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Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 739 records · Page 41Linked to original sources

Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE.

Crosslinking of cell-bound IgE on mouse connective tissue-type mast cells (CTMC) by multivalent antigen or anti-IgE antibody induced clonal growth of CTMC in methylcellulose culture containing IL-3. Continuous presence of antigen, IgE antibody, and IL-3 in culture was required for extensive proliferation of CTMC. Optimal concentrations of antigen and anti-IgE antibody for proliferation of sensitized CTMC approximately corresponded to those for maximal histamine release from the cells, and it was observed that most dividing cells stimulated by antigen had pericellular degranulation halos in culture. Experiments of both single cell culture and serum free culture provided evidence for a direct effect of antigen stimulation on proliferation of CTMC. Neither accessory cells nor some factors in FCS were required for the clonal growth of CTMC in our culture condition. Compound 48/80, a direct stimulator of CTMC, also triggered histamine release from CTMC but failed to support their proliferation. These results suggest that stimulation of CTMC via IgE receptors not only triggers the release of chemical mediators from the cells but induces clonal growth of CTMC in the presence of IL-3. Our data indicate the possibility that antigen stimulation may play another role in the proliferation of CTMC.

Animals↗

Effect of N-benzyl-D-glucamine dithiocarbamate on the renal toxicity produced by subacute exposure to cadmium in rats.

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity produced by subacute exposure to cadmium in rats was studied. Rats were injected sc with CdCl2 (1.5 mg Cd/kg) daily for 26 days and thereafter they received 13 injections of BGD (400 mumol/kg) every other day. Urinary protein concentration and AST activity significantly increased after 20 days of cadmium treatment. The pattern of the increase in the urinary excretion of cadmium after cadmium treatment was consistent with that in the urinary excretion of protein and AST. Urinary excretion of amino acid increased gradually after the cessation of cadmium treatment. BGD treatment significantly decreased the urinary excretion of protein, aspartate aminotransferase (AST), and amino acid. Plasma AST activity was elevated 8 days after the beginning of cadmium treatment, indicating that the hepatic damage occurred prior to the renal damage. In addition, the microscopic examination of renal tissue from cadmium-treated rats revealed the necrosis of the proximal tubular cells. The cadmium concentrations in liver and kidney were significantly decreased by BGD treatment. The results of this study indicate that BGD treatment is effective in decreasing the cadmium concentrations in liver and kidney, resulting in the therapeutic effect on the cadmium-induced renal damage.

Amino Acids↗

Enhancement of plasminogen activator activity in cultured endothelial cells by granulocyte colony-stimulating factor.

A hitherto unknown function of granulocyte colony-stimulating factor (G-CSF) was found using cultured endothelial cells. G-CSF stimulated activity of plasminogen activator (PA) in both extracellular and intracellular milieus of endothelial cells obtained from bovine carotid and aortic artery. This effect was dependent on the concentration of G-CSF added to the culture medium and on the treatment time. The extracellular activity was enhanced approximately 5-fold at a concentration of 5,000 colony-forming unit (CFU)/ml (2.6 nM) and in about a 15-hr treatment period. Analyses by fibrin and reverse fibrin autography revealed that activity of PA was much more increased than that of PA inhibitor in endothelial cells treated with G-CSF.

Animals↗

Cholesterol enhances the delivery of liposome-encapsulated gallium-67 to tumors.

The effect of incorporation of cholesterol (CH) into liposome membranes on the delivery of 67Ga encapsulated in liposomes to tumors was studied. The changes of the blood clearance of liposomes, liposome stability in serum and liposome uptake by the liver and spleen were also examined. Liposomes were prepared from distearoylphosphatidylcholine with various amounts of CH. It became clear that large amounts of CH (above 33 mol%) dramatically enhanced liposomal delivery of 67Ga to sarcoma 180 solid tumor in mice. Large amounts of CH increased the liposome stability in serum and decreased liposome uptake by the liver and spleen after intravenous injection, thus prolonging the blood clearance of liposomes. These observations suggested that the large delivery of 67Ga by CH-rich liposomes resulted from the extended retention and increased amount of liposomes in the circulation, caused by the incorporation of large amounts of CH. Small amounts of CH decreased liposome stability and hastened blood clearance, but had little effect on 67Ga delivery to the tumor. CH-rich liposomes showed high tumor uptake, with high tumor to blood and tumor to tissue ratios of 67Ga. It is anticipated that 67Ga-carrying liposomes will be an excellent tumor imaging agent for clinical use, provided that a correct choice of CH content is made.

