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Biomedical subjects

R Crowe

Publications and source records attributed to R Crowe.

At least 37 records · Page 2Linked to original sources

Changes in the VIPergic, cholinergic and adrenergic innervation of human penile tissue in diabetic and non-diabetic impotent males.

Penile tissue (consisting of corpus cavernosum and tunica albuginea) was obtained from 19 patients undergoing surgery for the implantation of penile prostheses. The tissue was examined for vasoactive intestinal polypeptide-like immunoreactivity in nerves, acetylcholinesterase-positive staining in nerves and noradrenaline content. Impotence was due to a variety of causes; 11 patients were classified as a 'non-neuropathic' group on the basis of their clinical history which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. Vasoactive intestinal polypeptide-like immunoreactive and acetylcholinesterase-positive nerves were present and the pattern and distribution were similar in each patient in this group. The noradrenaline content of the tunica albuginea was significantly lower than the corpus cavernosum (p less than 0.02), although there was a linear relationship between the noradrenaline contents of the two regions (r = 0.95, p less than 0.01). By comparison, a complete absence of vasoactive intestinal polypeptide-like immunoreactivity in nerves was observed in a patient with a cauda equina lesion. Five out of six diabetic patients studied revealed a marked reduction in vasoactive intestinal polypeptide-like immunoreactivity in nerves associated with the cavernous smooth muscle, while acetylcholinesterase-positive staining was reduced in three out of five diabetic patients studied. The noradrenaline content of the corpus cavernosum from diabetic patients was significantly lower (p less than 0.02) than that of the 'non-neuropathic' group. The noradrenaline content of the tunica albuginea, however, was similar in both groups. The results provide evidence that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and thus may contribute to the development of impotence in diabetic patients.

Acetylcholinesterase

Reduction of nerves containing vasoactive intestinal polypeptide and serotonin, but not neuropeptide Y and catecholamine, in cerebral blood vessels of the 8-week streptozotocin-induced diabetic rat.

The perivascular autonomic nerves of the major blood vessels on the ventral surface of the brain were studied in the streptozotocin-induced diabetic rat, an animal model for juvenile onset of diabetes. Histochemical and immunohistochemical techniques were used to determine the pattern and density of perivascular nerves containing catecholamine, 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). A significant reduction in the density and/or fluorescence intensity of 5-HT-immunoreactive nerves was observed in the circle of Willis and its main arterial branches namely: basilar, superior cerebellar, internal carotid, posterior communicating, middle cerebral and anterior cerebral arteries, while a significant reduction of VIP-immunoreactive nerves was observed in the internal carotid, middle cerebral and anterior cerebral arteries, but not in the basilar, superior cerebellar and posterior communicating arteries 8 weeks after the onset of diabetes. However, no changes were observed in the density of NPY- and catecholamine-containing nerves. The results are discussed in relation to autonomic neuropathy of the cerebral blood vessels in diabetes.

Animals

Intramural neurons of the guinea-pig urinary bladder: histochemical localization of putative neurotransmitters in cultures and newborn animals.

Histochemical methods have been used to study the distribution of putative neurotransmitters in the urinary bladder of newborn guinea-pigs and in cultures of intramural ganglia. Following the nicotinamide adenine dinucleotide (NADH)-diaphorase reaction which specifically labels nerve cell bodies, up to 66 ganglia were observed in stretch preparations of the newborn urinary bladder. Each ganglion contained 2-50 nerve cell bodies. Vasoactive intestinal polypeptide was localized in a few nerve cell bodies of intramural ganglia both in in situ and culture preparations. In the in situ preparations it was widely distributed in nerve fibres to the muscle, being most dense at the base of the bladder, and in some mucosal epithelial cells. Somatostatin was contained in numerous neuronal cell bodies in the detrusor muscle both in situ and in culture. Extensively distributed varicose fibres were found in culture and in the muscle, submucous and mucosal layers in situ. Substance P immunofluorescence was demonstrated in a few neuronal cell bodies in ganglia both in situ and in vitro, particularly in those of the mucosa at the base of the bladder. In the in situ preparations varicose nerve fibres containing substance P were seen in the muscle coats with greatest density in the bladder base. Met-enkephalin-immunoreactive nerve cell bodies were not seen either in situ or in culture. Nerve fibres in in situ preparations were found largely enveloping neuronal cell bodies within the ganglia. Neither serotonin-immunoreactive nor catecholamine-containing neuronal cell bodies were seen in the in situ bladder preparation. However, some nerve cell bodies in culture showed positive staining, possibly as a result of selective uptake of serotonin and catecholamine known to be contained in foetal calf serum in the culture medium or possibly as the result of increased synthetic activity in certain neurones in the culture situation. In whole-mount stretch preparations, no serotonin-immunoreactive nerve fibres were seen, but catecholamine-containing small intensely fluorescent cells and nerve fibres were observed. Acetylcholinesterase-positive nerve cell bodies and nerve fibres were observed both in in situ and culture preparations of the bladder. Quinacrine-positive nerve cell bodies (as an indicator of purinergic neurones) were found in numerous intramural neurones examined. in situ; however, under the culture conditions used, non-selective staining of all cell types occurred.

