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Biomedical subjects

M D Kendall

Publications and source records attributed to M D Kendall.

At least 73 records · Page 4Linked to original sources

Have we underestimated the importance of the thymus in man?

Recent immunological research has concentrated on the complex and subtle interactions between T cells, B cells and accessory cells. In these studies, little attention has been given to the adult thymus gland. Modern textbooks of disease and anatomy all stress that the gland undergoes fatty involution with age in man but omit reference to the statements here and there in the literature that the gland is active and produces lymphocytes throughout life. To suggest that the bone marrow, which also builds up fat throughout life, is atrophic and not important to adult man would deny all modern hematological concepts. Yet few people today take a parallel view of the thymus except perhaps those investigating aging and thymic hormones. In both of these areas of research it is obvious that the thymus must be active throughout life for continued good health. This brief review urges that a thorough understanding of the vital importance of the thymus in adult life is now needed. From it could emerge a new philosophy on the treatment of immune diseases in both the young (SCID and AIDS patients) and in the aged (autoimmune conditions and cancers) and it would aid our treatment of patients recovering from illness and from many drug treatments.

Acquired Immunodeficiency Syndrome↗

Heterogeneity of epithelial cells in the human thymus. An ultrastructural study.

To evaluate interrelationships among epithelial cells, and between morphology and function in the microenvironment, we studied the ultrastructural morphology of epithelial cells in sections of human thymus from donors aged 2 months to 31 years. Six types of epithelial cells were observed: "subcapsular-perivascular" (type 1); "pale" (type 2); "intermediate" (type 3); "dark" (type 4); "undifferentiated" (type 5); and "large-medullary" (type 6). Cells of types 2, 3 and 4 were found throughout the organ. The type-2 to -4 epithelial cells may represent various stages in a differentiation process. In this, type-2 cells are very active and type-4 cells are possibly degenerating elements. Type-4 cells can also contribute to Hassall's corpuscles. Type-5 cells were located mainly in the cortico-medullary region and showed the morphological characteristics of undifferentiated elements. Type-6 cells were located exclusively in the medulla and displayed characteristics of cellular activity. Small Hassall's corpuscles consisted of type-6 epithelial cells; in larger corpuscles many nuclei of type-6 cells were found. Cells of types 2 and 6 contained tubular structures (diameter approximately 20 nm). Concerning the function of thymus epithelial cells, the features associated with protein synthesis observed in cellular types 2 and 6 make them likely candidates for humoral factor-producing and/or secreting elements. In addition, type-2 and -3 cells in the cortex appear to contribute to a special pattern of epithelium-lymphocyte interaction ("thymic nurse cells"), as demonstrated by the intracytoplasmic location of lymphocytes in the epithelial cells. The various steps in intrathymic T-cell maturation occur at locations in a microenvironment composed of morphologically distinct epithelial cells.

Adolescent↗

Comparative distributions of zinc, cadmium and mercury in the tissues of experimental mice.

Different groups of mice were injected with cadmium, zinc and mercury. Zinc injections had no effect on zinc tissue levels while both mercury and cadmium accumulated in various tissues. Cadmium persisted in the tissues much longer than mercury, and while the mercury concentrations began to decline as soon as dosing ceased, cadmium concentrations in kidney and intestine increased even after dosing ceased. There appeared to be an interrelationship between cadmium concentrations in spleen and intestine which warrants some further investigations. There was a linear, but discontinuous, effect of cadmium on zinc concentrations in liver, kidney and pancreas which may depend on metallothionein biochemistry. Mercury injections had no effect on zinc metabolism. It is proposed that differences in the rate of excretion of cadmium and mercury from the kidney could explain the differential accumulation of cadmium and mercury in animals.

Animals↗

The nerves of the accessory pancreatic ducts of the common starling (Sturnus vulgaris): an ultrastructural and light microscopic study.

An ultrastructural and light microscopic study was undertaken to examine the nerves of the accessory pancreatic ducts of the starling (Sturnus vulgaris), previously noted (Vinnicombe, 1982) to have a particularly dense innervation. Large numbers of nerves were found in the ducts, predominantly in the lamina propria, and all contained exclusively unmyelinated axons. Probable neuron cell bodies were observed in the smooth muscle layer, but not in the lamina propria. Schwann cells invested all the axons, and these displayed terminal swellings in a 'synapse en passage' arrangement. The nerves of the lamina propria were most numerous in the region immediately beneath the epithelium and were present in the epithelial folds. One axon was observed to have penetrated the epithelial basal lamina and to lie between two epithelial cells. Examination of the terminal profiles and their contained synaptic vesicles showed the innervation to have probable pain afferent, cholinergic, adrenergic and perhaps peptidergic components. The results of this study were compared with reports on pancreatic duct innervation in other species, mostly as parts of wider studies on pancreatic innervation.

Animals↗

A study of the rete testis epithelium in several wild birds.

