Second testing for hypothyroidism.
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Biomedical subjects
Publications and source records attributed to G D Levine.
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1H-nuclear magnetic resonance spectroscopy (NMR) was adapted to isolated rabbit fundic glands and identification made of compounds responsible for several observed spectral resonances. A minimum gland concentration of 0.5 mg dry weight or 5 mg wet weight per 0.5 ml was needed for adequate signal-to-noise ratio. At physiological temperature and pH, the glands demonstrated reproducible spectra, stability for accumulation times greater than 30 min and responsiveness to histamine stimulation, as measured by oxygen consumption and aminopyrine uptake. The relatively anaerobic conditions favored use of proton compared to phosphorus NMR, since 1H-NMR allowed significantly shorter spectral accumulation times and therefore did not compromise glandular viability to the same extent as 31P-NMR. The most conspicuous resonance in the gland spectrum was assigned to the -N+(CH3)3 protons of choline and related compounds. In membrane-free lysates, several components of the signal were resolvable and assigned to choline, phosphatidylcholine, phosphocholine and L-alpha-glycerophosphocholine. Thin-layer chromatography verified that phosphatidylcholine and phosphatidylethanolamine were the major phospholipids present in gland lipid. Presumably, they represent the source of the surface-active phospholipids present in gastric juice, which may play a role in gastric cytoprotection.
The effect of short-term fiber ingestion on jejunal ion fluxes was evaluated in rats using a standard Ussing chamber technique. Ingestion of cellulose and pectin decreased the mucosal to serosal fluxes of both Na and Cl but did not significantly alter serosal to mucosal fluxes; net fluxes of both Na and Cl were significantly lower in the group supplemented with dietary fiber as compared to those animals fed a fiber-free diet. Both potential difference and short-circuit current were higher in the fiber-free group than in the group supplemented with dietary fiber; tissue conductance, however, was unaffected by fiber ingestion. The residual flux of all three groups was virtually identical suggesting that electrical alterations observed after cellulose and pectin ingestion are not the result of ion fluxes other than Na and Cl. These data, coupled with previous observations that short-term fiber supplementation impairs glucose and leucine absorption, suggest that fiber ingestion alters the intestinal membrane, specifically sites of active transport.
Five histologically distinct variants of thymic carcinoma are described: mixed small cell undifferentiated squamous cell carcinoma (three cases), basaloid carcinoma (two cases), mucoepidermoid carcinoma (one case), clear cell carcinoma (one case), and sarcomatoid carcinoma (one case). While forming a heterogeneous group, these tumors bear the common features of an anterior mediastinal location and lack of evidence of a primary tumor elsewhere, marking them as primary thymic neoplasms. All except the sarcomatoid variant are morphologically related to similar malignant neoplasms of other organs. These tumors should be recognized as morphological variants of primary thymic carcinoma and demonstrate the ability of thymic epithelium to differentiate toward a variety of different cell types.
Thirty-five cases of spindle-cell carcinoid tumors of the lung were studied. Fifteen patients were male and 20 female, and they ranged in age from 33 to 78 years, with a mean of 57.6 years. Eleven neoplasms were located in the left lung and 23 in the right lung; a disproportionately large number of neoplasms were present in the right middle lobe. The tumors were most commonly encountered as an incidental finding on chest roentgenogram. None of the patients had unequivocal evidence of the carcinoid or any other endocrine syndrome. All but two of the lesions were located n the periphery of the lung and most were subpleural. They ranged in size from 0.7 to 4 cm, with 82% of the neoplasms having a maximum dimension of 2 cm or less. Microscopically, the neoplasms were composed predominantly or entirely of spindle cells which were fairly uniform in length in any single lesion, but showed moderate variation from case to case. The shorter spindle cells were often arranged in an "organoid" pattern, while the neoplasms composed of larger spindle cells were more "mesenchymal" in appearance. Silver stains were performed on 12 cases and all were argyrophil-positive. Cytoplasmic dense-core granules were identified in all four neoplasms examined ultrastructurally. Twelve cases were treated by wedge resection or segmental resection, and 18 cases by lobectomy. Hilar lymph nodes were removed from seven patients, and in two there were microscopic lymph node metastases. One other patient had a single microscopic bony metastasis. Follow-up information was available for 22 patients and ranged from 1 to 13 years with a mean of 5.4 years. None of the patients have had metastases other than those described above and none of the patients had died of their disease.
