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Biomedical subjects

W M Ross

Publications and source records attributed to W M Ross.

At least 19 recordsLinked to original sources

Retinal structure and visual acuity in a polyprotodont marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata).

The visual system of the fat-tailed dunnart (Sminthopsis crassicaudata), a small polyprotodont marsupial, has been examined both anatomically and behaviourally. The ganglion cell layer was examined in cresyl-violet stained wholemounts and found to contain a mean of 81,400 ganglion cells (SD +/- 3,360); the identification of ganglion cells was supported by a correspondence to optic axon counts. Ganglion cells were distributed as a mid-temporally situated area centralis, embedded in a pronounced visual streak. Localised implants of horseradish peroxidase into retinal wholemounts revealed both A-type and B-type horizontal cells. Sections of the outer retina showed it to be rod-dominated, with a rod-to-cone ratio of 40:1 at the area centralis; cones were found to contain oil droplets but double cones were not a prominent feature. The retinal pigment epithelium consisted of squamous cells. Visual acuity, estimated from counts of peak ganglion cell density (8,300/mm2, SD +/- 1,180) and measurements of posterior nodal distance (2.9 mm), was found to be 2.30 cycles per degree. The value was close to that of 2.36 cycles per degree estimated by behavioural tests using a Mitchell jumping stand; values were similar at low, intermediate and high light levels. Our findings are discussed in relation to the lifestyle of the dunnart.

Animals↗

Relative alterations in blood mononuclear cell populations reflect radiation injury in mice.

Damage to the immune and hematopoietic systems following exposure to ionizing radiation, whether accidental or for therapeutic purposes, renders victims susceptible to opportunistic infections and diseases. Elucidating a reliable biological indicator or "biological dosimeter" to indicate rapidly the extent of injury sustained by an individual would be desirable. Total leukocyte count has been used historically as an indicator of immune damage, but it is not truly indicative of functional immunity post-irradiation. A flow cytometric (FCM) technique was developed to determine whether a rapid reproducible assay could be developed to assess the extent of radiation damage. To this end, peripheral blood leukocyte populations and subpopulations were monitored. C57BL/6 mice were exposed to 100-, 400-, or 700-cGy whole-body gamma-irradiation (WBI) and blood samples were collected from the retro-orbital sinus 1, 4, and 7 days post-irradiation. The blood samples were prepared for FCM by incubation with monoclonal antibodies (mAb) to various murine leukocyte CD surface markers. The results show that the proportion of CD4+ T lymphocytes increased approximately 2-fold on day 4 after 700 cGy, the proportion of B lymphocytes declined markedly at all doses relative to unirradiated controls, and natural killer (NK) cells rose dramatically (9-fold) by day 4 after 700 cGy. The patterns of alteration in the relative proportions of peripheral blood mononuclear cells (PBMC) populations observed post-irradiation, particularly in B lymphocytes and natural killer (NK) cells, seem to represent potent and consistent indicators of immune damage, allowing some inference as to the immune competence of the individual.

Animals↗

Radiation damage and immune suppression in splenic mononuclear cell populations.

We have examined alterations in all of the major splenic mononuclear cell (SMNC) populations in C57B1/6 mice following whole-body irradiation (0-700 cGy) in order to determine which populations may play a role in active immune suppression and/or haematopoietic recovery. A protocol has been established for characterization and differentiation by flow cytometric analysis (FCA) of the major MNC populations in the mouse spleen: T lymphocytes (CD4+ and CD8+ cells), B lymphocytes, natural killer (NK) cells, and monocytes/macrophages. Ionizing radiation caused decreased spleen cellularity and decreased ability of surviving SMNC to respond to mitogen. FCA revealed alterations in the relative composition of the constituent splenic cell populations following irradiation, reflecting differential radiosensitivity, with selective enrichment of NK cells (seven-fold) and CD4+ T lymphocytes (three-fold). Enrichment developed during the 7-day post-irradiation period. In addition, some MNC became activated in a dose- and time-dependent fashion following whole-body irradiation, as indicated by expression of CD71, the transferrin receptor. These cells were CD34+ and Thy 1.2+, but were CD4- or CD8- as well as CD45- (B cell). The observed increase in NK cells corresponds with a previously reported increase in natural suppressor (NS) cells following total-lymphoid irradiation (TLI). The balance of recovery-inhibiting NK cells and recovery-enhancing CD4+ T lymphocytes following irradiation may reflect or influence the degree of haematopoietic recovery, and may provide an indication of the extent of damage (biological dosimetry).

