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Biomedical subjects

C C Chou

Publications and source records attributed to C C Chou.

At least 127 records · Page 7Linked to original sources
PubMed1991

A recombinant chimeric plasminogen activator with high affinity for fibrin has increased thrombolytic potency in vitro and in vivo.

A recombinant plasminogen activator with high fibrin affinity and specificity was expressed by transfecting hybridoma cells with a plasmid that combines sequence coding for low molecular mass (32 kDa) single-chain urokinase-type plasminogen activator [scuPA(32kDa)] and anti-fibrin monoclonal antibody 59D8. The expression of the recombinant molecule [r-scuPA(32kDa)-59D8] was optimized by replacing the 3' untranslated region (initially that of high molecular mass scuPA) in the plasmid with the 3' untranslated region of either beta-globin or mouse immunoglobulin. This modification resulted in a greater than 100-fold improvement in the level of protein expression. The 103-kDa r-scuPA(32kDa)-59D8 protein displayed catalytic activity indistinguishable from that of high molecular mass scuPA and fibrin binding comparable to that of native antibody 59D8. r-scuPA(32kDa)-59D8 was 6 times more potent than high molecular mass scuPA in lysing a human plasma clot in vitro and was 20 times more potent than high molecular mass scuPA in the rabbit jugular vein model of thrombolysis. Molecules of this type may serve as prototypes for highly specific, antibody-targeted enzymes suitable for human use.

Animals↗
PubMed1991

Interleukin 2 therapy in severe atopic dermatitis.

Interleukin 2 (IL-2) at a dose of 10,000 to 20,000 U/kg/q 8 hr was given for 9-12 days to six patients with cases of severe atopic dermatitis (AD) which were refractory to conventional therapy. After IL-2 therapy, the clinical symptoms and signs of eczema including pruritus, scratching, papulovesicles, and lichenification were much improved, but all of them recurred 2-6 weeks after stopping treatment. Adverse reactions were similar to those reported previously, but all of them subsided after discontinuation of therapy. Laboratory findings showed decreased T-cell subsets, especially CD4+ cells, and increased IL-2R+ (CD25) cells, but there was no significant change in serum IL-2, serum IgE, or in vitro IgE production. Immunopathological studies of the skin biopsies showed decreased mononuclear-cell infiltration, depletion of CD4+ cells, and enhanced expression of CD25 and HLA-DR antigens. As lymphokine-activated killer (LAK)-cell activity against cultured fibroblasts was similar in patients with AD and in normals and CD1+ Langerhans cells were not decreased after IL-2 therapy, we speculate that the depletion of helper/inducer CD4+ cells and hence abrogation of the exaggerated antigen processing and cellular activation in diseased skin are the explanation for the transient efficacy of IL-2 in the treatment of atopic dermatitis.

CD4-Positive T-Lymphocytes↗
PubMed1991

Adenosine is a vasodilator in the intestinal mucosa.

The vasoactivity of adenosine in the intestinal mucosa of anesthetized dogs was determined using two experimental techniques. By use of the microsphere technique, infusion of adenosine (1 mumol/min ia) was found to increase significantly venous outflow and mucosal and muscularis blood flows in both jejunum (+77, +72, and +78%) and ileum (+111, +146, and +71%). In constant flow jejunal preparations, intra-arterial adenosine significantly decreased perfusion pressure (-32%), an index of vascular resistance, but did not significantly alter the blood flow distribution between the mucosa and muscularis as determined by microspheres. Thus adenosine equally dilated the mucosal and muscularis vasculatures. Using the second experimental technique, we found that local mucosal application of adenosine or non-metabolizable adenosine analogues [N6-cyclohexyladenosine or 5'-(N-ethylcarboxamido)-adenosine] dose dependently increased jejunal venous outflow. Almost all of the adenosine absorbed from the lumen was localized in the mucosal tissue, suggesting that the above hyperemia resulted from exposure of the mucosal vasculature to these compounds. The hyperemia produced by the luminal placement was not mediated by stimulation of the mucosal nerves, because the hyperemia was unaltered after treating the mucosal surface with a local anesthetic. The present results demonstrate therefore that adenosine is a vasodilator in the canine intestinal mucosa.

Adenosine↗
PubMed1990

Jejunal adenosine increases during food-induced jejunal hyperemia.

