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Biomedical subjects

M A Blank

Publications and source records attributed to M A Blank.

At least 55 records · Page 3Linked to original sources

Decrease of vasoactive intestinal polypeptide (VIP) in the penises from impotent men.

Vasoactive intestinal polypeptide (VIP)-containing nerves were depleted in the penises of 28 impotent men. The extent of the decrease in VIP-containing nerves broadly reflected the severity of erectile dysfunction. VIP-immunoreactive nerves were most depleted in those men with complete erectile impotence, irrespective of the aetiology of the dysfunction, whereas in those men in whom some erectile function persisted, loss of VIP-immunoreactive nerves was more variable and less complete. Conventional histology demonstrated only mild changes (muscle atrophy and occasional thickening of blood vessel walls). VIP levels, measured by radioimmunoassay of tissue extracts, were depleted by more than 80% in penises from impotent diabetics (43.4 +/- 9.9 pmol/g wet weight [mean +/- SEM]), when compared with 6 controls (189.9 +/- 45.9 pmol/g). These findings not only support the contention that VIP may be the principal neurotransmitter involved in penile erection, but also suggest that depletion of this powerful vasodilatory peptide may play a key role in the development of penile impotence.

Adult↗

Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat.

In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.

Anal Canal↗

Regional distribution of bombesin and seven other regulatory peptides in the human brain.

In order to compare within the same brains the quantitative distributions of a range of neuropeptides, bombesin, N- and C-terminal glucagon, cholecystokinin, neurotensin, somatostatin, substance P and vasoactive intestinal polypeptide immunoreactivities were determined by radioimmunoassay in 24 regions of 5 normal adult human brains. Each peptide showed a different distribution pattern. Of the peptides not previously mapped in detail in the human brain, bombesin-like immunoreactivity was present in all regions with the highest concentrations in particular areas of the hypothalamus, septal nuclei, nucleus accumbens, globus pallidus, amygdala, periaqueductal grey and substantia nigra. C- and N-terminal glucagon immunoreactivities were detected only in the ventromedial hypothalamus. The concentrations of the remaining 5 peptide immunoreactivities, and their molecular forms, were in good general agreement with those reported individually by others in both human brains and those of experimental animals. The quantitative mapping of the regulatory peptides in the human brain provides an essential base for further comparative study in diseased postmortem brains.

Adult↗

Peptide-immunoreactive nerves in the mammalian female genital tract.

Vasoactive intestinal polypeptide, substance P, neuropeptide Y and peptide histidine isoleucine immunoreactivities have been demonstrated in the female genitalia of rat, cat, mouse and guinea-pig using immunocytochemistry and radioimmunoassay. They were localized to nerves. Each type of immunoreactive nerve showed a distinct pattern of distribution, though all were associated to some degree with blood vessels and smooth muscle. Vasoactive intestinal polypeptide-immunoreactive and neuropeptide Y-immunoreactive nerves were the most abundant. Higher concentrations of peptides were detected in the female genitalia of the mouse than those of the other species studied. Vasoactive intestinal polypeptide-immunoreactive nerves were particularly concentrated in the cervix (89.1 +/- 17.2 pmol/g, mean +/- S.E.M.) and the uterus (57.4 +/- 14.8 pmol/g) of the mouse, while neuropeptide Y immunoreactivity was more abundant in the Fallopian tube of the mouse (31.6 +/- 11.8 pmol/g) and the vagina of the rat (38.6 +/- 4.8 pmol/g) than in other regions. Separate populations of ganglion cells in the paracervical ganglia were found to contain vasoactive intestinal polypeptide and neuropeptide Y immunoreactivities. Peptide histidine isoleucine-immunoreactive and vasoactive intestinal polypeptide-immunoreactive nerves were similarly distributed, but the former were much less frequent. Substance P-immunoreactive nerves were seen mainly beneath the epithelium of the vagina and were, in general, more numerous in the guinea-pig than in other species. The significance of these peptide-immunoreactive nerves in the female genital organ remains to be determined.

Animals↗

Effects of VIIth (facial) nerve degeneration on vasoactive intestinal polypeptide and substance P levels in ocular and orbital tissues of the rabbit.

Levels of vasoactive intestinal polypeptide (VIP)- and substance P (SP)-like immunoreactivity were measured in ocular and orbital tissues of albino rabbits. Substantial amounts of VIP were detected in the choroid (22.6 +/- 3.6 pmol g-1), and in the lacrimal (13.6 +/- 4.4 pmol g-1) and Harderian glands (20.2 +/- 4.9 pmol g-1). Somewhat less was found in the anterior uvea (3.6 +/- 1.1 pmol g-1), retina (5.4 +/- 1.3 pmol g-1) and optic nerve head (4.1 +/- 1.1 pmol g-1). Other tissues, including conjunctiva and extraocular muscle showed very little VIP-like immunoreactivity. Seven days after diathermic damage to the region of the pterygopalatine ganglion VIP was virtually eliminated from all these tissues. SP levels were also reduced, notably in the anterior uvea, probably due to concurrent destruction of sensory fibres. Electron microscopy revealed extensive degeneration of unmyelinated axons in the short ciliary nerves and in the choroid. No changes in ocular VIP levels were detected after sympathetic denervation, although a significant rise in SP was observed in the anterior uvea. The decrease in retinal VIP, believed to be confined to the amacrine cells, is considered to be a result of post-operative lid closure, rather than of VIIth nerve degeneration. Nevertheless, with this exception, VIP in ocular and orbital tissues of the rabbit appears to be contained exclusively within parasympathetic fibres of facial nerve origin.