Animals↗

Wiring up the visual system.

1. In this review we describe some of our recent studies on the developing marsupial visual pathway. The description focuses on retinal ganglion cells, considering the formation of their dendritic trees, the outgrowth of axons and the formation of connections within the brain. 2. Both dendritic trees and outgrowing axons undergo a period of exuberance, followed by one of refinement. The dendritic tree transiently develops a more complex branching pattern than is found in adults. Short side branches, referred to as spines, are a feature of immature dendrites and, to a lesser extent, of axons. These structures are mostly lost as development proceeds. However, they are retained on the dendritic trees of small-field ganglion cells and, for a proportion of axons, on that part within the nerve fibre layer of the retina. Although most axons navigate fairly direct routes towards their targets, a minority follow inappropriate courses, such as doubling back towards the eye or entering the opposite optic nerve at the chiasm. As such errant axons are not seen in the adult, we assume that their parent cell bodies die during development. 3. Throughout development, optic axons are arranged in an approximate retinotopic order along the length of the visual pathway; as a result, axons approach the visual centres aligned to form, at least, a crude retinotopic map. Axons from dorsal and ventral retina exchange locations along the optic nerve and in this way correct for the inversion of the image brought about by the lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The retinal ganglion cell layer and optic nerve in a marsupial, the honey possum (Tarsipes rostratus).

We examined the retina and optic nerve of one of the smallest mammals, the honey possum (Tarsipes rostratus), a marsupial. Ganglion and displaced amacrine cells were distinguished by morphological criteria in retinal wholemounts stained with cresyl violet. There was a mean of 90,000 ganglion cells which were distributed as an area centralis in the mid-temporal retina with a peak density of 9,000/1 mm2 falling in a concentric shallow gradient to 2,000/1 mm2 at the periphery. The unimodal and positively skewed spectra of soma diameters gave no indication of ganglion cell classes. Displaced amacrine cells numbered only 15,000, being outnumbered 6:1 by ganglion cells. This value represents by far the lowest percentage of displaced amacrine cells yet reported for a mammalian retina. The displaced amacrine population was evenly distributed. Counts of optic axons from electron micrographs were within 1-5% of the ganglion cell estimates. In the retrobulbar portion of the nerve, a substantial proportion of axons (26-43%) were unmyelinated, and many of these were concentrated within the lateral quadrant. This specialisation may represent the outflow of the area centralis. At the level of the foramen, the percentage of unmyelinated axons fell to 4-6%, and axons were more uniform in their distribution. Axon diameters were lower for the unmyelinated than the myelinated populations at both levels. As for ganglion cells, however, the spectra of axon diameters were unimodal and positively skewed for both unmyelinated and myelinated axons.

Animals↗

Prevalence of skin and other cancers in patients with psoriasis.

The prevalence of skin and internal malignancies was estimated from the general practitioners' notes of 2247 patients with psoriasis and 4494 age- and sex-matched controls. The prevalence of skin cancer in the psoriatics was 155% that of controls, but this was not significant at the 5% level. Subgroup analysis showed an increase in skin cancers in women (P < 0.05). There was no difference in the age of onset of skin cancers between psoriatics and controls and there was no evidence of a cumulative therapeutic risk. There was no difference in the prevalence of non-skin cancers between psoriatics and controls.

Adult↗

Modification of mitogen-induced proliferation of murine splenic lymphocytes by in vitro tocopherol.

