GIANT CELL CARCINOMA OF THE PANCREAS

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67-year-old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.     

Co-expression in CHO cells of two muscle proteins involved in excitation-contraction coupling

Summary Ryanodine receptors and dihydropyridine receptors are located opposite each other at the junctions between sarcoplasmic reticulum and either the surface membrane or the transverse tubules in skeletal muscle. Ryanodine receptors are the calcium release channels of the sarcoplasmic reticulum and their cytoplasmic domains form the feet, connecting sarcoplasmic reticulum to transverse tubules. Dihydropyridine receptors are L-type calcium channels that act as the voltage sensors of excitation-contraction coupling: they sense surface membrane and tranverse tubule depolarization and induce opening of the sarcoplasmic reticulum release channels. In skeletal muscle, ryanodine receptors are arranged in extensive arrays and dihydropyridine receptors are grouped into tetrads, which in turn are associated with the four subunits of ryanodine receptors. The disposition allows for a direct interaction between the two sets of molecules.CHO cells were stably transformed with plasmids for skeletal muscle ryanodine receptors and either the skeletal dihydropyridine receptor, or a skeletal-cardiac dihydropyridine receptor chimera (CSk3) which can functionally substitute for the skeletal dihydropyridine receptor, in addition to plasmids for the ₂, and subunits. RNA blot hybridization gave positive results for all components. Immunoblots, ryanodine binding, electron microscopy and exposure to caffeine show that the expressed ryanodine receptors forms functional tetrameric channels, which are correctly inserted into the endoplasmic reticulum membrane, and form extensive arrays with the same spacings as in skeletal muscle. Since formation of arrays does not require coexpression of dihydropyridine receptors, we conclude that self-aggregation is an independent property of ryanodine receptors. All dihydropyridine receptor-expressing clones show high affinity binding for dihydropyridine and immunolabelling with antibodies against dihydropyridine receptor. The presence of calcium currents with fast kinetics and immunolabelling for dihydropyridine receptors in the surface membrane of CSk3 clones indicate that CSk3-dihydropyridine receptors are appropriately targeted to the cell's plasmalemma. The expressed skeletal-type dihydropyridine receptors, however, remain mostly located within perinuclear membranes. In cells coexpressing functional dihydropyridine receptors and ryanodine receptors, no junctions between feet-bearing endoplasmic reticulum elements and surface membrane are formed, and dihydropyridine receptors do not assemble into tetrads. A separation between dihydropyridine receptors and ryanodine receptors is not unique to CHO cells, but is found also in cardiac muscle, in muscles of invertebrates and, under certain conditions, in skeletal muscle. We suggest that failure to form junctions in co-transfected CHO cell may be due to lack of an essential protein necessary either for the initial docking of the endoplasmic reticulum to the surface membrane or for maintaining the interaction between dihydropyridine receptors and ryanodine receptors. We also conclude that formation of tetrads requires a close interaction between dihydropyridine receptors and ryanodine receptors.     

A comparison of three bioelectrical impedance analyses for predicting lean body mass in a population with a large difference in muscularity

This study tested the hypothesis that, as compared to whole-body bioelectrical impedance (BI) analysis, segmental BI analysis can estimate lean body mass (LBM) more accurately in a population with a large difference in muscularity. In addition to whole-body BI, which determines impedance (Z) between the wrist and ankle, two segmental BI analyses which determine the Z value of every body segment in each of (1) the arms, legs and trunk (distal BI) and (2) the upper arms, upper legs and trunk (proximal BI) were applied to a group of 125 male athletes and 75 non-athletes. The subjects were divided into validation and cross-validation groups. Simple and multiple regression analyses were applied to (length)²/Z (BI index) values for the whole-body and each body segment, to develop the prediction equations of LBM measured using air-displacement plethysmography. In the validation group, the SE of estimation was similar in the whole-body (3.4 kg, 5.4%), distal (3.4 kg, 5.5%) and proximal BI (3.3 kg, 5.2%) analyses. However, the whole-body and distal BI analyses produced systematical errors in the estimates of LBM. Moreover, the residuals in the two methods significantly (P<0.05) correlated with the ratios of BI indices of the upper arms and upper legs to those of the arms and legs, respectively, calculated as variables approximating the relative development of lean tissues at the proximal area of limbs. On the other hand, the proximal BI analysis was validated and cross-validated. Thus, the accuracy of estimating LBM was similar in the whole-body and the two segmental BI analyses. However, the prediction equations derived from the use of the whole-body BI index and a combination of the arms, legs and trunk BI indices produced a systematical error relating to the difference between the limb segments in lean tissue development.     