The effects of acute and chronic dietary fiber (cellulose and pectin) supplementation on both intestinal glucose absorption and oral glucose tolerance were studied in rats. The effect of intraluminal fiber on intestinal glucose absorption was evaluated in perfused jejunal loops as was the effect of a single cellulose or pectin-supplemented meal on serum glucose responses to a carbohydrate load. Neither pectin nor cellulose impaired jejunal glucose absorption, but pectin did decrease serum glucose responses to an oral carbohydrate load. Chronic fiber supplementation significantly decreased intestinal glucose absorption in rats who had received for 5 wk a fiber-free diet supplemented with either cellulose (10%) or pectin (5%). Chronic supplementation with cellulose or pectin impaired intestinal glucose absorption and decreased serum glucose responses. These results suggest that differences in glucose homeostasis observed after ingestion of single high-fiber meals may be caused by viscosity-related delays in the rate of gastric emptying, whereas differences noted after chronic supplementation of dietary fiber are related to adaptive changes in the intestine.
Electron microscopy of the normal human thymus demonstrates a supporting framework of epithelial-reticular cells with long branchticular cell processes lie lymphocytes, macrophages, and rare myoid cells. Both small and large lymphocytes are evident. No desmosomes are observed between the lymphocytes and the epithelial-reticular cells. Macrophages are most numerous in the cort(x were they often contain phagocytized nuclear debris. The possible functional significance of the above-described fine structural features is discussed.
Although the term thymic hyperplasia is used most commonly to indicate the occurrence of germinal centers in the thymus, cognizance must be taken of the fact that such centers may occur in apparently normal thymuses in both children and adults. A concept of thymic compartmentalization is proposed with origin of germinal centers in the perivascular space (extraparenchymal compartment) of the thymus. These germinal centers contain a high percentage of B lymphocytes in contrast to the true thymic parenchyma. Although the significance of germinal centers in the thymus parenchyma. Although the significance of germinal centers in the thymus in myasthenia gravis remains controversial, removal of nonneoplastic thymus in this condition is of proven therapeutic value. A variety of neoplasms originating in the thymus have previously been lumped together under the single term "thymoma." It is apparent, however, that thymoma, thymic carcinoid, various lymphomas, and germ cell tumors that arise in the thymus differ not only pathologically but also in their clinical behavior. Thymoma is regarded as an epithelial neoplasm and ultrastucturally is characterized by many desmosomes and tonofilaments. The lymphocytes do not behave in a malignant manner, and lymphomas of the thymus should be sharply separated from true thymoma. Poorly differentiated thymic carcinoma and histiocytic lymphoma may be distinguishable only by the electron microscopic demonstration of desmosomes and filaments in the thymic carcinoma. The evidence that Hodgkin's disease of the thymus ("granulomatous thymoma") is not a variant of thymoma appears overwhelming. Lymphoblastic lymphoma of the thymus is a distinctive neoplasm that is especially prevalent in teenage males. High levels of terminal transferase characterize the lymphoblasts and there is a striking tendency for leukemia to occur. Thymic carcinoid is usually nonfunctional, although one-third of the reported cases are associated with Cushing's syndrome. On light microscopy a ribbon pattern and punctate necroses are characteristic of thymic carcinoids. Electron microscopic demonstration of many dense core granules is invaluable in establishing this diagnosis. An important clue to the diagnosis of thymic seminoma (a neoplasm that shows the same radiosensitivity as its testicular counterpart) is the frequent presence of epithelioid and giant cell granulomas and germinal centers. Separation of the various thymic neoplasms described not only is justifiable on pathologic grounds but is often essential for appropriate patient investigation and treatment.
