Transgenic rabbits with increased VEGF expression develop hemangiomas in the liver: a new model for Kasabach-Merritt syndrome

Clinical studies have provided ample evidence that high (either systemic or local) levels of vascular endothelial growth factor (VEGF) are associated with several pathophysiological disorders, including hemangiomas. To investigate whether elevated VEGF expression could directly affect these disorders, we created a transgenic (Tg) rabbit model with increased hepatic expression of the human VEGF(165) transgene under the control of the human alpha-antitrypsin promoter. Tg rabbits exhibited marked hepatomegaly, with livers 2.5-fold heavier than those of control rabbits. Histological analysis revealed that the livers of Tg rabbits showed prominent dilation of the sinusoids and formed various-sized blood vessel networks, a feature of diffuse hemangiomas. Immunohistochemical staining revealed that the hepatocytes produced VEGF(165), whereas plasma VEGF(165) was not detected. Furthermore, Tg rabbits suffered from hemolytic anemia, thrombocytopenia and splenomegaly, which was associated with marked extramedullary hematopoiesis. The manifestations of Tg rabbits mimic many of the features of hemangiomatous disorders in humans such as the Kasabach-Merritt syndrome, and therefore this model may be potentially useful for the study of the pathogenesis and complications of hemangiomas as well as the investigation of angiogenesis inhibitors.     

Light and electron microscopic analyses of immediate and late tissue damage caused by radiofrequency ablation in porcine liver

Radiofrequency ablation (RFA) is an effective procedure for localized hepatocellular carcinoma. Contrast-enhanced CT depicts the ablated area as a hypoattenuated area without hepatic blood flow; however, light microscopy does not show obvious necrosis in the ablated area. We evaluated liver tissue changes after RFA by light microscopy and electron microscopy. The normal livers of three anesthetized pigs were coagulated using RFA after laparotomy. The liver was examined immediately, and 1 week after operation by light and electron microscopy. After RFA, the liver parenchyma surrounding the needle electrode was brown in color and surrounded by a red marginal zone separate from the normal liver parenchyma. Hematoxylin-eosin staining of the central area did not show cell necrosis, and the structures of liver sinusoids, liver cell cord and the nuclei of hepatocytes were preserved. However, electron microscopic examination of tissue immediately after RFA showed destruction of mitochondria of hepatocytes and fixation of sinusoidal cells. One week later, there was a large quantity of debris in the enlarged sinusoids, in addition to irreversible destruction of hepatocyte organelles. RFA of the porcine liver causes hepatocyte damage. This damage was not evident by light microscopy but clearly identified by electron microscopy.     

Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography

The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) uptake by human muscles during 35?min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150?beats per minute. [¹⁸F]FDG [62.9 (14.8)?MBq, mean (SD)] was injected after 15?min of running. PET imaging was started immediately after the running ended. The ratio of [¹⁸F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.     

Numerous eosinophilic globules (skeinoid fibers) in a duodenal stromal tumor: An exceptional case showing smooth muscle differentiation

A unique case of duodenal stromal tumor In a 51-year-old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of tangled 45 nm thick fibrils, which were ultrastructurally Identical to 'skelnoid fibers'. The presence of glycogen granules in the tumor cells and the Immunoreactivity for α-smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultra-structural features indicating neural differentiation. In previous studies, the presence of such 'skeinoid fibers' was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings In the present case suggest that numerous 'skeinoid fibers' can be Identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.     

Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease

Formalin-fixed paraffin-embedded hippocampal sections of brains with early-onset and late-onset Alzheimer's disease were studied immunohistochemically with antisera against cathepsin D and cathepsin B. In addition to the staining of neuronal perikarya, some of the senile plaques visualized by Bielshowsky silver staining and some of reactive astrocytes were positively stained with the antisera against cathepsin D and cathepsin B in brains with Alzheimer's disease. Abnormal localization of cathepsin D and cathepsin B immunoreactivity in neuronal perikarya was observed in brains with early-onset Alzheimer's disease. These findings demonstrate that the distribution of lysosomal proteases was altered in brains with Alzheimer's disease, suggesting the primary and/or secondary involvement of the lysosomal proteases in the pathological process of Alzheimer's disease.     

