[Management of complications and adverse effects of apheresis].
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Adolescent↗
Biomedical subjects
S Kojima
Publications and source records attributed to S Kojima.
Effect of repeated administration of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.
The effects of the repeated administration of D-penicillamine, 2,3-dimercaptosuccinic acid, 2,3-dimercaptopropane sulphonate, and N-(2-mercapto-2-methylpropanoyl)-L-cysteine 24 h after gold sodium thiomalate (AuTM) injection on the distribution, excretion, and renal toxicity of gold in rats were investigated. Three i.p. injections of these chelating agents (1.2 mmol/kg) at 1, 3, and 5 days after AuTM injection (0.026 mmol/kg) removed gold from kidney and liver through urinary and fecal excretion, and protected against the renal damage induced by AuTM. These findings indicate that these compounds are useful antidotes for gold toxicity.
Animals↗
[Electrolyte transport in the blood cell membrane and essential hypertension].
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Biological Transport↗
A gender difference in the association between salt sensitivity and family history of hypertension.
We examined 174 subjects (82 men and 92 women) with essential hypertension to determine whether gender played an important role in the association of blood pressure (BP) familial disposition, and hypertension. To evaluate the salt sensitivity of BP, we measured changes in blood pressure after restricting salt intake from about 15 g/day to less than 3 g/day. The familial disposition to hypertension was categorized into four groups according to the presence or absence of hypertension in the father, mother, and siblings. If none, one, two, or three family members had hypertension, they were assigned the FH(-), FH(+), FH(++), and FH( ) groups, respectively. Only in women did the FH(-) group show a significantly smaller blood pressure reduction than that of the other groups. The mean BP reduction in the four groups was 4.1 +/- 1.9, 8.5 +/- 1.1, 10.1 +/- 1.5, and 11.2 +/- 2.8 mm Hg (mean +/- SEM), respectively. This difference in BP reduction was not observed in men. Multiple regression analysis, using percent changes in mean BP as the dependent variable and other factors as independent variables, also showed a significant partial correlation coefficient for familial disposition to hypertension only in women. Thus, the relationship between salt sensitivity and familial disposition to hypertension differed according to gender. This difference may provide an important insight into the hereditary nature of hypertension.
Adult↗
Human herpesvirus-6 infection in bone marrow transplantation.
Twenty-five pediatric patients who received bone marrow transplantation (BMT) were studied prospectively to determine the relationship between BMT and human herpesvirus-6 (HHV-6) infection by the virus isolation from peripheral blood and/or bone marrow and by determining neutralizing antibodies to HHV-6 during the 2 months following BMT. All of the 25 donors and the recipients were immune to HHV-6 at the time of BMT and the virus was not isolated from them. HHV-6 was isolated from peripheral blood and/or bone marrow mononuclear cells in ten (40%) of the 25 recipients between day 14 and day 22 of BMT, but not from any other day. Two additional recipients showed a significant increase in the antibody titer. Thus, infection with HHV-6 was confirmed in 12 (48%) of the 25 recipients. Four of the 12 developed skin rashes; three of these four had a febrile episode when the virus was isolated, whereas none of the remaining 13 developed the skin rash. These results suggest a frequent infection with HHV-6 only a few weeks after BMT and a close association between the infection with the virus and the development of skin rashes.
Adolescent↗
Different mechanisms of polyuria and natriuresis associated with paroxysmal supraventricular tachycardia.
The mechanism of polyuria associated with paroxysmal supraventricular tachycardia (SVT) was investigated in 8 patients. SVT was induced artificially and sustained for 60 minutes. Urine and blood samples were collected every 30 minutes. During the latter half of SVT, urine flow increased twofold in the control subjects before SVT. Urinary sodium excretion increased significantly (p less than 0.01) within 30 minutes after SVT. Urinary excretion of antidiuretic hormone (ADH) decreased (p less than 0.01) during the latter half of SVT and increased (p less than 0.01) after SVT, respectively. Plasma level of ADH did not change during SVT but increased (p less than 0.05) after SVT. The concentration of plasma atrial natriuretic polypeptide (ANP) increased significantly (p less than 0.05) before SVT ended. Urinary excretion of prostaglandin E2 increased significantly (p less than 0.05) after termination of SVT. The percent changes in the urinary excretion of prostaglandin E2 were correlated (r = 0.713, p less than 0.001) with those of ADH. There was also a correlation (r = 0.6, p less than 0.001) between the percent changes in the urinary excretion of prostaglandin E2 and those of sodium. Their findings suggest that the polyuria during SVT is attributed mainly to the inhibition of ADH release and that the natriuresis after SVT is due not only to the increased ANP but also to the increased renal prostaglandin E2 probably stimulated by ADH.
