A 5 year-old boy with ADA deficiency has been treated with gene therapy which is the first trial in Japan since Augast 1995. T cells of patient's peripheral blood lymphocytes activated with anti-CD 3 antibody and recombinant IL-2 were transduced by a recombinant retrovirus vector, LASN, which contained cDNA of human ADA gene and then re-infused to the patient intravenously after 711 day-culture. We have already performed 10 cycles of the infusion without any side effects. Concerning the transduction efficinecy of LASN in vitro, in situ PCR method showed 3-7% of ADAcDNA-positive cells after transduciton procedures. On the other hand, ADAcDNA has been detected in 10-20% of his peripheral blood lymphocytes by semi-quantitave PCR method. ADA enzyme activity in peripheral blood lymphocytes indreased progressively from below 1.0 units to 13.6 units during the therapy. The count of his peripheral blood lymphocytes became to keep over 1,000/μl after the six in fusion. We have also found the improvement in both humoral and cellular immunological function tests such as specific antibody respones, serum immunoglobulin levels, isohemagglutinin titers, lymphocyte proliferation responses and DTH skin tests. These results suggest definitely that genetically modified peripheral blood lymphocytes improve immune function in vivo after the repeated infusions. In addition to no major side effects we have never detected replication competent retrovirus in his peropheral blood during the course.
To elucidate the current status in the management of gout and hyperuricemia, questionnaires were sent to general physicians and / or orthopedists and specialists in gout management and responses from 901 generalists and 85 specialists were cross-sectionally analyzed. Several important differences were observed between the two groups of doctors. Restriction of total calorie intake and recommendation about drinking water were regarded a part of preferable self-care by most specialists but not by general practitioners. One-fourth of the generalists prescribed urate-lowering agents for the treatment of acute arthritis, while only one-half of the generalists recognized Uralyt as an urate-lowering agent. Thus, confusion in therapeutic approaches to acute gouty arthritis was revealed among general practitioners. Howevere, as to the criteria for the management of hyperuricemia, differences in opinion were noted among both specialists and general doctors, suggesting the absence of consensus regarding therapeutic strategy. Thus, greater effort should be given to spread useful information among general practitioners by establishing definitive therapeutic guidelines for the management of gout and hyperuricemia.
we report high-performance liquid chromatographic method with column switching for urinary orotidine. Analysis was carried out with a reversed-phase column and an anion-exchange column connected by a column switch and controlled automatically by a computerized system controller. Each sample required only 20 min and 100 samples could be analyzed consecutively. The relationship between standard concentrations and peak heights was linear in the concentration range from 1-1000μmol/l. The recovery of orotidine added to urine was between 96.8% and 100.8%. With our method urinary orotidine can be measured simply and accurately.