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Biomedical subjects

C M Payne

Publications and source records attributed to C M Payne.

144 records · Page 8Linked to original sources

The effect of steroids on peripheral blood lymphocytes containing parallel tubular arrays.

The response of lymphocytes containing cytoplasmic inclusions called parallel tubular arrays (PTA) was determined after the administration of the glucocorticoid dexamethasone to 10 healthy volunteers. The percentage of these lymphocytes was found to increase during the lymphopenia induced by steroid administration. The size and number of parallel tubular arrays per cell showed no differences before and after steroid administration, indicating that the increase was a result of a change in the proportion of whole cells. This indicates, for the first time, that a morphologically defined population of lymphocytes from the normal peripheral circulation has been linked to a specific response, ie, steroid resistance. The possible mechanism of steroid resistance is discussed.

Adult↗

Fingerprint inclusions. Ultrastructural demonstration of muscle fiber type specificity.

Fingerprint inclusions were identified in the skeletal muscle of a child with severe hypotonia. The mean Z-line and M-line widths from each of 19 muscle fibers containing the fingerprint inclusions were calculated. The mean Z-line widths were 85-99 nm, and the mean M-line widths were 75-101 nm. According to out present system of fiber typing, all of these fibers would be classified as Type I. The possible pathogenesis and fiber type specificity of the fingerprint inclusion is discussed.

Child, Preschool↗

Parallel tubular arrays in severe combined immunodeficiency disease: an ultrastructural study of peripheral blood lymphocytes.

The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these inclusions was quite variable, with some attaining a length of 1.7 micrometer. They contained a tubular substructure with a diameter of 36--44 nm. The PTA were mostly located in the centriolar and Golgi regions of the cytoplasm, and were sometimes membrane bound. A centriolar origin of the inclusion was suggested. A second inclusion, the tubuloreticular structure, was found in only 1.4% of the circulating lymphocytes from one SCID patient. The origin of the PTA and its occurrence in severe combined immunodeficiency disease are discussed.

Female↗

Concentric laminated bodies. Ultrastructural demonstration of muscle fiber type specificity.

Concentric laminated bodies were identified in the skeletal muscle of 3 children affected by muscle weakness and hypotonia with probable cerebral involvement. The mean Z-line and M-line widths from each of 11 muscle fibers containing the concentric laminated bodies were calculated. The mean Z-line widths were 61-81 nm and the mean M-line widths from 7 out of 11 fibers were 54-65 nm. According to our present system of fiber typing, the majority of these fibers would be classified as subtype IIB. The possible pathogenesis and fiber type specificity of the concentric laminated body is discussed.

Child, Preschool↗

Intranuclear inclusions in a case of Creutzfeldt-Jakob disease: an ultrastructural study.

Two types of intranuclear inclusions were described in a brain biopsy from a patient with Creutzfeldt-Jakob disease. The first type of intranculear inclusion was papova virus-like and was observed within 20% of the nuclei of all astrocytes and neurons examined. The particles measured 32 nm in diameter and consisted of a dense core surrounded by a multi-layered shell. The second type of intranuclear inculsion was a granulo-fibrillar nuclear body found within the nuclei of astrocytes and neurons. The possible significance of these inculsions to the etiology of Creutzfeldt-Jakob disease is discussed.

Astrocytes↗

Ultrastructural fiber typing in normal and diseased human muscle.

The differential staining of the 3 fiber types for oxidative enzyme activity at the histochemical level provides the basis of their identification at the ultrastructural level. Type I fibers have the largest and most numerous mitochondria, the Type IIA smaller and less numerous mitochondria, and Type IIB have the smallest and least numerous mitochondria as studied in 4 patients without neuromuscular disease. Type I fibers could be distinguished from Type II fibers on the basis of mean Z-line width and IIA fibers could be distinguished from IIB fibers on the basis of mean M-line width. Type I fibers had wide Z-lines (95 nm) and wide M-lines (89 nm), Type IIA had narrow Z-lines (74 nm) and wide M-lines (79 nm) and Type IIB fibers had narrow Z-lines (69 nm) and narrow M-lines (60 nm). This system of fiber typing based on relative Z-line and M-line widths was applied to several abnormal muscle biopsies each of which showed a deficiency in at least 1 of the major histochemical fiber types. In each case, the same deficiency was revealed at the ultrastructural level by measuring the relative Z-line and M-line widths of the remaining fiber types.

