Biomedical subjects
Publications and source records attributed to M W Kanan.
We report the synthesis of the fluorescent 2'-deoxycytidine analogue 5-methylpyrimidin-2-one nucleoside, its incorporation at three specified sites in a single 60-nucleotide DNA molecule, and the use of its total and polarized intrinsic fluorescence to characterize RecA-DNA complexes. [reaction: see text]
The structure of hairs from three patients with sulphur-deficient hair, trichothiodystrophy, has been studied by light, plane-polarizing and scanning electron microscopy. Severe cuticular and secondary cortical degeneration was evident along almost the entire length of the hair shaft, with cuticle loss, trichorrhexis nodosa formation and trichoschisis. The severity of these changes varied between patients. The role of the cuticle in protecting hair from environmental damage is discussed.
Fenestrated capillaries were observed prenatally in the lateral nasal wall and in glandular capillaries of the nasal mucosa of the rat. The number of fenestrations increased towards full term and during postnatal life. Specific ultrastructural features in the vascular bed were found to be primarily determined in utero.
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Fibroblasts of skin explants from three normal men and six patients with recessive epidermolysis bullosa dystrophica (EBD-R) were cultured in Dulbecco's medium, grown to confluence, sectioned and studied with the electron microscope. The normal control fibroblasts from the 6th to 13th passage (secretory phase) showed irregular or lobed nuclei with centrally scattered chromatin. They also had prominent RER, Golgi complexes, variously shaped mitochondria and cytoskeletal microfibrils. Their peripheral cytoplasm exhibited many vacuoles and a small number of these were autophagic lysosomes. In addition to the ultrastructural features described in the control fibroblasts, the EBD-R cells from the 6th passage contained remarkable numbers of strongly electron dense lysosomal bodies through their entire cytoplasm with very few empty vacuoles. It is speculated that the accumulation of these lysosomes may be connected with a primary metabolic cellular defect in the dermal fibroblasts of patients with EBD-R akin to that described in mucopolysaccharide storage diseases.
Measurement of the PO2 in the mucosal cells and at various depths of the lamina propria lining the nasal cavity in five male goats using Silver's special microelectrodes, revealed relative hypoxia in the anterodorsal part of the nasal septum and tips of naso- and maxilloturbinals. In these sites PO2 values varied between 55-65 at the surface and 30-35 in the superficial subepithlial layer while elsewhere in the nose, lip and tongue, PO2 values of 85-90 were obtained. Temperature measurements with the thermistor in two goats yielded readings of 34-34-5 degrees C. in the hypoxic areas against 36-37 degrees C. in the posterior parts, the roof and floor of the nasal cavity. However, the oxygen tension diminished steadily in all areas as the microneedle electrode approached the chondro-osteal tissues but PO2 values of 0-10 in the perichondrium. The significance of these findings in the predilective localization of granulomata and various forms of vasculitis in the anterior endonasal tissues has been discussed.
On the basis of clinical, histological and bacteriological assessments, 31 patients in Central India were selected and classified as having active but early lepromatous leprosy and 4 patients as having early borderline leprosy. From the nose of each patient an average of 4 biopsies were taken from particular sites of the septum and turbinates either by punch biopsy or dissection with a scalpel. The nasal tissues from all the lepromatous patients contained many acid-fast bacilli; no bacilli or abnormalities were seen in nasal tissues from the borderline patients. The histopathology of these highly bacilliferous tissues is described. Bacilli were universally seen in macrophages, but they were also seen in blood monocytes and polymorphs, fibroblasts, squamous and pseudo-columnar epithelium, keratin, peri- and endo-neurial cells of tiny nerve bundles, erectile tissue, vascular plain muscle, perivascular histiocytes and frequently and abundantly in the cytoplasm of endothelial lining cells of lymphatics and of small blood vessels and free within the lumina of these vessels. Five basic mechanisms of escape of bacilli from the submucosa on to the surface, and thus into the external environment, are described. Secondary infection, in the presence of an expansile lepromatous infiltrate, together with simple trauma to the surface epithelium, are the main factors in the discharge of bacilli. These histopathological observations are consistent with the findings from other recent studies on the nose in leprosy regarding (1) the large numbers of morphologically intact and viable Myco. leprae excreted in the nasal mucus of lepromatous patients; (2) the clinical changes observed in the nose of such patients, and (3) the similar nasal involvement and excretion of Myco. leprae from the nose of mice inoculated with leprosy bacilli of human origin. Of particular interest was the frequency and intensity of bacilli within the endothelial lining cells of small blood and lymph vessels and the presence of bacilli free within the lumina of these vessels or within monocytes and polymorphs. The possible dynamic significance of these observations in the pathogenesis of leprosy is discussed. The significance of all these observations in relation to (1) the spread of leprosy; (2) local factors in the nose which might favour the growth of Myco. leprae, and (3) the nose as a portal of entry, are discussed.
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Seven guinea-pigs were inoculated intravenously with a rich suspension of Leishmania enriettii. During the sixth to the seventh week from inoculation, all of them developed lesions within the anterior nasal mucosa and in the vulva or scrotum. In one animal nodules occurred in the forepaws during the tenth week. The histology of the latter showed an epithelioid granuloma with multinucleate giant cells, while in all the others macrophages and monocytes highly parasitized with leishmania bodies, formed the main elements in the granulomatous infiltrate. Lesions seem to develop in the cool, non-hairy areas of the integument and those areas of the nasal mucosa which are constantly bombarded by the inhaled cool air stream. The anterior nasal mucosa, with its leaking venular network, its cool timperature, relative stasis and hypoxia probably provides the optimum micro-environment for the localization, survival and multiplication of the leishmanial protozoon.
A single dose of 8-16 mg of carbon C11/1431a was injected intravenously into rats, guinea-pigs, mice, goats and two pigs. Examination with the naked eye, dissecting microscope, light microscope and electron microscope of tissues from these animals sacrificed minutes, hours, weeks and up to 23 months after the injection revealed phogocytosis of most of the infected carbon by the professional phagocytes of the reticuloendothelial system (RES). However, in the non-RES sites carbon was trapped in significant amounts in the endothelial cells, the interendothelial spaces, pericytes and perivascular macrophages of the subepithelial capillaries and venules in the anterior nasal mucosa. The catchment area often showed partially fenestrated capillaries and redundant porous basement membrane around the venules. The leakage of carbon through these vessels was through these vessels was thought to be caused partly by the unusual porosity of the vascular walls and partly due to vascular stasis induced by constant loss of heat to the inspired air stream in post-natal life. The importance of these findings in the predilective localization of several granulomatous diseases and various forms of vasculitis in the nasal mucosa id discussed.
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