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Biomedical subjects

A Tomlinson

Publications and source records attributed to A Tomlinson.

At least 19 recordsLinked to original sources

Colocalization of nitric oxide synthase and NADPH-diaphorase in rat adrenal gland.

The distribution and colocalization of nitric oxide synthase (NOS) and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was studied in the neuronal elements of the adrenal gland of the rat. Ganglion cells and many nerve fibres in the gland showed both NOS-immunoreactivity and NADPH-diaphorase staining. The adrenal cortical cells showed NADPH-diaphorase staining but were not immunoreactive for NOS. Positive labelling for both NADPH-diaphorase and NOS was found in bundles and in single fibres with varicosities, preferentially located around the noradrenaline (NA)-storing cells. Adrenaline (A)-storing cells and ganglion cells in the medulla, along with the cortical cells and blood vessels in the zona glomerulosa, received relatively fewer positive fibres.

Adrenal Glands

Sex and age as factors influencing the vascular reactivity in Watanabe heritable hyperlipidaemic (WHHL) rabbits: a pharmacological and morphological study of the hepatic artery.

The responses to vasoactive agents and the fine structure of hepatic arterial ring segments from male and female Watanabe heritable hyperlipidaemic (WHHL) rabbits (4, 6, and 12 months) were compared with those of age- and sex-matched New Zealand White (NZW) rabbits. In males only, KCl-induced contractions were reduced in WHHL rabbits compared with NZW rabbits. In male and female WHHL rabbits, maximum noradrenaline-induced contractions and sensitivity to noradrenaline were greater than those of male and female NZW rabbits. In female WHHL and NZW rabbits only, maximum noradrenaline-induced contractions and the EC50 values were reduced at 6 months. Endothelium-dependent relaxation: In females only, maximum relaxant responses and the sensitivity of WHHL rabbits to acetylcholine increased with age, while there was a decrease in NZW rabbits. Similarly, relaxation to substance P increased with age in WHHL rabbits and decreased in NZW rabbits, but this occurred in both male and female animals. In addition, substance P-induced relaxation in female WHHL rabbits was greater than in male WHHL rabbits. Endothelium-independent relaxation: In both male and female WHHL rabbits, calcitonin gene-related peptide-induced and vasoactive intestinal polypeptide-induced relaxation did not change with age. However, there was an age-related decrease in the response of NZW rabbits to these peptides. Electron microscopic evaluation of hepatic arteries from WHHL rabbits showed occasional ruptures in the internal elastic lamina at 4 months. At 6 months, widespread intimal thickening associated with smooth muscle cell migration was apparent, but this became less obvious at 12 months. No obvious differences in structure between male and female hepatic arteries were observed. It is suggested that a "compensatory vasodilatation" develops in atherosclerosis, initially at the level of the endothelium, and then with the progression of the disease extends to changes in the smooth muscle. This may occur in order to offset the thickening of the arterial wall. Sexual dimorphism in vascular reactivity has been demonstrated.

Acetylcholine

Effect of ibuprofen on contrast sensitivity.

Therapeutic doses of ibuprofen (2-4'-isobutylphenyl-propionic acid) have been shown to have many deleterious effects on the nervous system. However, visual disturbances have been reported in fewer than 1% of the patients taking recommended doses of ibuprofen. The most commonly reported visual disturbances include: amblyopia, scotomata, and changes in color vision. To our knowledge, no studies have examined the effects of ibuprofen therapy on the contrast sensitivity function of an affected individual. Contrast sensitivity, Snellen visual acuity, color vision (D-15 test), and Goldmann visual fields were measured on 1 affected subject during and after ibuprofen therapy (800 mg/day for 2 days). Snellen visual acuity, color vision, and Goldmann visual fields were unaffected by the treatment. However, the contrast sensitivity was significantly depressed at low spatial frequencies while the subject was taking ibuprofen. The results, in concert with previous reports concerning the visual effects of ibuprofen, suggest that this drug can result in transient multifocal lesions of the visual pathway.

