Ruthenium-catalysed asymmetric hydrosilylation of ketoximes using chiral oxazolinylferrocenylphosphines.

Chiral ruthenium(II) complexes, RuCl2(PPh3)(oxazolinylferrocenylphosphine), have been found to be effective catalysts for asymmetric hydrosilylation of ketoximes to give the corresponding primary amines in good yields with high enantioselectivities (up to 89% ee) after acid hydrolysis.

Formation of ammonia in the reactions of a tungsten dinitrogen with ruthenium dihydrogen complexes under mild reaction conditions.

Treatment of cis-[W(N2)2(PMe2Ph)4] (5) with an equilibrium mixture of trans-[RuCl(eta 2-H2)(dppp)2]X (3) with pKa = 4.4 and [RuCl(dppp)2]X (4) [X = PF6, BF4, or OTf; dppp = 1,3-bis(diphenylphosphino)propane] containing 10 equiv of the Ru atom based on tungsten in benzene-dichloroethane at 55 degrees C for 24 h under 1 atm of H2 gave NH3 in 45-55% total yields based on tungsten, together with the formation of trans-[RuHCl(dppp)2] (6). Free NH3 in 9-16% yields was observed in the reaction mixture, and further NH3 in 36-45% yields was released after base distillation. Detailed studies on the reaction of 5 with numerous Ru(eta 2-H2) complexes showed that the yield of NH3 produced critically depended upon the pKa value of the employed Ru(eta 2-H2) complexes. When 5 was treated with 10 equiv of trans-[RuCl(eta 2-H2)(dppe)2]X (8) with pKa = 6.0 [X = PF6, BF4, or OTf; dppe = 1,2-bis(diphenylphosphino)ethane] under 1 atm of H2, NH3 was formed in higher yields (up to 79% total yield) compared with the reaction with an equilibrium mixture of 3 and 4. If the pKa value of a Ru(eta 2-H2) complex was increased up to about 10, the yield of NH3 was remarkably decreased. In these reactions, heterolytic cleavage of H2 seems to occur at the Ru center via nucleophilic attack of the coordinated N2 on the coordinated H2 where a proton (H+) is used for the protonation of the coordinated N2 and a hydride (H-) remains at the Ru atom. Treatment of 5, trans-[W(N2)2(PMePh2)4] (14), or trans-[M(N2)2(dppe)2] [M = Mo (1), W (2)] with Ru(eta 2-H2) complexes at room temperature led to isolation of intermediate hydrazido(2-) complexes such as trans-[W(OTf)(NNH2)(PMe2Ph)4]OTf (19), trans-[W(OTf)(NNH2)(PMePh2)4]OTf (20), and trans-[WX(NNH2)(dppe)2]+ [X = OTf (15), F (16)]. The molecular structure of 19 was determined by X-ray analysis. Further ruthenium-assisted protonation of hydrazido(2-) intermediates such as 19 with H2 at 55 degrees C was considered to result in the formation of NH3, concurrent with the generation of W(VI) species. All of the electrons required for the reduction of N2 are provided by the zerovalent tungsten.

Validity and reliability of a revised Japanese version of the Arthritis Impact Measurement Scales version 2 (AIMS2).

Abstract This study aims to evaluate the validity and reliability of a Japanese version of the Arthritis Impact Measurement Scales, version 2 (AIMS2) for patients with rheumatoid arthritis (RA). The Japanese version of the AIMS2 questionnaire was administered to 1643 patients with classical or definite RA at 11 hospitals nationwide in Japan. Reliability was assessed by a test-retest procedure, 4 weeks apart, using 75 randomly selected patients. Internal consistency was measured by Cronbach's α, and factor analysis was used to obtain the proportion of variance explained by the first factor in principal component analysis. The validity of the AIMS2 scales was assessed by internal standards. Internal consistency (α coefficients, 0.84-0.94), test-retest reliability (intraclass correlation coefficients, 0.75-0.93), and factor analysis (0.62-0.85) of the AIMS2 health status scales proved that they are highly reliable in the Japanese version. Validity, as measured by the relationships among the scores on the questionnaire items, was also sufficiently secured. The validity and reliability of the Japanese version of the AIMS2 are sufficient for all practical purposes when compared with the original and with other translated versions of the questionnaire.

