Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

At least 163 records · Page 9Linked to original sources

PubMed1995

Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines: implication for c-fos control via surface immunoglobulin and T cell antigen receptors.

Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C, cAMP, and calcium. Kinase C mediates its effects via phosphorylation of serum response factor (SRF) which interacts with the serum response element (SRE); cAMP and calcium mediate their effects via phosphorylation of CREB (cAMP regulatory element binding protein) presumably by activation of a protein kinase A or calmodulin-regulated kinase. We have examined the function of these elements in Burkitt's lymphoma cells (Ramos and Daudi) as well as a T lymphocytic cell line (Jurkat). We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction. However, kinase C activation (PMA stimulation) combined with either cAMP (forskolin plus MIX) or calcium stimulation (ionophore) leads to greatly enhanced c-fos induction. By contrast, cAMP in the presence of calcium shows no synergy in c-fos induction. Okadaic acid augments PMA- as well as calcium-mediated activation of c-fos, and has little or no effect when combined with cAMP. The main difference between Ramos (B cells) and Jurkat (T cells) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos. Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity. Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium, and results in c-fos mRNA induction. Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well. That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig induction of c-fos. These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors.

Antibodies, Anti-Idiotypic↗

PubMed1995

Characterization of the MN gp120 HIV-1 vaccine: antigen binding to alum.

PURPOSE: The characterization of recombinant MN gp120/alum vaccine requires the study of the gp120-alum interaction for the successful formulation of an alum-based HIV-1 vaccine. METHODS: Several observations suggest that the gp120-alum interaction is weak, wherein buffer counterions such as phosphate, sulfate, bicarbonate may cause the desorption of gp120 from alum. Comparison of gp120 with other proteins using particle mobility measurements shows that the weak binding of gp120 to alum is not an anomaly. Serum and plasma also cause desorption of gp120 from alum with a half-life of only a few minutes, wherein this half-life may be faster than the in-vivo recruitment of antigen presenting cells to the site of immunization. RESULTS: Immunization of guinea pigs, rabbits and baboons with gp120 formulated in alum or saline demonstrated that alum provides adjuvant activity for gp120, particularly after early immunizations, but the adjuvant effect is attenuated after several boosts. CONCLUSIONS: These observations indicate that both the antigen and the adjuvant require optimization together.

AIDS Vaccines↗

PubMed1995

Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns.

BACKGROUND: Human growth hormone is an anabolic agent that attenuates injury-induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up-regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering > 40% of total body surface area. OBJECTIVE: The authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. METHODS: Ten massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. RESULTS: Donor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. CONCLUSION: Results indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural proteins and other components needed to rebuild the junctional structures.

Adolescent↗

PubMed1995

Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients.

OBJECTIVE: To determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. SUMMARY BACKGROUND DATA: In critically ill patients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. METHODS: Nine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized. Data were derived from a model based on a primed-continuous infusion of L-[15N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. RESULTS: Net leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. CONCLUSIONS: Exogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients.

Adolescent↗

PubMed1995

Hypertonic acetate dextran achieves high-flow-low-pressure resuscitation of hemorrhagic shock.

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.

Acetates↗

PubMed1995

In vitro antimicrobial susceptibilities of strains of Yersinia pestis.

The in vitro activities of 14 antimicrobial agents were determined for 78 strains of Yersinia pestis. The most active antibiotics were ceftriaxone and ciprofloxacin, followed by ofloxacin and ampicillin. The agents traditionally used for the treatment of plague (streptomycin, tetracycline, and chloramphenicol) were considerably less active. Azithromycin showed poor activity against all strains.

Anti-Bacterial Agents↗

PubMed1995

Effect of inducible thrB expression on amino acid production in Corynebacterium lactofermentum ATCC 21799.

Amplification of the operon homdr-thrB encoding a feedback-insensitive homoserine dehydrogenase and a wild-type homoserine kinase in a Corynebacterium lactofermentum lysine-producing strain resulted in both homoserine and threonine accumulation, with some residual lysine production. A plasmid enabling separate transcriptional control of each gene was constructed to determine the effect of various enzyme activity ratios on metabolite accumulation. By increasing the activity of homoserine kinase relative to homoserine dehydrogenase activity, homoserine accumulation in the medium was essentially eliminated and the final threonine titer was increased by about 120%. Furthermore, a fortuitous result of the cloning strategy was an unexplained increase in homoserine dehydrogenase activity. This resulted in a further decrease in lysine production along with a concomitant increase in threonine accumulation.