Adult↗
Mechanisms of temporary inhibition in Streptomyces subtilisin inhibitor induced by an amino acid substitution, tryptophan 86 replaced by histidine.
Just one amino acid substitution (Trp86 replaced by His), which is more than 30 A away from the reactive site, changed the inhibitor, Streptomyces subtilisin inhibitor (SSI), into a temporary inhibitor without a change in the inhibition constant. When the inhibitor was in excess of subtilisin BPN', the wild-type SSI was stable under protease attack, while the mutant inhibitor was hydrolyzed to peptide fragments in an all-or-none manner. The mechanism of this temporary inhibition induced by the amino acid substitution was studied on the basis of structural, thermodynamic, and kinetic data obtained by a combined use of NMR, hydrogen-deuterium exchange, differential scanning calorimetry, and gel filtration HPLC. The mutation did not induce major structural changes, and in particular, the structure of the enzyme-binding region was virtually unaffected. The denaturation temperature of SSI, however, was decreased by 10 deg upon mutation, although it still remained a thermostable protein with a denaturation temperature of 73 degrees C. Furthermore, the activation enthalpy for denaturation was reduced dramatically, to half that of the wild type. When the mutated SSI is present in excess of the enzyme, the proteolysis followed first-order reaction kinetics with respect to the total concentration of the mutated SSI molecules present. From these combined results, we conclude that the proteolysis proceeds not through the native form of the inhibitor in the inhibitor-enzyme complex but through the denatured (unfolded) form of the inhibitor whose fraction is increased by the mutation. This conclusion states that the necessary condition for being a serine protease inhibitor lies not only in the design of the reactive site structure that is highly resistant to protease attack but also in the suppression of such structural fluctuation that brings about cooperative denaturation. In contrast, when the protease existed in excess of the mutated inhibitor, the proteolysis reaction was accelerated by more than 2 orders of magnitude. Furthermore, the reaction occurred even in the wild-type SSI at a comparable rate as in the mutated protein. This indicates that in the enzyme excess case another, more efficient digestion mechanism involving fluctuation within the native manifold of the inhibitor dominates.
Bacterial Proteins↗
Correlation of response of aplastic anemia patients to antilymphocyte globulin with in vitro lymphocyte stimulatory effect: predictive value of in vitro test for clinical response.
Therapy with antilymphocyte globulin (ALG) has been shown to be effective in restoring hematopoiesis to some patients with aplastic anemia. It would be useful to have a method for predicting those likely to be responders versus nonresponders. The mode of immunostimulatory action of ALG is of interest in addition to its immunosuppressive action. We examined in vitro the distribution of the proliferative responses of ALG-stimulated peripheral blood mononuclear cells (PBMCs) obtained from 18 patients with aplastic anemia, eight of whom responded to ALG and 10 who did not. We found a significant difference in the proliferative response of PBMCs obtained from the eight responders versus the 10 nonresponders (P less than .01). Two-color flow cytometry analysis of the patients' PBMCs stimulated by ALG in vitro showed that the CD4-positive subsets were activated to a greater extent by ALG than the CD8-positive subsets. Moreover, a positive correlation with the clinical response of patients to ALG with granulocyte-macrophage colony-stimulating factor produced by their PBMCs stimulated by ALG suggests that the immunostimulatory property of ALG has an important role in the treatment of aplastic anemia. Our results suggest that the clinical response to ALG therapy is correlated with its lymphocyte proliferative effect in vitro, and indicates that the assessment of the proliferative response of PBMCs in vitro would be useful in predicting the clinical response to ALG therapy.
Adolescent↗
Protection against cis-diamminedichloroplatinum-induced nephrotoxicity in rats by N-benzyl-D-glucamine dithiocarbamate.
Sodium N-benzyl-D-glucamine dithiocarbamate (BGD) was evaluated for its efficacy as an inhibitor of cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity in a rat model. Treatment with 2.0 mmol/kg of BGD immediately after DDP injection effectively prevented nephrotoxic effects of DDP, but administration of BGD -1 or 1 h after DDP afforded a small protection. Concurrent treatment with 0.5 mmol/kg of BGD could not prevent renal damage. The platinum concentrations in liver and kidney were significantly decreased by BGD treatment. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by administration of BGD (2.0 mmol/kg).
Animals↗
Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor.