Animals↗

Enhancement of clearance of plant lectins as radiopharmaceuticals by chemically glycosylated antilectin antibody.

The influence of chemical glycosylation on clearance of plant lectins, employed as radiopharmaceuticals, was assessed. Controlled chemical modification of the antibody to concanavalia ensiformis agglutinin did not affect its immunologic activity, but led to rapid clearance from circulation. In tumor-bearing mice, notable increases of selected tumor/non tumor ratios even after only 1 h of presence of the galactosylated antibody to the lectin in circulation were observed. Similarly, galactosylated antibody to pisum sativum agglutinin caused significant increases of tumor/non tumor ratios.

Animals↗

Induction of resistance in Oncomelania hupensis nosophora against Schistosoma japonicum, but not against Paragonimus ohirai, using irradiated miracidia.

Oncomelania hupensis nosophora snails sensitized with X-irradiated Schistosoma japonicum miracidia demonstrated resistance against a following challenge infection with non-irradiated homologous miracidia. The resistance in O. h. nosophora against S. japonicum was acquired within 1 day of sensitization, and it was strongest in a group challenged at an interval of 3 days. The resistance persisted for at least 4 weeks. Histological examinations revealed amoebocyte accumulation around the challenged S. japonicum sporocysts. On the other hand, when O. h. nosophora sensitized by exposure to X-irradiated P. ohirai or S. japonicum miracidia were subsequently challenged with normal P. ohirai miracidia, no resistance was observed, although they expressed the resistance against heterologous S. japonicum infection.

Animals↗

Removal of intracellular waste products by hemofiltration.

Because the total amount of waste products removed by hemofiltration can be measured exactly, it was divided into two components, that removed from the extracellular compartment and that removed from the intracellular compartment, using inulin as a marker for extracellular fluid in five uremic patients treated with hemofiltration in the postdilution mode. The amount removed from the extracellular compartment as a proportion to the total amount removed from the whole body by hemofiltration was 86.5% +/- 10.6% for guanidinosuccinic acid, 69.1% +/- 15.6% for sodium, 59.4% +/- 3.3% for uric acid, 56.4% +/- 2.1% for inorganic phosphate, 45.6% +/- 5.3% for creatinine, 43.1% +/- 7.2% for potassium, 42.9% +/- 3.1% for guanidinoacetic acid, 42.5% +/- 7.5% for methylguanidine, 37.2% +/- 8.4% for chloride, 36.3% +/- 2.8% for urea, and 6.9% +/- 2.9% for glucose. These results show that extracellular substances such as sodium and guanidinosuccinic acid were removed mainly from the extracellular compartment. On the other hand, glucose was removed only from the intracellular compartment, since blood glucose level is regulated. Although uric acid, inorganic phosphate, creatinine, potassium, guanidinoacetic acid, and methylguanidine are intracellular substances, they accumulated also in the extracellular fluid in renal failure, and were removed from both compartments, intracellular as well as extracellular, by hemofiltration.

Body Fluids↗

Clinical application of sodium-23 nuclear magnetic resonance for measurement of red cell sodium concentrations.

Red cell sodium (RBC-Na+) concentrations were measured using 23Na nuclear magnetic resonance (NMR), without the destruction of erythrocyte membranes. Subjects were categorized into four groups: 20 normotensive subjects (NT group), 20 age-matched essential hypertensive patients (EHT group), 10 patients with primary aldosteronism (PA group), and 18 patients treated with digoxin (DIG group). Although RBC-Na+ concentrations were similar between the NT group (6.14 +/- 0.80 (Mean +/- SD) mmol/l) and the EHT group (5.92 +/- 0.99), they were significantly higher in both the PA group (7.55 +/- 0.88, p less than 0.001) and the DIG group (8.43 +/- 3.81, p less than 0.02). In the PA group, RBC-Na+ concentrations decreased significantly after resection of the adenoma, and there was an inverse relationship between serum potassium and RBC-Na+ concentrations (r = -0.65, p less than 0.01). In the DIG group, RBC-Na+ concentrations tended to increase in proportion to serum digoxin levels (r = 0.53, p less than 0.05). These results support the view that RBC-Na+ concentrations are determined primarily by Na+/K+-pump activity of red cell membranes. This study showed also that Na+ NMR is an useful method determining intracellular Na+ concentrations.

