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Biomedical subjects

J M Kay

Publications and source records attributed to J M Kay.

At least 19 recordsLinked to original sources

Cancer services.

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Cancer Care Facilities

Transferrin glycosylation in hypoxia.

The aim of this study was to examine the effect of reduced O2 tension on the glycosylation of transferrin. Rats were placed in a hypobaric chamber (380 mmHg) that corresponded to an altitude of 5486 m above sea level for 21 days. The animals responded with marked increases in hematocrit (from 44 to 76%) and cardiac weight, and with reductions in the concentration of plasma transferrin averaging 15%. Analyses of their plasma transferrin by serial anion-exchange and lectin affinity chromatography revealed no changes in the extent of glycan branching. However, there was a moderate rise in the proportion of fucosylated transferrin molecules (fucosylation index) and a slight decrease in the transferrin fraction bearing a tetrasialylated biantennary glycan. The fucosylation index correlated positively with plasma transferrin concentrations in the test animals, but not in the controls. In contradistinction to the situation with transferrin, hypoxic rats exhibited a reduced fucosylation index of immunoglobulin G.

Animals

Prevalence and geographic distribution of Fanconi syndrome in Basenjis in the United States.

A survey was conducted to ascertain the prevalence of Fanconi syndrome in Basenjis and to determine in which geographic regions the greatest number of affected dogs resided. A thousand questionnaires were distributed nationally, and 624 (62%) were returned. Through this survey, prevalence, geographic distribution, and breeder involvement were successfully correlated with the overall association of the disease with the Basenji breed. Ten percent (96/959) of all Basenjis involved in the survey had Fanconi syndrome. Half (50%; 48/96) of the Basenjis affected were between 4 and 8 years old. Seventy-six percent (44/58) of owners of Basenjis with Fanconi syndrome were breeding their dogs, and 93% (52/56) had owned other Basenjis before the survey was conducted. Females outnumbered males (3:1) in frequency of the disease. This ratio reflected the higher breeder participation in the survey, rather than being a true gender predilection for the disease.

Animals

Ductal adenoma of the breast.

Ductal adenoma is a recently described benign tumour of the breast that can be mistaken for carcinoma in both frozen and paraffin sections. Such a case is presented. Fortunately a mastectomy was not performed, but the patient did undergo axillary node dissection. Surgeons and pathologists should familiarize themselves with this lesion so that patients do not have to undergo unnecessary mastectomies and axillary node dissections.

Axilla

Enhanced cancer metastasis after monocrotaline-induced lung injury.

The lung is a target in several models of environmentally induced injury and is also a common site for the growth of metastases from circulating cancer cells. In these experiments, we have tested the hypothesis that pulmonary damage can facilitate the metastasis of cancer to the lung. We have studied the effect of monocrotaline-induced lung injury on the retention and metastasis of intravenously injected Walker carcinosarcoma 256 cells in the lung and the effect of this injury on spontaneous metastasis in animals with intramuscular tumor transplants. Female Wistar rats were given a single subcutaneous injection of monocrotaline (60 mg/kg). The degree of lung injury after monocrotaline was assessed by bronchoalveolar lavage, by histological and ultrastructural examination, and by measurement of right ventricular hypertrophy. To assess the effects of monocrotaline on metastasis, animals were injected iv with 2 X 10(7) [125I]iododeoxyuridine-labeled or unlabeled Walker 256 carcinosarcoma cells at various periods of time (1 day to 20 days) after monocrotaline. The retention of labeled cells was determined by gamma counts of lungs 24 hr after injection. There was a direct correlation between the severity of lung injury and the number of cancer cells retained in the lung 24 hr after injection. Metastasis was quantified by morphometric analysis of histologic sections prepared from lungs 1 week after an injection of unlabeled cells. The median area of lung involved by tumor after iv injection was 39% for rats injected with cancer cells 10 days after monocrotaline vs 3% for controls. In studies on spontaneous metastasis, rats were given an intramuscular injection of Walker 256 cells 5 days after monocrotaline and metastasis was quantified by morphometry 7 days after tumor transplantation. The median tumor burden of animals pretreated with monocrotaline was 37% vs 8% for controls. We conclude that lung injury initiated by monocrotaline can facilitate the spread of the rat Walker 256 carcinosarcoma.

Animals

Cellular characteristics of sputum from patients with asthma and chronic bronchitis.

The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%); the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation.

Adult

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep.

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure-flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 microns diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.

Animals

Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry.