Acetylcholinesterase

Vasoactive intestinal polypeptide-, somatostatin- and substance P-immunoreactive nerves in the smooth and striated muscle of the intrinsic external urethral sphincter of patients with spinal cord injury.

Specimens obtained by transurethral sphincterectomy from patients with spinal cord injury and carcinoma of the bladder were studied immunohistochemically. In the smooth muscle region of the sphincter, vasoactive intestinal polypeptide-, substance P- and somatostatin-immunoreactive fluorescent, varicose nerve fibers were seen. In the striated muscle region, VIP-immunoreactive nerves were found around striated muscle fibers and bundles, while somatostatin- and substance P-immunoreactive nerves were confined to nerve bundles. In both the smooth and striated muscle regions of the intrinsic external urethral sphincter, VIP-immunoreactive nerves were seen around blood vessels. No differences were observed in the immunohistochemical localization of these peptide-containing nerves in the two groups of patients. No immunofluorescence for [Met]enkephalin, bombesin, neurotensin or serotonin was found in any nerves in the urethra.

Adolescent

Adrenergic and cholinergic innervation of the smooth and striated muscle components of the urethra from patients with spinal cord injury.

The adrenergic and cholinergic innervation of the smooth and striated muscle components of the urethra from spinal cord injury patients with detrusor sphincter dyssynergia were investigated neurochemically and histochemically. Catecholamine fluorescence histochemistry provided no evidence for the presence of adrenergic nerves associated with the skeletal muscle. The noradrenaline content of this region probably reflects the endogenous levels in adrenergic nerves associated with the blood vessels supplying the skeletal muscle. Choline acetyltransferase activity in the skeletal muscle was significantly lower in patients with cervical lesions than in those with thoracic lesions (p less than 0.01). The noradrenaline content of the smooth muscle was significantly lower in cervical lesions than in thoracic lesions in both the mid (p less than 0.02) and the distal (p less than 0.001) regions of the urethra. The proximal region revealed similar noradrenaline levels in both groups of spinal cord injury patients. The results are discussed in relation to the role of the autonomic nervous system in the control of voiding and to the presence of increased sympathetic outflow in patients with spinal cord lesions at higher levels.

Adolescent

Genetic approach to heterogeneity in psychoses: relationship of a family history of mania or depression to course in bipolar illness.

A specific family history or genetic background may be used to distinguish valid subgroups in patients who show similar symptoms. Also, a familial background may predict differences in other characteristics, i.e. course of illness, response to treatment or biological characteristics. Two hundred and fifty-one bipolar patients were separated according to their family history, 20 with a family history of mania with or without depression, 86 with a family history of depression only, and 145 with a family history of neither mania nor depression. The group that had a family history of mania was notable in that it showed more episodes of affective illness and was more likely to be readmitted to hospital. This difference in course suggests a familial association with multiple episodes and mania. In other respects than in course of illness, the groups separated by family history were similar.

Adult

Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P.

The distribution of vasoactive intestinal polypeptide (VIP) and substance P-like immunoreactivities was studied by immunohistochemistry in the myenteric plexus and circular muscle layer of the ileum and proximal colon of rats 8 wk after induction of diabetes with streptozotocin. A consistent increase was observed in fluorescence intensity of VIP-like immunoreactivity in the nerve fibers, and intensely stained cell bodies were significantly more frequent in the myenteric plexus of the ileum (p less than 0.001) from diabetic animals. Some varicosities of VIP-like immunoreactive fibers in the myenteric plexus appeared to be enlarged. Vasoactive intestinal polypeptide-like immunoreactivity was increased and VIP-like immunoreactive nerves appeared thicker in the circular muscle layer of both diabetic ileum and proximal colon. The VIP levels were measured biochemically in tissue consisting of the smooth muscle layers and myenteric plexus. A significant increase in the VIP content per centimeter of intestine was found in both the ileum (p less than and proximal colon (p less than 0.01) from diabetic rats. In contrast, no apparent change in substance P innervation was observed immunohistochemically in the myenteric plexus and circular muscle layer of either diabetic ileum or proximal colon when compared with controls. The results are discussed in relation to the symptoms of autonomic neuropathy of the gut in diabetes.

