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Biomedical subjects

G W Morgan

Publications and source records attributed to G W Morgan.

At least 19 recordsLinked to original sources
PubMed2002

Growth promotion in chickens by interleukin-2.

Chicken interleukin-2 (cIL-2), which was prepared by sensitizing chicken lymphocytes with concanavalin A, was administered to fertile broiler eggs on Day 18 of embryonation (0.1 mg in 200 mL distilled water). Controls (CON) received distilled water. Hatched chicks were reared to 6 wk. Body weight (BW), as well as abdominal fat pad, liver, bursa of Fabricius, a thymic lobe, spleen, and gonads were excised and expressed relative to BW at 2, 4, and 6 wk of age. Additionally, hematocrit (HCT), hemoglobin (HGB), and plasma protein (PP) levels were determined at the three time intervals. Finally, chicks were sensitized against human gamma globulin (HGG) and challenged at 6 wk by intradermal injections into the wattles. Delayed type hypersensitivity (DTH) to HGG was used as a direct measure of cell-mediated immunity. In ovo cIL-2 increased BW consistently, relative fat pad weights at 2 wk, relative bursa and liver weights at 2 and 6 wk, HBG and relative thymic weight at 2 and 4 wk, and PP at 2 wk. Delayed type hypersensitivity to HGG was not affected by cIL-2. Potential metabolic and immunologic mechanisms to explain in ovo cIL-2 effects are discussed.

Adipose Tissue↗
PubMed2001

A randomized trial of tacrolimus (FK506) versus total lymphoid irradiation for the control of repetitive rejection after cardiac transplantation.

Recurrent cardiac rejection is a major cause of morbidity during the initial 6 months following transplantation. We compared treatment with tacrolimus versus total lymphoid irradiation in 13 heart transplant recipients on a cyclosporine, azathioprine, and prednisolone regimen, who experienced repetitive rejection. The mean number of episodes of rejection significantly decreased in both groups, with no deaths and no increase in the incidence of infection, hypertension, diabetes, or renal impairment following either treatment at 12-month follow-up. Conversion to tacrolimus or a course of lymphoid irradiation are equipotent strategies, of comparable cost, for the prevention of further rejection in patients with recurrent rejection.

Adult↗
PubMed2001

Radiation oncology in Australia: workforce, workloads and equipment 1986-1999.

Regular national surveys of all public and private radiation oncology facilities in Australia have been carried out between 1986 and 1999. Workforce data recorded were numbers of radiation oncologists and trainees, radiation therapists, medical physicists and physics technicians, nursing staff, data managers, social workers and clerical staff. Workloads included treatments with megavoltage beams (linear accelerators, cobalt-60), orthovoltage/superficial X-rays, brachytherapy, total body irradiation and stereotactic radiosurgery. Major equipment recorded included numbers of megavoltage and orthovoltage/superficial X-ray machines, planning simulators, computerized dosimetry systems and brachytherapy equipment. The use of radiotherapy beds and the public-private mix of treatments were also documented. Data were assembled for Australia based on each individual state. Within Australia the number of public and private treatment facilities has increased by 44% from 18 in 1986 to 26 in 1999. The population has increased by 16.4%, cancer incidence by 51.8% and megavoltage workloads (fields) by 102%. The number of radiation therapists and physicists and the number of linear accelerators have, in general, increased with the growth in workloads. The number of radiation oncologists has increased by 60% from 4.5 full-time equivalent (FTE) radiation oncologists per million population in 1986 to 7.2 per million in 1999. There is currently a deficit of at least 40 radiation oncologists to be able to treat the 50% of newly diagnosed cancer patients requiring radiotherapy. In addition, a significant deficiency exists in numbers of radiation therapists, nursing staff, data managers, social workers and clerical staff. Clearly the demands for medical physicists has increased but the data are insufficient to comment on deficiencies. Despite the increases in workloads the proportion of patients with cancer receiving radiotherapy remains below 40%. A positive correlation has been shown between the proportion of newly diagnosed cancer patients treated and the number of FTE radiation oncologists, the number of megavoltage machines and number of radiation therapists. This was shown for Australia as a whole, for each state and for the years 1986 to 1999. This was also the case when total megavoltage fields was used as the dependent variable. Multiple regression analysis using the same independent variables confirmed these positive correlations. It is concluded that the low treatment rate with radiation oncology for cancer patients in Australia is due mainly to the lack of resource allocation. The stated commitment of governments and health departments to a 50% treatment rate can only become a reality if there is a concerted effort to increase the numbers of radiation oncologists, radiation therapists, megavoltage machines and support staff. Otherwise at least one in every 10 newly diagnosed cancer patients will continue to be denied adequate and equitable access to radiotherapy - in 1999 that total figure was 9400 persons.

