gene-related peptide positive, but substance P negative, fibers were observed with a similar distribution pattern as the vasoactive intestinal polypeptide immunoreactive fibers and these fibers were suggested to be of sympathetic origin.

Adult↗
PubMed1989

Vasoactive intestinal polypeptide stimulates cell proliferation and adenylate cyclase activity of cultured human keratinocytes.

An increasing body of evidence has suggested trophic effects of peripheral nerves. In this study, the growth stimulatory properties of the sensory neuropeptides vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin generelated peptide (CGRP), and somatostatin (SOM) on cultured human keratinocytes were investigated. It was shown that VIP, in the presence of lethally treated 3T3 fibroblast feeder cells and epidermal growth factor (EGF), stimulated proliferation of keratinocytes in a dose-dependent manner, whereas SP, CGRP, and SOM were ineffective. VIP stimulated adenylate cyclase activity in membranes obtained from cultured keratinocytes in a dose-dependent manner, indicating an involvement of cAMP as second messenger in this reaction. Furthermore, 125I-labeled VIP was shown to bind to cultured keratinocytes and this binding could be displaced by addition of unlabeled VIP, suggesting the presence of specific receptors. It is therefore possible that VIP, released from sensory nerve endings in the skin, may act as a local mitogenic factor for human keratinocytes by stimulating adenylate cyclase activity via specific VIP receptors.

Adenylyl Cyclases↗
PubMed1989

Stimulation of human B lymphocyte differentiation by the neuropeptides substance P and neurokinin A.

Substance P (SP) at a concentration of 10(-7) M significantly increased the number of IgG-producing cells induced by the polyclonal activator Staphylococcus aureus protein A (SpA) in 11 out of 22 cultures of enriched human blood B lymphocytes, in nine cultures SP did not significantly affect the SpA response and in three cultures IgG secretion was decreased in the presence of SP. Stimulation by SP was observed in cultures at days 6 and/or 8. In 3 out of 4 cell cultures depleted of monocytes SP did not affect the cell response to SpA stimulation. SP antagonists inhibited the enhancing effect of SP on B-cell antibody secretion induced by SpA. SP alone did not stimulate B lymphocytes. Neurokinin A (NKA) had similar effects as SP and enhanced the IgG secretion induced by SpA in 5 out of 9 experiments, in two experiments was inactive, and in one decreased the IgG secretion. The effect of SP and NKA on B lymphocytes suggest that the neuropeptides interact with the regulation of the immune response.

Amino Acid Sequence↗
PubMed1989

Direct mounting of cultured epidermal grafts. A way to enhance the transplantation area.

Cultured epidermal grafts were prepared in a new way, not allowing the epidermal sheets to shrink before mounting. Using this procedure, the graft area was increased by about 100%. Furthermore, this procedure is also quicker than the conventional technique. The directly mounted grafts take just as well as conventionally prepared grafts and their macroscopical and histological appearances are similar.

Burns↗
PubMed1988

Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A.

The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP- and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting on a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calcium/calmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growth-stimulatory effect on cultured SMC.

Animals↗
PubMed1988

Growth-inhibitory properties of vasoactive intestinal polypeptide.

It has recently been demonstrated that several neuropeptides can affect cell growth. The mammalian tachykinins substance P and neurokinin A, which are present in peripheral sensory neurons, stimulate growth of cultured connective tissue cells. Substance P-like immunoreactivity has been demonstrated in neuroblastoma cell lines. Neuroblastoma cells also produce other neuropeptides, among them vasoactive intestinal polypeptide (VIP). We report here that VIP is a potent inhibitor of serum-induced DNA synthesis in cultured smooth muscle cells (SMC), whereas no growth-inhibition was seen in SMC exposed to neurokinin A, calcitonin-gene related peptide, neuropeptide Y, somatostatin, or cholecystokinin. The growth-inhibitory effect of VIP was closely related to its ability to induce formation of cyclic AMP. Our results raise the possibility that peptides released by neurons, endocrine cells, as well as by transformed cells, may not only function as mitogens but also as inhibitory modulators of cell growth.

