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Biomedical subjects

D Heath

Publications and source records attributed to D Heath.

At least 73 records · Page 4Linked to original sources

The occurrence and distribution of certain polypeptides within the human carotid body.

Both carotid bodies from 26 patients coming to necropsy were fixed in 10% neutral buffered formalin and sections 4 microns thick were stained for various peptides by use of the immunogold technique. The results show that the human carotid body contains met- and leu-enkephalin, substance P, vasoactive intestinal peptide (VIP), neurotensin and bombesin. The distribution of these six peptides within the carotid body differs. Thus met- and leu-enkephalin are both present predominantly within glomic chief cells but with a marked tendency to favour the dark variant of these cells. Substance P and VIP both show a weak immunoreactivity in comparison to the enkephalins and are present in all three variants of chief cell. Neurotensin shows the weakest immunoreactivity of all and is restricted to a few glomic chief cells in a minority of cases. Bombesin also shows a weak immunoreactivity in glomic chief cells but a strong reaction in glomic arteries and arterioles. In these vessels bombesin appears to be confined to smooth muscle cells in the media but we cannot say whether it is secreted by them or merely bound to receptor sites on their membranes. These findings are related to quantitative data on the concentration of peptides in the human carotid body from a previous paper with which we were associated.

Bombesin↗

Pulmonary vascular disease in a rabbit at high altitude.

A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.

Altitude↗

Histopathology of the carotid bodies in neonates and infants.

A histological study was made of the carotid bodies obtained at necropsy in 40 fetuses, neonates, infants and young children, ranging in age from 23 weeks of gestation to 11 years of age. Prominence of the dark variant of chief cells was found in diseases such as bronchiolitis which are associated with sustained hypoxaemia. Such cells have copious cytoplasm known to be rich in peptides such as enkephalins. The same histological features were found in two cases clinically diagnosed as sudden infant death syndrome but in which there was associated bronchiolitis and tracheo-bronchitis respectively, thought to have given rise to hypoxaemia. In a case of sudden infant death syndrome without infection there was overgrowth of sustentacular cells with predominant progenitor cells in the absence of dark cells. We associate this appearance with inability of the carotid bodies to respond adequately to changes in arterial oxygen tension.

Carotid Body↗

The histopathology of 36 cases of plexogenic pulmonary arteriopathy.

A detailed histopathological study was made of the lungs of 36 cases of plexogenic pulmonary arteriopathy coming to combined heart-lung transplantation. It revealed two dissimilar processes involved in the pathogenesis of this disease. One comprised histological appearances consistent with constriction of muscular pulmonary arteries, a condition that would be likely to be reversed by pulmonary vasodilators. The other was the proliferation of myofibroblasts in the intima and lumen of pulmonary arteries, a disorder of growth unlikely to be influenced by this type of therapy. In previous ultrastructural studies we have shown that the source of these cells of muscular pedigree is muscle cells from the inner half of the media which migrate into the intima through gaps in the inner elastic lamina. In the present study we found a similar proliferation of myofibroblasts in the intima, not only of pulmonary arteries, but also of pulmonary veins, in plexogenic pulmonary arteriopathy. Arterial thrombi found were considered to be a complication rather than a cause of plexogenic pulmonary arteriopathy. Siderophages, cholesterol granulomas and focal fibrosis in the lung were considered to be a consequence of intrapulmonary haemorrhage early in the course of the disease. It is concluded that, while plexogenic pulmonary arteriopathy has an important vasoconstrictive element, it is also based on a disorder of growth of cells of muscular pedigree. This view has clear implications for the therapy of primary plexogenic pulmonary arteriopathy.

Adolescent↗

Pulmonary endocrine cells in hypertensive pulmonary vascular disease.

A study was made of the number of pulmonary endocrine cells, immunoreactive for gastrin-releasing peptide (bombesin) or calcitonin, in the terminal bronchioles of 39 cases of pulmonary vascular disease. In 25 of these, the form of vascular disease was plexogenic pulmonary arteriopathy, primary in 12 and secondary in 13, while the remaining 14 subjects had a wide range of other varieties of hypertensive pulmonary vascular disease. We found that pulmonary endocrine cells, especially those containing bombesin, were increased in number in both the primary and secondary forms of plexogenic pulmonary arteriopathy but not in other varieties of pulmonary hypertension. The prominent bombesin-containing cells were found in cases with cellular plexiform lesions but occurred even more prominently at an earlier stage when vascular smooth muscle cells were migrating from the inner media into the intima.