Adenosine Triphosphatases↗

Intercostal muscle biopsy in human neuromuscular disease. Histochemical and electron microscopic studies.

External intercostal muscle biopsies were examined histochemically and by electron microscopy. The use of this muscle allowed correlation with physiological and pharmacological studies on the same specimens. Changes observed in musclar dystrophy and motor neurone disease resembled those previously described in biopsied limb muscle and underline the particular usefulness of this preparation in the study of human neuromuscular disease.

Adenosine Triphosphatases↗

Myopathy associated with linear scleroderma. A histochemical and electron microscopic study.

Pathologic findings in biopsied rectus femoris muscle underlying an area of linear scleroderma are described. The affected muscle was weak and atrophic. On electromyography it showed motor unit potentials of decreased amplitude and duration. Light microscopic changes were minimal. There was atrophy of some histochemical type I fibers. More prominent changes were found at the ultrastructural level, where many of the capillary basal laminae were thickened and reduplicated. Most striking was the presence of two types of electron-dense, rounded inclusions within the mitochondria, one ranging from 29 to 47nm in diameter and the other from 54 to 131 nm in diameter.

Action Potentials↗

Mitochondrial perturbation attenuates bile acid-induced cytotoxicity.

Hydrophobic bile acids such as deoxycholate (DOC) are known to damage liver cells during cholestasis and promote colon cancer. Cellular stresses induced by bile acids, which include mitochondrial and endoplasmic reticulum (ER) stresses, can result in apoptosis. We found that inhibition of mitochondrial complexes I-V with rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, myxothiazol or oligomycin strongly protected against DOC-induced apoptosis of HCT-116 cells. To understand the mechanism of this protection, we explored the ability of these specific inhibitors to reduce DOC-induced mitochondrial and ER stresses. Different inhibitors markedly reduced DOC-induction of mitochondrial condensation, the DOC-induced decrease in mitochondrial membrane potential and the DOC-induced dilatation of the ER (evidence of ER stress). A dramatic induction of nucleolar segregation by antimycin A and myxothiazol, two distinct complex III inhibitors, was also observed. These findings strongly implicate mitochondrial crosstalk with apoptotic signaling pathways and mitochondrial-nucleolar crosstalk in the development of apoptosis resistance in the colon.

Antimycin A↗

Lymphomas of the mediastinum.

The purpose of this clinicopathologic overview is to describe the types of lymphomas that present in the mediastinum. A comparison of the frequency of the different subtypes of lymphoma that are found in children and adults is provided. In general, immunohistochemistry and immunophenotyping studies are essential to the laboratory workup of neoplasms presenting in the mediastinum. An assessment of proliferative index in lymphoma is most helpful to determine tumor aggressiveness and patient prognosis. Electron microscopy is most helpful in the differential diagnosis of mediastinal neoplasms, where lymphomas may be distinguished from nonlymphomatous neoplasms using key ultrastructural features. The role of electron microscopy in the subclassification of lymphomas is mostly academic, with a few exceptions. The varied ultrastructural appearance of Hodgkin's cells and of different subtypes of non-Hodgkin's lymphoma is illustrated, using cases from our patient files. An ultrastructural study of lacunar cells in Hodgkin's disease provides evidence that the formation of lacunae may have a structural and/or physiologic basis. Mummified cells showing some of the features of a physiologic form of cell death, called apoptosis, are also described.

Humans↗

A multidisciplinary approach to the diagnosis of cutaneous T-cell lymphomas.

The cutaneous T-cell lymphomas (CTCLs) comprise a spectrum of non-Hodgkin lymphomas with a predilection for the skin. This heterogeneous group of CTCLs include the prototypic CTCL mycosis fungoides (MF) and the recently described Ki-1+ lymphomas. MF is notoriously difficult to diagnose in its early stages. The histologic appearance of early MF is indistinguishable from that of chronic dermatitis. The limitations of light microscopy in the diagnosis of the CTCLs have led to the development of other diagnostic laboratory techniques. The best approach to the diagnosis of the CTCLs is a multidisciplinary one and should include ultrastructural morphometry, immunophenotyping, immunogenotyping, and histologic evaluation whenever possible. It is the purpose of this overview to point out the strengths and weaknesses of each of these techniques and, together with clinical input, to provide a comprehensive and rational approach to patient care.