Digoxin↗

Hypotensive mechanisms of antihypertensives based on the water tank model.

Mechanisms of hypotensive action of antihypertensive drugs were theoretically considered using the water tank model on body fluid volume-blood pressure regulation. If a cock is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume, and output from the cock, which represent mean arterial pressure (MAP), cardiac output (CO), and urinary Na+ excretion rate. The height of the cock from the tank bottom and the size of the cock correspond to the x-intercept and slope of the renal function curve (pressure-natriuresis relationship). Vasodilators lowered the cock height and enlarged the base area (reduced TPR), resulting in an increase in the volume (CO). beta-Blockers not only lowered the height, but also decreased the size of the cock. Because they do not alter TPR (base area), CO (volume) must be reduced. Converting-enzyme inhibitors had the same effects on the height and size of the cock as beta-blockers, but enlarged the base area (reduced TPR), resulting in an increase in the volume (CO). Diuretics increased the cock size without affecting the cock height or the base area, resulting in a decrease in CO. The effects of antihypertensive drugs on the cock (kidney) seemed essential in their hypotensive action, similarly as abnormality of the renal function curve is essential in the genesis of hypertension. These analyses can illustrate schematically the hemodynamic changes induced by antihypertensive drugs.

Antihypertensive Agents↗

Effect of dietary sodium on the Na-K ATPase inhibitor in patients with essential hypertension.

To study the circulating humoral factor modifying transmembrane sodium transport, plasma was obtained from 12 patients with essential hypertension (EH) fed a high sodium diet (NaCl 15 to 17 g/d) for seven days and thereafter a low sodium diet (NaCl 2 to 3 g/d) for seven days. Ouabain-sensitive 86Rb+ influx into the red blood cells (RBC) obtained from a healthy subject, and incubated with the plasma obtained during the high sodium diet was significantly lower than that incubated with the plasma obtained during the low sodium diet (3.74 +/- 0.26 v 3.97 +/- 0.30 nmol/10(8) cells, P less than .05). The changes in mean blood pressure from the high to low sodium diet showed a significant positive correlation with the changes in the ouabain-sensitive Rb influx into RBC in the plasma from the high to low sodium diet. These results suggest that a humoral factor modifying the sodium pump might be altered by sodium balance in EH, especially in salt-sensitive hypertension.

Aldosterone↗

Effects of salt, prostaglandin, and captopril on vascular responsiveness in essential hypertension.

To examine the influence of dietary sodium, prostaglandin, and captopril on vascular reactivity, 12 patients with essential hypertension (EH) and seven normotensive subjects (NT) were given a high sodium diet and thereafter a low sodium diet, each for ten days. Indomethacin (IND) (150 mg/d) was administered during the last three days of each dietary period. Blood pressure and cardiac output (CO) (by impedance cardiography) were measured during the angiotensin II (Ang II) infusion before and after the IND treatment of each dietary period. In eight patients with EH, captopril 100 mg was given before Ang II infusion. EH patients were classified as either salt sensitive (SS) or nonsalt sensitive (NSS). The mean blood pressure (MBP) response to Ang II was significantly higher on high sodium intake than on low sodium intake in NSS and NT, but not in SS. IND significantly increased the MBP response to Ang II on low sodium intake in NSS and NT, but not in SS. IND significantly increased the TPR response to Ang II on low sodium intake, remarkably in NSS and NT compared with SS. Salt sensitivity (% decrease in MBP from high to low sodium intake) highly correlated with the increase in the TPR response to Ang II by IND on low sodium intake (r = -0.90). After captopril administration, IND still increased the MBP and TPR response to Ang II on low sodium intake. These results suggest that the modulation of the vascular responsiveness to Ang II by prostaglandins is altered by sodium balance and salt sensitivity in EH.

