Biomedical subjects
Publications and source records attributed to C Tang.
The case of a 63-year-old man who developed Candida albicans osteomyelitis is reported. Because of renal impairment, fluconazole was chosen as treatment rather than amphotericin B. The patient made a full recovery. This is the first report of the successful use of fluconazole in the treatment of candidal osteomyelitis.
The presence of pneumococcal capsular antigen (PCA) in the oropharynx was sought in subjects without respiratory tract infection. Saliva specimens from 239 subjects were analysed by counter-current immunoelectrophoresis using 'Omniserum'. 15.5% gave positive reactions but only 24% of positive samples were typable and therefore due to pneumococcal or pneumococcal-like antigens. Given that oropharyngeal production of antigens occurs we investigated whether PCA in expectorated sputum arose from oropharyngeal contamination. Sixteen patients with pneumococcal pneumonia, and with sputum positive for PCA, were investigated in detail. On the basis of serotyping and concentration the PCA in sputum was thought to arise from the lower respiratory tract in all cases. This was confirmed by a simple, novel approach involving the comparison of concentrations in concomitant samples of saliva and sputum. Thus while oropharyngeal production of antigens poses a potential diagnostic problem the latter approach can be used to exclude contamination.
The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura-2 as fluorescent Ca2+ indicator, we found that both methyl-mercury (MeHg; 0.02-2 microM) and inorganic mercury (HgCl2; 0.01-1 microM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration-dependent manner. The effect of MeHg was rapid and the increase of Ca2+ level was sustained in time, while HgCl2 caused a slow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCl2 quench between control and mercury-treated cells. However, HgCl2 (1 microM) and MeHg (2 microM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca(2+)-free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCl2 had no effect. Heparin, an inhibitor of inositol 1,4,5-trisphosphate-induced Ca2+ mobilization partially blocked this rise of [Ca2+]i, while carbonyl cyanide m-chlorophenylhydraxone (CCCP), an inhibitor of mitochondrial function, had a lesser effect. When added together, heparin and CCCP almost completely block the response to MeHg. These results suggest that MeHg and HgCl2 exert their effects of [Ca2+]i in different ways: MeHg-induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCl2 causes only Ca2+ influx from the extracellular medium.
BACKGROUND: Severe hyperkalemia is a serious problem during orthotopic liver transplantation. The effectiveness of insulin in decreasing serum potassium concentration during the anhepatic stage of orthotopic liver transplantation was investigated. METHODS: Forty patients with serum potassium concentrations greater than 4.0 mM/L at the onset of the anhepatic stage were randomized into two groups. Control group patients (n = 20) received no treatment, and treatment group patients (n = 20) received an intravenous bolus of regular insulin (20 u) 10 min into the anhepatic stage, followed by a glucose infusion (500 ml 5% dextrose in water) over 15 min. RESULTS: In the control group, the potassium concentration did not change, whereas in the treatment group, it decreased from 4.70 +/- 0.54 to 4.18 +/- 0.63 mM/L (mean +/- SD) within 15 min and to 3.57 +/- 0.55 mM/L 60 min after therapy. The potassium concentration was less in the treatment group than in the control group within 30 min of treatment (3.97 +/- 0.52 vs. 4.49 +/- 0.43 mM/L, respectively; P < 0.05). The potassium concentration increased similarly 30 s after graft reperfusion in both groups of patients, but was less in the treatment group (5.91 +/- 1.63 vs. 7.37 +/- 1.67 mM/L, respectively; P < 0.05). The potassium concentration returned to prereperfusion levels within 5 min after graft reperfusion. CONCLUSIONS: In patients undergoing orthotopic liver transplantation, the administration of insulin rapidly decreases serum potassium concentration, even in the absence of the liver, suggesting an important contribution by extrahepatic tissues in the insulin-stimulated uptake of potassium.