Functional tyrosine kinase inhibitor profiling: a generally applicable method points to a novel role of platelet-derived growth factor receptor-beta in tuberous sclerosis

A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.     

Electron microscopic study of the prenatal development of the thoracic aorta in the rat

Prenatal development of the thoracic aorta of the rat during the period ranging from gestational days 12 to 21 was examined by transmission electron microscopic and morphometric studies. The process of wall formation occurred in four major phases. At phase I (gestational day 12), the dorsal aorta consists of an endothelium and loosely surrounding mesenchymal cells. Collagen fibrils and fine filamentous materials are sparsely present in the intercellular space. At phase II (days 13 to 16), the mesenchymal cells begin to differentiate to myoblasts, which have small clusters of myofilaments with dense bodies, rough endoplasmic reticulum, and a discontinuous basal lamina. The differentiating cells form a few compact cell layers around the endothelium. Elastic fibers first occur sparsely in juxtacellular spaces at days 13–14. The thickness of the aorta increases rapidly from 1–3 layers of cells at day 13 to 5–8 layers at day 17, leading to a maximum of 5–9 cell layers at day 20. The differentiation of myoblasts and elastogenesis are initiated in the inner layers, and later progress toward the outer layer of the aortic wall. At phase III (days 17 to 19), the myoblasts continue to develop into typical smooth muscle cells, and elastic fibers rapidly increase in both size and number. At phase IV (day 20 and later), smooth muscle cells have well-developed myofilaments in the cell periphery, and rough endoplasmic reticulum and other organelles tend to accumulate in the apical portion of the cytoplasm. Elastic laminae appear in a few inner layers of the aortic wall.     

BRONCHIOLO-ALVEOLAR ADENOCARCINOMA WITH MULTIPLE CYSTS

An autopsy case of bronchiolo-alveolar adenocarcinoma in the lung is reported. The patient is a 70-year-old male who complained of severe cough with 500–600 ml watery sputum a day, loss of weight, and general fatigue. Autopsy revealed numerous whitish tumors in various sizes with multiple cysts in both lungs, with no metastasis being found in any other organs. Histological findings identified the tumor as a bronchiolo-alveolar adenocarcinoma originating from the lungs. Electron-microscopic findings showed that the tumor cells were covered by prominent microvilli, and contained abundant irregulary-shaped cytoplasmic vacuoles suggestive of mucin.     

Four cases of wheat-dependent exercise-induced anaphylaxis with negative gluten cap-rast score]

BACKGROUND: Either omega-5 gliadin or high molecular weight glutenin is known to be a major allergen in wheat-dependent exercise-induced anaphylaxis (WDEIA). It is generally considered that gluten specific IgE score is more reliable than that of wheat specific IgE score for the diagnosis of WDEIA. Our aim was to verify the significance of gluten specific IgE in the diagnosis of WDEIA. METHODS: We evaluated the result of gluten CAP-RAST score and omega-5 gliadin specific IgE score on four WDEIA patients who visited our hospital during the years 2004 and 2005, whose diagnosis were onfirmed by prick tests, immunoblot tests and provocation tests. RESULTS: Contrary to our expectations, all four patients showed negative gluten CAP-RAST scores, however all patient's omega-5 gliadin specific IgE scores were positive. CONCLUSION: Our results suggest that gluten specific CAP-RAST score is unreliable in the diagnosis of WDEIA. On the other hand omega-5 gliadin specific IgE score is possibly a better candidate as a diagnostic tool for WDEIA.     

Koebner phenomenon in lupus erythematosus with special consideration of clinical findings

The isomorphic response of Koebner can be observed not only in psoriasis, but also in other diseases, such as lichen planus and some systemic diseases including LE (lupus erythematosus) or sarcoidosis. Several clinical findings in LE skin were presented and discussed in this review. The mutually-interactive-, negative-, and internal-Koebner phenomena were introduced and discussed with some speculative views. Many forms of environmental stress on the skin were reported as provocating factors of the Koebner phenomenon, including trauma, scratching, UV-exposure, and various types of dermatitis. Clinical observations of the nature, localization, and movement of lesions should be carefully made. The pathophysiology of the Koebner phenomenon may be classified into two steps. A first non-specific inflammatory step and a second disease-specific step. The inflammatory products released from the first step would be targeted in the second step. In the first step, there could be many substances including cytokines, stress proteins, adhesion molecules, or autoantigens translocated from intra-cellular areas. In the second step after latent periods, there may be disease-specific reactions, including ones by T-cells, B-cells, autoantibodies, and immune deposits, under the restriction of genetic backgrounds. The Koebner phenomenon may prove useful in understanding the pathophysiology of diseases of unknown origin.