The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.     

Portal vein replacement by hepatic vein transposition

Successful reconstruction after portal vein resection in extended liver surgery has been performed by end-to-end anastomosis, patch, or graft interposition. Previously described techniques to obtain venous grafts for portal replacement necessarily have either an additional incision or an unsuitable diameter. We developed a new method of portal vein replacement using the excised hepatic vein. This technique can be applied in major liver resections for tumors infiltrating the portal vein that have a safe distance from the hepatic vein.     

Giant plexiform schwannoma: a report of two cases with soft tissue and visceral involvement

We report two cases of massive, solitary, plexiform schwannoma. One was a 9-cm subcutaneous lesion on the hip of a 72-year-old man who had become aware of the slow-growing tumor 50 years earlier; the other is the first reported plexiform schwannoma to arise in a visceral organ: it arose in the ascending colon of a 54-year-old man and exhibited a dumbbell configuration with submucosal and subserosal components. Neither patient had neurofibromatosis or schwannomatosis. Both tumors were well-circumscribed and multinodular, and both showed a plexiform architecture. Microscopically, the nodules were composed primarily of Antoni A tissue, replete with nuclear palisading and Verocay bodies. Examination by immunohistochemistry and electron microscopy demonstrated the features of well-differentiated Schwann cells; nodules were surrounded by attenuated, residual perineurium. Both patients followed a benign clinical course, without recurrence or metastasis. Neither the large tumor size nor the unusual locations affected the biologic behavior of these neoplasms. A massive plexiform schwannoma must be distinguished from a malignant peripheral nerve sheath tumor and from a plexiform neurofibroma, a tumor prone to malignant transformation.     

Periodic limb movement disorder in neuroleptic-induced akathisia

We recorded all-night polysomnograms of four schizophrenic patients with neuroleptic-induced akathisia (NIA) before and during treatment with clonazepam. Also, four non-akathitic schizophrenic patients were recorded all-night polysomnograms as control subjects. Daily treatment with 1.5 to 3 mg clonazepam improved subjective complaints of all the 4 patients with NIA. Three of 4 patients with NIA exhibited periodic limb movements (PLM) on bilateral legs, but none of 4 control subjects showed PLM. Total number of PLM and PLM per hour decreased during clonazepam treatment. Moreover, mean inter-movement intervals of PLM of 3 patients were prolonged on bilateral legs. NIA might change its feature as PLM during night sleep.     

Novel hepatitis C virus protease inhibitors: thiazolidine derivatives

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.     

Effects of combined topical metronidazole and mechanical treatment on the subgingival flora in deep periodontal pockets in cuspids and bicuspids

The Effect on the subgingival microflora of a single topical administration of a 95% collagen and 5% metronidazole device in combination with debridement was investigated in 30 adult periodontitis patients in comparison with mechanical treatment alone. For each patient, plaque samples from test and control sites in cuspids and bicuspids were collected for culture and enumeration of total anaerobically cultivable bacteria (TA), black-pigmented anaerobes (BPA), and Actinobacillus actinomycetemcomitans (Aa). Spirochetes and fusiforms were quantified by direct microscopic examination after Giemsa staining. A decrease was observed for all parameters, and a significant difference in comparison with the control group was found for fusiforms. After treatment, a lower number of Aa positive sites were observed in the test group (13/25). These results show that a single application of topical metronidazole seems to be effective as adjunctive antimicrobial treatment in adult periodontitis.     

Lack of carcinogenicity of medium-viscosity liquid paraffin given in the diet to F344 rats

The carcinogenicity of medium-viscosity liquid paraffin was examined in Fischer 344 rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 wk. Slight increases in food consumption and body weight were observed in both sexes of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematology findings. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumour type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, does not have any carcinogenic potential in F344 rats. Furthermore, granulomatous inflammation observed in mesenteric lymph nodes were not associated with any development of neoplastic lesions.     

The importance of electrochemistry-related etching in thegate-groove fabrication for InAlAs/InGaAs HFETs

For the first time, the surface metal on nonalloyed ohmic electrodes is found to significantly change the profiles of gate grooves, when resist openings are employed to monitor drain current during wet-chemical gate recess for sub-micron InAlAs/lnGaAs heterojunction field-effect transistors (HFETs). The surface metal of Ni enhances the etching rate in comparison with that in the absence of electrodes by a factor of 4 and 10, laterally and vertically, which is favorable to fabricate deep gate grooves with small side etching. The Pt surface metal, however, leads to preferential etching of InGaAs over InAlAs, which can be useful to realize large side etching. The existence of an electrochemistry-related etching component, which arises when the ohmic electrodes are present during recess etching, is considered to be responsible for these behaviors     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.