Animals

Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks.

Patients who met DSM-III criteria for agoraphobia with panic attacks underwent dexamethasone suppression tests (DSTs) before, during, and after treatment with alprazolam or placebo. Similarly, outpatients with major depression were given multiple DSTs as they participated in a study of desmethylimipramine efficacy. The likelihood of an abnormal escape from dexamethasone was similar in the two diagnostic groups; nonsuppression was somewhat more likely among patients with primary depression, but comparisons with agoraphobic groups remained statistically insignificant. These results apparently did not reflect misclassification of primary depression patients as agoraphobics since a history of major depression was not related to the likelihood of nonsuppression within that group. Moreover, change in DST results during treatment reflected clinical change among agoraphobics. After a review of relevant followup and family studies, we conclude that panic disorder and primary depression are separate illnesses and that hypothalamic-pituitary-adrenal axis hyperactivity is an epiphenomenon of both.

Adult

Quinacrine-positive neurones in some regions of the guinea-pig brain.

Quinacrine, which has been shown to bind to neurones in the peripheral nervous system, was localized in Purkinje cells in the cerebellum and pyramidal cells in the cerebral cortex and hippocampus of the guinea-pig brain. In the basal ganglia, different populations of fluorescent nerve cell bodies as well as a dense quinacrine-positive nerve plexus were demonstrated. The possibility that quinacrine-positive neurones contain high levels of ATP is discussed.

Adenosine Triphosphate

Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process.

The effects of adenine nucleotides and nucleosides on the contractile response to perivascular nerve stimulation were compared in the isolated portal vein of rabbit, rat and guinea-pig. 2-Chloroadenosine was more potent than adenosine and ATP, which were equipotent in producing inhibition of neurogenic contractions in the rabbit and rat via prejunctional P1-purinoceptors. In contrast, neurogenic contractions of the guinea-pig portal vein were not inhibited by adenosine and were potentiated by 2-chloroadenosine and, to a lesser extent, by ATP. Fluorescence histochemical localization of quinacrine, which binds to high levels of ATP, revealed a dense perivascular nerve plexus in the portal vein of rabbit and rat but not of guinea-pig. After chemical sympathectomy, quinacrine-positive nerves persisted in the rabbit (supporting other evidence for the presence of purinergic nerves) but not in the rat (supporting other evidence for ATP as a cotransmitter in adrenergic nerves). It is concluded that a prejunctional purinergic modulatory mechanism operates in adrenergic neurotransmission in the portal vein of rabbit and rat but not guinea-pig, and it is suggested that this indicates a physiological mechanism.

2-Chloroadenosine

Myenteric plexus in streptozotocin-treated rats. Neurochemical and histochemical evidence for diabetic neuropathy in the gut.

Adrenergic, cholinergic, and serotoninergic nerves were studied in the myenteric plexus of ileum and colon from streptozotocin-treated rats, an animal model of juvenile-onset diabetes. In view of clinical reports implicating diabetic autonomic neuropathy as the cause of gastrointestinal dysfunction in diabetes mellitus, neurochemical and histochemical techniques were used to study changes in the innervation of the gut. In the myenteric plexus of the ileum from diabetic animals, adrenergic nerves displayed signs of degeneration and the brightness of fluorescence in serotoninlike immunoreactive nerves was lower. Cholinergic nerves, however, did not display any signs of reduction in the ileum, and both choline acetyltransferase and acetylcholinesterase activities per centimeter were increased. In contrast, in the proximal colon 8 wk after induction of diabetes, neurochemical assays revealed significant increases in noradrenaline and serotonin levels as well as choline acetyltransferase activity, although no obvious changes in the pattern of innervation could be detected histochemically. The results indicate that changes do occur in the innervation of the gut of the streptozotocin-diabetic model shortly after the induction of diabetes, although they differ significantly in the ileum and colon; these may be of relevance to the types of gastrointestinal dysfunction displayed in human diabetes.

Animals

Vasoactive intestinal polypeptide-like immunoreactive nerves in diabetic penis. A comparison between streptozotocin-treated rats and man.

Vasoactive intestinal polypeptide (VIP) has been demonstrated by immunofluorescence histochemistry in nerves in human and rat penile tissue. A reduction in VIP-like immunoreactivity in nerves was revealed in tissue from streptozotocin-diabetic rats and a human diabetic with impotence. These results suggest that an impairment in the VIP-ergic innervation in penile tissue may be an important factor in the development of impotence in diabetes. They also support the view that the streptozotocin-treated rat is a useful experimental model for diabetic autonomic neuropathy.