Color Perception

Effects of long-term laxative treatment on neuropeptides in rat mesenteric vessels and caecum.

In order to investigate the toxic effects of long-term treatment with anthraquinone laxatives, rats were fed either chocolate alone, or chocolate adulterated with senna or danthron (1,8-dihydroxyanthraquinone) for 5 months. Mesenteric blood vessels and the outer muscle layers of the caecum, together with the myenteric plexus, were examined using ultrastructural, histochemical, immunohistochemical and immunoassay techniques. There was no ultrastructural evidence of degeneration in either the mesenteric vessels or the caecum. In the mesenteric vessels, levels of neuropeptide Y were significantly reduced in the danthron-fed rats, but levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were unaffected by all treatments. In the caecum, VIP-, SP- and CGRP-immunoreactivity and catecholamine-fluorescence were unchanged by the laxative treatments.

Animals

Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study.

BACKGROUND: To date no attempts have been made to determine the role of the endothelial cell derived product, endothelin-1 (ET-1) in granulation tissue development. This study investigates the cellular immunolocalization of ET-1 and its pharmacologic effect on myofibroblast-mediated rat croton oil-induced granulation tissue contraction. EXPERIMENTAL DESIGN: The distribution, cellular localization and temporal production of ET-1 in the tissues was determined by immunohistochemistry at days 7, 14, 21, and 28. The contractile response of the granulation tissue to ET-1 was tested over the same time period, and it effects modified by use of calcium antagonists. The pharmacologic profile was correlated to the ultrastructural development of contractile fibroblast-like cells within the tissue. RESULTS: Endothelin-1 caused reversible concentration-dependent contraction of the granulation tissue. The 21-day granulation tissue was the most responsive, with a maximum increase in tension of 458.9 +/- 41.1 mg; this response could be inhibited by use of calcium antagonists. Of the calcium antagonists tested, verapamil (1 x 10(-4) M) was the most potent inhibitor, giving a 43% reduction in maximum amplitude of the response. It is suggested that entry of extracellular calcium via the L-type potential operated calcium channel, is involved in ET-1 induced responses in contractile fibroblast-like cells or myofibroblasts. Ultrastructural analysis showed a correlation between the pharmacologic sensitivity of the tissue and the development of contractile fibroblast-like cells. The number of cells expressing the phenotypic characteristics of a myofibroblast increased with time, and were first observed at day 7. Immunohistochemistry revealed the presence of increasing numbers of ET-1 labeled cells throughout the time course of study. The ET-1 positive cells were localized to the capillaries. Immunolabeling of serial sections with the rodent endothelial cell specific lectin, Bandeiraea simplicifolia isolectin B4 and factor VIII-related antigen, confirmed the specific localization of ET-1 to endothelial cells. CONCLUSIONS: We present evidence that ET-1 may be an endogenous modulator of myofibroblast-mediated granulation tissue contraction and that the use of calcium antagonists could afford a possible therapeutic control in the treatment of fibrocontractive diseases.

Animals

Localization of arginine-vasopressin in endothelial cells of rat pulmonary artery.

The localization of arginine-vasopressin in the endothelial cells of rat pulmonary artery was investigated by immunocytochemistry at the light and electron microscopic levels. The immunogold silver staining method was used for light microscopy of sheets of endothelium, removed from the artery, and the pre-embedding peroxidase-antiperoxidase technique was used for electron microscopy of cross sections of the artery. With both of the methods used, numerous vasopressin-positive endothelial cells were observed. None of the subendothelial elements showed labelling for vasopressin. The results are discussed in terms of the involvement of the endothelium in local control of the pulmonary circulation.

Animals

An immunohistochemical study of endothelial cell heterogeneity in the rat: observations in "en face" Häutchen preparations.

