Crystallization and preliminary X-ray diffraction studies of guanidinoacetate methyltransferase from rat liver

This is the publisher's version, also available electronically from http://scripts.iucr.org/cgi-bin/paper?S0907444999010318.Guanidinoacetate methyltransferase is the enzyme which catalyzes the last step of creatine biosynthesis. The enzyme is found ubiquitously and in abundance in the livers of all vertebrates. Recombinant rat-liver guanidinoacetate methyltransferase has been crystallized with guanidinoacetate and S-adenosylhomocysteine. The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 54.8, b = 162.5, c = 56.1 Å, [beta] = 96.8 (1)° at 93 K, and typically diffract beyond 2.8 Å

Osteoarticular infections in childhood

Objectives : Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Here, we examined the outcomes of OM / SA at a pediatric emergency core hospital in Japan. Methods : This was a single-center, retrospective, observational cohort study at a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012–2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. Results : Fifteen OM / SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n = 6) and methicillin-resistant S. aureus (13.3 %, n = 2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9 ± 1.8 days, and 4.9 ± 2.2 days, respectively. All OM / SA patients recovered without complications or sequelae. Conclusions : In this study, all patients with OM / SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM / SA

Anti-viral actions and viral dynamics in the early phase of three different regimens of interferon treatment for chronic hepatitis C: differences between the twice-daily administration of interferon-beta treatment and the combination therapy with interferon-alpha plus ribavirin.

To improve the efficacy of interferon (IFN) treatment for chronic hepatitis C, we have proposed the twice-daily administration of IFN-beta as a promising induction therapy. In this study, we demonstrated differences between the clearance of circulating HCV-RNA and the induction of anti-viral actions during the first 2 weeks of treatment. Nine patients with a high viral load and genotype 1b were randomly assigned to 3 groups: group A received 3MU of IFN-beta twice a day at intervals of 5 and 19 h; group B received 3MU of IFN-beta twice a day at intervals of 10 and 14 h; group C received 6MU of IFN-alpha once a day with ribavirin. The expression of OAS2, PKR, and MxA in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction method. The viral clearance showed a bi-phasic pattern, and those in the second phase of groups A and B were significantly steeper than that of group C. The peak level of OAS2 during the first phase was correlated with the first phase decay. The MxA expression tended to be higher in group A and B than in group C. The expression of these 3 proteins tended to decrease at day 6 in group C, but increase in groups A and B. These might make differences in the viral decay during the second phase</p

悪性脳腫瘍における UFT の pharmacodynamics

UFT, a mixture of FT-207 and uracil in a molar ratio 1 : 4, has been noticed to have the higher antitumor activity to various tumors other than FT-207. We studied the pharmacodynamics of UFT (900 mg for FT-207) after oral administration on 3 cases of malignant glioma and 4 cases of metastatic brain tumor by using high performance liquid chromatography, and the following results obtained; 1. Most of unchanged FT-207, 5-FU and uracil were excreted in the urine within 24 hours. 2. The t1/2 of α-phase of FT-207 was 4.59 hours and that of β-phase was 9.99 hours. The t1/2 ofα-phase of 5-FT was 0.75 hours, and that ofβ-phase was 11.04 hours. The AUC of 5-FU was 12.434 µg· hrs/ml. This drug was found to stay in the plasma over a long period, followed by a slow elimination. In CSF, the higher concentration of 5-FU stayed over a longer period. 3. The concentration of FT-207 in the brain tumor tissues was 17.11 µg/g on the average in malignant glioma and 17.61 µg/g on the average in metastatic brain tumor. The concentration of 5-FU was 0.02 µg/g on the average in the former, and 0.47 µg/g on the average in the latter, which indicating an efficient transfer to the tissues of metastatic brain tumor. The concentration of FT-207 and 5-FU in the brain tissues adjacent to the tumor was approximately the same as that in the brain tumor tissues, indicating an effective transfer to the brain tissues adjacent to the tumor. 4. On the basis of the results of this study, uracil seems to inhibit the degradation of 5-FU in the liver and/or in the tumor tissues themselves, and to enhance the concentration of 5-FU in the brain tumor tissues and the brain tissues adjacent to the tumor. UFT would be useful as a chemotherapeutic agent agent for malignant brain tumors