Both spontaneous (SOS) and 4‐hydroxyaminoquinoline 1‐oxide (4‐HAQO)‐induced osteosarcomas (COS) could be serially transplanted in the subcutaneous back space of syngeneic F344 rats, the success rate becoming 100% within 5 passage generations. Transplanted tumors demonstrated rapid growth and displayed high potential for metastasis to the lung in later generations. Tbus, a 100% lung metastasis rate was observed for SOS after the 20th and for COS after the 14th generation. The histological features of the primary SOS and COS were retained during serial transfer. These model systems should be useful for investigation of the biology of this very important tumor type.
Disilaferra- and disilaruthenacyclic complexes containing mesityl isocyanide as a ligand, 3' and 4', were synthesized and characterized by spectroscopy and crystallography. Both 3' and 4' showed excellent catalytic activity for the hydrogenation of alkenes. Compared with iron and ruthenium carbonyl analogues, 1' and 2', the isocyanide complexes 3' and 4' were more robust under the hydrogenation conditions, and were still active even at higher temperatures (∼80 °C) under high hydrogen pressure (∼20 atm). The iron complex 3' exhibited the highest catalytic activity toward hydrogenation of mono-, di-, tri-, and tetrasubstituted alkenes among currently reported iron catalysts. Ruthenium complex 4' catalyzed hydrogenation under very mild conditions, such as room temperature and 1 atm of H. The remarkably high catalytic activity of 4' for hydrogenation of unfunctionalized tetrasubstituted alkenes was especially notable, because it was comparable to the activity of iridium complexes reported by Crabtree and Pfaltz, which are catalysts with the highest activity in the literature. DFT calculations suggested two plausible catalytic cycles, both of which involved activation of H assisted by the metal-silicon bond through σ-bond metathesis of late transition metals (oxidative hydrogen migration). The linear structure of M-C≡N-C (ipso carbon of the mesityl group) played an essential role in the efficient hydrogenation of sterically hindered tetrasubstituted alkenes.
Bone marrow (BM) transplantation (BMT) is one of the treatment strategies for congenital metabolic disease, but leukemia secondary to intensive cytoreductive treatment is a major concern. Besides BM cells, mesenchymal stem cells (MSC) are also used for transplantation. An 8-month-old girl with hypophosphatasia underwent transplantation of haploidentical BM cells followed by two transplants of MSC obtained from her father to facilitate osteogenesis. Fludarabine(Flu)/cyclophosphamide (CPA)/anti-thymocyte globulin were used for myeloablative conditioning, but the patient developed therapy-related leukemia harboring t(9;22)(q34;q11.2); minor BCR-ABL (t-leukemia with Ph) at the age of 32 months. At the age of 40 months she underwent a second BM and third MSC transplant from the same donor. Thereafter, she achieved complete histological and molecular remission. The present case suggests that the combination of cytotoxic agents (Flu/CPA) and MSC led to t-leukemia with Ph as a consequence of chromosome instability and suppression of host anti-tumor immunity.
levated levels of serum total or low-density lipoprotein cholesterol have been related to increased risk of coronary heart disease (CHD) in many prospective studies in Western countries, [1][2][3][4] and it has been consistently shown in randomized controlled trials that lowering blood cholesterol reduces both the incidence and recurrence of CHD events. [5][6][7][8][9][10][11][12][13] A positive association between serum total cholesterol and CHD has been observed in Asian populations with relatively low levels of serum total cholesterol and at low risk of CHD, 14,15 but it is unclear whether the beneficial effect of lowering blood cholesterol observed in Western populations is directly applicable to Japanese subjects with hypercholesterolemia. A small clinical trial in Japan showed that the use of pravastatin resulted in regression of coronary atherosclerosis, 16 but a randomized controlled trial regarding the prevention of CHD events by medication for hypercholesterolemia has never been successfully completed. 17 We designed a case -control study, the Fukuoka Heart Study, 18,19 to investigate the relationship between medication for hypercholesterolemia and the risk of nonfatal acute myocardial infarction (AMI) in Japanese men and women. MethodsThe study was designed and implemented in accordance with the Declaration of Helsinki adopted by the 18th World Circulation Journal Vol.66, May 2002Medical Assembly; observational studies were not the subject of review by the institutional ethical committee at the time of the survey. Study subjects were patients with a first episode of AMI and matched community controls. Written informed consent was given by all participating individuals. Cases and ControlsEligible cases were patients aged 40-79 years who were admitted to hospital for a first AMI during September 1996 to September 1998 and who recovered well enough to be interviewed within 1 month after the onset of AMI. The eligible cases were originally restricted to residents of Fukuoka City, but were extended to those of 21 adjacent municipalities in June 1997. Thirteen hospitals were selected to cover the patients in Fukuoka City when the study began, and 9 other hospitals outside Fukuoka City were subsequently included. These collaborating hospitals were staffed with one or more expert cardiologists and were equipped with facilities for treating AMI.Research nurses visited each hospital weekly, checked all admissions with a diagnosis of AMI or suspected AMI, and asked eligible patients to participate in the study. Collaborator cardiologists were in charge of the diagnosis of AMI, which was made on the basis of electrocardiographic findings, ischemic cardiac pain lasting at least 30 min, and enzyme changes in accordance with the criteria used in the Lipid Research Clinics Coronary Primary Prevention Trial. 20 Of 756 eligible patients, a total of 660 (87%) participated in the study. Reasons for non-participation were impaired ability to communicate (n=9), discharge before interview (n=65), and refusal (n=22). Two cas...
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