If adenosine mediates postprandial intestinal hyperemia, increases in local adenosine release must accompany the hyperemia. We tested this by determining jejunal venous and arterial plasma adenosine concentrations, jejunal blood flow, and oxygen consumption before and during placement of normal saline or predigested food plus bile into the jejunal lumen of anesthetized dogs. Adenosine concentrations were measured by high-pressure liquid chromatography. Luminal placement of food significantly increased blood flow (+46%), oxygen consumption (+40%), venous adenosine concentration (+56 nM), and adenosine release (+1.7 nmol.min-1.100 g tissue-1) during the initial 3 min of placement. Whereas blood flow and oxygen consumption remained elevated for the entire 15-min placement period, venous adenosine concentration and release returned to control levels at 7 and 11 min after placement, respectively. Placement of the same volume of normal saline did not significantly alter any variables measured, indicating that the food-induced changes were because of constituents of food. In conclusion, introduction of predigested food into the jejunal lumen significantly increases adenosine releases into the local venous blood during the initial several minutes of food placement. The increased adenosine production and release may play a role in postprandial jejunal hyperemia.

Adenosine↗
PubMed1990

Thromboxane plays a role in postprandial jejunal oxygen uptake and capillary exchange.

The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments. In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069. SQ 29548 (2.0 micrograms ia) per se did not significantly alter resting jejunal blood flow, oxygen uptake, capillary pressure, or Kfc. Before SQ 29548, placement of food plus bile into the jejunal lumen increased blood flow +42 +/- 9%, oxygen uptake +28 +/- 7%, and Kfc +24 +/- 6%. After SQ 29548, the food placement increased blood flow +37 +/- 8%, oxygen uptake +52 +/- 11%, and Kfc +63 +/- 20%. The food-induced increases in oxygen uptake and Kfc after SQ 29548 were significantly greater than those induced before the blocking of TxA2-endoperoxide receptors by SQ 29548. Our study indicates that endogenous thromboxane does not play a role in regulating jejunal blood flow, capillary filtration, and oxygen uptake under resting conditions. However, it plays a role in limiting the food-induced increases in jejunal oxygen uptake and capillary exchange capacity without influencing the food-induced hyperemia.

Animals↗
PubMed1989

Prostanoids in regulation of postprandial jejunal hyperemia and oxygen uptake.

The role of prostanoids in regulation of jejunal blood flow (JBF) was studied in anesthetized dogs. Intra-arterial infusions of arachidonate produced biphasic changes and dose-dependent decreases in jejunal vascular resistance (JVR) in untreated and aspirin-pretreated dogs, respectively; mefenamate abolished these responses. The jejunum released prostaglandin I2 (PGI2) greater than PGE2 greater than thromboxane A2 (TXA2) (radioimmunoassay) under resting conditions, and food enhanced the release of PGE2 greater than PGI2 greater than TXA2 greater than PGF2 alpha. Addition of arachidonate to food enhanced TXA2 and PGF2 alpha releases and decreased PGI2 and PGE2 releases, while inhibiting the food-induced increases in JBF and O2 uptake; mefenamate inhibited these arachidonate actions. A TXA2 receptor antagonist (SQ-29548) reversed the arachidonate vascular and metabolic actions. Intra-arterial infusions of PGI2 or PGE2 decreased, whereas TXA2 analogue U-44069 or PGF2 alpha increased JVR. A mixture of these prostanoids infused at blood concentrations similar to the increase observed during food placement did not alter JVR. At concentrations similar to the increases observed when arachidonate was added to luminal food, the infusions increased JVR and abolished the food-induced decrease in JVR. In conclusion, jejunal productions of PGI2, PGE2, TXA2, and PGF2 alpha increase during nutrient absorption. Addition of arachidonate to food attenuates the former two and enhances the latter two releases, which act to attenuate food-induced jejunal hyperemia.

Animals↗
PubMed1989

Effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, O2 extraction, and O2 uptake in halothane-anesthetized ponies.

The effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, oxygen extraction, and oxygen uptake were determined in 10 anesthetized ponies ventilated with a mixture of halothane and 100% oxygen, using isolated autoperfused jejunal segments. Physiologic saline solution or butorphanol tartrate (0.2 mg/kg of body weight) was administered as a single bolus into the left jugular vein. By 2 minutes, butorphanol decreased arterial blood pressure and intestinal blood flow, and increased intestinal oxygen extraction. However, intestinal vascular resistance and oxygen uptake were unaffected. Results of this study indicate that butorphanol tartrate induces a hypotension that secondarily decreases intestinal blood flow, but intestinal vascular resistance and metabolism are not adversely affected. We conclude that butorphanol tartrate does not compromise intestinal viability in halothane-anesthetized ponies and, therefore, may be a good analgesic choice for the equid destined for abdominal surgery.

Anesthesia, General↗
PubMed1989

Effects of distention and neostigmine on jejunal vascular resistance, oxygen uptake, and intraluminal pressure changes in ponies.

