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Biomedical subjects

T Cowen

Publications and source records attributed to T Cowen.

88 records · Page 5Linked to original sources
PubMed1982

Functional and non-functional nerve-smooth muscle transmission in the renal arteries of the newborn and adult rabbit and guinea-pig.

Isolated renal arteries from newborn and adult guinea-pigs failed to respond to electrical stimulation of the intramural nerves, using parameters identical to those which elicit large neurogenic contractions in renal arteries from newborn and adult rabbits. The threshold stimulation frequency was lower and responses were greater in adult compared with neonatal rabbits. Comparisons of noradrenaline EC50 values showed that guinea-pig renal arteries are significantly less sensitive to noradrenaline that rabbit vessels. Quantitative fluorescence histochemistry of the perivascular adrenergic nerves in renal arteries revealed that the density of innervation gradually declines in the guinea-pig but substantially increases in the rabbit during postnatal development. The lack of neurogenic response of the guinea-pig renal artery, despite the existence of a varicose, adrenergic nerve plexus, is discussed.

Aging↗
PubMed1982

The effect of surgical procedures on blood vessel innervation. A fluorescence histochemical study of degeneration and regrowth of perivascular adrenergic nerves.

Four commonly used surgical procedures have been shown to cause extensive damage to the sympathetic nerves which supply and accompany blood vessels. One of these procedures, which produced a localised crush lesion, was shown by fluorescence microscopy to cause extensive degeneration of adrenergic nerves in two densely innervated blood vessels of different character in the guinea pig: the elastic carotid artery and the muscular mesenteric artery. The extent of denervation was different in the two vessels: in the carotid artery the crush lesion destroyed all the nerves near the lesion, but left undamaged sparse nerves which reached the vessel wall along its length with the vasa vasorum; in the mesenteric artery all the nerves ran with the artery, consequently denervation could be extensive (at least 2 cm distal to the crush), although the largest nerve bundles were resistant to crush injury. The regrowth rate of nerves in the mesenteric artery was faster than that found in the carotid artery. A plexus of normal density and appearance was re-established between 3 and 8 weeks, and hyperinnervation was observed in some specimens. In the carotid artery this process was usually not complete by 8 weeks and involved both the regrowth of injured fibres and collateral sprouting distal to the lesion of the sympathetic nerve fibres that had not been injured. Axon sprouting was observed in both vessels near the lesion site. Explanations for these differences are discussed.

Adrenergic Fibers↗
PubMed1980

Quantitative analysis of the density and pattern of adrenergic innervation of blood vessels. A new method.

Automated quantitative image analysis (QIAF) was used to measure and compare the adrenergic nerve plexuses of 4 blood vessels from the guinea pig, demonstrated by glyoxylic acid fluorescence (GAF). The results showed considerable quantitative variation of plexus density, size of bundles, and numbers of varicosities. A range of alternative procedural and anatomical sources of variability were investigated and assessed. The carotid artery was found to have a dense plexus with more nerves than that of the mesenteric artery; the mesenteric vein and abdominal aorta had sparse plexuses. The carotid artery plexus, despite the density of its nerves, possessed only half the number of varicosities of the mesenteric artery plexus. This sparse varicosity population was shown to have a similar density to the varicosities demonstrated by QIAF in the scattered nerves of the mesenteric vein and abdominal aorta. QIAF confirmed visual estimates of adrenergic plexus density, and was able to demonstrate less obvious differences of nerve density and size, and varicosity populations, between the different plexuses studied. The method is applicable to stretch preparations and transverse sections of many adrenergically innervated tissues.

Adrenergic Fibers↗
PubMed1979

Mast cell population density, blood vessel density and histamine content in normal human skin.

Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites. Mast cell and blood vessel counts were made in 1--1.5 micrometer thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorimetric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject.

Adult↗
PubMed1979

Distribution of mast cells in human dermis: development of a mapping technique.

A new method was developed to define the distribution of mast cells in normal human skin. The population density was determined in a number of zones of different depth in the dermis. Two regions of the same limb were studied systematically. Both were shown to have mast cell populations of similar size and distribution, with a maximum density immediately below the dermo-epidermal junction, gradually falling to a minimum density in the deeper layers of the dermis. Small secondary peaks were less clearly defined at the base of the dermis. These findings should provide baseline data for comparisons with mast cell population size and distribution in different areas of normal skin, or in similar areas in clinical disorders or experimental conditions.

Adult↗
PubMed1978

Half-and-half cells in lichen planus. A possible clue to the origin and early formation of colloid bodies.

In the course of a study of wound healing in four patients with lichen planus, we found transformed keratinocytes with a hitherto undescribed ultrastructure in both wounded and undisturbed papules. We have called these epidermal cells half-and-half cells because they showed changes on the one hand of increased synthetic activity and, on the other hand, of fibrillar transformation closely resembling that seen in fully developed colloid bodies. We suggest that these half-and-half cells may provide a useful clue to the early changes occurring in colloid body formation.

Colloids↗
PubMedDate not supplied

A microscopical assay using a densitometric application of image analysis to quantify neurotransmitter dynamics.