Novel Catalytic Hydrogenolysis of Trimethylsilyl Enol Ethers by the Use of an Acidic Ruthenium Dihydrogen Complex.

The heterolytic cleavage of H(2) is the key to the novel catalytic hydrogenolysis of trimethylsilyl enol ethers catalyzed by [RuCl(eta(2)-H(2))(dppe)(2)]OTf (dppe = 1,2-bis(diphenylphosphanyl)ethane, OTf = trifluoromethanesulfonate), which results in the formation of a ketone and Me(3)SiH (see scheme). In addition, the stoichiometric, ruthenium-assisted protonation of a prochiral lithium enolate with H(2) gave a chiral ketone with high enantioselectivity (up to 75 % ee).

Bimetallic system for nitrogen fixation: ruthenium-assisted protonation of coordinated N2 on tungsten with H2

Treatment of the tungsten dinitrogen complex cis-[W(N2)2(PMe2Ph)4] (Me = methyl, Ph = phenyl) with an equilibrium mixture of [RuCl(dppp)2]X and trans-[RuCl(eta2-H2)(dppp)2]X [X = BF4, PF6, or OSO2CF3; dppp = 1,3-bis(diphenylphosphino)propane] under 1 atmosphere of dihydrogen at 55 degrees Celsius for 24 hours gave NH3 in moderate yield. The same reaction in the presence of acetone produced acetone azine in high yield. None of these reactions proceeded in the absence of dihydrogen.

An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis.

To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering and pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing ICAM-1 to type B cells of the pannus. ICAM-1 positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition, VLA-3, VLA-4 and, particularly, VLA-5 were the predominant beta 1 integrins expressed by rheumatoid synovial pannus. Sine these three integrins all function as fibronectin receptors, it is possible that the fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a receptor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in beta 1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.

The role of adhesion molecules in synovial pannus formation in rheumatoid arthritis.

To elucidate the mechanism of cell binding to cartilage, using an immunoperoxidase technique with monoclonal antibodies against adhesion molecules, the pattern of distribution of these molecules at the rheumatoid pannus-cartilage junction has been investigated. Treatment with purified anti-human-monoclonal antibody CD54 anti-(ICAM-1) resulted in membrane staining of most of the large cells infiltrating the synovial tissue and bordering the pannus cartilage junction. When the specimen was treated with purified anti-human-monoclonal antibody CDw49d anti-(VLA-4), purified anti-human-monoclonal antibody CDw49e anti-(VLA-5), most of the cells in the cartilage pannus junction stained, but there were few staining cells against purified anti-human-monoclonal antibody CD11a anti-(LFA-1). There were some anti-ICAM-1 and anti-VLA-5 staining of the chondrocytes at or close to the junction. Human umbilical vein ECBBA1 (ELAM-1) staining was only observed on the endothelial cells of postcapillary venules in the synovial tissue. These results show that the specific adhesion molecules tested may play a role in rheumatoid pannus formation and that the increased expression of VLA-4, VLA-5, and ICAM-1 at the cartilage pannus junction may represent interaction with matrix protein. The VLA interaction appear to be involved in pannus attachment, whereas LFA-1 and ICAM-1 are involved in cell-cell interaction and may upregulate molecules such as VLA that are involved in attachment.

Adhesion molecules in the lymphoid cell distribution in rheumatoid synovial membrane.

The staining pattern of a group of adhesion molecules on the immunoreactive cells in the lining layer of lymphocytic infiltrates of the rheumatoid synovial membrane was studied, using monoclonal antibodies by immunoperoxidase staining method against LFA-1, VLA-4, VLA-5, ELAM-1, and ICAM-1. The cells of the lining layer were strongly ICAM-1+ and VLA-5+, suggesting (1) that ICAM-1 may function to facilitate the adhesion of ICAM-1 bearing type A cells to type B cells, and (2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at the surface of the synovial membrane. In the lymphocyte-rich and transitional area, the endothelial cells of the postcapillary venules were both ELAM-1+ and ICAM-1+. ICAM-1 staining of mononuclear cells was weak in lymphoid aggregates, but strong in the transitional area, indicating a paucity of ICAM-1 bearing cells in the lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the lymphoid aggregates and only moderate in transitional areas. This suggests that the large numbers of T4 cells in the lymphocyte rich areas are sufficiently activated to express substantial levels of LFA-1, and also that the LFA-1 molecule is an important receptor for emigration from postcapillary venules. In germinal center-like areas in lymphoid aggregates, most of the cells stained strongly for ICAM-1 and VLA-4, suggesting that the proliferation of B lymphocytes may be facilitated by LFA-1 and VLA-4 dependent T and B cell interaction. The VLA molecules stained in the transitional areas may provide appropriate adhesion and anchorage for the achievement of the variety of immune reactions which occur in these areas.

