First International Conference on the Acquired Immunodeficiency Syndrome.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
K J Donald
Publications and source records attributed to K J Donald.
The effect of dietary restriction, adrenaline, hydrocortisone and surgery on the rates of death of 125IUdR-labelled, intravenously injected tumour cells in the lungs of mice.
Dietary restriction, adrenaline hydrocortisone or surgery reduced the rate at which pulmonarily arrested 125IUdR-labelled murine tumour cells were lost within 7 h of intravenous (i.v.) injection. Mice that had been adrenalectomised 10 days previously showed a normal intrapulmonary tumour cell loss rate with further surgery reducing this rate to approximately half that observed in normal mice that had been subjected to surgery. Thus, although it is likely that adrenal hormones play an important role in decreasing the rate of early intrapulmonary tumour cell loss, additional factors must be implicated. Mice subject to dietary restriction, adrenaline, hydrocortisone or surgery had reduced levels of in vitro growth inhibitor(s) in their sera. Despite this, individual surgically treated animals showed no correlation between serum in vitro-growth inhibitor levels and rate of loss of i.v. injected tumour cells from the lungs. Furthermore, the 24 h pre-incubation of tumour cells in inhibitor-rich serum did not influence the subsequent loss rate of such cells following i.v. injection into mice. Electron microscopic studies indicated that dietary restriction, adrenaline and surgery reduced the rate of intravascular tumour cell death. The decreased tumour cell death rate in mice receiving these treatments could not be related, however, to any consistent morphological change in the pulmonary vasculature. The decreased rate of intravascular tumour cell death in treated mice was followed by an increased number of lung tumours with only one of the tumour lines studied, indicating that the intravascular death rate need not be a major determinant of pulmonary tumour incidence.
Animals↗
Antigen of Haemophilus influenzae in bronchial tissue.
Haemophilus influenzae antigen was detected in five of seven bronchial biopsies obtained from patients undergoing diagnostic bronchoscopy. Antibody against H influenzae antigens was obtained from a patient with bronchiectasis. Immunofluorescent techniques were used. This provides further evidence to support the pathogenicity of H influenzae in lower respiratory tract disorders.
Adult↗
The effect of 125I-5-iodo-2'-deoxyuridine labelling on murine tumour cells.
Labelling with 125IUdR at radioactivity concentrations commonly employed in studied with i.v. injected tumour cells (1.0-0.1 microCi/ml) was shown to reduce considerably the in vitro reproductive viability of mastocytoma tumour cells. Velocity sedimentation cell separation studies on mastocytoma cells that had been labelled for 12 h with 0.8 microCi/ml 125IUdR yielded a population that varied markedly between fraction with respect to distribution of label and, in parallel, with respect to induced loss of reproductive viability. A similar population of mastocytoma cells that had been labelled for 36 h with 0.01 microCi/ml 125IUdR yielded fractions where distribution of label was not associated with reduced reproductive viability. Although in vivo survival (as distinct from reproductive viability) of tumour cells injected i.v. and i.p. was not significantly altered within 7 h and 30 h respectively by the commonly used concentrations of 125IUdR, it is suggested that in studies of the fate of injected tumour cells exponentially growing cells be labelled with 125IUdR for intervals well in excess of population doubling times at concentrations less than or equal to 0.025 microCi/ml.
Animals↗
The autopsy in quality assurance. Clinical practice in a teaching hospital.
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Aged↗
The effects of major and minor trauma on lymphocyte kinetics in mice.
The effects of major and minor trauma on the circulating white blood cell populations of C57BL mice were followed. The results showed that not only major trauma (nephrectomy) but minor injury and stress (e.g. injection, bleeding) triggered a highly significant fall (50-70%) in the number of lymphocytes circulating in the blood. The fall was a gradual one, with the maximal drop 2 h after the operation or handling procedure. Major trauma resulted in a fall in both B and T lymphocytes. Minor trauma produced a fall in B lymphocytes only. A 3-4 fold increase in circulating polymorph numbers also accompanied major trauma, but no increase was observed after minor trauma. The blood picture returned to normal generally within 24 h of both minor and major trauma. Repetition of the trauma stimulus after recovery led to a renewed trauma response. Bilateral adrenalectomy abolished the lymphocyte response to major and minor trauma and decreased the polymorph response to major trauma by more than 50%, indicating that stress hormones played a role in these changes. Studies with 51chromium-labelled lymphocytes, transferred into traumatized and adrenalectomized animals, suggested that decreased entry of lymphocytes into the blood (rather than increased exit from the blood into the tissues, or cell death) was the most likely mechanism of the lymphopenia following trauma.
Adrenalectomy↗
Non-immunological cell death of intravenously injected murine tumour cells.