Qualitative and quantitative studies were performed on pulmonary blood vessels in lung tissue obtained by biopsy, pneumonectomy, or autopsy from 58 patients in the Registry of Primary Pulmonary Hypertension sponsored by the Heart, Lung, and Blood Institute of the National Institutes of Health. In 49 patients (84%), the hypertensive vascular disease involved predominantly or exclusively muscular pulmonary arteries and arterioles. In each of these 49 patients, pulmonary artery medial hypertrophy was observed, and in 48 patients, it was also associated with intimal or luminal lesions. On the basis of the predominant histopathologic features, 25 of the 48 patients were classified as having pulmonary arteriopathy with plexiform lesions characterized by a combination of concentric laminar intimal fibrosis, eccentric intimal fibrosis, and plexiform lesions; in nine of these 25, recanalized thrombi were also present. Pulmonary arteriopathy with thrombotic lesions, defined by the presence of both eccentric intimal fibrosis and recanalized thrombi but without plexiform lesions, was observed in 19 patients. Intimal fibrosis, either concentric or eccentric, without plexiform or thrombotic lesions was found in four patients. Among the remaining nine patients in the Registry, pulmonary veno-occlusive disease was present in seven and chronic pulmonary venous hypertension in one. Pulmonary blood vessels were microscopically normal in a lung biopsy specimen from another patient. In general, patients with plexiform lesions and those with veno-occlusive disease had a much poorer prognosis than patients with thrombotic lesions. The present study shows the existence of several distinct histopathologic patterns of pulmonary vascular disease in individuals with primary pulmonary hypertension diagnosed by standardized clinical and laboratory criteria.

Humans

Ultrastructure of carotid body in rats living at a simulated altitude of 4300 metres.

We studied the ultrastructure of the carotid body of three normal rats and three rats living in a hypobaric chamber at a pressure of 460 mm Hg for 27, 28 and 35 days respectively. The type I cells of the carotid bodies of our hypoxic rats were enlarged due to an increase in the volume of their cytoplasm. Many of their dense core vesicles were vacuolated and the core was displaced eccentrically to become adherent to the limiting membrane of the vesicle. The concentration and distribution of dense core vesicles remained unaltered and there were no obvious changes in the mitochondria, ribosomes or Golgi apparatus. There was pronounced capillary dilatation in the carotid bodies of all three rats exposed to chronic hypoxia. This change was accompanied by attenuation of capillary endothelial cells and increased frequency of endothelial fenestrations. There were no structural changes in the type II cells.

Altitude

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

Exposure to acute hypoxia (barometric pressure 263 mmHg) for 8 hours did not lead to increased numbers of mast cells in the lungs of rats. In contrast, in adult rats kept for 35 days at a barometric pressure of 380 mmHg there was a proliferation of mast cells around the pulmonary blood vessels and in the alveolar septa. This hyperplasia of lung mast cells in response to chronic hypoxia was reversible on removal of the hypoxic stimulus. There was a correlation between the logarithm of the perivascular lung mast cell density (defined in the paper) and the logarithm of the right ventricular weight. There was no increase in the mast cells in the carotid bodies of the hypoxic rats. Young male, old male, young female, and old female rats which had been subjected for 39 days to a barometric pressure of 380 mmHg showed a proliferation of mast cells around the pulmonary blood vessels and in the alveolar walls. This response was greatest in the adult animals and independent of their sex. In the age and sex experiment there was a correlation between the perivascular lung mast cell density and the medial thickness of the muscular pulmonary arteries. Since mast cell hyperplasia has been reported as preceding right ventricular hypertrophy, it is conceivable that mast cell proliferation in the lung may be a defence mechanism to limit the severity of hypoxic pulmonary hypertension rather than to mediate it.

Age Factors

Unexplained pulmonary hypertension with pulmonary arteritis in rheumatoid disease.

The case is described of a 24-year-old woman who died after suffering from rheumatoid arthritis for eight years. During the last four months of her life there was clinical evidence of pulmonary hypertension. At necropsy the heart showed right ventricular hypertrophy but no congenital defect. Microscopic examination of the lungs disclosed evidence of hypertensive pulmonary vascular disease with medial hypertrophy and intimal fibrosis of muscular pulmonary arteries together with hypertensive changes in the pulmonary arterioles. Some of the muscular pulmonary arteries also showed fibrinoid necrosis of their media and acute arteritis. It was concluded that the fibrinoid necrosis was a minifestation of severe hypertensive pulmonary vascular disease rather than being a primary rheumatoid arteritis of the lung.

Adult