Congenital pseudarthrosis of the tibia: analysis of the histology and the <Emphasis Type="Italic">NF1</Emphasis> gene

Background Congenital pseudarthrosis of the tibia (CPT) is frequently, but not always, associated with neurofibromatosis type 1 (NF1). Double inactivation of the NF1 gene has been reported to be the pathogenesis of CPT in NF1 cases. Methods We analyzed the loss of heterozygosity (LOH) of the NF1 gene in cases of CPT with NF1 to examine whether double inactivation was seen in the case. In addition to morphological analysis, immunoexpression of differentiation markers was examined. Results and discussion The tibia tapered with the zone phenomenon from mature to immature bone with osteoblastic rimming, resembling osteofibrous dysplasia. Osteosclerotic bowed bone with a small number of osteoclasts suggested dysfunction of bone remodeling. Fibrous tissue at the site of pseudarthrosis was associated with the periosteum and demonstrated myofibroblastic differentiation accompanied by massive cartilage formation, suggesting some misdirection during the differentiation of periosteum to myofibroblasts or chondrocytes. LOH of the NF1 gene locus was not seen in fibrous tissue. This result suggests that CPT is not accompanied by double inactivation in every NF1 case.     

Clinical studies on the transabdominal resection of esophagocardial cancer and cervical anastomosis using bypass methods. Analysis of data on 76 patients

Transabdominal resection for esophagocardial cancer and reestablishment of alimentary continuity using bypass methods were performed in 76 patients. Thirteen underwent a bypass with a gastric tube and in 30, a colonic segment was prepared. In the remaining 33, a jejunal segment was used as a bypass organ, with considerable success. The 5 year survival rates were 68.8 per cent in those with stages (I+II), 16.5 per cent in those with stage III, 12.6 per cent in those with stage IV and 22.5 per cent in all cases, indicating similar results compared to those with cancer located in the upper third of the stomach with the limited proximal extension within the esophagocardial junction and operated on during the same period.     

Management of unruptured intracranial aneurysm in Japan: a Markovian decision analysis with utility measurements based on the Glasgow Outcome Scale.

The purpose of this study was to analyze the management of individual patients with unruptured intracranial aneurysms (UN-ANs) using a decision-analytic approach. Transition probabilities among Glasgow Outcome Scale (GOS) categories were estimated from the published literature and data from patients who had been treated at Kitasato University Hospital. Utilities were obtained from 140 health providers based principally on the GOS. Baseline analysis for a healthy 40-year-old man with an anterior UN-AN less than 10 mm in diameter showed that the quality-adjusted life expectancies for preventive operation and follow-up were 15.34 and 14.66 years, respectively. For a follow-up strategy to be preferred, the annual rupture rate had to be as low as 0.9%. These results were sustained through extensive sensitivity analysis. The results support preventive operation for UN-ANs, and identify problems that can be clarified with a well-designed stratified clinical trial.     

Analysis of Responsive Cells in Tolerance by the Oral Administration of Ovalbumin

The induction of immune tolerance is the most common consequence of protein feeding, i.e., “oral tolerance”. In this study we investigated the genetic basis of oral tolerance using various kinds of recombinant and congenic mice, and the cells involved in the development of this phenomenon in mice. The footpad swelling response to ovalbumin (OVA) was inhibited in mice that were orally fed OVA 7 days before sensitization. No effect of strain of mouse was seen in this inhibition. This inhibition could be transferred by Peyer's patch cells. The CD4^-8⁺ T cells were responsible for the inhibition of footpad swelling. The number of CD4⁺ cells from OVA-fed tolerant mice decreased significantly, but CD8⁺ cells did not.

The number of CD4^-8⁺ T cells was increased in Peyer's patches of OVA-fed tolerant mice, and were involved in the development of oral tolerance.     

Giant cell tumor of the scapula

This study reviews the demographic, radiologic, and histologic characteristics of 13 cases of an important primary skeletal neoplasm, giant cell tumor of bone, occurring in an uncommon location, the scapula. that eight of 13 patients presented prior to 20 years of age contrasts significantly with the typical age distribution (between 20–40 years) encountered in giant cell tumors arising in long bones. As it does elsewhere in the skeleton, giant cell tumor of the scapula frequently demonstrates cystic and/or telangiectatic components on histologic examination. The radiologic appearances of giant cell tumor in the scapula and in more typical locations are similar and include: (1) well-defined (geographic) margins, occasionally with a delicate sclerotic rim, (2) prominent trabeculations, (3) expanded bone contour, (4) frequent extension to the subchondral plate, and (5) absence of internal mineralization. Tumor sites within the scapula included: coracoid process, acromion, and body (three cases each); glenoid (two cases); and superior and inferior angles (one case each).The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of Defense, or the Uniformed Services University of the Health Sciences.     

Clinical significance of reverse redistribution in exercise thallium-201 SPECT after percutaneous transluminal coronary angioplasty

Clinical significance of reverse redistribution on thallium image was evaluated in 54 patients who had undergone PTCA. Thallium SPECT imaging was performed one week and three to six months after PTCA. Reverse redistribution was detected eight of 54 patients one week after PTCA and five of 38 patients three to six months after PTCA. In the segments with reverse redistribution, reduced regional wall motion and lesser degree of coronary stenosis was common features (p less than 0.05) angiography. In conclusion, reverse redistribution had a tendency to appear in the region with mild myocardial injury and relatively high coronary blood flow after PTCA. But in cases with new occurrence and disappearance of reverse redistribution during follow up period, we can not assess the factors to explain these phenomena. In these segments, "coronary flow reserve", "stunned myocardium", "hibernating myocardium" or other factors may be related.     

Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis

Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.     

Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity

Fas ligand (CD95L) is synthesized both on the cell surface membrane and in a soluble form. Although CD95L contributes to immune privilege in the cornea and testis, the functions of these alternatively processed proteins are not well understood. Some reports suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent responses in vivo, including hepatocyte apoptosis that causes liver failure. We show here that extracellular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity. The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on tissue culture plates coated with these matrix proteins; this effect was mediated by trimeric soluble CD95L. With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin. In addition, immunohistochemical analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix. The retention of soluble CD95L on extracellular matrices is likely to play an important role in the development of peripheral tolerance in immune-privileged sites.