We have attempted to demonstrate the technical requirements and performance of a microscopical assay using a densitometric application of image analysis to measure immunohistochemical stain intensity. Not surprisingly, the techniques required were more demanding than those used for the quantification of field and object parameters in the nervous system. The following areas of methodology have been shown to be important: (1) use of buffers free of metallic ions for tissue processing, (2) selection and titration of first and second layer antibodies, (3) reduction and control of fading of fluorescence, (4) selection of microscopical and imaging equipment to give accurate, sensitive and uniform representations of low-light biological images, and (5) use of appropriate image analysis algorithms in order to generate binary images that match the spatial and intensity distributions of immunostaining. Incorporation of these techniques into our assay system gave sensitive measurements of the time-scale of uptake of 5-hydroxy-tryptamine (5-HT) into sympathetic nerve terminals. The microscopical assay appears to have advantages over alternative approaches used for studies of neurotransmitter dynamics, particularly in small, heterogeneous tissue samples.

Algorithms↗
PubMedDate not supplied

Neurodegeneration in sweat glands and skin of aged rats.

In order to compare age-associated neurodegenerative changes in peripheral nerves of laboratory mammals and humans, we have investigated the density and pattern of different nerve populations innervating sweat glands of ageing rats and compared our results with a previous study of the innervation of human sweat glands. We have also studied age-changes in subepidermal afferent nerves that may be involved in reflex activation of sweat glands. Total nerve density, measured by immunohistochemical staining for the general neuronal marker, protein gene product (PGP9.5) and image analysis, showed a significant decline around secretory coils of sweat glands of old compared to young rats. Marked reductions of acetylcholinesterase (AChE) histochemical staining and of vasoactive intestinal polypeptide (VIP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity were observed in nerves around sweat glands. In the sub-epidermis, PGP- and CGRP-like immunoreactive nerves were significantly reduced in old rats. The age-related changes in sweat gland innervation of old rats were comparable to those reported in elderly human subjects suggesting that these tissues may provide a suitable model for experimental studies of neuronal ageing.

Acetylcholinesterase↗
PubMedDate not supplied

Image analysis of catecholamine fluorescence.

Image analysis methods are being developed for measuring the density and distribution of perivascular noradrenergic nerves and their varicosities, demonstrated by fluorescence histochemistry. Image analysis is recommended in comparison with other methods for the quantitation of fluorescence, because image resolution is greater and larger areas of tissues can be scanned and measured more rapidly. Applications of image analysis have provided new and valuable information regarding sympathetic nerves: for example, we have shown rapid growth of perivascular nerves during perinatal development in the rabbit, and loss of nerves in different vessels in postnatal life and in old age; regional variations of nerve density and varicosity numbers in the central ear artery of the rabbit have also been demonstrated.

Adrenergic Fibers↗
PubMedDate not supplied

Responsiveness of sympathetic and sensory iridial nerves to NGF treatment in young and aged rats.

Altered neuronal responses to trophic factors may play a role in neuronal maintenance in adulthood and may also be involved in neuronal atrophy in old age. We have investigated this issue in the rat iris, studying responsiveness of sympathetic and sensory iridial nerves to a range of NGF concentrations in mature and aged rats. We show here that growth responses of sensory nerves to NGF, as measured by quantitative immunohistochemistry and image analysis, were unchanged in old rats. In contrast, there was a small but significant reduction in responsiveness of aged sympathetic neurons. The shapes of the dose-response curves for sensory and sympathetic neurons were different, with a larger response over a narrower range of concentrations in sensory neurons. Lower levels of p75 immunoreactivity were observed in iridial nerves from old compared to young rats. NGF treatment had no effect on receptor staining in young rats but restored 'young' levels of p75 staining in old rats. Our results do not support the hypothesis of a primary role for NGF in maintenance or atrophy of nerves in ageing.

Adrenergic Fibers↗
PubMedDate not supplied

NGF expression in the aged rat pineal gland does not correlate with loss of sympathetic axonal branches and varicosities.

The factors that determine the ability of some, but not all neurons, to sustain their axonal projections during aging remain largely unknown. Because sympathetic neurons remain responsive to nerve growth factor (NGF) in old age, it has been proposed that the selective decrease observed in the sympathetic innervation to some targets in aged rats may be the result of a deficit in target-derived NGF. In this study we utilized two different techniques to demonstrate decreased target innervation by sympathetic fibers in the aged rat pineal gland, which is an appropriate and relevant model for examining mechanisms of neuron-target interactions in aging. Tyrosine hydroxylase immunoreactive profiles were quantified in pineal glands of young and aged male Sprague-Dawley rats. The density of tyrosine hydroxylase-immunoreactive fibers was 30% lower in aged pineals, although the remaining fibers contained 20% more tyrosine hydroxylase-immunoreactivity. Othograde tracing of the pineal sympathetic innervation using biotinylated dextran revealed that average axon length, varicosity numbers, branch point numbers, and numbers of terminations were all decreased by approximately 50% in aged tissues, indicating possible functional deficits. These findings suggest that whole branches, along with their associated varicosities were lost in old age. A sensitive quantitative ribonuclease protection assay and a two-site ELISA assay were used to examine whether reduced NGF availability might correlate with sympathetic nerve atrophy. No significant differences were detected in either NGF mRNA or NGF protein levels when comparing young and aged pineal glands, suggesting that atrophy in aged sympathetic neurons is not causally related to reduced availability of NGF at the target. Our results indicate that mechanisms other than NGF expression need to be explored in order to explain the age-related axonal regression observed in this target.

Aging↗