Changes in the distribution of alpha 1-adrenergic receptors in two subcellular fractions, the plasma membrane and the light vesicle, of rat liver during sepsis were studied using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis). [3H]prazosin binding studies show that during early sepsis, the maximal binding capacity (Bmax) was increased by 35% in plasma membranes but was decreased by 28% in light vesicles; while during late sepsis, the Bmax was decreased by 30% in plasma membranes but was increased by 33% in light vesicles. The photoaffinity labeling studies revealed two major binding peptides with M(r) of 77,000 and 68,000 Da and one minor binding protein with M(r) of 39,000 Da. The total binding for the three labeled peptides during early sepsis was increased by 26% in plasma membranes but was decreased by 33% in light vesicles, while during late sepsis the total binding was decreased by 19% in plasma membranes but was increased by 35% in light vesicles. These data indicate that alpha 1-adrenergic receptors in the rat liver were externalized from light vesicles to plasma membranes during the hyperglycemic phase while they were internalized from surface membranes to intracellular sites during the hypoglycemic phase of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
The tumor promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), presumably through activation of protein kinase C, decreases the production of 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] and increases that of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] by primary cultures of chick kidney cells. We have previously shown that the regulation of the cellular output of 1,25(OH)2D3 and 24,25(OH)2D3 by PTH and 1,25(OH)2D3 can be quantitatively accounted for by altered hydroxylase activities within isolated mitochondria. In the present paper, we examined the effects of TPA and 1-oleoyl-2-acetyl-glycerol (OAG) on the state of mitochondrial protein phosphorylation and on 25-hydroxyvitamin D3 [25(OH)D3] metabolism. There was a good correlation between 25(OH)D3- 1 alpha- and 24-hydroxylase activities in mitochondria isolated from cells pretreated with either TPA or OAG and the pattern of 1- and 24-hydroxylation of 25(OH)D3. The most notable change in protein phosphorylation in the molecular mass range of 10-60 kilodaltons (kDa) was a dramatic decrease in the phosphorylation of a 12.5-kDa mitochondrial matrix protein after treatment of kidney cells with TPA or OAG. The amino acid composition of the 12.5-kDa protein was similar to bovine and human ferredoxins and it comigrated with bovine and human ferredoxins in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 12.5-kDa phosphoprotein was immunoprecipitated specifically by an antipeptide polyclonal antibody for chick ferredoxin. The dephosphorylation of ferredoxin in response to TPA was both rapid and transient, with the phosphate content of the 12.5-kDa protein reduced by 70% after a 5-min exposure and returning to control levels by 20 min. A similar transience was observed with regard to the rapid effects of TPA on 1 alpha-hydroxylase activity, again showing maximal inhibition at 5 min. The results of our studies are consistent with the idea that ferredoxin phosphorylation plays a role in the regulation of steroid hydroxylation.
Recently, high dose Ara-C (HIDAC) has been shown to induce leukemic cell death in vitro by the alternative process of programmed cell death (PCD) or apoptosis which correlates with the inhibition of their clonogenic survival. Since co-treatment with hemopoietic growth facts (HGFs) GM-CSF and IL-3 have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells, we examined the effect of HGFs pIXY 321 (a GM-CSF/IL3 fusion protein) and G-CSF on HIDAC induced PCD and related gene expressions as well as HIDAC mediated colony growth inhibition of human myeloid leukemia cells. Treatment with G-CSF or pIXY 321 alone for up to 24 hours neither suppressed nor induced PCD in HL-60 or KG-1 cells. However, exposure to either of the HGFs for 20 hours followed by a combined treatment for 4 hours with HIDAC plus either of the HGFs versus HIDAC alone significantly enhanced the intracellular Ara-CTP accumulation and the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of C-jun expression but a significant repression in BCL-2 and c-myc expressions. In addition, the treatment with either of the HGFs plus HIDAC versus HIDAC alone produced a significantly greater inhibition of the clonogenic survival of the myeloid leukemia cells. These findings underscore an additional mechanism of leukemic cell death induced by HIDAC which can be modulated by the HGFs to improve the antileukemic activity of HIDAC.