Animals

Small intensely fluorescent (SIF) cells and sympathetic nerves in the adult rabbit portal vein and during perinatal development.

The ontogenesis of small intensely fluorescent (SIF) cells and the adrenergic nerve plexus is described in stretch preparations of the rabbit portal vein. On the 25 to 26th days of gestation there was a predominance of SIF cells (8 to 30 microns in diameter), but a few nerve fibres in bundles were also present. Each portal vein preparation contained 6 to 9 groups of cells. The distribution and number of SIF cells and nerve bundles remained constant until the 31st day of gestation at which stage the number of SIF cells had decreased, while the density of the nerve plexus had increased approximately 4-fold. The adult portal vein exhibited a dense adrenergic plexus, but SIF cells were absent from nine out of ten preparations.

Amines

Fluorescent histochemical localisation of quinacrine-positive neurones in the guinea-pig and rabbit atrium.

Quinacrine-fluorescent nerve fibres and nerve cell bodies are described in the right and left atria of the guinea-pig and rabbit. The nerve cells (20 to 35 micrometers in diameter) are found predominantly in the right atrium in both species. The nerve fibres are varicose and innervate both the muscle and many blood vessels. The quinacrine fluorescent neural structures are unaffected by chemical sympathectomy with 6-hydroxydopamine. The distribution of quinacrine-positive nerve fibres and cell bodies are compared to the distribution of adrenergic and acetylcholinesterase-positive nerves in the atrium of both species. Quinacrine fluorescence appears to be selective for non-adrenergic, non-cholinergic nerves and the possibility that it is binding to high contents of ATP discussed.

Acetylcholinesterase

Regional differences in the density of perivascular nerves and varicosities, noradrenaline content and responses to nerve stimulation in the rabbit ear artery.

Quantitative image analysis of fluorescent nerve following histochemical localization of monoamines in stretch preparations of the rabbit ear artery (REA) reveals marked differences in the density of innervation between the proximal and distal regions. The innervation in the proximal region is about twice as dense as that in the distal region and there are approximately 10,500 and 6,500 varicosities per mm2 vessel area in these two regions, respectively. These varicosities have approximately the same mean diameter throughout the length of the vessel. The noradrenaline contents per gram wet weight of tissue in the proximal and distal regions are 1.93 and 0.94 microgram, respectively. It is estimated that noradrenaline contents per mm2 nerve plexus area are 0.30 and 0.08 ng and that the nerve endings consist 2.8 x 10(-14) and 1.2 x 10(-14) g per varicosity in the proximal and distal REA, respectively. Sympathetic nerve stimulation in vitro with frequencies up to 8 Hz elicits larger and faster contractions in the proximal REA and the threshold frequency is less than in the distal region. This study also indicates that care should be taken to use the same region when using the REA for pharmacological and physiological studies.

Adrenergic Fibers

Adrenergic innervation in autonomic failure.

In 10 patients with chronic autonomic failure, the sympathetic perivascular nerve plexuses from quadriceps muscle biopsies were studied by catecholamine fluorescence and electronmicroscopy. There was almost complete absence of catecholamine fluorescence and fewer than normal numbers of small granular (noradrenergic) vesicles in all nerves studied. The most marked depletion of noradrenergic vesicles was seen in two of the patients with pure autonomic failure, but more studies are needed for a full quantitative comparison of pure autonomic failure and autonomic failure with multiple system atrophy (Shy-Drager syndrome).

Aged

Non-adrenergic, non-cholinergic (purinergic?) inhibitory innervation of the rabbit rectococcygeus muscle.

A powerful non-adrenergic, non-cholinergic inhibitory innervation of the rabbit rectococcygeus was unmasked by atropine in preparations in which tone had been raised either by carbachol or prostaglandin E2-Flourescent histochemical localization of quinacrine (which binds ATP) revealed ganglia and associated nerve bundles which were neither adrenergic nor cholinergic both on the surface and within the rectococcygeus muscle. Treatment of the rabbit with 6-hydroxydopamine abolished catecholamine fluorescence without affecting quinacrine-stained neural elements. Release of ATP from the rectococcygeus increased 2-4 times above background levels during stimulation of intramural inhibitory nerves. In preparations in which the tone was raised, ATP caused an inhibitory response comparable to that produced by non-adrenergic, non-cholinergic nerve stimulation. Indomethacin reduced the increase in tone and spontaneous activity following washout of ATP in low tone preparations, and potentiated the relaxations produced by ATP in high tone preparations. These results suggest that the rabbit rectococcygeus, as well as receiving a cholinergic excitatory innervation and an adrenergic inhibitory innervation, is also innervated by purinergic inhibitory nerves.

Acetylcholinesterase