Giant mitochondria in alcoholic liver disease.
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Biomedical subjects
Publications and source records attributed to H Yokoo.
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Six cases of primary lung cancer that closely mimic malignant pleural mesothelioma clinically and anatomically are compared with four proven cases of malignant pleural mesothelioma. Findings on roentgenograms of the chest, clinical history, and gross examination of the lung specimens are not helpful in distinguishing between these two neoplasms. Microscopic examination of the hematoxylin and eosin-stained tissues is often inconclusive. Tissues were stained with hematoxylin and eosin, PAS with and without diastase treatment (DPAS), mucicarmine, alcian blue, toluidine blue, and colloidal iron with and without digestion by testicular hyaluronidase. Among these histochemical methods, DPAS was found to be particularly useful in distinguishing the primary lung cancers from the mesotheliomas. All primary lung cancers except one showed DPAS-positive material (mucin) in both the cytoplasm of the cancer cells and within the lumina of neoplastic glands. In contrast, none of the mesotheliomas showed the presence of DPAS-positive material. Histologically, all lung cancers were glandular. Five were classified as bronchiolar carcinoma, the remaining one as poorly differentiated adenocarcinoma. In two of the bronchiolar carcinomas, a small subpleural primary focus was demonstrated. This finding suggests a possible origin of these cancers as a small subpleural tumor that became widely disseminated via the subpleural lymphatics. This form of primary lung cancer possesses sufficient gross and microscopic characteristics that recognition should be given to it as a variant of primary lung cancer, with emphasis on differentiating it from pleural mesothelioma.
A tumor occurring in the ethmoid sinus in a 38-year-old man had the histological characteristic features of an typical fibroxanthoma. It recurred nine years after the initial excision, causing the clinical symptoms of progressive nasal obstruction.
Mallory bodies (MBs) were isolated from the livers of eight alcoholic patients. The method consisted of homogenization, velocity sedimentation in 60 per cent sucrose solution and two-phase polymer centrifugation using a polyethylene glycol-dextran system. MBs were isolated in large quantity and high purity (more than 95 per cent in some cases). Isolated MBs maintained the characteristic filamentous structures. They were solubilized in 6 M guanidine hydrochloride in 10 per cent or 1 per cent acetic acid by sonication or in 1 per cent sodium dodecyl sulfate with 5 per cent 2-mercaptoethanol and 8 M urea. The solubilized MB protein produced three peaks on Sephadex G-100 chromatography and at least five intense protein bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The fractions from control livers contained several bands which were identical with the major components of isolated MB protein. These findings suggest that MBs are not homogeneous protein, but that they are probably complexes of various proteins, and that some components of MBs are present in normal hepatocytes. The exact nature of MBs has yet to be established.
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Liver biopsies obtained from 24 patients with alcoholic liver disease were studied by light and electron microscopy. Comparisons of the same cells in adjacent sections revealed that alcoholic hyalin is a fibrillar deposit without limiting membranes and is readily distinguished from giant mitochondria. This characteristic fibrillar structure was encountered in hepatocytes, ductular cells and in benign and malignant hepatomas. Three distinct morphologic forms of alcoholic hyalin were observed: a) bundles of filaments in parallel arrays, b) clusters of randomly oriented fibrils and c) a granular or amorphous substance containing only scattered remains of fibrils. Closely associated with alcoholic hyalin and often found along its entire circumference, were bundles of fine filaments in parallel arrangement of much smaller size. These occasionally displayed variations in orientation and merged with the filaments in the alcoholic hyalin body. Similar fine filaments were observed, in considerable excess, in cells which did not contain alcoholic hyalin. According to our findings, the fine filaments and the significantly larger filaments in alcoholic hyalin could be parts of a contractile system elaborated by host cells during the course of hepatic injury.
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Acute and chronic effects of gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.
Tyrosine hydroxylase (TH) was assayed in eight regions of rat brain following repeated treatment with a TRH analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide). Repeated DN-1417 treatment (20 mg/kg/day, IP) for 7 days increased TH activity in the ventral tegmental area and decreased in the prefrontal cortex polar, medial and lateral fields and olfactory tubercles. No significant change in TH activity was found in the nucleus accumbens, striatum and substantia nigra. Kinetic analysis showed that the increased TH activity in the ventral tegmental area was due to an increase in Vmax, but not a change in the apparent Km of TH for a cofactor, 6-methyl-tetrahydropteridine. When TH was assayed at a suboptimal pH and in the presence of a subsaturating cofactor, the striatal TH was activated significantly after DN-1417. In the prefrontal cortex medial field, nucleus accumbens and olfactory tubercles, TH activity assayed under the suboptimal condition was not modified by DN-1417 treatment. These results suggest an intimate involvement of central dopaminergic systems in the actions of DN-1417.
A-52-year-old woman was admitted to a hospital because of 2-year history of abnormal behavior and impaired visual acuity. Magnetic resonance imaging delineated a sizable mass at the suprasellar region. The partially removed tumor was arranged in irregular lobules composed of an admixture of clusters of cobblestone-like small cells and process-bearing cells with ovoid nuclei, surrounded by a fine, neuropil-like matrix. The Zellballen structure was inconspicuous, and mitosis was absent. Immunohistochemically, the tumor cells were positive for chromogranin A, synaptophysin, class III beta-tubulin and neurofilament, while negative for glial fibrillary acidic protein, cytokeratin and all 6 pituitary hormones. S100 protein expression was limited to cells adjacent to stroma. The MIB-1 labeling index was 0.5%. Histopathological diagnosis was paraganglioma of abortive architecture. Ultrastructurally, numerous dense-cored vesicles were found within the processes and cytoplasm. Synapse formation was not demonstrated. Interestingly, crystalloids up to 3 microm in size were frequently found. They had hexagonal or quadrilateral architecture without limiting membranes. The interval between periodically arranged fibrils was variable, ranging from approximately 20 - 50 nm. Retrospective examination by light microscopy failed to reveal corresponding structures. Crystalloids are rare manifestation of paragangliomas, yet undescribed in those of intracranial origin. Furthermore, the ultrastructure of the present case differs from those of previous cases.