Most DBA mastocytoma and Sarcoma 180 cells trapped in the lungs of mice after i.v. injection died within 7 h. Rates of cell death were similar for both tumour cell lines. Rates of tumour cell death were unrelated to whether the cells were allogeneic or syngeneic, induced platelet aggregation or not, had different patterns of subsequent tumour growth, or were injected in varying numbers. Cell death was by coagulative necrosis, not apoptosis. Sarcoma 180 tumour cells were quickly localized in the lung and enclosed in platelet aggregates which remained, with degranulation, until the time of tumour cell death. However, platelet aggregation did not appear to play a role in tumour cell killing. The prevention of platelet aggregation by pretreatment of mice with an anticoagulant had little effect on the rate of death of tumour cells in the lung. Mastocytoma tumour cells did not cause platelet aggregation, yet died in the lung at similar rates to Sarcoma 180 cells. The killing of tumour cells in the lung did not appear to be cell-mediated. No mononuclear cells were seen in the vicinity of tumour cells and the type of cell death was not that associated with cell-mediated killing. The tumour cells did not die within 6 h of being injected into the peritoneal cavity. It is suggested that a nonspecific non-immunological process results in the death of intravenously injected tumour cells in the lung. This process was not affected by differing oxygen levels in the inhaled gas.
Animals↗
Immunoglobulin levels and electron microscopy in eosinophilic pneumonia.
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Adolescent↗
Immunofluorescence studies of lung biopsy tissue.
Thirty specimens of lung obtained by Abram's needle biopsy were examined using direct immunofluorescence. In 2 cases of Goodpasture's syndrome, linear deposits of IgG were demonstrated in alveolar walls. Diffuse deposits of IgG were found in the alveolar spaces of one patient with pigeon fancier's lung. Two subjects with cryptogenic fibrosing alveolitis had dense granular deposits of IgG in alveolar walls. Amorphous deposits of IgG were found in the pulmonary interstitium of a patient with desquamative interstitial pneumonitis. The small proportion of positive results obtained may reflect either the lack of a humoral immune background in the pathogeneses or only a fleeting involvement of humoral immunologic processes in each of the diseases studied. However, a small percentage of patients with diffuse interstitial disease do have antibody deposits demonstrable on small needle biopsy specimens. These require further investigation and may serve to define special groups. Various artifacts that were encountered led to difficulties in interpretation and these should be considered in reporting immunofluorescence studies of lung tissue. These included autofluorescence and nonspecific staining of connective tissue and cells. Nonspecific staining of eosinophils occurred frequently. The possible misinterpretation of artifacts as positive results is illustrated.
Alveolitis, Extrinsic Allergic↗
Inhibition of the growth of murine tumour cells in vitro by serum from non-immune syngeneic and allogeneic mice.
Sera from DBA/2 and Quackenbush mice (which are non-immune for mastocytoma and Sarcoma 180 respectively) contain a heat-labile (56 degrees for 30 min) component(s) that inhibits the in vitro growth of DBA Mastocytoma P-815 X-2 and Sarcoma 180. Adsorption of the sera with tumour cells at 4 degrees did not eliminate the factor(s), suggesting that it is not an antibody. In liquid suspension cultures inhibitory activity was observed at concentrations of mouse serum of 10--20% and in semisolid agar clonogenic cell assays at concentrations as low as 1%. The influences of the inhibitor(s) for both tumours and in both culture systems were parallel. However, there was a quantitative difference in susceptibility to other environmental factors (FCS concentration, bicarbonate concentration, and O2 tension) between the two tumours. These results parallel the in vivo findings where intravenously injected mastocytoma cells produced more tumours than did Sarcoma 180.
Animals↗
Carcinoid tumour of the thymus. A case report including discussion of the morphological diagnosis and the cell of origin.
This report concerns a 49 year old asymptomatic male who had a mediastinal mass demonstrated on routine radiography. A large encapsulated tumour composed of small regular cells arranged in clumps and acini with fine vascular stroma was removed. The differential diagnosis on routine H&E section included parathyroid tumor, medullary carcinoma arising in ectopic thyroid tissue, epithelial thymoma or carcinoid tumor of the thymus. The presence of compressed thymic tissue around the tumor, and of argentaffin granules together with the electron microscopic appearance characteristic of the "enterochromaffin" or "APUD" group of cells allowed the diagnosis of carcinoid tumor of the thymus to be made. Electron microscopy showed that the cell cytoplasm contained electron dense membrane bound granules, together with bundles of microfilaments. Vesicles of smooth surfaced reticulum were present but rough surfaced reticulum was inconspicuous. No desmosomes were demonstrated. Special stains for amyloid and glycogen were negative.
APUD Cells↗
Pulmonary haemorrhage in disseminated cardiac haemangiosarcoma.
