T lymphocytes bearing gamma/delta-type T-cell receptor in thymic tumor tissues.
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Humans↗
Biomedical subjects
G Kimura
Publications and source records attributed to G Kimura.
A lymphocyte-specific protein tyrosine kinase, p56lck, regulates the PMA-induced internalization of CD4.
p56lck, a member of the src family of non-receptor protein tyrosine kinases (PTKs), is expressed predominantly in T-lymphocytes. Association of p56lck with CD4 and CD8 T-cell receptor (TcR) accessory molecules suggests that p56lck may play a specialized role in antigen-induced T-cell activation. CD4 and CD8 molecules are known to stabilize the interaction between TcR and the major histocompatibility complex during T-cell activation. To examine the role of p56lck in the dynamics of the CD4 molecule, p56lck-expressing transfectant cell clones were prepared by the transfection of an lck-gene plasmid containing an inducible promoter into a CD4+lck- human monocytoid cell line. When these transfectant cells were stimulated with phorbol ester, CD4 internalization on these p56lck-expressing cell lines was selectively and markedly retarded, as compared to p56lck-negative control cell lines. When cell-surface CD4 and intracellular CD4 were selectively precipitated after stimulation, the intracellular CD4 molecules were dissociated from p56lck whereas the surface-retained CD4 molecules were still associated with p56lck. Moreover, the dissociation of p56lck from CD4 appeared to occur prior to the PMA-induced internalization of CD4. These data indicate that p56lck regulates the PMA-induced internalization of CD4 possibly via its association with CD4. Treatment with genistein, a PTK inhibitor, revealed that the PTK activity of p56lck might not be involved in this regulatory effect of p56lck on CD4 internalization.
Blotting, Western↗
Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor.
The purpose of this study was to elucidate a possible immune response to tumor cells mediated by tumor-infiltrating lymphocytes (TIL) in lung cancer. In flow cytometry, the majority of T-cells of TIL were CD45RA-, CD45RO+, and CDw29high, and expressed HLA-DR. The expression of interleukin 2 receptor beta chain increased in both CD4+ and CD8+ TIL compared with both types of T-cells in peripheral blood. These results indicate that the major population of TIL is activated memory T-cells. The TIL preparation, which was usually contaminated with 5 to 10% tumor cells, did not exhibit any response in autologous mixed lymphocyte-tumor culture even in the presence of interleukin 2 (IL-2) in all five cases tested. Although purified T-cells from TIL showed the positive response in only 1 of 10 cases tested without addition of IL-2, it occurred in 7 of 10 cases in the addition of a low concentration of IL-2. The IL-2-dependent response to irradiated autologous tumor cells was suppressed when nonirradiated autologous tumor cells were added to the culture. Culture supernatants of four lung cancer cell lines and freshly prepared lung cancer cells obtained from 6 cases exhibited suppressive activity against anti-CD3 antibody-induced mitogenesis of peripheral blood mononuclear cells from healthy donors. We suggest that, taken together, (a) the major population of TIL in lung cancer are activated memory T-cells, and they include tumor-reactive ones, and that (b) the function of the TIL is impaired by unavailability of IL-2 and/or by suppression due to lung cancer cell-derived factor(s).
Antigens, CD↗
The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein.
A human CD4+ T cell line, Jurkat, was transfected with a constructed plasmid, which has the envelope gene of the human immunodeficiency virus (HIV) under the transcriptional control of the human metallothionein IIA promoter, and these transfected cells were then cloned. JME2, one of the cloned cell lines, expressing the envelope glycoprotein after induction with metal ions, showed the ability to form syncytia involving other CD4+ cells not expressing the HIV envelope protein. When several CD4+ cell lines were examined for their susceptibility to syncytium formation by JME2 cells, the p56lck-expressing cell lines were found to be more susceptible to syncytium formation than the p56lck-non-expressing cell lines. To substantiate the role of p56lck in the syncytium formation, a CD4+, p56lck-non-expressing monocytoid cell line, U937 clone 2, was transfected with an lck-expressing construct. Using such transfectant cell clones, it was demonstrated that p56lck-positive cells are markedly more susceptible to the syncytium formation than p56lck-negative cells, implying a regulatory role for p56lck in syncytium formation mediated by the HIV envelope and CD4 molecule. Moreover, it was suggested, in the experiments using CD45 cross-linking or a protein tyrosine kinase inhibitor, genistein, that p56lck affects syncytium formation through its protein tyrosine kinase activity. A putative mechanism by which p56lck affects the syncytium formation is also discussed.