Animals↗

Peptide-containing nerves in human urinary bladder.

Nerves containing immunoreactive vasoactive intestinal polypeptide (VIP), substance P and two newly discovered peptides, neuropeptide tyrosine (NPY) and PHI (peptide having N-terminal histidine and C-terminal isoleucine), have been found in the human urinary bladder by immunocytochemistry and radioimmunoassay. Somatostatin immunoreactivity was detected by radioimmunoassay. The VIP-immunoreactive nerves were widely distributed in all regions, but were particularly dense beneath the epithelium and in the muscle layer. Scattered intramural ganglia were found to be reactive to VIP antiserum. Higher concentrations of extractable VIP were detected in the trigone than in the dome. VIP- and PHI-immunoreactive nerves were similarly distributed, the latter being less numerous. NPY-immunoreactive nerves were seen mainly in the muscle layer, particularly in the trigonal area. The distribution patterns of VIP- and NPY-immunoreactive nerves resembled those of the previously reported cholinergic and adrenergic nerves, respectively. Many blood vessels were found to be innervated by both types of immunoreactive nerves. Scattered substance P-immunoreactive fibers were occasionally seen, being present in the submucosa and around the detrusor muscles. The significance of these nerves remains to be elucidated.

Fluorescent Antibody Technique↗

Effect of peripheral nerve section and nerve crush on spinal cord neuropeptides in the rat; increased VIP and PHI in the dorsal horn.

An increase in vasoactive intestinal polypeptide (VIP) immunoreactivity in the dorsal lumbar hemisegment L4 of the spinal cord was observed by both radioimmunoassay and immunocytochemistry following sciatic nerve section or crush. Compared to the contralateral control hemisegment there was 125% and 35% more VIP immunoreactivity in the L4 hemisegment ipsilateral to the lesion 14 days following nerve section and crush respectively. The contralateral control hemisegment contained levels similar to L4 hemisegments from unoperated control rats. This increase appeared by immunocytochemistry to be confined to the substantia gelatinosa, in the region of termination of the majority of unmyelinated sciatic nerve afferents. Similar increases to VIP were observed for the peptide PHI, which is closely related to VIP. However, spinal cord substance P and somatostatin immunoreactivities were reduced following nerve section and unchanged following nerve crush whilst neurotensin and bombesin immunoreactivities were not affected following either lesion. Previous studies have shown that peripheral nerve injury produces a number of electrophysiological and biochemical changes in the dorsal horn of the spinal cord, including depletion of substance P in primary afferent neurones. The location of the cell bodies of fibres showing increased immunoreactivity remains to be established. Further studies are required to elucidate how these peptide changes are related to the adaptive processes which occur centrally following peripheral nerve injury.

Animals↗

Effects of tactile and electrical stimuli upon release of vasoactive intestinal polypeptide in the mammalian penis.

Plasma levels of vasoactive intestinal polypeptide (VIP) in the corpora cavernosa penis and dorsal penile veins greatly exceeded those measured in the limb or caudal veins during anaesthesia in various mammals (Bennett's wallaby, Barbary sheep, cheetah, puma, sooty mangabey, pigtail macaque and chimpanzee). Tactile stimulation of the penis immediately before or during collection of blood samples resulted in an increase. In the wallaby, VIP levels (mean +/- S.E.M.) in blood samples collected from the flaccid penis in the absence of tactile stimulation were very low (0.6 +/- 0.5 pmol/l). A 36-fold increase in VIP occurred after manual extension of the flaccid penis (24.8 +/- 3.2 pmol/l) or during manually stimulated erections (25.1 +/- 1.7 pmol/l). Electrical stimulation of erection produced no significant increase in VIP levels (2.3 +/- 0.9 pmol/l) unless accompanied by tactile stimulation (17.5 +/- 1.4 pmol/l). These studies provide the first demonstration that sensory feedback from the penis plays an important role in regulating vasoactive intestinal polypeptidergic activity. Since VIP is a potent vasodilator its release due to tactile stimuli during copulation may play a role in the maintenance of penile erection.

Acinonyx↗

Distribution of bombesin, somatostatin, substance-P and vasoactive intestinal polypeptide in feline and porcine skin.