Kawasaki disease in a father and son.

The pathogenesis and etiology of Kawasaki disease are unknown, but some studies suggest increased genetic susceptibility. The case is presented of an infant with Kawasaki disease whose father suffered from the same illness 21 years previously. The A, B and C loci of the HLA antigens were examined.

Modified Van Praagh's operation for interrupted aortic arch with severe subaortic stenosis in a neonate.

A 26 day old neonate with Type B interrupted aortic arch, a ventricular septal defect and severe subaortic stenosis underwent a successful modified Van Praagh's operation, consisting of insertion of a graft between the main pulmonary artery and descending aorta, ligation of the patent ductus arteriosus and main pulmonary artery banding distal to the graft. This palliative procedure was effective and easily performed without the aid of cardiopulmonary bypass even in this severely ill neonate with such a complex defect.

Ventilatory and cardiovascular responses to hypoxic and hyperoxic static handgrip exercise in man.

The purpose of this study was to evaluate the ventilatory and cardiovascular responses to static handgrip exercise at different levels of arterial chemoreceptor activation. The study was done on 10 healthy subjects. They performed handgrip of 50% of maximal voluntary contraction on a background of either hypoxia (PE'O2 approximately 47 mm Hg) or hyperoxia (PE'O2 approximately 216 mm Hg), i.e., enhanced or suppressed chemoreceptor activity. The subjects were able to sustain the handgrip for 50-60 sec, during which time no steady-state responses were attainable. Minute ventilation (VI), cardiac output (Q), heart rate (HR), and a number of other variables were recorded. Handgrip exercise resulted in a rapid initial VI rise followed by a subsequent slow increase. Hyperoxia diminished the VI response over the exercise range. The ventilatory response was associated with an HR acceleration, increased arterial pressure and peripheral vascular resistance. No appreciable changes in Q were noted, nor was there any particular relationship between ventilatory and circulatory changes. These results provide no support for the Q mediated ventilatory stimulus during static handgrip exercise in man. It is concluded that the ventilatory and cardiovascular responses are of independent nature.

[Clinical efficacy and safety of norfloxacin tablets in pediatrics].

We have evaluated norfloxacin (NFLX) tablets for therapeutic effectiveness and safety in children. The results are summarized as follows. 1. A clinical study was performed on 14 children with infections, including 12 with urinary tract infections and 2 with acute bronchitis. Doses ranging from 1.7 to 5.4 mg/kg body weight were given b.i.d. or t.i.d.. Lengths of treatment ranged from 3 to 15 days. The therapeutic responses were considered "excellent" in 8 and "good" in 5, with an efficacy rate of 93%. 2. Side effects were observed in 2 cases, one with light-headed feeling and one with vomiting. In clinical laboratory tests, eosinophilia was found in 2 cases and GOT was slightly elevated in 1 case. It has been concluded that NFLX is a usable drug for the treatment of bacterial infections in children.

Effect of unilateral pulmonary vagotomy on respiratory control in man.

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.

Contribution of chemical and non-chemical drives to breath-holding determined by visual analog scale (VAS).

Chemical and non-chemical contributions to breath-holding time (BHT) were directly determined by using a visual analog scale (VAS). These values were compared with those indirectly calculated from the method proposed by Godfrey and Campbell (1968). The magnitude of non-chemical factor at low PCO2 in our study was substantially less than the one obtained by the above investigators. We conclude that Godfrey and Campbell's model postulating linear augmentation of non-chemical sensation is inappropriate to explain dyspnea profile during breath-holding.