CD4 Antigens↗
Sodium and noradrenaline in cerebrospinal fluid and blood in salt-sensitive and non-salt-sensitive essential hypertension.
1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.
Adult↗
Intracellular free magnesium of red blood cells in patients with renal disease.
While serum magnesium (Mg) level is increased in patients with end-stage renal disease (ESRD), it is decreased in renal transplant recipients (TR) receiving ciclosporin. This study was performed to examine the cation metabolism of red blood cells (RBC) in these patients. Intracellular free Mg was measured with 31P-nuclear magnetic resonance spectrometry, and ouabain-sensitive sodium (Na) efflux rate (Eos) was measured from the increase in RBC-Na concentration when RBC were incubated in the presence of ouabain. The ouabain-sensitive Na efflux rate constant (ERCos) was obtained by dividing Eos by RBC-Na concentration. RBC free Mg and ERCos were significantly higher in the TR group than in the ESRD group. There was a significant correlation between RBC free Mg and ERCos (r = 0.474, p less than 0.01). These results support the views that the regulation mechanism for intracellular free Mg is different from that for extracellular Mg in patients with renal disease, and intracellular free Mg modulates Na pump activity of RBC.
Adenosine Triphosphate↗
Calcification in human osteoblasts cultured in medium conditioned by the prostatic cancer cell line PC-3 and prostatic acid phosphatase.
A medium that had been conditioned by PC-3 cells stimulated the calcification of a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The calcification of the osteoblasts was stimulated maximally at a 25% concentration of the conditioned medium. Calcification activity was markedly enhanced by the addition of both prostatic acid phosphatase (PAP) and its substrate, alpha-glycerophosphate, to the medium; however, PAP added alone did not enhance this activity. These results suggest that human prostatic carcinoma cells produce a factor that stimulates the calcification of the human osteoblasts. Results have also suggested that PAP is a requisite for osteogenesis provided that its substrates are abundant in the medium.
Acid Phosphatase↗
Acute depressor effect of alcohol in patients with essential hypertension.
To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers.
Adult↗
Induction of DNA synthesis by fibroblast growth factor in temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts arrested at restrictive temperature.
Four temperature-sensitive cell-cycle mutants of rat 3Y1 clonal fibroblasts representing separate complementation groups (3Y1tsD123, 3Y1tsF121, 3Y1tsG125 and 3Y1tsH203) are arrested at restrictive temperature, primarily with a G1-phase DNA content (temperature arrest). We examined various factors affecting signal transduction for activity which induces DNA synthesis at the restrictive temperature when added to the temperature-arrested cultures of these mutants. The factors examined were theophylline, dibutyryl cyclic AMP, cholera toxin (CT), dibutyryl cyclic GMP, sodium nitroprusside, phorbol 12-myristate 13-acetate, 1-oleoyl 2-acetylglycerol, bombesin, vasopressin, basic fibroblast growth factor (FGF), platelet-derived growth factor, A23187, monensin, epidermal growth factor (EGF), insulin and fetal calf serum (FCS). None of these factors induced DNA synthesis in 3Y1tsH203. In one mutant (3Y1ts121), FGF, EGF and FCS individually induced DNA synthesis. In the other 2 mutants (3Y1tsD123 and 3Y1tsG125), FGF and CT individually induced DNA synthesis. The FGF-induced DNA synthesis was suppressed by islet-activating protein (IAP) in 3Y1tsD123 and 3Y1tsG125, but not in 3Y1tsF121. The CT-induced DNA synthesis was also suppressed by IAP, as previously shown. When temperature-arrested cultures were shifted to a permissive temperature, all 4 mutants initiated DNA synthesis in the presence of IAP. These results suggest that (1) a cell can prepare for the initiation of DNA synthesis by using several independent signal transduction pathways, and (2) in a given situation, the cell uses a particular pathway because of its availability, which depends on the culture conditions.
Animals↗
Effects of butyrate on cell cycle progression and polyploidization of various types of mammalian cells.