Material from six wild non-breeding starlings (Sturnus vulgaris), twelve adult wild quelea (Quelea quelea) in prenuptial, full and post-breeding condition and one wild puffin (Fratercula arctica) was examined by light and electron microscopy. Contrary to previous accounts of avian material, the epithelium of the rete testis was composed of a mixture of numerous non-ciliated and fewer ciliated cells. Both cell types contained many inclusions in the cytoplasm all of which indicated that the cells could modify the luminal contents. All rete testis epithelial cells showed a strong reaction with stains for alkaline phosphatase.

Alkaline Phosphatase↗

Ultrastructural studies on the thymus gland after the administration of phenylhydrazine to bank voles (Clethrionomys glareolus).

The thymus glands of wild and laboratory reared bank voles (Clethrionomys glareolus) were examined for ultrastructural changes before and after the administration of low (20 mg/kg) and high (60 mg/kg) doses of phenylhydrazine (PhZ) given intraperitoneally on days 0, 1 and 3 of a dosing regime. Erythrocytes developed in focal aggregations in the subcapsular and outer cortical zones. There was a marked depletion of the subcapsular cortex following drug treatment that was reversed with time. A large number of granulocytes were visible in the cortex after PhZ, and mast cells developed in situ.

Animals↗

X-ray microanalysis of proximal and distal tubule cells in the mouse kidney, and the influence of cadmium on the concentration of natural intracellular elements.

Quantitative X-ray microanalysis of frozen freeze-dried sections of mouse cortex have been used to determine the concentrations of Na, Mg, P, S, Cl, K, Ca and Cd in normal mice and those subjected t 0.7 mumol of cadmium chloride in two subcutaneous injections. These injections result in tissue levels of approximately 100 mg Cd/kg dry weight (less than 1 mM) in whole kidney when analysed by atomic absorption spectrometry. There were distinct and characteristic differences -- 'fingerprints' -- in the elemental composition of both cytoplasm and mitochondria in proximal and distal tubules of normal mice that were distributed by the cadmium treatment. The most significant effect of the cadmium injections was a highly significant increase in the sulphur content of the cytoplasm and mitochondria of distal tubules and a loss in concentration of Mg, P, Cl, K, and particularly Na, from the mitochondria. These results are discussed in the light of current concepts of metallothionein induction (metallothionein is a sulphur-rich protein that acts to bind, amongst other metals, cadmium) and the lack of damage observed in the distal tubules.

Animals↗

The fine structure of dark or intercalated cells from the distal and collecting tubules of avian kidneys.

Dark or intercalated cells were identified in the terminal portion of the distal tubules and in the intralobular collecting tubules of four species of birds. The morphological features of these cells varied only slightly from species to species and were very similar to cells found in topographically analogous regions of mammalian nephrons. Characteristic vesicles usually filled the apical region of the dark cells and were often in direct continuity with the apical plasma membrane which was frequently thrown into elaborate folds, microvilli and microplicae. Observations suggested that the cells might be involved in some form of cyclical secretory activity. The similarity in structure between avian and mammalian dark cells suggested that they might perform similar functions and that the study of avian cells might aid the elucidation of the mammalian cell function. The possible functions of the avian cells were discussed in relation to physiological studies in mammalian kidneys and it was suggested that they might be involved with proton and potassium pumping and control of urinary buffer concentrations.

Animals↗

The accessory pancreatic ducts of the starling Sturnus vulgaris: an ultrastructural and light microscopic study.

Wild starlings (Sturnus vulgaris) were utilised for a study of the small accessory pancreatic ducts that pass from the pancreas to the loop of the duodenum. These ducts do not appear to have been described before in the literature. Each duct was composed of an epithelial lining of a main cell type, which had small numbers of two other cell types intermixed. A lamina propria consisting of a loose collagenous network, richly endowed with a thick nerve plexus, separated the epithelium from the muscle coat. The muscle consisted of inner longitudinal, middle transverse and outermost spiral layers. This was surrounded by a dense collagenous tunica adventitia, and the ducts were accompanied by large blood vessels. The main columnar cells of the epithelium had a strong PAS positivity, and an alcian blue-positive reaction at high molarities of magnesium chloride (greater than 0.5 M). This indicated the presence of mucopolysaccharides with a high degree of sulphation, such as heparan sulphate. Both of the staining reactions were limited to a fine apical surface reaction which probably did not extend into the cells themselves. At the electron microscope level it could be seen that the surface coat corresponded to a filamentous layer overlying short stubby microvilli on the apical surface of the epithelium. Numerous apical electron-dense inclusion granules did not appear to participate in the histochemical reaction. Comparisons of these findings with work on the main ducts of the pancreas in other species have been made and discussed.

Animals↗

The ultrastructure of the centroacinar cells within the pancreas of the starling (Sturnus vulgaris).

Tissues from the dorsal lobe of the pancreas of 8 starlings (Sturnus vulgaris) were examined electron microscopically using conventionally prepared samples. Centroacinar cells were distinguished from exocrine pancreas cells by differences in size, shape, distribution, position and zymogen granule content. The centroacinar cells closely resembled ductal cells and were separated from them only by position. Both electron-lucent and electron-dense forms of centroacinar cells were observed. Centroacinar cells show a prominent single nucleus, often displaying at least one nucleolus, surrounded by cytoplasm in which lies a spectrum of both primary and secondary lysosomes, mitochondria which appear to have some tubulovesicular cristae amongst the predominating transverse cristae, a sparse para- or supranuclear Golgi apparatus, and variable populations of ribosomes and profiles of both rough and smooth endoplasmic reticulum. Cell surface features include microvilli, 'blebs' and the occasional single cilium. Centroacinar cells are believed to be involved in electrolyte secretion although, from a study of their ultrastructure, the absence of beta cytomembranes with numerous mitochondria in their neighbourhood, would appear to contra-indicate the maintenance of an osmotic gradient between the extracellular fluid and any secretory product.