Gene Rearrangement↗

An image analysis workstation designed for multiple users: application of quantitative digital imaging techniques to electron microscopy.

The purpose of the present study is to describe the setup of an image analysis workstation designed for multiple users, and to show the application of digital imaging techniques to the analysis of electron microscopic images. The image analysis system consists of a conventional light microscope mounted on a table-top, vibration-free platform, a light box for viewing negatives, two separate video cameras, a switch box, a video monitor, a digitizing tablet, a computer, and morphometric software packages. The system can quantitate the amount that each of the 256 gray levels contributes to the image, perform morphometric analysis (eg, shape and size) on individual gray level-defined subimages, and perform statistical analysis. Each operator has access to his or her own data and program setups through the use of 21.4-Mb removable Bernoulli cartridges. This setup for multiple users prevents the cluttering of the hard drive of the computer and avoids the possibility of accidentally removing the stored data of another user. The quantitative capabilities of the digital imaging system is demonstrated using an image of a normal lymphocyte and an apoptotic cell (ie, a cell which has undergone programmed cell death), both captured on the same electron microscopic negative. A comparison of the histograms of nuclear densities determined for these two cells reveals subtleties in gray level distribution not appreciated by the naked eye.

Clinical Laboratory Techniques↗

Use of the uranaffin reaction in the identification of neuroendocrine granules.

This overview emphasizes the utility of the uranaffin reaction in the diagnosis of tumors derived from neuroendocrine cells. The history, cell organelle specificity, tissue specificity, pH requirements, and detailed procedure of the uranaffin reaction is provided. Uranaffin-positive granules are also identified within the NS granules of the stem cell paraneuron (archiparaneuron) of coelenterates, and a hypothetical evolutionary scheme depicting the possible origins of the key biochemical features of the advanced mammalian NS granule is included. The role of nucleotides, a major component of true NS granules, is discussed. A possible intragranular function of ATP as a regulator of osmotic pressure and the extracellular physiologic effects of secreted intragranular nucleotides are discussed in some detail.

Adenosine Triphosphate↗

Role of apoptosis in biology and pathology: resistance to apoptosis in colon carcinogenesis.

The overview of apoptosis presented here emphasizes cell deletion in the immune system, with particular reference to T- and B-lymphocyte development, and the in vivo and in vitro senescence of human neutrophils. Some biochemical criteria that are used to identify apoptotic cells are described. Pitfalls in using agarose gel electrophoresis as the sole method for the identification of apoptotic cells are discussed. There are multiple modes of cell death that can be identified at the morphologic level. Thus the central role of microscopic methods, and in particular, electron microscopy, as an important tool in the study of cell death mechanisms, is presented. Apoptosis has a protective role against disease and could, a priori, have an important role in either the initiation or progression of cancer. Two paradoxes concerning the relationship of tumor aggressiveness at the clinical level to mitotic activity have been explained by an evaluation of apoptotic index. In the first case, basal cell carcinomas grow slowly but show a high rate of mitosis. Here, the apoptotic rate is quite high, but just below the mitotic rate, thereby accounting for the slow rate of growth. A second instance is follicular lymphoma, which has a low rate of mitosis that is less than that described for reactive germinal centers. However, apoptosis is markedly reduced in follicular lymphomas compared with that seen in reactive germinal centers, thus providing an explanation for the progressive growth of the follicle. We present a brief description of recent work from our laboratory that indicates that apoptosis may play an important role in colon carcinogenesis. We have shown that sodium deoxycholate, the particular bile salt present in highest concentration in the colon, induces apoptosis in the goblet cells of the human colonic mucosa in an in vitro assay. The intriguing finding is that cells of the normal-appearing mucosa of colon cancer patients are resistant to bile salt-induced apoptosis. This suggests a novel hypothesis about the etiologic role of bile salts in colon cancer. The chronic presence of bile salts that accompany a high-fat diet could select for apoptosis-resistant epithelial cells in the colon over time. Thus, a resistance-to-apoptosis bioassay may prove useful as an intermediate biomarker for determining which individuals are at high risk for colon cancer.

Apoptosis↗