Corynebacterium↗

PubMed1995

Effects of manganese superoxide dismutase on lung fluid balance after smoke inhalation.

There is evidence of increased oxygen free radical activity after smoke inhalation with and without concomitant burn injury. We determined the effects of manganese superoxide dismutase (Mn SOD) on lung fluid balance as measured by lung microvascular permeability coefficient (sigma), filtration coefficient (Kf), and lymph flow. Merino breed ewes (n = 6/group) were surgically prepared. The SOD group (SOD) received Mn SOD (9,000 U/kg) as an intravenous bolus and was insufflated with smoke. The control group (CON) received saline and smoke. sigma and Kf were determined 24 h before and 24 h after smoke injury. Lymph flow, arterial O2-to-inspired O2 fraction ratio, systemic hemodynamics, and pulmonary arterial and capillary pressures were measured. The sigma was significantly (P < 0.05) higher after smoke insufflation in SOD compared with CON (0.71 +/- 0.03 vs. 0.53 +/- 0.05). Kf was significantly lower after smoke insufflation in SOD compared with CON (0.038 +/- 0.010 vs. 0.061 +/- 0.010). Lymph flows were significantly lower during the 24 h after smoke insufflation in SOD compared with CON (33 +/- 7 vs. 55 +/- 8 ml/h at 24 h). Arterial O2-to-inspired O2 fraction ratio was significantly improved at 6 and 12 h after smoke insufflation in SOD compared with CON at the same time points. Mn SOD meliorates the lung microvascular permeability changes associated with smoke inhalation injury.

Administration, Inhalation↗

PubMed1995

The role of lipoprotein A-I and lipoprotein A-I/A-II in predicting coronary artery disease.

The aim of this study was to examine the role of HDL subparticles with apolipoprotein (apo) A-I alone (LpA-I) and with apoA-I and apoA-II (LpA-I/A-II) in predicting coronary artery disease. Concentrations of these HDL subparticles were compared in 184 subjects with angiographically confirmed significant coronary artery disease (> 50% stenosis of at least one vessel) and 191 age- and sex-matched control subjects without clinical coronary artery disease. LpA-I and LpA-I/A-II were measured with magnetic beads coated with anti-apoA-II antibodies to separate particles containing apoA-II from plasma. Total plasma cholesterol and triglyceride levels were similar in both groups. Although subjects with coronary artery disease had lower HDL cholesterol, plasma apoA-I, LpA-I, and LpA-I/A-II than age- and sex-matched control subjects without coronary artery disease, plasma apoA-I was the best predictor of coronary artery disease. In conclusion, LpA-I and LpA-I/A-II are lower in subjects with coronary artery disease but do not add to plasma apoA-I in predicting the presence of coronary artery disease.

Aged↗

PubMed1995

Complications of skull base surgery.

The increasing number of patients undergoing resection of complex skull base lesions with good outcome is indicative of the interest and expertise in treating tumors of the skull base. Advances in surgical techniques and improved knowledge of the microanatomy have contributed to the ability to manage these tumors aggressively. These procedures are not without morbidity, such as neurologic deficits, infection, and hemorrhage. These complications are expected and, with appropriate and timely management, can be minimized.

Blood Vessels↗

PubMed1995

Short course of ofloxacin for treatment of multidrug-resistant typhoid.

In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever.

Adolescent↗

PubMed1995

Cephalosporin vs penicillin.

The correlation between late infection of an orthopedic prosthesis and a dental bacteremia remains controversial. Transient bacteremia does occur after dental treatment, usually involving streptococcal bacteria, but many orthopedic surgeons choose an anti-staphylococcal agent as their prophylactic antibiotic of choice. This article reports the results of a recent survey designed to determine, from orthopedic surgeons, antibiotic premedication coverage and, specifically, the rationale for a chosen regimen for patients having dental surgery. The responses showed no common agreement for the choice of a specific antibiotic and little rationale regarding the need for prophylaxis.

