Cytoskeletal properties of alveolar soft part sarcoma

The immunohistochemical expression of cytoskeletal proteins in alveolar soft part sarcoma (ASPS) was studied by light and electron microscopy. Of the five cases examined by the avidinbiotin-peroxidase complex method, variable numbers of immunoreactive cells for desmin were found in three, for vimentin in two, for muscle-specific actins in three, and for alpha-smooth muscle actin in four. Immunoelectron microscopic study demonstrated that desmin and vimentin were localized on whorled bundles of intermediate filaments in the perinuclear cytoplasm. In addition, a few dispersed intermediate filaments became evident in specimens treated with saponin and fixed with tannic acid. These immunohistochemical results indicate that a few tumor cells of ASPS may express some properties of the cytoskeleton of smooth muscle cells in addition to those of skeletal muscle cells. Considering the discrepancies reported in the actin isoforms demonstrated in myogenic tumors, we conclude that ASPS is probably a peculiar, primitive myogenic tumor that does not show any distinctive features of rhabdomyogenic or leiomyogenic differentiation.     

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.     

Generation of peroxynitrite and apoptosis in placenta of patients with chorioamnionitis: possible implications in placental abruption

The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolities may play an important role in this cascade.     

Conversion of normal Ly-1-positive B-lineage cells into Ly-1-positive macrophages in long-term bone marrow cultures

We obtained eight different cell lines in the long-term bone marrow culture system that showed a germ-line configuration of the joining (J) region segments of the Ig heavy-chain (IgH) genes. Their surface markers were CD45R+, Ly-1+, Lyb-2+, cIgM-, sIgM-, Ia-, Thy-1-, Mac-1-, and IL-2R (Tac)+. Use of very young mice and the presence of IL-5 were important for preferential promotion of the survival of B-lineage lymphocytes bearing the Ly-1 markers. When we treated two of them (J8 and J10) with 5-azacytidine for 24 h followed by co-culture with stromal cells and IL-5, they became Ly-1+, sIgM+ B cells, and Ly-1+, Mac-1+ macrophagelike cells, respectively. After other early lymphoid lines (J1, J8, and J13) were maintained by co-culture with ST2 and IL-5 for more than a year, they showed a heterogeneous DNA rearrangement profile of the J region segment of the IgH gene, although only J13 rearranged the kappa-light chain gene. Northern blot analysis revealed that these cell lines expressed C mu-mRNA, and lambda 5-mRNA, consistent with normal pre-B cells. Intriguingly, J1, J8, and J13 expressed c-fms mRNA constitutively. When J13 cells were co-cultured with ST2 and GM-CSF in place of ST2 and IL-5, they acquired Mac-1 expression and retained Ly-1 expression. They were morphologically macrophages, nonspecific-esterase-positive, and showed phagocytosis of latex beads. These results support evidence for a close relationship between the myeloid and Ly-1+ B-cell pathways of differentiation, and indicate that our IL-5-dependent clones are multipotential intermediates in differentiation from pro-B cells to B cells and macrophages.     

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

Epitopic heterogeneity of the CD36 antigen expressed by normal and neoplastic endothelial cells. An immunohistochemical study with a novel monoclonal antibody 8C9.

Phenotypic and functional heterogeneity of endothelial cells (ECs) is being recognized with increasing frequency. Here we report a novel murine monoclonal antibody (MoAb), named 8C9, that detects a unique epitope on the leukocyte differentiation antigen CD36 (platelet glycoprotein IV or IIIb) expressed by both normal and neoplastic ECs. In immunohistochemical and flow-cytometric studies, 8C9-immunoreactivity was detected on capillary ECs, adipocytes, monocytes, platelets and a human monocytoid cell line U-937, which are known to express the CD36 antigen. Blocking experiments using U-937 cells and studies on cryostat sections revealed that a murine MoAb OKM5, which detects the CD36 antigen, blocked the binding of 8C9 to its antigen. Immunoblot analysis showed that 8C9 bound to a 97-kDa membrane protein expressed by U-937 cells treated with phorbol ester. These results indicate that 8C9 detects the CD36 antigen. However, the findings that some OKM5-positive normal ECs in the liver, spleen and lymph nodes as well as neoplastic ECs in a cutaneous angiosarcoma did not react with 8C9, together with the fact that the CD36 antigen does not form a complex or associate with other proteins, suggest epitopic heterogeneity of the CD36 antigen expressed by these tissues.     

Malignant nerve sheath tumor of acoustic nerve

A malignant nerve sheath tumor of the acoustic nerve was found in a 54-year-old man whose right acoustic nerve signs had shown gradual worsening during the previous five years. No stigmata of von Recklinghausen's disease were noted. The tumor at autopsy extensively involved the brain stem, cerebellar hemisphere, tentorium of cerebellum, and cerebral occipitotemporal lobe on the right side. Histologically, the tumor was characterized by extreme hypercellularity, pleomorphism, and high mitotic activity. Ultrastructurally, there was an external lamina around the interdigitated cytoplasm of the tumor cells. Long-spacing collagens and junctional devices were also noted. This case is, to our knowledge, the first reported of a malignant nerve sheath tumor in the acoustic nerve.