The content and distribution of several regulatory peptides in the skin of cats and pigs, freshly obtained at surgery, have been investigated. Immunoreactive bombesin was evenly distributed at low concentrations in both species, being below the detection limit in the body and nose of the cat, and showing a peak value of 1.6 +/- 0.7 pmol/g in the tip of the pig's ear. Similar concentrations of somatostatin-immunoreactivity (-IR) were found but greater regional variation occurred in the pig with a low in the mid back of 0.4 +/- 0.1 and the highest value in the snout of 3.1 +/- 0.8. Substance-P-IR in the pig showed a marked variation in concentration, apparently parallelling skin sensitivity, with a low in the back of 0.4 +/- 0.7 and higher values around the anus (8.1 +/- 1.6), legs (6.8 +/- 1.8) and snout (13.5 +/- 3.6) whilst in the cat values ranged from 0.3 +/- 0.06 in the body to 5.0 +/- 0.9 in the front footpads. In contrast, vasoactive intestinal polypeptide (VIP)-IR showed greater variability in the cat, being below the assay's detection in the body and highest in the front and rear footpads (17 +/- 7 and 29 +/- 6 respectively), but in the pig most regions exhibited low concentrations with the exception of the snout which peaked at 12.0 +/- 5.0. Immunocytochemical localisation showed the peptides to be present in nerve fibres. Substance-P-IR was particularly localised in the snout of the pig just below the epithelium while VIP-IR was more concentrated in deeper layers, often associated with sweat glands and blood vessels.

Animals↗

Vasoactive intestinal polypeptide in the normal and unstable bladder.

The possible involvement in idiopathic detrusor instability of a newly discovered type of autonomic nerve containing vasoactive intestinal polypeptide (VIP) has been studied. Immunocytochemistry and radioimmunoassay, using specific antibodies against VIP, were carried out on 20 biopsy specimens from the bladders of patients with detrusor instability and 20 specimens from control patients. The concentration of VIP in the unstable bladders was found to be markedly reduced from 36.52 +/- 4.8 pmol/g (mean +/- SEM) to 7.62 +/- 1.84 pmol/g (P less than 0.01). The number of VIP immunoreactive nerves was greatly decreased in all of the layers but particularly in the muscle layer of the unstable bladder in comparison with the controls. These findings may provide important information about the mechanism of this disorder.

Adult↗

Bombesin and vasoactive intestinal polypeptide in the developing lung: marked changes in acute respiratory distress syndrome.

The quantitative distribution of bombesin- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities was determined by RIA and immunocytochemistry in regions of trachea, bronchus, and whole lung at various stages of human fetal development and in neonates, children, and adults. In addition, these two immunoreactivities were studied in infants that had died of the acute respiratory distress syndrome. The concentration of bombesin-like immunoreactivity in the whole respiratory tract steadily increased during gestation, reaching a plateau at birth. In the lung, the bombesin concentration remained almost unchanged during childhood, but decreased to one tenth in the adult. In neonates with the acute respiratory distress syndrome, there was a significantly lower bombesin content in all regions of the respiratory tract compared to either normal full-term infants or 24- to 28-week-old fetuses. Immunocytochemistry localized bombesin immunoreactivity within mucosal neuroendocrine cells present in the airway epithelium throughout the respiratory tract and particularly in the intrapulmonary airways. The number of cells increased throughout gestation, reflecting the pattern found by RIA, and were greatly decreased in acute respiratory distress syndrome patients. VIP concentrations were much lower than those of bombesin and did not change significantly with gestational age. In contrast to bombesin, VIP was mainly concentrated in the upper respiratory tract. In infants with the respiratory distress syndrome, the VIP content was not different from normal. These results are compatible with the possibility that bombesin-like peptides may have a role in the normal development of the human lung.

Acute Disease↗

Mapping, quantitative distribution and origin of substance p- and VIP-containing nerves in the uvea of guinea pig eye.

VIP- and substance P-like immunoreactivities were found in considerable concentrations (VIP: 17.3 +/- 4.8 pmol/g, mean +/- SEM; substance P:11.1 +/- 1.8 pmol/g) in the uveal portion of the guinea pig eye. Immunocytochemistry localised these two regulatory peptides to nerve fibres found principally in a plexus in the iris (substance P) and in an extensive network surrounding the blood vessels of the choroid (VIP). A remarkable anatomical demarcation of the two types of peptide-containing nerves was established by the staining of substance P-containing nerves, which stops at the level of the ciliary body. This uveal area is known to be involved in the ocular responses to nociceptive stimuli. At the ultrastructural level, immunoreactivity for both peptides was localised to distinct subpopulations of p-type nerves, distinguishable by the size of their large dense-cored vesicles. Those immunoreactive for VIP were significantly larger (p less than 0.0005) than those immunoreactive for substance P (95 +/- 7 nm and 82 +/- 9 nm respectively; mean +/- SD). Interruption of the trigeminal pathway produced a remarkable decrease of substance P immunoreactivity in the anterior portion of the uvea (9.1 +/- 1.5 pmol/g, mean +/- SEM, control; 5.3 +/- 1.3 pmol/g, denervated), but not of VIP immunoreactivity in the choroid. Following colchicine treatment, VIP-immunoreactive neuronal cell bodies were localised in the choroid. The separate anatomical localisations and distributions of the two uveal peptides appear to be related to their different origins and functional roles in the response of the eye to noxious stimuli.

Acetylcholinesterase↗