Australia↗
PubMed2001

Developmental and morphological regulation of clathrin-mediated endocytosis in Trypanosoma brucei.

Essentially all macromolecular communication between Trypanosoma brucei and its host is confined to vesicular trafficking events occurring at or around the flagellar pocket. The vertebrate stage bloodstream form trypomastigote exhibits an extremely high rate of endocytosis required for nutrient uptake and probably also evasion of the host immune system. However, the rate of endocytosis is very low in the procyclic vector parasite, indicating that endocytosis is subject to a marked level of developmental regulation. Previous ultrastructural studies and crude biochemical fractionations have indicated the presence of coated pits and vesicles that are analogous to clathrin coats in the bloodstream form, but not in the procyclic. However, a definitive description of the components of this coat and its molecular function in T. brucei has remained elusive. We describe the molecular cloning and initial characterisation of components of the T. brucei endocytic coats: clathrin heavy chain (TbCLH) and a beta-adaptin (TbAPbeta1). TbCLH is markedly upregulated in the bloodstream form compared with the procyclic, whereas TbAPbeta1 is subject to more limited developmental regulation. We generated antisera against both proteins and show that the clathrin coat is tightly associated with the flagellar pocket in both major life stages. However, in bloodstream parasites TbCLH is also extensively distributed throughout the posterior end of the cell on numerous large vesicular and tubular structures. By cryo-immuno EM, clathrin is localised to collecting tubules at the flagellar pocket and is also associated with the trans-Golgi network. These EM data confirm that the electron dense coats reported on trypanosome vesicles and tubules contain clathrin. The TbAPbeta1 exhibits an atypical distribution relative to previously characterised adaptins, associating not only with the trans-Golgi but also with other tubular-vesicular elements. Localisation of TbAPbeta1 is also subject to developmental regulation. These data describe major endocytic coat proteins in T. brucei for the first time, and indicate stage-specific expression of the clathrin heavy chain. Modulation of clathrin expression is likely to be an important factor in the developmental regulation of endocytosis and recycling in the African trypanosome.

Adaptor Protein Complex beta Subunits↗
PubMed2001

A developmentally regulated rab11 homologue in Trypanosoma brucei is involved in recycling processes.

Endocytosis in the parasitic protozoan Trypanosoma brucei, a deeply divergent eukaryote, is implicated as important in both general cellular function and virulence, and is strongly developmentally regulated. We report the characterisation of a previously undefined endosomal compartment in T. brucei based on identification of a new trypanosome gene (TbRAB11) homologous to Rabll/Ypt31. Northern and western analyses indicated that TbRAB11 expression was significantly upregulated in the bloodstream stage of the parasite, the first trypanosome Rab to be identified with a developmentally regulated expression profile. In procyclic form parasites TbRAB11 localised to a compartment positioned close to the basal body, similar to mammalian Rab11. By contrast, in bloodstream form parasites, TbRAB11-containing structures were more extensive and the TbRAB11 compartment extended towards the posterior face of the nucleus, was more elaborate and was not always adjacent to the basal body. Colocalisation studies by light and confocal microscopy demonstrated that TbRAB11 was located on a compartment that did not correspond to other established trypanosomal organelles or markers. Using concanavalin A internalisation and temperature block procedures, TbRAB11 was observed on endomembranes anterior to the flagellar pocket that are juxtaposed to the collecting tubules. TbRAB11 colocalised with the trypanosomal transferrin receptor and internalised anti-variant surface glycoprotein. Further, we show that the collecting tubules contain TbRAB5A, suggesting that they are the trypanosomatid early endosome. Hence, TbRAB11 is present on endosomal structures that contain recycling cargo molecules and is under developmental regulation, suggesting a role in stage-dependent endocytic processes.