Animals↗
PubMed1988

Calcitonin gene-related peptide (CGRP) and transcutaneous electrical nerve stimulation (TENS) increase cutaneous blood flow in a musculocutaneous flap in the rat.

The effect of blood flow on transcutaneous electrical nerve stimulation (TENS) and injection of calcitonin gene-related peptide (CGRP) was studied in a musculocutaneous flap of the rat, using laser Doppler flowmetry. The circulatory border was estimated before and after treatment. It was shown that repeated treatments with TENS gradually increased the blood flow, moving the circulatory border distally more than 100% after three treatments. Injection of NaCl into the dorsal central vein of the flap resulted in no increase in blood flow, whereas CGRP 10(-10) M increased the blood flow, so that the circulatory border moved distally 70% and 60%, respectively.

Animals↗
PubMed1988

Transcutaneous electrical nerve stimulation (TENS) increases survival of ischaemic musculocutaneous flaps.

The effect of transcutaneous electrical nerve stimulation (TENS) on the survival of a dorsal musculocutaneous flap was studied in the rat. Postoperative TENS treatment significantly increased the flap survival area in groups of rats receiving different modes of TENS. The flap survival area was up to 95% in the TENS-treated groups compared with 33-45% in the control groups. Repeated (3 days) high intensity (20 mA), high-frequency (80 Hz) TENS applied segmentally at the base of the flap was shown to be the most effective treatment in increasing the flap survival. Preoperative TENS did not increase flap survival area compared with untreated controls. It is concluded that postoperative TENS treatment markedly increases the experimental flap survival area and may be of clinical value for treatment of local ischaemia.

Animals↗
PubMed1988

The anatomy and histology of the cranially based dorsal musculocutaneous flap of the rat.

The cranially based dorsal musculocutaneous flap of the rat is commonly used to study the effects of various pharmacological compounds of flap survival. In the present study the anatomy and histology of the flap are described. It is shown that the central vessel of the flap is a vein and that this vein can be used for injection of substances into the capillary network of the flap. The sensory innervation of the flap is studied using indirect immunohistochemical technique.

Animals↗
PubMed1987

Calcitonin gene-related peptide increases survival of a musculocutaneous critical flap in the rat.

Calcitonin gene-related peptide (CGRP) was shown to increase the survival area of ischaemic tissue from 45% in control animals to about 90% in treated animals. This effect was demonstrated in a musculocutaneous flap model in the rat. The concentrations used were 2 X 10(5) times lower than those known to cause an increase in skin blood flow under normal conditions. Treatment with one single dose up to 36 h postoperatively was found to increase the flap survival area. It is suggested that the mechanism/s by which CGRP increases survival of ischaemic tissue may be different from vasodilation or that the sensitivity is altered during ischaemic conditions and that CGRP may be a powerful tool to reduce ischemia in various clinical conditions.

Animals↗
PubMed1987

Sensory reinnervation and sensibility after superficial skin wounds in human patients.

In humans the innervation and sensibility after a superficial skin wound, the donor site for medium split thickness skin grafts, was investigated using sensibility tests and indirect immunohistochemistry with antibodies to neurofilament. After one to two weeks extensive sprouting of neurofilament immunoreactive nerve fibers was observed. Four weeks after the operation the wound had healed and the sensibility and distribution of neurofilament-positive nerve fibers resembled that of normal unoperated skin. These findings are discussed in view of recent studies indicating a role of sensory neurons in inflammation and wound healing.

Fluorescent Antibody Technique↗
PubMed1987

Regrowth of lesioned dorsal root nerve fibers into the spinal cord of neonatal rats.

In postnatal rat pups the L4 and L5 dorsal roots were lesioned. After 3-6 months the spinal cord of the rats was subjected to tracing studies of regenerated dorsal root axons with transganglionically transported horseradish peroxidase (HRP) and immunohistochemistry with antibodies to calcitonin gene-related peptide (CGRP). In rats operated at birth (0-2 days old) HRP-filled profiles as well as CGRP staining were found in the outer lamina of the spinal cord dorsal horn. Signs of dorsal root nerve fiber regrowth in the spinal cord could not be found in rats which had been operated at the end of the first postnatal week or later.

Animals↗