Angiotensin II↗

Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia.

Lymphocyte subpopulations were measured in the blood of 21 children with severe aplastic anaemia (SAA). Five children with hepatitis-associated AA appeared to constitute a unique group. Compared with children with idiopathic AA, four of five children had a striking increase in percentage of activated suppressor T lymphocytes, which were defined by binding of both anti-Leu 2a and anti-HLA DR monoclonal antibodies (children with hepatitis-associated AA, 21.8 +/- 19.9% [mean +/- SD], children with idiopathic AA, 2.9 +/- 1.2%). However, there was no difference in the mean absolute number of the activated suppressor T lymphocytes between the two groups, because the mean number of lymphocytes was markedly less in children with hepatitis-associated AA (0.28 +/- 0.06 x 10(9)/l) than in those with idiopathic AA (1.64 +/- 0.74 x 10(9)/l). The mean helper: suppressor T lymphocyte ratio was significantly lower in children with hepatitis-associated AA (0.58 +/- 0.74) than in those with idiopathic AA (1.22 +/- 0.44). On the other hand, we did not find such a remarkable alteration of lymphocyte subpopulations in children with non-A non-B hepatitis who did not develop AA. These findings suggested that an imbalance of lymphocyte subpopulations and T lymphocyte activation may have pathogenetic relevance in some of the children with hepatitis-associated AA.

Adolescent↗

Ultrastructural and ultracytochemical differences between transient myeloproliferative disorder and megakaryoblastic leukaemia in Down's syndrome.

Ultrastructural and ultracytochemical studies were performed on blast cells from 12 Down's syndrome neonates with transient myeloproliferative disorder (TMD) and 13 Down's syndrome patients with megakaryoblastic leukaemia (MKL), in order to clarify the cytological characteristics of these cells. Average platelet peroxidase-positivity in blast cells of TMD patients was similar to that found in cases of MKL. Blast cells from subjects with TMD contained a number of different granules, namely, alpha granules, those that were myeloperoxidase (MPO)-positive, electron-lucent or basophil-like, and those containing membrane components or ferritin particles. On the other hand, granules found in the blast cells of MKL patients with Down's syndrome included the electron-lucent variety, those with membrane components and a few that were basophil-like, but not alpha and MPO-positive granules nor those containing ferritin particles. A demarcation membrane system was observed in blasts from the TMD group, but not in the MKL group. These findings suggest that blast cells in TMD patients differentiate to megakaryocytes, neutrophils, basphils and erythroblasts, while those in cases of MKL show limited differentiation to immature megakaryocytes, erythroblasts and, sometime, basophils. Such results correspond well with those of culture studies, in which TMD blasts were found to be precursors of various types of blood cells.

Bone Marrow↗

[Long-term results of percutaneous transluminal angioplasty in patients with renovascular hypertension--a follow-up study on renal function and renal size].

Twenty patients with renovascular hypertension were followed for at least 1 year (mean 3.3 years) after successful percutaneous transluminal angioplasty (PTA). Renal arteries were patent in 13 (65%) patients and were re-stenosed in 7 (35%). In 12 patients with unilaterally stenosed renal artery which were patent at the end of the follow up period, 6 patients were normotensive, the other 6 patients had less degree of hypertension. Determinations of renal vein renin were only of limited prognostic value. Renal blood flow pattern by doppler echography improved after PTA in the 12 patients. Radioisotope renogram showed tendency of improved Tmax ratio (stenotic kidney/nonstenotic kidney) from 1.5 +/- 0.8 to 1.0 +/- 0.2 (mean +/- SD, p less than 0.1). Serum creatinine levels decreased significantly from 1.2 +/- 0.5 mg/dl to 1.0 +/- 0.2 mg/dl (p less than 0.05) and creatinine clearance increased from 72.1 +/- 18.5 ml/min to 99.6 +/- 31.7 ml/min (p less than 0.02). The size of the stenosed kidneys increased from 11.2 +/- 0.7 cm to 12.0 +/- 0.8 cm (p less than 0.01), while the size of the contralateral kidneys did not change. These results indicate that PTA has favorable long-term effects on blood pressure and renal function with restoration of renal size in cases with patent renal arteries after this procedure.

Adult↗