"En face" sheets of endothelium, in which cellular spatial relationships were maintained, were prepared from proximal pulmonary and femoral arteries and aortae of the Wistar rat, in order to visualise patterns of heterogeneity in populations of endothelial cells. These preparations, termed Häutchen, were immunolabelled with antibodies to angiotensin II, endothelin and Factor-VIII-related antigen, and visualised by an avidin/biotin peroxidase complex. Clusters of cells, which accounted for approximately 30% of the total endothelial cell population, and which were positively immunostained for angiotensin II, were found perpendicular to the longitudinal axis of the aorta and femoral artery. Cells in the pulmonary artery were immunonegative for angiotensin II. The majority of cells in all three vessels were immunopositive for endothelin; groups of intensely stained cells were present in both the femoral artery and aorta, but not in the pulmonary artery. Immunoreactivity to Factor-VIII-related antigen was heterogeneous, with intensely stained amorphous patches of endothelial cells present in the femoral artery and aorta. Häutchen preparations present an opportunity for the investigation of endothelial cell heterogeneity, both within and between vessels; this may provide a basis for the interpretation of the heterogeneity of endothelium-dependent responses in vessels of differing origin.

Angiotensin II

Tear production and evaporation in the normal eye.

The volume of tears in the eye depends on the rate of production and the rate of elimination by drainage and evaporation. A mechanism for the regulation of tear production mediated through changes in tear tonicity has been suggested. High evaporation of tears with a patent drainage system has been thought to be related to reduced tear volume, increased tonicity and an eventual stimulus to production. In this study no significant correlation was found between tear evaporation, measured by a modified evaporimeter system, and tear production, as measured by the turnover rate with a scanning fluorophotometer. This result suggests that regulation of tear production through the mechanism of tonicity change may not be the only, or principal, mechanism in the normal eye.

Adult

Effect of preservatives in artificial tear solutions on tear film evaporation.

It has been suggested that certain preservatives in artificial tears may affect the stability of the tear film lipid layer. In the present study, tear film evaporation rate (TER) was measured with a modified Servomed Evaporimeter to determine whether preservatives affected tear stability. Two solution combinations were compared in a cross-over study of eight non-contact lens wearers. These combinations consisted of identical solutions, one preserved with either benzalkonium chloride (0.004%) or chlorobutanol (0.5%), the other non-preserved. Grouped data analysis showed no significant difference in TER with either solution combination. Individuals showed differences, but these were not related to the preservative. It is suggested that these concentrations of chlorbutanol and benzalkonium chloride did not affect the stability of the tear film lipid layer as indicated by an altered TER.

Adult

Effect of artificial tear solutions and saline on tear film evaporation.

The effect on tear evaporation of two artificial tear solutions is compared with that of an equal volume of saline instilled into the eye. Changes in tear evaporation rates (TER) were measured with a modified Servomed Evaporimeter in a cross-over study of nine subjects. Initial increases in TER were found with all three solutions; however, slight evidence exists for a faster return to baseline with artificial tear solutions.

Analysis of Variance

Reprogramming cell fate in the developing Drosophila retina: transformation of R7 cells by ectopic expression of rough.

In the developing eye of Drosophila, the homeo box gene rough is required in the developing photoreceptor cells R2 and R5 for the correct development of the neighboring R3 and R4 cells. We have expressed rough ectopically in a limited subset of developing ommatidial cells using the sevenless enhancer. Expression of rough in the presumptive R7 cell transforms this cell into an R1-6 type photoreceptor. This transformation is cell autonomous in contrast to the apparent nonautonomy of the rough mutant phenotype and depends on the presence of the sevenless gene. We propose that in wild type, rough functions autonomously in the specification of R2/5 photoreceptor cell identity but by itself cannot initiate neural development.

Animals

Monovision.

Monovision has been a controversial contact lens correction modality for over 30 years. This paper addresses the major issues and concerns and considers them in the light of patient safety, visual efficiency and practitioner liability.