Twenty children (aged 1 to 17 years) with severe or moderate aplastic anemia were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 400 micrograms/m2 per day administered as a 30-minute intravenous (IV) infusion daily for 2 weeks. This treatment increased the neutrophil counts (2.7- to 28.0-fold) in 12 of the 20 patients. Increasing doses (800 or 1,200 micrograms/m2 per day) were administered to five patients who had not responded to the initial dose, and three showed an increase in neutrophil count. Differential counts of bone marrow (BM) aspirates showed an increase in the myeloid/erythroid ratio. The response was transient, however, and the neutrophil count returned to baseline within 2 to 10 days of discontinuing treatment. No severe toxicity attributable to rhG-CSF was observed. The results suggest that this agent is effective in stimulating granulopoiesis in children with aplastic anemia. Our study also indicates that rhG-CSF will be particularly useful in managing patients with aplastic anemia complicated by bacterial or fungal infection.
Adolescent↗
Reactivation of herpesvirus type 6 in children receiving bone marrow transplants for leukemia.
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Adolescent↗
Infant leukemia in Japan: clinical and biological analysis of 48 cases.
Forty-eight Japanese infants with acute lymphoid leukemia (ALL) (n = 24) and acute nonlymphoid leukemia (ANLL) (n = 24) were analyzed on the basis of clinical and laboratory data. Morphologically, 20 of the 24 infants with ALL were of the FAB L1 type, and 20 of the 24 infants with ANLL were of the M4 or M5 type. Markedly enlarged liver and spleen, and hyperleukocytosis (more than 50,000/microliters) were seen in 9, 12, and 14 infants with ALL and 10, 11, and 10 infants with ANLL, respectively. Initial CNS leukemia was evident in 2 infants. Chromosome studies of the leukemic cells showed abnormal karyotypes in 9 of the 21 infants with ALL and 19 of the 22 infants with ANLL, consisting mainly of translocation 11, 12, and inversion 16. By surface marker analysis, only 7 of the 22 infants with ALL (32%) were diagnosed as having common ALL (HLA-DR+, CD19+, CD10+). Of the 15 infants with ANLL, 12 and 5 infants also showed reactivity to HLA-DR and CD19, respectively. All of the 5 ANLL infants with lymphoid markers showed different leukemic cell features at the time of relapse. Twelve of the 19 infants with ALL (63%) who achieved a complete remission relapsed within the first 2 years; 8 of the 21 with ANLL (38%) relapsed within the first year. Analysis of event-free survival shows that the ALL infants with hyperleukocytosis have a poorer prognosis than those without hyperleukocytosis (p less than 0.05). Infant leukemia originates in a multipotent cell with lymphoid and myeloid features, and intensive multiagent chemotherapy is necessary for the treatment of infants with acute leukemia.
Antineoplastic Combined Chemotherapy Protocols↗
Effects of heterologous helminth infections on passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum.
Passive transfer of immunity using a mouse monoclonal IgE antibody against Schistosoma japonicum was found to be enhanced by heterologous helminth infections. BALB/c mice were infected with Toxocara canis or Nippostrongylus brasiliensis so as to induce eosinophilia prior to a challenge infection with S. japonicum. Recovery of adult schistosomes decreased in a group of mice that had been infected with T. canis and challenged with cercariae at the cutaneous site of sensitization with the IgE antibody as compared with that in mice that had been similarly treated with normal serum in the absence of T. canis infection. Histological examinations revealed a close association of polymorphonuclear cells, including eosinophils, with damaged schistosomula in the skin of T. canis-infected mice that had received the IgE antibody. An enhancement in worm reduction was also observed in mice harboring either of both nematodes when the monoclonal antibody had been injected intraperitoneally during the phase of migration of schistosomula from the skin to the lungs. In vitro studies on macrophage-mediated damage to schistosomula suggested that the enhancement in worm reduction was at least partly due to the activation of macrophages induced by the heterologous infections.
Animals↗
Protective effects of chelating agents against renal toxicity of gold sodium thiomalate in rats.