The present results demonstrate that the exposure of human myeloid leukemia HL-60 and KG-1 cells to clinically achievable concentrations of taxol produced internucleosomal DNA fragmentation of approximately 200 base-pair multiples, and the morphologic changes characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Taxol-induced PCD was associated with a marked inhibition of suspension culture growth and clonogenic survival of HL-60 cells. In addition, taxol treatment decreased BCL-2 oncogene expression, which is known to block PCD. The exposure to taxol moderately decreased c-myc expression, but did not induce c-jun expression--which has been previously noted for a variety of DNA interactive, antileukemic drugs. These findings indicate that taxol may induce leukemic cell death partly by the alternative but gene-directed and active mechanism of PCD.
In autologous bone marrow transplantation in patients with acute myeloid leukemia (AML), 4-hydroperoxycyclophosphamide (4-HC) is a commonly used ex vivo purging agent for leukemic blasts. In the present report, we demonstrate that exposure to high concentrations of 4-HC for 1 hour, as used in ex vivo bone marrow purging, produces internucleosomal DNA fragmentation characteristic of apoptosis, or programmed cell death (PCD), in human myeloid leukemia HL60 cells. Lower concentrations of 4-HC (10, 20, or 50 microM/L) failed to cause this effect, while higher concentrations (> or = 200 microM/L) produced random DNA fragmentation. 4-HC-mediated internucleosomal DNA fragmentation was associated with a marked induction in c-jun and significant reductions in bcl-2 and c-myc oncogene expressions. A combined treatment with interleukin-3 (IL-3) plus IL-6 for 18 hours before an additional, 1-hour concurrent treatment with 4-HC (100 microM/L) significantly increased 4-HC-induced DNA fragmentation as well as colony growth inhibition of HL60 cells. The effects of cotreatment with IL-3 plus IL-6 were also associated with a further, modest decrease in bcl-2 and c-myc and augmentation of c-jun expression. These findings highlight an alternative mechanism of 4-HC-induced leukemic cell death that can be potentially enhanced by cotreatment with IL-3 plus IL-6.
The muscarinic agonist oxotremorine produced a concentration-dependent increase in membrane fluidity in intact viable rat splenic lymphocytes in vitro. This effect was antagonized by atropine, but only at high concentrations (1 mM), while scopolamine was ineffective. Two other muscarinic agonists, carbachol and pilocarpine, did not affect membrane fluidity in lymphocytes. The fluidizing effect of oxotremorine occurred at both 10 and 37 degrees C with a similar time-course. Oxotremorine also increased membrane fluidity in liposomes of DMPC in gel phase, although its effect was less pronounced than in lymphocytes. The data suggest that the fluidization caused by oxotremorine is primarily nonreceptor-mediated and associated with a nonspecific physicochemical effect.