Animals↗
PubMed2000

The rate of breast-conserving surgery in early breast cancer: an audit of surgical practice at St Vincent's campus, NSW in 1990 and 1994.

An audit was undertaken to document the use of breast-conserving surgery (BCS) in the management of early breast cancer (EBC) at St Vincent's campus during two time periods, the calendar years 1990 and 1994. The medical records of all women diagnosed with a new primary breast cancer at St Vincent's Public and Private Hospitals initially treated during 1990 and 1994 were reviewed to document patient, tumour and treatment characteristics. Comparisons were made with data on BCS in EBC from the Australian medical literature. A total of 228 patients was managed with a definitive surgical procedure in the years 1990 and 1994. There were no major differences in the manner of presentation, the tumour subtypes or the treatment techniques between the two years. There was an apparent increase in the number of tumours < 2 cm managed in 1994 but no major difference in the use of BCS. The BCS rates for the two years were 33 and 36%, respectively. There were wide variations in the rate of BCS between surgeons, and for the same surgeon, between the two calendar years. These data from a major teaching hospital serving a largely non-mammographically screened population would suggest that BCS rates for EBC are lower than expected. The data on BCS rates for EBC in Australia are limited and the optimal rate of BCS in current practice is unknown.

Breast Neoplasms↗
PubMed1999

Aggressive cutaneous malignancies following cardiothoracic transplantation: the Australian experience.

BACKGROUND: The development of malignancies in recipients of a cardiothoracic transplant (CTT)--that is, heart, lung, or heart and lung recipients-is of concern. Cutaneous and lymphoproliferative malignancies comprise the two major groups of malignancies encountered. A small subgroup of patients will develop potentially life-threatening aggressive cutaneous malignancies (ACM); these are poorly defined and documented in the literature. The authors report the results for 619 CTT recipients from a single institution. METHODS: Between 1984 and 1995, 619 recipients received a CTT. With a minimum follow-up of 2 years, 66 patients (10.7%) were diagnosed with a major malignancy, and 27 of these 66 patients developed ACM. ACM were defined as having one or more of the following characteristics: local invasion and/or regional metastases at diagnosis, poor differentiation, and locoregional and/or systemic relapse following therapy. All malignant melanomas were considered ACM. Data on malignancy occurrence were documented in the clinical notes of the heart and lung transplant unit. A retrospective analysis was undertaken from these notes. RESULTS: Tumor histology was predominantly poorly differentiated squamous cell carcinoma (55%) (SCC) and malignant melanoma (30%) (MM). No patient developed Kaposi sarcoma (KS). The median time from transplant to diagnosis of ACM was 52 months (range, 8-127 months). Thirteen of 27 patients have died; 10 of them died of metastatic disease. The mean time to death was 20 months (range, 8-54 months). Of 14 patients alive, 5 have disease. All but one of the 19 patients diagnosed with nonmelanoma ACM received radiotherapy, either as part of initial treatment or on relapse. Eight patients have subsequently suffered an infield relapse. CONCLUSIONS: The development of ACM in CTT recipients resulted in substantial morbidity and mortality. Poor results were obtained with standard surgery and radiotherapy. Treatment modalities for and the underlying pathobiology of ACM in organ transplant recipients require detailed research if improved outcomes are to be achieved.

Adult↗
PubMed1998

A synopsis of radiation oncology in Australia, with particular reference to New South Wales.