Adult↗

Small pulmonary arterial vessels of Aymara Indians from the Bolivian Andes.

A study was made of the qualitative histological features of the small pulmonary arterial vessels of 25 adult citizens of La Paz, Bolivia (altitude 3600 m) coming to necropsy. Abnormalities found included muscularization of pulmonary arterioles, the development of longitudinal muscle in the intima of pulmonary arteries and arterioles, and the formation of muscular tubes lining the longitudinal muscle which extended through arterioles into the precapillaries of the lung. Arteriolar muscularization was found in three of the 13 Aymaras and in two of the 12 Mestizos studied. Intimal longitudinal muscle was present in four Aymaras and five Mestizos. Muscular tubes were found in only one case, a young Aymara. The features were very similar to those found in chronic obstructive airways disease. The appearances are consistent with a growth of new vascular smooth muscle in response to alveolar hypoxia as opposed to hypoxic vasoconstriction.

Adolescent↗

Chronic carotid glomitis and the glomus pulmonale.

A histological study was made of the carotid bodies and glomus pulmonale in 50 consecutive subjects over the age of 50 years who came to necropsy to determine if chronic glomitis is confined to the carotid bodies or whether it also occurs in other glomera. Lymphoid aggregates and plasma cell activity were found in the glomus pulmonale just as they were in the carotid bodies. Chronic pulmonary glomitis sometimes occurred in association with chronic carotid glomitis and sometimes independently of this. The mean age of the affected subjects was 76 years in isolated pulmonary glomitis and 79 years in chronic carotid glomitis. Chronic carotid glomitis affected seven (14%) subjects and predominated in women (six to one). In the seven cases of isolated pulmonary glomitis women predominated five to two. Chronic glomitis seems to be a disease process which may affect at least two members of the non-chromaffin paraganglionic system, but it is not clear why focal chronic inflammation affects the glomus pulmonale of one person but not of another.

Aged↗

Pulmonary endocrine cells in plexogenic pulmonary arteriopathy.

A study of the numbers of pulmonary endocrine cells per cm2 of section of lung obtained at combined heart-lung transplantation in 25 cases of plexogenic pulmonary arteriopathy demonstrated that the peptide which may become unduly prominent in pulmonary arterial disease is bombesin. The type of vascular disease in which bombesin becomes prominent is plexogenic pulmonary arteriopathy, be this primary or secondary to congenital heart disease. The increased prominence of bombesin appears to be related to the stage reached in the arteriopathy. Increased numbers of pulmonary endocrine cells are found in association with classic cellular plexiform lesions with narrow vascular channels. Their numbers are within normal limits when the plexiform lesions are mature with wide vascular channels and narrow intervening septa. The pulmonary endocrine cells are most prominent in the pre-plexiform stage when smooth muscle cells in the inner half of the media of the pulmonary artery show increased electron density, and migrate through gaps in the inner elastic lamina to reach the intima. Here they are transformed into myofibroblasts and proliferate. The migration of muscle cells may be related in some way to long-acting trophic factors released from the pulmonary endocrine cells into the surrounding tissues from which they reach the blood and hence the pulmonary arteries.

Adolescent↗

The distribution of enkephalins in human carotid bodies showing cellular proliferation and chronic glomitis.

Human carotid bodies obtained at necropsy that showed prominence of either the sustentacular cell or the dark variant of chief cell or chronic carotid glomitis were studied by an immunogold labeling technique. The peptides methionine and leucine enkephalin had a similar distribution to that found in the normal human carotid body. They were localized prominently and predominantly in the dark and progenitor variants of chief (type I) cells. The sustentacular (type II) cells showed no immunoreactivity for the enkephalins. Cell counts on immunolabeled chief cells in cases of sustentacular cell hyperplasia and chronic carotid glomitis were found to be at the lower end of the normal range, whereas those in dark cell prominence occurred nearer the upper limit.

Aged↗

Focal chronic thyroiditis and chronic carotid glomitis.