Animals↗

The occurrence of erythropoiesis in the thymus of the bank vole (Clethrionomys glareolus).

The thymus of wild young and adult bank voles (Clethrionomys glareolus) was examined by histological methods for the presence of developing erythroid cells. Nucleated erythroid cells were observed in 26% of the glands examined by light microscopy and in 69% of the glands examined by electron microscopy. The largest number of developing erythroid cells was observed in the thymus of pregnant females, also showing raised reticulocyte counts (3.1-10.2%). However, erythropoiesis could also be found in breeding and non-breeding, first year and older animals. Erythroid cells were mainly located in the cortex, sometimes in small groups interspersed between lymphoid cells, and also randomly scattered in the cortex. Occasionally, macrocytic erythroid cells were also present. Pyknotic cells were commonly present, and granulopoiesis was frequently observed.

Animals↗

The weight of the human thymus gland at necropsy.

The wet, lipid and lean dry weights of 574 thymus glands from Coroner's necropsies were examined for age-related changes. Despite enormous variation in wet and lipid weights at all ages there was a gradual decrease in wet weight with age and a significant increase in lipid weight until 40--50 years of age, with little change thereafter. There was a small decrease in lean dry weight with age, but it is not known if this reflects a change in cellularity. Multiple regression analysis showed that lower wet and lipid thymic weights were associated with long-term stressful conditions, and higher weights with deaths from asphyxia (largely in younger persons) and five groups of cardiovascular conditions. The percentage of lipid in these groups was not increased.

Adolescent↗

The presence of erythroid cells in the thymus gland of man.

Biopsies of the right lobe of normal thymus glands without signs of neoplasia or germinal centre formation from 35 patients ranging in age from 20 to 60 years of age, and from 3 children aged 6, 7 and 12, showed on electron microscopic examination of the material from 14 patients that in 12 cases erythroid cells of all stages of development past the beginning of haemoglobinisation were present in some degree. Earlier erythroid cells could not be identified on morphological grounds with certainty, but cells which could have been lymphoblasts, proerythroblasts and stem cell were all observed. A section of a megakaryocyte was seen in one thymus. The importance of erythropoiesis within the thymus gland is briefly discussed.

Adult↗

Ultrastructural studies on erythropoiesis in the avian thymus. I. Description of cell types.

Thymus lobes from three species of birds, Quelea quelea, Passer domesticus and Sturnus vulgaris, have been examined ultrastructurally. The component cell types are compared with their counterparts in mammalian thymus glands, and found to be similar. Greater differences between small, intermediate and enlarged lobes of one species than exist between species. Developing erythroid cells are present in most enlarging and some enlarged glands. They appear to be developing at the expense of lymphoid cells in some birds. The origin of these cells is discussed. Cells that are possible candidates for the production of some thymic hormones are also described.

Animals↗

Ultrastructural studies on erythropoiesis in the avian thymus. II. A stereological analysis of the lymphoid and erythroid cells.

The cortex of enlarging thymic lobes from adult haemorrhaged Quelea quelea were found to be similar to those of wild birds where the thymic enlargement was occurring naturally. A detailed stereological analysis of cells broadly designated as lymphoid, and the construction of models to account for the results, indicates that the enlarging thymic lobe contains both large and small blast cells, a heterogenous group of medium lymphocytes, erythroid cells, and two types of very small lymphocytes. The distinction between early erythroid cells and some lymphocytes, despite this detailed analysis is very difficult, but it is possible in enlarging thymic lobes that up to 42% of the lymphoid cells may have erythroid characteristics.

Animals↗

The effect of haemorrhage on the cell populations of the thymus and bone marrow in wild starlings (Sturnus vulgaris).

Following the withdrawal of blood from the brachial vein of adult wild starlings (Sturnus vulgaris) changes in the cell populations within the bone marrow and thymus were observed over an eight day period. The packed cell volume, haemoglobin content and reticulocyte count of the peripheral blood was determined before and after haemorrhage. The maximum effect of the haemorrhage was observed in the bone marrow after four days when the population of small lymphocytes, and basophilic erythroid precursors were reduced to less than 1%. At the same time the percentage of another line of erythroid cells increased to 68%. This second erythroid lineage was the major erythroid line in the thymus, and again maximum representation occurred at 4 days post haemorrhage. After this the thymus became predominantly lymphoid and started to increase in size. The two erythroid lines are described and their status with regard to avian thrombocytes is also discussed. The peripheral blood had not attained the pre-haemorrhagic values for reticulocyte counts by eight days although the packed cell volumes and haemoglobin contents were similar.

Animals↗