We studied the effect of butyrate on cell cycle progression and polyploidization in three fibroblast (rat 3Y1, human IMR-90, and human embryo lung HEL) and two epithelial (human embryo kidney HEK and monkey kidney BSC-1) cells. In these cells, except for 3Y1, G1 arrest with butyrate was incomplete, and the production of tetraploid cells was detectable in the presence of butyrate. G2 arrest with butyrate was also incomplete in HEL and BSC-1 cells, and the number of HEL cells increased in the presence of butyrate. On the contrary, most BSC-1 cells that divided in the presence of butyrate were unstable and the number of attached cells decreased. These results indicate that the effect of butyrate on cell cycle progression varies with the cell type and that polyploidization can be induced by a single treatment with butyrate.
Animals↗
Vascular responsiveness to angiotensin II and phenylephrine, the tubular function and the prostaglandin, renin-angiotensin system in a patient with Bartter's syndrome.
In a 39-yr-old female patient with Bartter's syndrome, vascular responsiveness to angiotensin II and phenylephrine was studied. Pressor responses to angiotensin II and to phenylephrine were markedly decreased prior to treatment and were improved by administration of indomethacin, dextran, KCl, captopril, propranolol or pindolol. Moreover, the responses of total peripheral vascular resistance to angiotensin II and phenylephrine were markedly decreased before treatment and were improved by the treatment. A relatively low fractional distal chloride reabsorption was found, and that was not changed after the administration of KCl or indomethacin. The results of this patient were compatible with the primary cause of Bartter's syndrome, defective chloride reabsorption at the loop of Henle, but the possibility of an abnormality in the vascular wall could not be denied.
Adult↗
[Studies on IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen in asthmatics].
T-cell-derived lymphokine, IFN-gamma, has potent effects on B-cell differentiation and leukotriene C4 production in leukocytes, and inhibits the effect of IL-4 on IgE production. To investigate the role of IFN-gamma in the pathogenesis of bronchial asthma, we examined IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen and serum Candida specific IgG1 antibody from 20 asthmatics. The results were as follows: 1) IFN-gamma production in non-atopic severe asthmatics was significantly higher than in healthy subjects, atopic mild and moderate asthmatics, and atopic severe asthmatics (p < 0.05). 2) There was a significant correlation between IFN-gamma production induced by Candida antigen and serum Candida specific IgG1 antibody (r = 0.72, p < 0.01). These results suggest that IFN-gamma may play an important role in the pathogenesis of non-atopic severe bronchial asthma.
Adult↗
Effect of manidipine, a new calcium antagonist, on intrarenal hemodynamics in essential hypertension.
The effect of manidipine, a new Ca2+ antagonist, on intrarenal hemodynamics was assessed in essential hypertension and compared with nicardipine, a previously studied Ca2+ antagonist. Identical 2-week studies were repeated before and during the administration of manidipine (10 mg once daily, 2 weeks) in 3 patients with essential hypertension who were given regular- and sodium-restricted diets for 1 week each. The renal function curve (pressure-natriuresis relationship) was drawn by plotting the urinary sodium excretion rate on the y-axis as a function of the systemic mean arterial pressure (MAP) on the x-axis. Assuming that the difference between MAP and the extrapolated x-intercept of the renal function curve represents the effective filtration pressure across the glomerular capillary walls, the intrarenal hemodynamics were calculated (e.g., afferent arteriolar resistance (RA), efferent arteriolar resistance (RE), and glomerular pressure (PG)). During the regular sodium diet, MAP was lowered from 100 +/- 7 to 93 +/- 5 mmHg (p < 0.04) and the effective filtration pressure was lowered from 20 +/- 2 to 10 +/- 3 mmHg (p < 0.05); the renal plasma flow rate (pre: 560 +/- 74 vs. post: 627 +/- 108 mL/min) and glomerular filtration rate (82 +/- 10 vs. 78 +/- 5 mL/min) were not altered. RA remained unchanged (3,800 +/- 700 vs. 3,400 +/- 300 dyn.sec.cm-5; % reduction: 4 +/- 16%) whereas RE was reduced from 4,300 +/- 700 to 3,300 +/- 800 dyn.sec.cm-5 (19 +/- 15%). Thus, PG was lowered from 58 +/- 2 to 50 +/- 2 mmHg (13 +/- 3%), which parallels with the reduction in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗
[Studies of lymphocyte activation on late asthmatic response in adult asthma].