Adaptation, Ocular

The molecular basis of pattern formation in the developing compound eye of Drosophila.

Throughout metazoan development cells select pathways of specialization that lead to the differentiation of specific cell types. Differential gene activation converts initially homogeneous populations of cells into spatial arrangements of diverse cell types. As discussed in other articles in this issue, the signals specifying divergent pathways can be encoded in a cell's lineage, its environment, or a combination of both. This article reviews recent analyses of the developing Drosophila compound eye which have focussed upon the mechanisms by which cells assess environmental information in order to determine their fate. More specifically, it examines the molecular mechanisms used by cells to communicate signals which instruct the developmental pathways of other cells.

Animals

The innervation of the adrenal gland. IV. Innervation of the rat adrenal medulla from birth to old age. A descriptive and quantitative morphometric and biochemical study of the innervation of chromaffin cells and adrenal medullary neurons in Wistar rats.

The innervation of the adrenal medulla has been investigated in normal Wistar rats from birth to old age and ultrastructural findings compared with biochemical markers of the cholinergic innervation of the adrenal gland and catecholamine storage. Morphological evidence of the immaturity of the innervation during the first postnatal week is provided and using quantitative morphometry the innervation of chromaffin cells is shown to reach a mean total of 5.4 synapses per chromaffin cell during the period 26 days to 12 weeks of age. The variation in contents of synaptic profiles is discussed in the light of recent work that demonstrates a major sensory as well as visceral efferent innervation of the gland. Adrenal medullary neurons usually occur in closely packed groups, intimately associated with Schwann cells. Axodendritic and axosomatic synapses on these neurons are described and the likely origin of axonal processes innervating the neurons discussed. In old age the density of innervation remains the same as in young adult animals even though the medulla shows evidence of hyperplasia and hypertrophy of individual chromaffin cells.

Adrenal Glands

Explanation for good visual acuity in uncorrected residual hyperopia and presbyopia after radial keratotomy.

It has been observed that, after radial keratotomy (RK), uncorrected residual hyperopes may have better visual acuity than expected and that some presbyopes, corrected only for distance, have adequate near-vision. We offer a possible explanation for these observations by showing that the increased spherical aberration after RK may produce a second focus 1.5 diopters or more in front of the principal focus of the eye.

Contrast Sensitivity

Cellular communication in the developing Drosophila eye.

Undetermined cells are directed to their fate in the Drosophila eye by positional cues which are probably presented by adjacent differentiating cells. The sevenless protein is thought to function as a signal-receiving protein on the plasma membrane of the cell destined to form the seventh photoreceptor, R7. Localization of the protein indicates the interactions between undetermined and differentiating cells and suggests the existence of other receptor proteins similar to sevenless.

Animals

The development and maturation of adrenal medullary chromaffin cells of the rat in vivo: a descriptive and quantitative study.

A descriptive account and morphometric study of the adrenal medulla and adrenal chromaffin cells of Wistar rats aged from birth to 22 months is presented. Distinct adrenaline and noradrenaline-storing types of chromaffin cells are first identified in 4-day-old animals, prior to that time individual cells contain both adrenaline- and noradrenaline-storing granules. Primitive sympathetic cells and phaeochromoblasts occurs up to 2 days postnatally. Mitotic figures occur in chromaffin cells of a maturity and appearance appropriate to age and most frequently in adrenaline-storing cells. The adrenal medulla continues to increase in volume throughout the period and chromaffin cells increase in number and in some cases volume. There is a corresponding increase in neuronal elements. In 22-month-old rats individual cells or groups of chromaffin cells show evidence of hypertrophy and changes in cytoplasmic organelles, in particular lysosomes, rough endoplasmic reticulum and storage granules and vesicles. Some hypertrophied chromaffin cells contain a heterogeneous population of granules suggesting a degree of functional plasticity in some cells in aged rats.

Adrenal Medulla