The protective effects of various chelating agents such as D-penicillamine (D-PEN), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane sulphonate (DMPS), and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), on the renal damage induced by gold sodium thiomalate (AuTM) in rats were studied. Rats were injected i.v. with AuTM at doses of 0.026, 0.066, 0.132, and 0.198 mmol/kg. Urinary excretion of protein, aspartate aminotransferase (AST), and glucose in rats injected with AuTM significantly increased compared to the control levels within 1 day after the injection and thereafter decreased nearly to the control levels at 3 or 7 days. Gold was excreted rapidly during the first day after AuTM injection and excreted gradually thereafter. The concentrations of gold in the kidney and liver at 1 or 7 days after AuTM administration were approximately dose dependent. Treatment with D-PEN, DMSA, DMPS, and bucillamine (1.2 mmol/kg) significantly prevented increases in the urinary excretion of protein, AST, and glucose and the BUN level after AuTM (0.026 mmol/kg) injection. The injection of the chelating agents after AuTM administration showed that D-PEN, DMSA, and DMPS enhanced mainly the urinary excretion of gold and that bucillamine enhanced mainly the fecal excretion of the metal. These chelating agents significantly decreased the gold concentrations in the kidney and liver. The findings suggest that the chelating agents tested can ameliorate the renal damage induced by AuTM.
Animals↗
Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure.
Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa(O)(2) with a 6 cmH(2)O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10 cmH(2)O. In IRV group step-wise prolongation of the I : E ratio from 1 : 1.9 to 2.6 : 1 or 4 : 1 was applied as a Pa(O)(2) was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10 cmH(2)O after one hour period irrespective of Pa(O)(2). Inversed ratio ventilation and PEEP increased significantly Pa(O)(2)/F i(O)(2), the increase being observed 6 hrs (I : E = 2 : 1) and 2 hrs (10 cmH(2)O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I : E ratio was prolonged up to 2.6 : 1 or 4 : 1. These results suggested that combinations of IRV with PEEP were effective and an I : E ratio of 2 : 1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.
Journal Article↗
The effects of dopamine infusion during operation on the postoperative liver dysfunction.
Dopamine improves renal function and renal blood flow by increasing cardiac output but its effect to ameriolate postoperative liver dysfunction has not yet been defined. Effect of 3-5 microg.kg(-1).min(-1) dopamine was studied in 22 patients who had total gastrectomy (dopamine group), and was compared with 22 patients who underwent the same operation and without dopamine infusion (control group). Liver function was evaluated from serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) values. Although postoperative SGOT and SGPT values in both groups were increased significantly higher than the preoperative values, the increases in SGOT (40 +/- 14 IU) and SGPT (32 +/- 15 IU) values in the dopamine group were significantly less than those in the control group (67 +/- 27 IU, 43 +/- 19 IU) ( P < 0.05, P < 0.01).In conclusion, these results suggested that this observation might be explained by amelioration of the postoperative liver dysfunction by infusion of dopamine. Dopamine infusion at a small dose during upper abdominal surgery is beneficial for liver function.
Journal Article↗
Angiostrongylus costaricensis: culture of third-stage larvae to young adults in a defined medium.
The third-stage larvae of Angiostrongylus costaricensis were successfully cultured to young adults in a chemically defined medium. The most suitable medium for the development was Waymouth's medium among eight defined media examined. Twenty-eight days after cultivation in this medium, 77% of the larvae developed to young adults, although these worms gradually died thereafter. When Waymouth's medium was supplemented with mouse red blood cells, these young adult worms continued their development. The mean body lengths of the worms cultivated in Waymouth's medium supplemented with RBCs were significantly larger than those of the worms in the medium without RBCs on Days 14 and 21 after cultivation. Addition of RBCs was essential for their further development. At 28 days after cultivation, the maximum body length of the worms was 2.1 mm for males and 3.3 mm for females. Additions of serum, yeast extract lactalbumin hydrolysate, and growth factors to Waymouth's medium did not provide any additional benefits for worm development.
Angiostrongylus↗
Transformation of mammalian cells by luteoskyrin.
The transforming activity of luteoskyrin (LS), a bis-anthraquinoid mycotoxin produced by Penicillium islandicum Sopp., and a hepatocarcinogen in rodents, was examined by an in vitro transformation assay using mouse embryonal Balb/3T3 A31-1-1 cells. The results revealed that LS induced type III foci at 0.5 micrograms/ml, and that the cells selected from these foci by soft-agar cloning grew with a high saturation density. Thus, it was confirmed that LS not only induces hepatic tumours in laboratory animals, but also transforms in vitro cultured mammalian cells. The tumorigenicity of the transformants obtained was confirmed by transplantation into nude mice and by image analysis with IIIIn. A transfection assay, using calcium phosphate co-precipitation, demonstrated that the DNA of the cloned cells transformed NIH3T3 cells. Northern blot also revealed transcriptional activation of c-myc and c-Ha-ras oncogenes. The possible participation of LS-derived hydroxy radicals in the formation of genetic lesions was discussed.
Animals↗