Late asthmatic response (LAR) as well as delayed asthmatic response (DeAR) is an important clinical characteristic in adult severe asthma. These responses might be based on cell to cell interaction following lymphocyte activation. Therefore, to clarify the pathogenesis of LAR, we studied the lymphocyte functions of adult asthmatics with LAR provoked by inhalation of house dust and Candida antigen. The results revealed that mite antigen-specific lymphocyte blastogenesis, IL-2 and ECF production were significantly higher in asthmatics with LAR provoked by house dust antigen than in normal subjects and asthmatics with IAR by house dust and LAR by Candida, though there was no significant difference in NCF. Candida antigen-specific lymphocyte blastogenesis, IL-2, ECF and NCF production were significantly higher in asthmatics with LAR provoked by Candida antigen than in normal subjects and asthmatics with IAR or LAR provoked by house dust. There was a positive correlation between Candida antigen-specific IL-2 and NCF production in asthmatics with LAR provoked by Candida antigen. These results suggest that antigen-specific lymphocyte activation may play an important role in the pathogenesis of LAR, especially in asthmatics with LAR provoked by Candida antigen, and that LAR and DeAR should be considered inclusively as cell-mediated allergy.
Adolescent↗
The association between salt sensitivity of blood pressure and family history of hypertension.
1. The salt sensitivity index (SSI) and family history of hypertension were studied in 140 hospitalized patients with essential hypertension to clarify whether salt sensitivity of blood pressure is related to familial disposition to hypertension. 2. SSI was calculated by dividing the change of mean blood pressure by that of urinary sodium excretion when salt intake was restricted from 15 to less than 3 g/day. 3. Family history of hypertension was classified into three groups depending on the presence or absence of hypertension in the father, mother and siblings. 4. The group without a family history of hypertension showed a significantly lower SSI value than other groups. 5. In multiple regression analysis undertaken within each gender, SSI showed significant partial correlations with blood pressure and family history of hypertension in the female group (r = 0.402 and 0.265, respectively), whereas in the male group it showed a positive correlation only with blood pressure (r = 0.501). These results indicate that salt sensitivity of blood pressure is related to familial disposition to hypertension. This association was more apparent in the female than male group and its gender difference can be partially attributed to the fact that blood pressure in the female group is more sensitive to salt.
Blood Pressure↗
[Operation of female stress incontinence--comparison between Raz procedure and Gittes procedure].
We performed Raz procedure and Gittes procedure for female stress incontinence since October 1986. Raz procedure was performed on 19 patients between October 1986 and February 1990, and Gittes procedure was performed on 18 patients between June 1990 and May 1991. We followed up 17 patients who underwent Raz procedure and all the patients who underwent Gittes procedure at the time August 1991. Disappearance or marked improvement of incontinence was confirmed in 12 patients by Raz procedure, and 16 patients by Gittes Procedure. No serious complications were recognized. The reason why the result of Raz procedure was not sufficient was due to our immature operative technique and incorrect patient selection in our early experience. From this experience, we believe that both procedures can be very useful and minimal invasive operation for female stress incontinence.
Adult↗
[Role of intrarenal hemodynamics in sodium-sensitivity of blood pressure].
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Body Fluids↗
Changes in coagulation factors by passage through a dextran sulfate cellulose column during low-density lipoprotein apheresis.
To determine the extent of adsorption of coagulation factors by a dextran sulfate cellulose column used for selective removal of low-density lipoprotein (LDL), various coagulation factors were measured before and after application to the column during LDL apheresis. The column almost completely adsorbed many coagulation factors. Although the bradykinin concentration was markedly increased by passing the plasma through the column, this increment was suppressed by nafamostat mesilate which inhibits the initial contact phase of the intrinsic coagulation pathway. The von Willebrand factor, which forms a complex with factor VIII in plasma, is reduced in apheresis with nafamostat mesilate to the same extent as in apheresis without nafamostat mesilate. Thus, coagulation factors seem to be adsorbed by different mechanisms which include activation of the initial contact phase by the negative charges of dextran sulfate and concomitant adsorption with the phospholipid portion of lipoproteins containing apolipoprotein B or with von Willebrand factor.
Adolescent↗