A male forestry worker presented with chest pain followed by severe continuing haemoptysis and an extensive bilateral nodular pulmonary infiltrate. A needle biopsy of lung demonstrated micronodular deposits of malignant tissue. The patient died from respiratory failure. Necropsy showed a disseminated haemangiosarcoma arising in the right atrium. Haemoglobin and serum iron levels were normal. Electron microscopy of the lung biopsy showed a close relationship between tumour cells and basement membrane and suggested that haemorrhage occurred directly from the tumour nodules. The ultrastructure of alveoli adjacent to tumour deposits was normal. This case provides further indirect evidence that the clinical and histological features of idiopathic pulmonary haemosiderosis cannot be explained by the mere occurrence of alveolar haemorrhage.
Adult↗
Death of cells by apoptosis following attachment of specifically allergized lymphocytes in vitro.
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Animals↗
Fibrin-bound tumour cells on a sclerosed mitral valve.
The association of fibrin and tumour cells on a sclerosed mitral valve in a 62-year-old woman is described. This was the first indication of malignant disease but bilateral ovarian cancer was proved two months later. ino further tumour deposits have been found in fifteen months. The tumour deposit on the valve was most likely a metastasis but primary heart valve sarcoma has not been positively excluded. If the lesion was a secondary deposit this has possible implications for the role of fibrin in metastasis in humans.
Female↗
Secretory (juvenile) carcinoma of the breast.
A case of secretory (juvenile) carcinoma of the breast is reported in a 26-year-old multiparous woman who had been taking oral contraceptives for 7 months. The tumour recurred 8 months after local resection and axillary metastases were found at radical mastectomy. No further recurrence has been detected but the follow-up period is only 8 months. It is emphasized that secretory carcinoma of the breast originally described in children occurs also in adults. Early reports stressed the slow rate of growth, often with intervals of many years before recurrence, and the small risk of metastatic spread, many cases being cured by local resection. However, axillary metastases have been found in approximately 15% of the recorded cases. Consequently it is recommended that the initial treatment should be simple mastectomy with at least a low axillary resection.
Adult↗
Estimation of the migration of thoracic duct lymphocytes to non-lymphoid tissues. A comparison of the distribution of radioactivity at intervals following i.v. transfusion of cells labelled with 3H, 14C, 75Se, 99mTc, 125I and 51Cr in the rat.
The distribution of radioisotopes in tissues was measured following i.v. injection of labelled thoracic duct lymphocytes into syngeneic rats. The rate of elution of an isotope from the labelled cells and the subsequent fate of the eluted isotope were shown to be the most important factors limiting the usefulness of such isotopes for measuring cell localization particularly in non-lymphoid tissues. Comparison of labelling procedures using [3H] and [14C]uridine, [3H] and [14C]leucine, [75Se]-L-selenomethionine, [99mTc]sodium pertechnetate and [51Cr]sodium chromate in vitro and [3H]thymidine in vivo showed that 51Cr had the fewest disadvantages in the present context. Using 51Cr-labelled cells, the radioactivity was measured in a wide range of non-lymphoid tissues, and estimates of cell traffic were obtained. In skin, for example, the results indicate a cell flux in the range of 10(4)-10(5) lymphocytes/gm/hr. Evidence is presented which suggests that the early substantial localization of labelled cells in the lung is not an artefact due to sequestration or embolization of traumatized cells but probably reflects a slow intravascular transit time through this capillary bed. The primary lymphoid organs, thymus and bone marrow were shown to include a subpopulation of lymphocytes which belong to the recirculating pool. The thymus always contained a greater concentration of radioactivity at 24 hr than all non-lymphoid tissues except liver and kidney (approx. 0-1% of the recirculating lymphocyte pool) and the bone marrow was capable of temporarily accepting a substantial proportion (approx.25%) of the injected cells.
Animals↗
Necropsy as a control of death certification: some unexpected findings.
A comparison of death certificates and necropsy findings in a group of premenopausal women suggests that a number of diseases are either underdiagnosed in life. Atypical cases of intracerebral haemorrhage are frequently misdiagnosed. These occur in the frontal, temporal or parietal lobes in non-hypertensive women and may be suitable for surgical treatment. Their aetiology remains obscure. Pulmonary embolus is habitually underdiagnosed in premenopausal women and myocardial infarcts appear to be overdiagnosed. The study reemphasizes that death certificates are inaccurate and that low necropsy rates render accurate statistics of diseases in the community difficult ot obtain.
Adult↗
An ultrastructural study of the pathogenesis of tissue injury in limited Wegener's granulomatosis.
Intravascular lysis of leucocytes was an early event in the process of tissue injury in a patient with limited Wegener's granulomatosis. This lysis, with consequent liberation of free organelles into the circulation, was followed by platelet aggregation and fibrin deposition in vessels with intact endothelial cells. Necrosis of endothelial cells also occurred early in the tissue injury. Complete obstruction of vessel lumina, with necrosis of their walls and of alveolar pneumocytes, followed. The alveolar spaces filled with fibrin and cell debris, and macrophages and fibroblasts migrated into these areas. The ultrastructural findings offer a rationale for current therapy. Cyclophosphamide therapy led to improvement in the clinical state, pulmonary function and histological changes.
Capillaries↗