The specialty of radiation oncology had its beginning in Australia in 1896 following the discovery of X-rays by Roentgen. The new technology was eagerly embraced and the use of X-rays and radium for the treatment of cancer, even in the early 1900s, produced results which, although far from satisfactory by today's standards, resulted in cure and palliation of more superficial tumours. In the era immediately prior to World War II the specialty was regarded as having only a limited role to play in cancer management. The introduction of cobalt-60 units and linear accelerators in the 1950s allowed for treatment of deep-seated tumours without the skin, bone and other complications of orthovoltage machines (deep X-rays). But the introduction of radiotherapy treatment into cancer care was blocked by other specialties anxious to preserve their own 'turf and by medical administrators who believed the counter-claims that either cancer was incurable or 'the cure for cancer was just around the comer' and it was therefore foolish to waste money on an expensive technology that had a limited future. With further developments in technology, modern radiotherapy is now a highly sophisticated treatment using sharply focused and deeply penetrating X-rays and electron beams. Specialized treatments, such as automated afterloading brachytherapy, total body irradiation, stereotactic radiosurgery and computerized 3-D planning to improve dose distribution, are now widely available. The outcomes of cancer patients with radiotherapy have also improved considerably and organ preservation (e.g. in breast and larynx cancer) has resulted in improved quality of life. However, the specialty has only recently begun to expand in specialist numbers and profile. This is partly due to the lack of undergraduate training in cancer in general and radiotherapy in particular and also because understaffing has meant that radiation oncologists have occupied a purely service role (in the basement with their machines) rather than being an active part of the treatment 'team'. As a consequence radiation oncology has not been projected as an important component in cancer management and as a challenging and fulfilling career option to medical students and new graduates. The failure to act on the (repeated) recommendations of the 42 reports, inquiries, etc. into radiation oncology in Australia since 1982 (in addition to many more at local level) would suggest that the 'message' has yet to be accepted by Health Departments and health administrators. As a result there has been a totally uncoordinated approach to provision of radiation oncology services. The restriction of services and specialist numbers and training posts has led to radiotherapy being underutilized and undervalued in the treatment of cancer, ultimately to the detriment of cancer patients.

Australia↗
PubMed1996

Both in vitro and in vivo irradiation are associated with induction of macrophage-derived fibroblast growth factors.

Fibrosis in the lung directly underlying the field of irradiation is an almost universal long term sequelae of thoracic irradiation. It is assumed to represent the consequence of direct damage to local tissues and/or vascular endothelium by ionizing radiation. This view, however, is not in keeping with our current understanding of fibrotic processes, which suggest that growth factors for fibroblasts (including platelet-derived growth factor (PDGF), insulin-like growth factor I (IGF-I)) and cytokines stimulating collagen synthesis (notably transforming growth factor-beta) are largely responsible for this process. Since a major source of these factors is the macrophage, present in large numbers within the lung, it appeared possible that radiation-induced fibrosis might be mediated by similar mechanisms. Therefore, a study was designed to determine, first, whether in vitro irradiation of mononuclear phagocytes could induce the release of growth factors for fibroblasts. Second, we wished to ascertain whether these same growth factors might also be secreted by bronchoalveolar cells from humans who had undergone in vivo thoracic irradiation. The results of this study indicate that irradiation of a number of different types of mononuclear phagocytes resulted in the dose-dependent synthesis and release of several growth factors for fibroblasts, including PDGF, tumour factor-alpha (TNF-alpha) and IGF-I. Further, cells obtained by bronchoalveolar lavage from patients undergoing thoracic radiation spontaneously released PDGF following irradiation. These findings strongly support the contention that synthesis and release of macrophage-derived growth factors for fibroblasts (particularly PDGF and IGF-I) occur after thoracic irradiation and play a significant role in the pathogenesis of irradiation-induced pulmonary fibrosis in humans.

Breast Neoplasms↗
PubMed1995

Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury.