The influence of distention (high baseline intraluminal pressure) and neostigmine methylsulfate on intestinal vascular resistance, oxygen uptake, and intraluminal pressure changes (rhythmic contractions) was studied in terminal jejunal segments, which were perfused at a constant rate, in 16 anesthetized ponies. When baseline intraluminal pressure was increased to 10 mm of Hg, the intestinal vascular resistance and amplitude of rhythmic contractions were increased. Neostigmine induced cyclic increases in amplitude of rhythmic contractions whether intraluminal pressure was 0 or 10 mm of Hg. Neostigmine also increased intestinal oxygen uptake at intraluminal pressures of 0 mm of Hg, but not at 10 mm of Hg, and vascular resistance was not altered at either intraluminal pressure. The results indicate that intestinal hemodynamics are adversely affected by distention. Further, neostigmine did not adversely affect intestinal hemodynamics while increasing rhythmic contractions, suggesting that neostigmine may be useful in the treatment of ileus in equids.

Animals↗
PubMed1989

Effects of ischemia and dimethyl sulfoxide on equine jejunal vascular resistance, oxygen consumption, intraluminal pressure, and potassium loss.

Physiologic effects of 1 hour of ischemia and 1 hour of reperfusion on equine jejunum and protective effects of systemic administration of dimethyl sulfoxide (DMSO, 1 g/kg of body weight) were investigated in 18 ponies, using neurally intact segments of jejunum perfused at constant flow with heparinized blood. Ponies were allotted to 4 groups: group 1, saline solution administered (control, n = 3); group 2, DMSO administered (DMSO, n = 3); group 3, ischemia induced and saline solution administered (ischemia, n = 6); and group 4, ischemia induced and DMSO administered (ischemia-DMSO, n = 6). Intestinal vascular resistance (R, mm of Hg/ml/min/100 g), oxygen consumption (VO2, ml/min/100 g), frequency and amplitude of rhythmic changes in intraluminal pressure, intestinal compliance (C, ml/mm of Hg), and arteriovenous potassium concentration difference (delta AV [K+], mEq/L) were determined and compared with stable preischemic values within groups. There were no significant changes in any variable in ponies of groups 1 or 2. In ponies of group 3, significant (P less than or equal to 0.05) changes included: an initial increase in R during reperfusion, followed by a decrease to values below preischemic values by 15 minutes of reperfusion; decreased VO2 during the entire reperfusion period; increased amplitude of rhythmic contractions during initial reperfusion; decreased frequency of rhythmic contractions during ischemia; and increased delta AV [K+] during initial reperfusion. Changes in ponies of group 4 were identical to changes in ponies of group 3, with the exception that DMSO administration prevented the decrease in R during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Thromboxane synthesis inhibitors and postprandial jejunal capillary exchange capacity.

The effects of thromboxane synthesis inhibitors (imidazole and U 63557A; Upjohn) and the cyclooxygenase inhibitor, mefenamic acid, on jejunal capillary filtration coefficients (Kfc) were determined in dogs before and during the presence of predigested food in the jejunal lumen. The jejunal Kfc increased significantly soon after the placement of a predigested test food containing all major constituents of diet. The Kfc remained elevated as long as the food was present in the lumen (15 min). Mefenamic acid (10 mg/kg iv) did not significantly alter resting jejunal Kfc or alter the food-induced increase in Kfc. Imidazole (5.0 mg/min ia) or U 63557A (5.0 mg/kg iv) per se significantly increased jejunal Kfc. Placement of digested food further increased the Kfc to levels significantly higher than those observed before administration of the two thromboxane synthase inhibitors. Production of thromboxane B2 by jejunal tissue was significantly reduced and 6-ketoprostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) production was significantly increased after administration of U 63557A. Our study indicates that the relative production of endogenous thromboxanes and other prostanoids modulates jejunal capillary exchange capacity in the absence or presence of digested food in the jejunal lumen.

Animals↗
PubMed1988

Adenosine plays a role in food-induced jejunal hyperemia.

The aim of this study is to determine the role of adenosine in postprandial hyperemia in the jejunum of anesthetized dogs. The effect of two adenosine antagonists, aminophylline and 8-phenyltheophylline, on the vascular responses to intra-arterial infusion of adenosine and luminal placement of food was determined. The effect of aminophylline on the food-induced hyperemia was found to be dependent on motility. Aminophylline had no effect on the hyperemia when motility was high but inhibited the hyperemia when motility was low. Vasodilations produced by intra-arterial infusions of adenosine, however, were attenuated by aminophylline regardless of the level of motility. The more potent and specific adenosine antagonist, 8-phenyltheophylline, also inhibited both adenosine- and food-induced vasodilations. This inhibition occurred whether the intestinal motility was high or low. In conclusion, adenosine receptor blockade inhibits jejunal food-induced hyperemia, and adenosine may play a role in the hyperemia. The effect of aminophylline was complicated by motility.

Adenosine↗
PubMed1988

Selective IgG subclass deficiencies in patients with recurrent sinopulmonary infections: report of two cases.

