Biomedical subjects
Publications and source records attributed to K Ohta.
Rabbit antiserum to guinea pig IgE was prepared. This antiserum absorbed IgE antibodies to dinitrophenyl determinants when examined by passive cutaneous anaphylaxis. This antiserum also provoked contraction of tracheal rings from normal guinea pigs in vitro. This system is a new model for asthma in which only IgE among immunoglobulins reacts.
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A phase I-II study of N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BH-AC) was conducted by a cooperative study group. In phase I study, a total of 126 patients, 64 of whom had metastatic solid tumors and 62 of whom had leukemia, were administered BH-AC in a single IV dose at day 1 only or in daily IV doses for 3 to 21 days, with dose ranges of 1.5--10.0 mg/kg. Side effects included nausea and vomiting, which were significantly less in incidence and severity than those observed with ara-C. Myelosuppressive toxicity became severe with doses 3.6--5.0 mg/kg per day x 10 days. In phase II study, a total of 37 adult patients with acute leukemia were entered in the study. Responses were noted, with an overall rate of 35% complete remission. Of th 26 patients with AML, there were 13 CR. The recommended schedule of treatment for BH-AC, based on our data, is daily infusion of 4--5 mg/kg over 3 h for approximately 3 weeks. The results with BH-AC in patients with acute leukemia are superior to those which have been reported for ara-C.
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The topographic distribution pattern and morphological features of Lafora-like bodies in the spinal cord of the dog, cat, fox, and baboon were examined by light and electron microscopy. The caudal lumbar and the coccygeal parts of the spinal cords were the predilection sites for the bodies in all animals and were very prominent in the ventral columns and intermediate substance. The bodies mainly composed of branching filaments were preferentially located in neuronal processes and rarely in astocytes. The histochemical characteristics of the bodies were identical in all animals and consisted mainly of polyglucosan.
Tryptophan and indolic tryptophan metabolites were measured in the serum of normal subjects and chronic renal failure patients. The tryptophan free/total ratio was 0.07 in the normal serum, but the other tryptophan metabolite values were below detectable levels. The free/total ratio was 0.66 in patients with chronic renal failure, and both increase of free tryptophan and decrease of total tryptophan were observed. At the same time, 5-hydroxyindoleacetic acid, indole acetic acid, 5-hydroxytryptophol, and N-acetyltryptophan also increased in the serum of chronic renal failure patients, existing not only in free form but in protein-bound form. In the serum samples, following hemodialysis the indolic tryptophan metabolites showed a tendency to decrease, and the tryptophan free/total ratio of 0.42 a approached the normal value. When indolic tryptophan metabolites were added to normal serum in vitro, the free tryptophan level rose, and competition for binding to albumin between tryptophan and indolic tryptophan metabolites was observed. These findings suggested that the cause of the decrease in protein-bound tryptophan in uremic serum may be an accumulation of indolic tryptophan metabolites which complete for binding to albumin in uremia.
Administration of ticlopidine, a new inhibitor of platelet aggregation, during hemodialysis to two patients with thrombotic occlusion of external A-V shunts markedly suppressed the obstruction of the shunt and improved anemia. Consequently, it was concluded that this drug may be useful for maintaining good blood flow and good patency of shunts in patients undergoing dialysis. In order to determine the dialyzer efficiency during dialysis, the reduction rate of the dialyzer was determined in vitro. The dialyzer reduction rates for urea, creatinine, uric acid, and phosphoric acid were all lowered after dialysis, and the administration of ticlopidine resulted in a suppression of the drop in the reduction rate. Based on the inhibitory effect of ticlopidine on platelet aggregation, it was assumed that a close correlation may exist between adhesion and aggregation of platelets and the drop in the efficiency of the dialyzer during dialysis as well as thrombotic obstruction of shunts.
When hemofiltration and hemodialysis are compared, the former is more effective in removing larger substances, whereas the latter is superior in removing small substances. We consider hemodiafiltration, in which the advantages of the two treatment methods can be adopted, as the most effective and practical method. In the studies of hemodiafiltration, we demonstrated that disequilibrium syndrome associated with the treatment can be prevented by employing a high sodium concentration in the dialysate. The dialysate was successfully used for treating intracellular overhydration. However, it could not be used without causing adverse effects such as thirst in patients whose intracellular overhydration had already been treated and resulted in increase in their body weight. However, these patients were treated successfully by decreasing the high sodium concentration gradually or in a stepwise manner.
Human IgE biosynthesis in vitro was studied by co-culturing T and B cells from atopic patients and normal controls in the presence of 10 microliter/ml pokeweed mitogen for 7 days. IgE and anti-mite IgE ab in the culture media significantly correlated with those in plasma. Normal T cells suppressed in vitro production of IgE and IgE ab significantly more than did atopic T cells but no difference was found in IgG production. The culture of B cells alone (T-depleted fraction) produced IgE equally as well as the co-culture of T and B cells. Anti-mite IgE ab was also produced by B cells alone from mite-sensitive patients. However, IgE biosynthesis in vitro was not consistently affected by pokeweed mitogen. The results suggest a deficiency of the T suppressor system in atopy and the existence of T-independent IgE-producing cells.
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The present genetic studies were designed to investigate a possible correlation of spontaneous polyclonal activation of B cells with the spontaneous production of natural thymocytotoxic autoantibody (NTA) in female (NZB X NZW)F1 X NZW backcross mice. We analyzed the spontaneous polyclonal activation of B cells by determining the serum level of naturally occurring anti-hapten (dinitrophenyl, DNP) IgM antibodies. Based on comparisons of the magnitude of the serum DNP binding activities among NZB, NZW, the F1, and the backcrosses to NZW mice, we found that the abnormal polyclonal activation of B cells depends largely on the contribution of NZB genomes. Similar observations were made on serum IgM levels in these mice, and there were made on serum IgM levels in these mice, and there was a highly significant correlation between these two measures in the backcross mice. Despite striking similarities in several observations between NTA and the anti-DNP antibodies, as well as the serum IgM level, there was no significant correlation between the spontaneous production of NTA and the abnormal levels of the anti-DNP antibodies and serum IgM in the backcross mice in both quantitative and qualitative analyses. We also found no significant association between these polyclonal activation of B cells and H-2 complex.
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