PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Clinical, light- and electron microscopic, and immunohistochemical findings of a 44-year-old woman with progressive multifocal leukoencephalopathy were presented. Autopsy revealed a wide distribution of the demyelinating lesion in the cerebrum, cerebellum, brain stem and spinal cord, and intranuclear inclusion bodies and papova-like virions in transmission electron microscopy in the nuclei of oligodendrocytes. SV40 antigen was immunohistochemically detected in these inclusion bodies. The widespread extension of the lesions seemed to correlate with the duration of the patient's illness. The prolongation of the clinical course in this case may be dependent upon the lack of serious underlying diseases except for a small nodule of thyroid carcinoma, SV40 infection rather than JC virus infection and/or improved care of that kind of patient.     

Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

Porous Ti-6Al-4V alloy fabricated by spark plasma sintering for biomimetic surface modification

Porous compacts with both biological and biomechanical compatibilities and high strength were developed. Spherical powders of Ti-6Al-4V alloy, which were either as received or surface modified with the use of calcium ions by hydrothermal treatment (HTT), were fabricated by a spark plasma sintering process. The porous compacts of pure Ti were used as reference materials. Porosity was approximately 30%, and compressive strengths were 113 and 125 MPa for the as-received Ti alloy powders and those modified by the HTT process, respectively. The bending strength and elastic modulus of as-received Ti alloy powders were 128-178 MPa and 16-18 GPa, respectively. Each of the compacts was immersed in simulated body fluid (SBF). The amount of adsorption/precipitation of calcium phosphate through the compacts was measured by weight change and was observed by SEM. The compacts were covered with calcium phosphate after 2 weeks of immersion in SBF. The compacts of Ti alloy had plenty of precipitated apatite crystals, and modification by HTT accumulated more precipitation. Because calcium phosphate is a mineral component of bone, apatite, which is precipitated on the surface of the compacts, could adsorb proteins and/or drugs such as antibiotics. It is expected that a large amount of proteins and/or drugs could be impregnated when the porous compacts developed are used.     

Malignant peripheral nerve sheath tumor of small round cell type with pleomorphic spindle cell sarcomatous areas

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation.     

Evaluation of the clinical pathway for laparoscopic cholecystectomy and simulation of short-term hospitalization.

The effectiveness of the clinical pathway for laparoscopic cholecystectomy was evaluated, and the efficiency of medical care was analyzed. The duration of hospitalization and the number of National Health Insurance (NHI) points for medical service fees were compared between 86 patients treated after introduction of the clinical pathway (pathway group) and 56 patients treated before introduction of the clinical pathway (pre-pathway group). In the pathway group, variance from the pathway occurred in 24 patients (27.9%) due to postponement of discharge in 7 patients, to earlier discharge in 5 patients, and to insertion of a bile duct catheter in 5 patients. Total and postoperative hospitalization times were significantly shorter in the pathway group than in the pre-pathway group (8.0 +/- 1.6 vs 13.7 +/- 9.0 days, p<0.0001, 5.4 +/- 1.1 vs 6.5 +/- 2.2 days, p<0.0001, respectively). In the pathway group, the total number of NHI points was lower and the number of points per day was higher. By simulation, the total number of NHI points for the 5-day pathway (discharge on postoperative day 3 or earlier) was significantly lower than that for the current 7-day pathway. Moreover, the weekly profit per bed with the 3-day pathway (discharge on postoperative day 1) was more than twice that with the current pathway. The results suggest that the clinical pathway for laparoscopic cholecystectomy is beneficial for patients and useful for the introduction of diagnosis procedure combination in our hospital.     

Multiple epithelial cysts of the spleen and on the splenic capsule, and high serum levels of CA19-9, CA125 and soluble IL-2 receptor

An 18-year-old woman with abdominal pain was diagnosed as having splenic cysts by computed tomography scan. She had high serum levels of CA19-9 (2886.8 U/mL; normal value, <35 U/mL), CA125 (131.1 U/mL; normal value, <35 U/mL) and soluble IL-2 receptor (1490 U/mL; normal range, 220-530 U/mL). The resected spleen weighed 1050 g, was 14 x 28 cm, and had more than 10 macroscopic cysts up to 10.3 x 9.5 cm. There were numerous microscopic cysts in the spleen and several on the splenic capsule. The levels of CA19-9 and CA125 in the cyst fluid were 2165550 U/mL and 160400 U/mL, respectively. After the surgery, the serum levels of the tumor markers decreased gradually. The inside of the largest cyst was mainly covered by granulation tissue with a focal lining of epithelial cells, and the other macroscopic cysts had stratified squamous epithelium. The microscopic splenic cysts and cysts on the splenic capsule were lined by either attenuated single-layered or multilayered epithelial cells. The lining epithelial cells of these cysts were positive for epithelial membrane antigen and cytokeratins. CA19-9 and CA125 were detected in the lining cells of the splenic cysts. In the present case, it is suspected that the splenic cysts were derived from the capsular lining cells that showed migration from the capsule or formed microcysts on the splenic capsule, as in the case of ovarian inclusion cysts.     

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.     

A pore-forming toxin produced by Aeromonas sobria activates Ca2+ dependent Cl- secretion

Bacteria produce many types of hemolysin that induce diarrhea by mechanisms that are not completely understood. Aeromonas sobria hemolysin (ASH) is a major virulence factor produced by A. sobria, a human pathogen that causes diarrhea. Since epithelial cells in the intestine are the primary targets of hemolysin, we investigated the effects of ASH on ion transport in human colonic epithelial (Caco-2) cells. ASH increased short-circuit currents (Isc) in a dose-dependent manner, and it also activated a 125I efflux from Caco-2 cells. ASH-induced Isc increases and 125I efflux activations were both suppressed by low Ca2+ levels in the extracellular solution or by pretreatment with the Ca2+ chlelator BAPTA-AM. Intracellular Ca2+ levels were increased by ASH in a biphasic fashion characterized by a rapid sharp increase (peak 1) followed by a sustained low plateau (peak 2). ASH-induced peak 1 was inhibited by pretreatment with pertussis toxin, indicating that Ca2+ was mobilized from intracellular stores, and peak 2 was induced by an influx of extracellular Ca2+. Peak 2 but not peak 1 was related to Cl- secretion. These results indicate that ASH activates Ca2+-dependent Cl- secretion.