Two patients with recurrent sinopulmonary infections and normal total serum immunoglobulin levels were found to have selective deficiencies in IgG subclasses. The serum of one patient contained abnormally low IgG2 and IgG4; and the other was deficient in IgG4. Both patients responded to the treatment with high dose intravenous immunoglobulin. The experiences on these two cases strongly suggest that IgG subclasses should be checked in patients with recurrent sinopulmonary infections in face of normal total immunoglobulins.

Child↗
PubMed1988

Effects of flunixin meglumine on jejunal blood flow, motility, and oxygen consumption in ponies.

Using isolated autoperfused intestinal segments, the effects of flunixin meglumine administration on systemic arterial blood pressure, jejunal blood flow, vascular resistance, motility, arteriovenous oxygen difference, and oxygen consumption were determined in 10 anesthetized ponies ventilated with a mixture of halothane and oxygen. Saline solution or flunixin meglumine (1.1 mg/kg of body weight) was infused as a single bolus into the left jugular vein. By 10 minutes, flunixin meglumine increased systemic arterial blood pressure and increased intestinal vascular resistance. The jejunal blood flow, however, was not significantly decreased until 1 hour after flunixin meglumine administration. Intestinal motility, arteriovenous oxygen difference, and oxygen consumption were unchanged. Results indicated that acute administration of flunixin meglumine increases systemic arterial pressure and intestinal vascular resistance, but the resulting intestinal vasoconstriction does not lead to compromise of intestinal viability.

Animals↗
PubMed1987

mRNA species regulated during the differentiation of HL-60 cells to macrophages and neutrophils.

Using cDNA clone banks from differentiated and undifferentiated HL-60 promyelocytic leukemia cells, we have selected clones for genes which are regulated during this differentiation. Regulation of the corresponding mRNAs in HL-60 cells during both monocytic and neutrophilic differentiation was measured for 21 of these clones. The levels of mRNA hybridizing to some of these clones changed by more than 100-fold during differentiation. Unlike erythropoiesis or myogenesis, in which the synthesis of a few new proteins is synchronously regulated, mRNAs in differentiating HL-60 cells are asynchronously regulated, suggesting a complex series of regulatory events. About half of these regulation-selected clones contained repeat sequences, including both Alu and novel repeat families. Most of the regulated genes are members of extensive gene families.

Cell Differentiation↗
PubMed1987

Gamma-actin: unusual mRNA 3'-untranslated sequence conservation and amino acid substitutions that may be cancer related.

beta-Actin mutations in chemically transformed human cell lines have been associated with tumorigenicity, an association consistent with other evidence suggesting that altered cytoskeletal proteins may have an important role in cancer initiation or progression. From a human promyelocytic leukemia cell line, we have isolated a gamma-actin cDNA clone with amino acid substitutions in a region highly conserved in the many actins analyzed. To our knowledge, this is the first example of a variant gamma-actin in a human neoplasm. A separate finding from the analysis of this clone is that the gamma-actin 3'-untranslated region is among the most highly conserved of all 3'-untranslated sequences so far reported, but is entirely different from the beta-actin 3'-untranslated region. The high degree of evolutionary conservation suggests that the 3'-untranslated regions of these two mRNAs have important and distinct functional roles that were already fully differentiated more than 100 million years ago. Mutations affecting four major cytoskeletal components have now been identified in human neoplastic cells. These findings suggest that mutated cytoskeletal genes may be members of a class of oncogenes, fundamentally different from both the nuclear-acting (e.g., myc and simian virus 40 large tumor antigen) and growth factor/receptor/protein kinase-related (e.g., sis, erbB, and ras) types of oncogenes.

Actins↗
PubMed1987

Intestinal prostacyclin and thromboxane production in irreversible hemorrhagic shock.

Arterial and intestinal venous blood were sampled every hour for measurement of thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, stable metabolites of thromboxane A2 and prostacyclin, respectively, in dogs subjected to hemorrhagic hypotension at 32.8 +/- 1.4 mm Hg for 3 h, followed by reinfusion of the remaining shed blood. Control dogs were treated alike without hypotension. Arterial and intestinal venous TXB2 significantly increased during hypotensive and post-transfusion periods, the venous concentration being significantly higher than the corresponding arterial. The arterial and venous 6-keto-PGF1 alpha increased during hypotension but decreased during post-transfusion periods. Furthermore, arterial and venous TXB2 to 6-keto-PGF1 alpha concentration ratio increased. Intestinal TXB2 release (blood flow X arteriovenous concentration difference) increased progressively, whereas 6-keto-PGF1 alpha release decreased. No significant changes occurred in the control dogs. This study shows an imbalance in intestinal production and release of TXA2 and PGI2, in favor of TXA2 during severe hemorrhagic hypotension and after blood transfusion. The imbalance may contribute to the development of irreversible hemorrhagic shock and reperfusion injury.

6-Ketoprostaglandin F1 alpha↗