Changes in the distribution of (Na+ + K+)-ATPase in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The alpha-subunit of (Na+ + K+)-ATPase was photoaffinity labeled with [alpha-32P]8-N3ATP. The results show that septic rat heart exhibits hyperdynamic (hypermetabolic) phase during early (9 hr post-CLP), followed by hypodynamic (hypometabolic) phase during late (18 hr post-CLP) sepsis. Marker enzyme and beta-adrenergic receptor assays depict that the light vesicle fraction is the intracellular site of surface receptor. The incorporation of the photolabel into the alpha-subunit (M(r) = 98,000) of the (Na+ + K+)-ATPase in sarcolemmal fraction was increased by 60% (P < 0.01) during early sepsis, but was decreased by 63% (P < 0.01) during late sepsis. In contrast, the binding of 98,000-M(r) peptide in light vesicles was decreased by 40% (P < 0.01) in early sepsis, but was increased by 102% (P < 0.01) during late sepsis. The ouabain-sensitive (Na+ + K+)-ATPase activity was increased by 31% (P < 0.05) during the early sepsis, but was decreased by 32% (P < 0.01) during late sepsis in the sarcolemmal fraction; while in the light vesicle fraction, the (Na+ + K+)-ATPase activity was decreased by 21% (P < 0.01) during early sepsis, but was increased by 47% (P < 0.01) during the late phase of sepsis. The yield of membrane proteins for each specific fraction remained unchanged for control, early sepsis, and late sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
High dose Ara-C (HIDAC) induces programmed cell death (PCD) or apoptosis in vitro in human myeloid leukemia cells, which correlates with the inhibition of their clonogenic survival. Hematopoietic growth factors (HGFs) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells. We examined the effect of pIXY 321 (a GM-CSF/IL-3 fusion protein) on HIDAC-induced PCD and related gene expressions as well as HIDAC-mediated colony growth inhibition of human myeloid leukemia cells. Unlike the previously described effects of HGFs on normal bone marrow progenitor cells, exposure to pIXY 321 alone for up to 24 hours did not suppress PCD in HL-60 or KG-1 cells. However, exposure to pIXY 321 for 20 hours followed by a combined treatment with Ara-C plus pIXY 321 for 4 or 24 hours versus treatment with Ara-C alone significantly enhanced the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of c-jun expression and a significant decrease in BCL-2. In addition, the treatment with pIXY 321 plus HIDAC versus HIDAC alone produced a significantly greater inhibition of HL-60 colony growth. These findings highlight an additional mechanism of HIDAC-induced leukemic cell death that is augmented by cotreatment with pIXY 321 and may contribute toward an improved antileukemic activity of HIDAC.
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Post-transcriptional regulation of genes important in iron metabolism, ferritin and the transferrin receptor (TfR), is achieved through regulated binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP), to RNA stem-loop motifs known as iron-responsive elements (IREs). Binding of the IRE-BP represses ferritin translation and represses degradation of the TfR mRNA. The IRE-BP senses iron levels and accordingly modifies binding to IREs through a novel sensing mechanism. An iron-sulfur cluster of the IRE-BP reversibly binds iron; when cytosolic iron levels are depleted, the cluster becomes depleted of iron and the IRE-BP acquires the capacity to bind IREs. When cytosolic iron levels are replete, the IRE-BP loses RNA binding capacity, but acquires enzymatic activity as a functional aconitase. RNA binding and aconitase activity are mutually exclusive activities of the IRE-BP, and the state of the iron-sulfur cluster determines how the IRE-BP will function.
The synthesis of 1,25(OH)2D3 is a critical control point in the regulation of calcium metabolism, and possibly in the growth and differentiation of a number of cell types. This paper reviews our current understanding of the regulation of this process at the cellular and molecular levels, with the emphasis on the mechanisms of feedback control 1,25(OH)2D3 itself, control of parathyroid hormone, the roles of cyclic AMP dependent protein kinase and protein kinase C, and the interaction between the various intracellular regulators of 1,25(OH)2D3 production.
An examination of medical and physiological changes before and after tennis competition was performed on 71 middle-aged persons and old people in order to know whether they were adapted to this intense match or not. The result was that in the male group 1 (50-59 yrs), the heart rate, respiration rate and blood pressure before and after the tennis game had no significant differences (P > 0.05), indicating that this group was fit for the tennis competition, in the male group 2 (60-69 yrs) and male group 3 (70-79 yrs), as age advances, the number of unfitness to this game was increased gradually; in the female group (50-59 yrs), 28.5% of them showed a marked increase in the heart rate after the competition. We think that when persons have an electrocardiogram showing a significant undue changes of the ST segment and T wave after the contest, they are not suitable to this violent competition. So the medical surveillance is very important for the old people to play violent games such as tennis. The periodical health examination should be done before any exercise event with emphasis on the cardiovascular system so that the old sportsman can choose the proper exercise item and take self-control during the exercise.
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A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.