Recent data from several investigators, including our unit, have provided additional information on the etiology of radiation-induced lung damage. These data suggest that there are two quite separate and distinct mechanisms involved: (a) classical radiation pneumonitis, which ultimately leads to pulmonary fibrosis is primarily due to radiation-induced local cytokine production confined to the field of irradiation; and (b) sporadic radiation pneumonitis, which is an immunologically mediated process resulting in a bilateral lymphocytic alveolitis that results in an "out-of-field" response to localized pulmonary irradiation. Both animal experiments and human studies show that classical radiation pneumonitis has a threshold dose and a narrow sigmoid dose-response curve with increasing morbidity and mortality over a very small dose range. Clinical pneumonitis rarely causes death, whereas in the animal and human studies of classical radiation pneumonitis, all subjects will eventually suffer irreversible pulmonary damage and death. The description of classical radiation pneumonitis is that of an acute inflammatory response to lung irradiation, which is confined to the area of irradiation. Recent studies have also shown that irradiation induces gene transcription and results in the induction and release of proinflammatory cytokines and fibroblast mitogens in a similar fashion to other chronic inflammatory states, and which ultimately results in pulmonary fibrosis. The description of classical radiation pneumonitis does not adequately explain the following observed clinical characteristics: (a) the unpredictable and sporadic onset; (b) the occurrence in only a minority of patients; (c) the dyspnoea experienced, which is out of proportion to the volume of lung irradiated; and (d) the resolution of symptoms without sequelae in the majority of patients. We have demonstrated a bilateral lymphocytic alveolitis of activated T lymphocytes and a diffuse increase in gallium lung scan uptake in patients studied before and 4 to 6 weeks after strictly unilateral lung irradiation. This is suggestive of a hypersensitivity pneumonitis, which gives rise to an "out-of-field" response to localized lung irradiation and hence more accurately describes the clinical picture of radiation pneumonitis. Reevaluation of the mechanisms of pulmonary injury from irradiation suggest that (a) a new term, sporadic radiation pneumonitis, should be introduced to describe the clinical picture of radiation pneumonitis, which is not adequately explained by the classical description and is quite clearly an entirely different process; and (b) that the chronic response to localized lung irradiation that leads to pulmonary fibrosis is largely mediated through the induction and release of tissues cytokines.

Animals↗
PubMed1993

Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction.

OBJECTIVE: To determine if unilateral thoracic irradiation results in a lymphoid alveolitis in both irradiated and unirradiated lung fields. DESIGN: A prospective, nonrandomized study. PATIENTS: Women receiving postoperative radiotherapy for carcinoma of the breast were evaluated both before and 4 to 6 weeks after radiotherapy. Findings after radiotherapy in 15 asymptomatic patients were compared with findings in a group of patients with clinical radiation pneumonitis. MEASUREMENTS: History, physical examination, chest radiograph, quantitative gallium lung scanning, respiratory function tests, bronchoalveolar lavage, and lavage lymphocyte subset analysis. RESULTS: After irradiation, lavage lymphocytes increased significantly (34.5% versus 46.8%; P = 0.01) in the 17 patients studied prospectively. There was an associated reduction in vital capacity (102.5% versus 95.5%; P = 0.04). Comparison of results in patients before treatment, after treatment without clinical pneumonitis, and after treatment with clinical pneumonitis showed a dramatic increase in total lymphocytes after irradiation (6.3 versus 9.4 versus 35.2 million, respectively; P = 0.005), particularly in those with clinical pneumonitis. Only in those with clinical pneumonitis was this accompanied by an increase in the gallium index (3.7 versus 3.4 versus 9.0, respectively; P < 0.001). Vital capacity was also progressively reduced (102.5% versus 96.9% versus 76.7%, respectively; P = 0.04), as was diffusing capacity (98.6% versus 91.4% versus 72.6%, respectively; P = 0.003). No statistical differences existed between irradiated and unirradiated sides of the chest in either lavage or gallium lung scan studies. CONCLUSION: In most patients, a lymphocytic alveolitis develops in both lung fields after strictly unilateral thoracic irradiation; this is more pronounced in patients developing clinical pneumonitis. These findings suggest that radiotherapy may cause a generalized lymphocyte-mediated hypersensitivity reaction.

Adult↗
PubMed1992

Quantitative pulmonary gallium scanning in interstitial lung disease.

The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P less than 0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P less than 0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin.

Bronchiolitis↗