The effect of alpha-tocopherol on in vitro proliferation of murine splenic lymphocyte cultures supplemented with various concentrations of the vitamin has been measured at sub-optimal, optimal and supra-optimal levels of the T-cell mitogen Concanavalin A (Con A). In the concentration range (1-25 micrograms/ml), tocopherol enhanced proliferation when administered up to 24 hours after exposure to sub-optimal and optimal concentrations of Con A; however, at supra-optimal levels of the mitogen, it appeared to inhibit proliferation. In the concentration range 50-100 micrograms/ml, tocopherol supplementation only enhanced proliferation in response to sub-optimal concentration of Con A. The spontaneous proliferation of lymphocytes in the absence of mitogens was increased by tocopherol supplementation at all concentrations tested. In contrast, there appeared to be only slight stimulation of B-cell proliferation in response to optimal concentration of bacterial lipopolysaccharide (LPS) by lower levels of vitamin E. Tocopherol supplementation of cultures over a broad range of concentrations (0.5-100 micrograms/ml) had no significant effect on cell viability before onset of proliferation at 18 hours after exposure to Con A, nor was there evidence of earlier onset of DNA synthesis in response to mitogen in the presence of 5 micrograms/ml of the vitamin. Although macrophage depletion of cultures impaired proliferation induced by Con A, tocopherol supplementation continued to stimulate proliferation at optimal and sub-optimal levels of mitogen.

Animals↗

Reticulo-fibroblastoid stromal cell progenitors (CFU-RF) in murine bone marrow.

The hemopoietic inductive microenvironment (HIM) of the bone marrow is responsible for secretion of growth factors that regulate hemopoiesis. It is composed of an extracellular matrix and a complex variety of cell types with a range of functions related to blood cell development. In order to understand how such a complex system operates, it will first be necessary to determine the role(s) of the integral parts. Several of the stromal cell types have been identified morphologically in various culture systems, and some of their functions have been elucidated. We have identified a new stromal cell type in mouse bone marrow that appears similar if not identical to its human counterpart. When bone marrow cells are placed in methylcellulose/plasma clot culture with phytohemagglutinin-stimulated human leukocyte-conditioned medium in the presence of bovine calf serum (BCS), mercaptoethanol, and hydrocortisone, extensive branching colonies develop within 14 days. These "reticulo-fibroblastoid" (RF) colonies arise from a putative reticulo-fibroblastoid colony-forming unit (CFU-RF) stem cell, and many become adipocytic by day 14; the addition of fresh medium, methylcellulose, and BCS on day 7 inhibits this change. The batch of human citrated plasma used in the culture system and the type and source of stimulating factor all influence the number of RF colonies that develop as well as the percent of colonies that become adipocytic. Whether this adipogenesis represents functional maturity or terminal differentiation is not yet known. Information gained on the role of these RF cells in normal and impaired hemopoiesis should contribute to the elucidation of the complicated interactive role of the microenvironment in the support and modulation of hemopoiesis.

Adipose Tissue↗

Radiation cataractogenesis induced by neutron or gamma irradiation in the rat lens is reduced by vitamin E.

Although cataract of the eye lens is a known late effect of ionizing radiation exposure, most of the experimental work to date has concentrated on single, acute high doses or multiple, fractionated, chronic exposures. Many papers have dealt with biochemical alterations in metabolism and cellular components, with microscopic and electron microscopic lesions to the epithelial and cortical layers, and with clinical cataract formation. However, the minimum cataractogenic dose for rats has for many years been considered to be about 2 Gy for a single, acute dose of low LET radiation. Our purpose in designing this pilot study was three fold: firstly, to determine whether any physical damage could be detected after low, acute exposure to neutron radiation (10 and 100 cGy); secondly, to compare the relative effectiveness of fast (14 MeV) neutrons with gamma-rays; and thirdly, to investigate the possibility that vitamin E could protect the lenses from radiation damage. The results revealed that morphological damage was already discernible within minutes after exposure to neutrons or gamma-rays, that it became greater after 24 hours, that neutrons were more damaging than gamma-rays, and that vitamin E could effectively reduce the cataractogenic damage induced by ionizing radiation. Control, non-irradiated lenses with or without vitamin E, either in vivo or in vitro, showed no damage. Also, it appeared that in vitro irradiation was more damaging to lenses than in vivo irradiation, so this culture technique may prove to be a sensitive tool for assessing early damage caused by ionizing radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Whats in a name?