The incidence of focal chronic thyroiditis and chronic carotid glomitis was studied by histological examination in 50 subjects over the age of 50 years coming to necropsy. The two conditions appear to be distinct, affecting different age groups. Focal chronic thyroiditis occurred as early as the sixth decade and was found on its own in 34 per cent of subjects. Chronic carotid glomitis was characteristic of the eighth and ninth decades and occurred on its own in 14 per cent of subjects. In a further 12 per cent, thyroiditis and glomitis co-existed. Chronic carotid glomitis has the same histological features as auto-immune thyroiditis, the infiltrate being composed of aggregates of lymphocytes and plasma cells, raising the possibility that it, too, has a basis in auto-immunity. The antigenic stimulus for the auto-immunity in the carotid bodies may be senescent nerve fibrils.

Age Factors↗

Pulmonary blood vessels and endocrine cells in subacute infantile mountain sickness.

A male infant of 16 months, of the Han race, died from subacute infantile mountain sickness in Lhasa (3600 m). At necropsy there was right ventricular hypertrophy secondary to muscularization of the pulmonary arteries and arterioles thought to have been induced by hypobaric hypoxia. In addition, there was intimal proliferation of myofibroblasts in the pulmonary arterioles, venules and veins. There were increased numbers within the bronchioles of pulmonary endocrine cells, containing calcitonin and bombesin, which could be related to hypoxia or trophic effects on the pulmonary vasculature. The relation of delayed effects of hypoxia to primary pulmonary hypertension is considered in this study.

Altitude Sickness↗

Chronic carotid glomitis.

Both carotid bodies were obtained at necropsy from each of 75 subjects, 38 male and 37 female, ranging in age from 14 to 90 years. In each case the histological features were classified as one of four age-related patterns. The presence and distribution of lymphocytes were noted. They presented either as a diffuse scattering throughout the stroma or as large focal aggregates. In subjects over the age of 50 years the diffuse infiltrates occurred in 56% of cases and were virtually all T-cells. In the same age group the aggregates of lymphocytes were found in 21% of cases. These findings indicate that there is a disease of human carotid bodies characterized by focal aggregates of lymphocytes that begins in middle age and becomes increasingly common with advancing years, affecting 29% of subjects aged 70 years or over. It is not related to any co-existing disease but seems to be a response to the degenerative changes in the glomic tissues that occur with age. By analogy with comparable changes in the thyroid and salivary glands, the disease may have a basis in auto-immunity.

Adolescent↗

Carotid body disease and the physician--chronic carotid glomitis.

There are three types of histological change in the carotid bodies which appear to have physiological and clinical associations. A prominence of the dark variant of chief cells with their contents of met-enkephalin and other peptides appears to be associated with acute exposure to hypoxia. Proliferation of sustentacular cells around the clusters of chief cells appears to be related to ageing and also to systemic hypertension. Recently we have described a new condition of chronic carotid glomitis which is characterized by follicles of lymphocytes and may have a basis in auto-immunity. In the present review we report for the first time plasma cell activity in the carotid bodies of an elderly man, especially around nerve fibrils and unmyelinated axons ensheathed in sustentacular cells. Such appearances are consistent with the view that ageing nerve fibrils may be the antigenic stimulus for the development of chronic carotid glomitis.

Autonomic Nervous System Diseases↗

Pulmonary endocrine cells in pulmonary arterial disease.

Pulmonary endocrine cells containing bombesin or calcitonin have been identified in human lungs by the peroxidase-antiperoxidase method. The numbers of such cells were greatly increased in patients with plexogenic pulmonary arteriopathy whether that condition was associated with primary pulmonary hypertension or with pulmonary hypertension from intracardiac shunts. The numbers of endocrine cells tended to be increased, but to a lesser extent in patients with pulmonary hypertension and medial hypertrophy of the muscular pulmonary arteries in the absence of plexogenic arteriopathy. Increased numbers of endocrine cells comprised both greater numbers of solitary cells and a pronounced clustering, often of a disorganized nature.

Adolescent↗

Subacute infantile mountain sickness.

A description is given of a disease of infants occurring in Lhasa, Tibet at an altitude of 3600 m. Typically if affects infants who have been born at low altitude and subsequently brought to residue in Lhasa, and it is usually fatal within a few weeks or months. There is extreme medial hypertrophy of muscular pulmonary arteries and muscularization of pulmonary arterioles, together with dilatation of the pulmonary trunk and massive hypertrophy and dilatation of the right ventricle. The disease is distinct from acute or chronic mountain sickness and appears to be the human counterpart of 'brisket disease' in cattle.

Altitude Sickness↗