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Biomedical subjects

J M Kay

Publications and source records attributed to J M Kay.

At least 37 records · Page 2Linked to original sources

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↗

Solitary fibrous tumour of the pleura: an ultrastructural and immunohistochemical study.

Solitary fibrous tumour of the pleura is a benign neoplasm differing from diffuse pleural mesothelioma. It was originally thought to be a variant of mesothelioma because it consists of a spindle cell stroma associated with branching tubular structures lined by cuboidal cells. In this study of two cases the tubular structures were lined with ciliated and non-ciliated cuboidal cells. Ultrastructurally most of the non-ciliated cells had the features of type II pneumocytes, while the stromal cells had all the characteristics of fibroblasts. Immunohistochemical staining showed the epithelial cells to be positive for both keratin and carcinoembryonic antigen, whereas the stromal cells were negative. The findings support the theory that these tumours are fibroblastic in origin, and that the biphasic pattern is due to entrapment of non-neoplastic bronchiolar and alveolar epithelial cells.

Humans↗

Electron microscopy of chronic eosinophilic pneumonia.

We have investigated two cases of chronic eosinophilic pneumonia using the electron microscope. The alveolar septa were thickened due to edema and an infiltrate of numerous mononuclear cells and eosinophils, with a few lymphocytes and occasional plasma cells. Macrophages were often located close to eosinophils and extracellular eosinophilic granules. Occasional eosinophilic granules were observed in the cytoplasm of mononuclear cells. The most striking finding was the presence of distinctive elongated, narrow, tubular inclusions in the cytoplasm of several of the mononuclear cells. These inclusions presented complex curved profiles which sometimes terminated in small, dilated, dense vesicles. Some of the narrow tubular sections of the inclusions presented a pentalaminar structure. Elsewhere, the tubular structures showed localized globular dilatations which contained granular material. Elongated strands of electron-dense material, identical to that forming the intracytoplasmic inclusions, were also located extracellularly, between adjacent mononuclear cells and between mononuclear cells and eosinophils. These inclusions are considered to be the product of phagocytosis of cellular debris and to be related to phagolysosomes rather than to Birbeck granules.

Adult↗

Lung angiotensin converting enzyme activity in chronically hypoxic rats.

A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were made on 11 groups of four rats, which were placed in the chamber for 24 days and then allowed to recover in room air for one to 153 days. After two days of hypoxia the mean Prvs (25.5 (SD 3.7] and the mean lung ACE activity (56 (4.6] did not differ significantly from control values. Exposure to hypoxia for four to 24 days caused a progressive increase in mean Prvs to 44.4 (5.9) and a progressive reduction in mean lung ACE activity to 34 (4.0). During recovery lung ACE activity increased and Prvs decreased, so that normal values were achieved by 15 and 56 days respectively. Decreased lung ACE activity may be related to haemodynamic factors associated with pulmonary hypertension rather than to hypoxia.

Animals↗

Pulmonary hypertension induced in rats by monocrotaline and chronic hypoxia is reduced by p-chlorophenylalanine.

We have studied the role of 5-hydroxytryptamine (5-HT) in monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats using p-chlorophenylalanine (PCPA) which inhibits 5-HT synthesis. We measured right ventricular mean systolic pressure (Prvs), right ventricular hypertrophy, medial thickness of muscular pulmonary arteries, and muscularization of pulmonary arterioles 17 days after a single dose of monocrotaline (60 mg/kg) and after 26 days of chronic hypobaric hypoxia (380 mm Hg). In monocrotaline pulmonary hypertension, pretreatment with PCPA (500 mg/kg) was associated with significant reductions (p less than 0.05) in Prvs (29%), right ventricular hypertrophy (33%), and medial thickness of muscular pulmonary arteries (14%). In chronic hypoxic pulmonary hypertension, pretreatment with PCPA was associated with significant reductions in Prvs (20%), right ventricular hypertrophy (28%), medial thickness of muscular pulmonary arteries (14%), and muscularization of pulmonary arterioles (47%). 5-HT may play a role in the development of monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats.

Animals↗

Pulmonary capillary hemangiomatosis.

We report a case of pulmonary capillary hemangiomatosis affecting a 35-yr-old Caucasian woman. Progressive pulmonary hypertension was documented by serial cardiac catheterizations, and pulmonary function studies showed changes suggestive of chronic pulmonary congestion. Although a difficult condition to diagnose during life as it may mimic veno-occlusive disease, capillary hemangiomatosis has a distinct histopathologic picture.

Adult↗

Polyclonal B cell hyperplasia associated with Epstein-Barr virus causing acute renal allograft failure.

Six weeks post cadaver renal transplantation, a patient developed a flu-like illness. Acute renal failure unresponsive to anti-rejection therapy occurred and he died four days later from Pneumocystis carinii pneumonia and Streptococcus viridans septicemia. Autopsy revealed a diffuse polymorphic polyclonal B cell infiltrate occupying most organs, including the allograft. Primary Epstein-Barr Virus (EBV) infection was established by 1) rising anti-EBV antibody titres; 2) the demonstration of EBV nuclear antigen in the infiltrate and 3) the presence of EBV specific DNA sequences in affected tissues. EBV associated polymorphic B cell hyperplasia can mimic rejection and result in acute allograft failure.

Antibodies, Viral↗