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.     

Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction

AIMS: To investigate the relation between localised amyloidosis and immunocytic dyscrasia. METHODS: Open lung biopsy specimens from a 72 year old man with multiple nodules in the right middle and lower lung were stained with haematoxylin-eosin, Congo red, and antibodies against IgG, IgA, IgM, and kappa and lambda light chains. Semi-nested PCR amplification for the immunoglobulin heavy chain (IgH) gene was performed using consensus primers for the VDJ region of the IgH gene, FR3A, LJH, and VLJH. RESULTS: The biopsy specimens contained eosinophilic amorphous material stained with Congro red and anti-kappa light chain, and surrounded by inflammatory cells intermingled with plasma cells. Plasma cells in the adjacent amorphous material showed cytoplasmic staining with anti-kappa. Polymerase chain reaction revealed a discrete amplified band of apparently uniform size with background smear. CONCLUSIONS: Primary AL type localised amyloidosis involves local accumulation of monoclonal plasma cells and their secreted products, as in nodular cutaneous amyloidosis. Localised AL type nodular amyloidosis is a separate entity in amyloidosis.     

Comparison of standard and hand-assisted laparoscopic radical nephrectomy for renal cell carcinoma.

A laparoscopic radical nephrectomy (LRN) for renal cancer can be performed using two methods, hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS). This institute initially used HALS to perform all radical nephrectomy, but gradually shifted to SLS. This study compared the two methods of radical nephrectomy: HALS vs. SLS, which were performed at a single institute. From March 1999 to November 2006, a total 129 patients with pathologically confirmed renal cell carcinoma underwent LRN, including 73 patients with the HALS and 56 patients with SLS. The median operative time was 264 minutes, and median estimated blood loss was 200 ml in the HALS group, respectively. The median operative time and median estimated blood loss in the SLS were 215 minutes and 100 ml, respectively. There was no significant difference in either the operative time or estimated blood loss between HALS and SLS. The median time to both postoperative oral intake and ambulation in the SLS were 1 day. Neither of these events after SLS was significantly shorter than that after HALS. The 4-year disease-free and overall survival rates in the HALS patients were 97.5% and 98.2%, respectively. Both the 4-year disease-free and overall survival rates in the SLS patients were 100%. Since no significant differences were observed between the two operative methods (SLS and HALS) regarding the operative data, postoperative course and oncological outcome, the surgical method for LRN can be selected according to characteristics of each surgical method.     

Elemental distributions and microtensile bond strength of the adhesive interface to normal and caries-affected dentin

The aim of this study was to evaluate the microtensile bond strength (microTBS) and the elemental contents of the adhesive interface created to normal versus caries-affected dentin. Extracted human molars with coronal carious lesions were used in this study. A self-etching primer/adhesive system (Clearfil Protect Bond) was applied to flat dentin surfaces with normal and caries-affected dentin according to the manufacturer's instructions. After 24 h water storage, the bonded specimens were cross-sectioned and subjected to a microTBS test and electron probe microanalysis for the elemental distributions [calcium (Ca), phosphorus (P), magnesium (Mg), and nitrogen (N)] of the resin-dentin interface after gold sputter-coating. The microTBS to caries-affected dentin was lower than that of normal dentin. The demineralized zone of the caries-affected dentin-resin interface was thicker than that of normal dentin (approximately 3 microm thick in normal dentin; 8 microm thick in caries-affected dentin), and Ca and P in both types of dentin gradually increased from the interface to the underlying dentin. The caries-affected dentin had lost most of its Mg content. The distributions of the minerals, Ca, P, and Mg, at the adhesive interface to caries-affected dentin were different from normal dentin. Moreover, a N peak, which was considered to be the collagen-rich zone resulting from incomplete resin infiltration of exposed collagen, was observed to be thicker within the demineralized zone of caries-affected dentin compared with normal dentin.