The tetrahydride-bridged complex ( C~M~~) R U (~-H )~R U ( C~M~~)(2) is synthesized by the reaction of [(C5Mes)RuCl212 (1) with LiAlH4, which is characterized as a classical hydride complex on the basis of the 2' 1 value and X-ray diffraction study. In the presence of acid, 2 decomposes to form a coordinatively unsaturated species, which is trapped by the 6-electron ligands to yield the cationic Welectron complexes. Treatment of 2 with ethylene yields (C5Me5)-Ru(CsMe5) (9), structural analogue of the intermediate 8. Thermolysis of 6 in toluene at 60 "C under 1 atm of ethylene generates a dinuclear ruthenacyclopentadiene complex ((25- M~~)R~(CHFCH~)(CM~=CHCH=CM~)R~(CSM~~)(10) as a result of the C-C coupling reaction among the coordinated ethylene and two vinyl ligands. The bis(palky1idene) complex (C6Me5)Ru(pL-CHMe) [pCMe(CH=CHCOMe)Ru(C5Me6) (13) which seems to be a model compound of the intermediate of the cyclometalation leading to 10 is obtained upon heating a divinyl complex (C~M~~)RU(CHFCHCOM~)(CH=CH~)~RU(C~M~~) (12) in refluxing toluene. The ethylene molecule coordinated in 10 inserts into the Ru-C bond of the ruthenacyclopentadiene to form (CsMes)Ru(CMe=CHCH=CMeCH=CH2)(p-H)Ru(CsMe5) (16) when 10 is heated in toluene at 110 "C. Regioselective insertion of a,P-unsaturated ketones into the Ru-C bond of the ruthenacycle giving (C5Me5)Ru(CMe=CHCH=CMeCR1=CCOR2) (p-H)Ru(C5Me5) (17, R1 = H, R2 = Me; 18, R1, R2 = (CH2)2; 19, R', R2 = (CH2)3) is demonstrated in the thermolysis of 10 in the presence of methyl vinyl ketone, cyclopentenone, and cyclohexenone. The molecular structures of several of the products are determined by single-crystal X-ray diffraction studies. Crystal data for 2: space group P 2 / a , a = 12.291(2) A, b = 8.521(1) A, c = 10.053(2) A, = 108.52(1)", V = 998.3(3) A3, and Dcdcd = 1.585 g cm3 for Z = 2. Least-squares refinement based on 2391 reflections converged to R = 0.0220 and R, = 0.0220. Crystal data for 6: space group PI, a = 11.335(2) A, b = 14.315(2) A, c = 8.401(2) A, a = 95.09(2)", p = 117,18(1)", y = 94.36(1)", v = 1197.4(6) A3, and D d c d = 1.538 g cm3 for z = 2. Least-squares refinement based on 2621 reflections converged to R = 0.0900 and R, = 0.1581. Crystal data for 9: space group Pbca, a = 17.876(2) A, b = 20.896(2) A, c = 17.690(2) A, V = 6608(1) g cm3, andDcdcd = 1.529 g cm3 for Z = 8. Least-squares refinement based on 2186 reflections converged to R = 0.057 and R, = 0.040. Crystal data for 10: space group P21/n, a = 14.882(2) A, b = 19.718(4) A, c = 8.794(1) A, = 92.30(2)", v = 2578.5(8) A3, and Dcdcd = 1.496 g ~m -~ for z = 4. Least-squares refinement based on 5731 reflections converged to R = 0.044 and R, = 0.041. Crystal data for 13: space group P21/a, a = 17.210(6) A, b = 9.693(6) A, c = 16.037(7) A, p = 100.366(3)", V = 2632(2) A3, andDdcd = 1.506 g ~m -~ for Z = 4. Least-squares refinement based on 3781 reflections converged to R = 0.037 and R, = 0.035. Crystal data for 16: space group E 1 / a , a = 18.814(2) A, b = 9.212(5) A, c = 15.068(5) A, p = 100.31(2)O, V = 2569(2)...

BACKGROUND Active suppression by CD4+CD25+ regulatory T cells plays an important role in the down‐regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies. METHODS The phenotypes of lymphocytes, particularly those of CD4+CD25+ T cells, were analyzed in peripheral blood in 149 patients with gastrointestinal malignancies and in ascites in 7 patients with peritoneal dissemination. In addition, cytokine production after in vitro stimulation was examined in CD4+CD25+ and CD4+CD25− T cells isolated from patients with malignant disease. RESULTS Compared with healthy volunteers, patients with gastrointestinal malignancies had a higher proportion of CD4+CD25+ T cells in peripheral blood, due to the presence of a drastically smaller number of CD4+CD25− T cells. Among patients with gastric carcinoma, those with higher percentages of CD4+CD25+ T cells had a poorer prognosis than did those with lower percentages. CD4+CD25+ T cells also were present in greater proportions in ascites from patients who had advanced‐stage disease with peritoneal dissemination. Isolated CD4+CD25+ T cells from patients with malignant disease produced interleukin (IL)‐4 and IL‐10 but not IL‐2 or interferon‐γ; these cells also inhibited cytokine production by CD4+CD25− T cells after in vitro stimulation. CONCLUSIONS The relative increase in CD4+CD25+ regulatory T cells may be related to immunosuppression and tumor progression in patients with gastrointestinal malignancies. This finding suggests that the use of immunomodulatory therapy to treat patients with gastrointestinal malignancies may be an effective strategy. Cancer 2003;98:1089–99. © 2003 American Cancer Society. DOI 10.1002/cncr.11618

Central nervous system high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3' end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features. In this study, we performed a clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S-100 protein and synaptophysin were observed in CNS HGNET-BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive tumors, only CNS HGNET-BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS.

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 antifibrotic 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 com- Abnormal accumulation of fibrin occurs within the interstitium and alveolar spaces of the lung in a variety of pulmonary diseases in which the integrity of the capillary alveolar barrier is damaged.

It is becoming increasingly important for clinicians to identify a safer intramuscular (IM) injection site in the deltoid muscle because of possible complications following the vaccine administration of IM injections. We herein examined 4 original IM sites located on the perpendicular line through the mid-acromion to establish a safer IM injection site. Thirty healthy volunteers participated in this study and the distances from our 4 IM sites to some anatomical landmarks on their left arms were measured. Ultrasonography (US) was also performed to measure the thickness of the deltoid muscle and identify the posterior circumflex humeral artery (PCHA) along the course of the axillary nerve. Subcutaneous thickness was measured using 2 methods: measuring the skin thickness with caliper after pinching the skin, and with US. The results obtained revealed that the intersection between the anteroposterior axillary line (the line between the upper end of the anterior axillary line and the upper end of the posterior axillary line) and the perpendicular line from the mid-acromion was the most appropriate site for IM injections because it was distant from the axillary nerve, PCHA, and subdeltoid/subacromial brusa. At this site, depth of needle insertions was 5 mm greater than the subcutaneous thickness at a 90° angle, which was sufficient to penetrate subcutaneous tissue in both sexes. Subcutaneous thickness can be assessed with almost the same accuracy by US or measuring with calipers after pinching the skin. The results of the present study support the improved vaccine practice for safer IM injections.