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Radiology↗

What's in a name?

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Radiology↗

Marrow reticulo-fibroblastoid colonies (CFU-RF derived) spontaneously release an erythroid colony (BFU-E) enhancing factor.

The marrow microenvironment is composed of an extracellular matrix as well as a heterogeneous population of cells. Isolation of the various cell types and analysis of their function is necessary for a better understanding of their roles in hemopoiesis. We have recently reported a colony assay for a cellular component of the marrow microenvironment. The assay consists of a cellular component of the marrow microenvironment. The assay consists of a plasma clot-methylcellulose marrow culture. The stimulator is PHA-stimulated leukocyte conditioned medium (PHA-LCM) and hydrocortisone (5 x 10(-5)M). The fibrin strands appear to act as a substrate for the growth of Reticulo-Fibroblastoid colonies derived from the CFU-RF precursor. RF colonies can be subcultured forming adherent layers when transferred to liquid cultures. Confluent adherent layers can be maintained for long periods of time by changing medium every 3 to 5 days. Supernatants derived from unstimulated RF cultures (RF-CM) were tested for growth promotion of hemopoietic precursors. We found: (1) RF-CM by itself does not induce colony formation. (2) In the presence of erythropoietin, RF-CM enhances the growth of BFU-E. (3) Recombinant IL 4 also enhances BFU-E formation, but in our assays IL 4 induced fewer colonies than RF-CM and the colonies were smaller. (4) Because neither IL 4 nor RF-CM, by themselves, can stimulate colony formation, we compared the effect of RF-CM on assays that are known to show other IL 4 functions. RF-CM did not induce proliferation of PHA induced blast T cells, a known property of IL 4.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

Advanced carcinoma of the ovary with central nervous system relapse.

Interdisciplinary protocols for management of advanced adenocarcinoma of the ovary have resulted in prolonged patient survival. A subset of patients is emerging in whom central nervous system (CNS) relapse occurs even following negative second-look procedures (SLP). Seven of 342 eligible patients entered in a National Cancer Institute of Canada Trial for Ovarian Cancer, from February 1, 1980 to March 31, 1984, had CNS relapse. All patients received adriamycin and cisplatin. SLP was performed in 5 patients, 3 of whom were complete responders (CR). Two additional patients failed to complete their chemotherapy and had progressive pelvic disease. The median age of these 7 patients was 57 years, their overall survival time was 28 months, compared with an average age of 58 years and survival of 21.6 months, for the entire group. Two patients had prolonged survival after their CNS relapse; 1 patient lived 26 months, and the other, who underwent craniotomy for primary management of the metastasis survived 18 months. Confirmation of metastatic disease was obtained in 4 of the 7 patients. The results of this study suggest that management of CNS involvement in adenocarcinoma of the ovary should be determined by overall performance status even in the presence of generalized disease.

Adenocarcinoma↗

Colonic lymphoid follicles associated with colonic neoplasms.

In 3,399 patients more than 40 years of age undergoing air-contrast enema examinations a prospective evaluation was done for the presence of colonic lymphoid follicles. In 3,315 patients there was no evidence of lymphoid follicles. Colonic neoplasms were diagnosed in 8.47% of these individuals. Eighty-four patients were found to have radiographically identifiable follicles. Fifty-eight of these 84 patients (69%) with lymphoid follicles had a synchronous (n = 19) or previous (n = 14) colonic neoplasm or a synchronous (n = 24) or previous (n = 1) colonic polyp. There were no consistent clinical or radiographic features that distinguished the patients with and without a neoplastic association. However, 90% of men with lymphoid follicles had associated neoplasms, whereas only 58% of women did. Because of the frequent association, detection of colonic lymphoid follicles in patients in this age group should lead to a vigorous search for subtle colonic neoplasms that may not be apparent because of technical limitations of the study.

Adult↗