We describe the clinical, histologic, and fine structural features of two thymic carcinoid tumors that had a major spindle cell component, and present the reason for classifying our two cases as variants of thymic carcinoid tumors. These tumors pursued an aggressive clinical course, demonstrated histologic features such as vascular invasion and mitotic activity, ultrastructurally contained numerous dense-core granules, and lacked prominent tonofilaments and well-formed desmosomes. Radiotherapy, even for apparently encapsulated cases, may be indicated for this aggressive mediastinal neoplasm, which can be clearly separated from the thymoma by clinical, histologic, and fine structural criteria.
This study describes the ultrastructural findings in 16 cases of nodular lymphoma, and compares these with normal germinal centers in order to determine the possible germinal center origin of the lymphomas. Long branching desmosome-associated dendritic reticulum cells, characteristic of germinal centers, were found in all 16 cases of nodular lymphoma. Desmosomes were observed only between dendritic cells and not between lymphoid cells, and they were seen in only 1 of 7 cases of diffuse lymphoma. Cells comprising the nodular lymphomas share cytologic features, such as nuclear blebs and marked nuclear indentations, with germinal center cells. It appears that nodular lymphomas have a close anatomical relationship to germinal centers, although their actual origin from these sites is not established by this study. They are composed of lymphoid cells; we have no evidence to confirm the view that nodular lymphomas are derived from dendritic cells. Light and electron microscopic findings have been compared in order to establish the nature of large "histiocyte-like" cells in the nodular lymphomas. Many of these cells appear to represent transformed lymphocytes rather than histiocytes. They are more numerous in so-called mixed "histiocytic" lymphocytic lymphomas than in poorly differentiated lymphocytic lymphomas, which otherwise are ultrastructurally similar. This study casts doubt upon the existence of a mixed lymphocytic and histiocytic lymphoma within the spectrum of the nodular lymphomas, and indicates that a cytologic continuum exists between cells interpreted as poorly differentiated lymphocytes and those heretofore identified as histiocytes.
Electron microscopy of the normal human thymus demonstrates a characteristic vascular-parenchymal relationship. The vascular lumen is always separated from the thymic parenchyma by: the endothelial cell cytoplasm, a muscular coat in arterioles and veins, the vascular basal lamina, a perivascular space containing collagen fibers and cells, the epithelial-reticular cell basal lamina and the epithelial-reticular cell cytoplasm. The width of this perivascular space is proportional to the size of the vessel it surrounds; it is wide around the vessels in the septa and at the cortical-medullary junction, but narrow around capillaries. While many cells are present in this space around larger vessels, only collagen is observed around the capillaries. Lymphocytes are the predominant cell type in the space; however, plasma cells, eosinophils, histiocytes, polymorphonuclear leukocytes, mast cells and unidentified granulated cells are also seen. The vascular complex described above may function as a blood-thymus barrier, as the initial site of exposure of the lymphocytes to circulating antigen and as the route of lymphocytes from the thymus.
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In this study, thymoma is defined as a neoplasm of the epithelial-reticular framework cells of the thymus. As in the normal thymus, these cells regularly displayed branching tonofilaments, macuale adherens, elongated processes, and basal lamina. These characteristics proved useful in the differential diagnosis of thymoma from a variety of anterior mediastinal tumors including thymic carcinoid, lymphoma, germinoma (seminoma type), and fibrous mesothelioma. Lymphocytes in the thymomas often showed mitotic activity and a moderate degree of transformation. The significance of this and the gland-like spaces, vacuolated epithelial cells, starry-sky appearance, emperipolesis, and perivascular spaces is discussed.
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