Antibiotic Prophylaxis↗

PubMed1994

Expressing murine beta 1,4-galactosyltransferase in HeLa cells produces a cell surface galactosyltransferase-dependent phenotype.

Beta 1,4-Galactosyltransferase is traditionally viewed as a biosynthetic component of the Golgi complex, but a portion of galactosyltransferase is also expressed on the cell surface, where it has been suggested to function as a receptor for extracellular oligosaccharide ligands. Although results from a variety of studies are consistent with a cell adhesion function for galactosyltransferase, the most rigorous test of surface galactosyltransferase function is to produce a surface galactosyltransferase-dependent phenotype in cells that normally express negligible levels of surface galactosyltransferase. In agreement with previous reports, human HeLa cells were found to express low levels of galactosyltransferase on their surface and, therefore, were stably transfected with cDNAs encoding murine galactosyltransferase. Murine galactosyltransferase was expressed both within the presumed Golgi complex and on the cell surface, as assayed by enzyme activity and with antiserum raised against the bacterially expressed murine enzyme. HeLa cell transfectants adhered more strongly to their extracellular substrates than did control transfectants, as evidenced by a flatter morphology in culture and a more rapid spreading upon plating. In contrast, cell spreading was low and similar among all cell types when plated on extracellular substrates that did not contain binding sites for galactosyltransferase. Antibodies and Fab fragments against recombinant murine galactosyltransferase inhibited the increased cell spreading characteristic of galactosyltransferase transfectants, as did soluble recombinant galactosyltransferase and a variety of galactosyltransferase perturbants. Thus, expression of heterologous galactosyltransferase produces a surface galactosyltransferase-dependent phenotype, confirming its function as a cell adhesion molecule.

Animals↗

PubMed1994

Relative contribution of photo-addition, helper oligonucleotide and RNase H to the antisense effect of psoralen-oligonucleotide conjugates, on in vitro translation of Leishmania mRNAs.

We investigated the properties of two antisense oligonucleotides, 11 alpha Pso and 14TMP, 11 and 14 nucleotides long, respectively, and conjugated to psoralen derivatives. These oligonucleotides were complementary to the mini-exon sequence of Leishmania amazonensis. Upon ultraviolet (UV) irradiation these oligomers were selectively cross-linked to DNA or RNA target sequences, either 14 or 35 nucleotides long. The yield of photo-addition was much lower on the longer targets than on the shorter ones, due to the presence of a hairpin structure. The co-addition of a helper oligonucleotide, whose binding site, on the 35-mer, was adjacent to that of the psoralen-derivatized antisense oligomer, improved the cross-linking efficiency. We then determined the effect of 14TMP on in vitro translation of Leishmania mRNA in cell-free extracts. Non-irradiated antisense oligonucleotide/mRNA complexes reduced the protein synthesis in wheat germ extract but not in rabbit reticulocyte lysate. Conversely, UV irradiation induced a 14TMP-dependent reduction of translation in reticulocyte lysate whereas the inhibition was not improved in the wheat germ extract. These results are discussed with respect to the involvement of RNase-H in the oligonucleotide-mediated effect on protein synthesis.

Animals↗

PubMed1994

Phosphoenolpyruvate carboxykinase of Trypanosoma brucei is targeted to the glycosomes by a C-terminal sequence.

Import of proteins into the glycosomes of T. brucei resembles the peroxisomal protein import in that C-terminal SKL-like tripeptide sequences can function as targeting signals. Many of the glycosomal proteins do not, however, possess such C-terminal tripeptide signals. Among these, phosphoenolpyruvate carboxykinase (PEPCK (ATP)) was thought to be targeted to the glycosomes by an N-terminal or an internal targeting signal. A limited similarity to the N-terminal targeting signal of rat peroxisomal thiolase exists at the N-terminus of T. brucei PEPCK. However, we found that this peroxisomal targeting signal does not function for glycosomal protein import in T. brucei. Further studies of the PEPCK gene revealed that the C-terminus of the predicted protein does not correspond to the previously deduced protein sequence of 472 amino acids due to a -1 frame shift error in the original DNA sequence. Readjusting the reading frame of the sequence results in a predicted protein of 525 amino acids in length ending in a tripeptide serine-arginine-leucine (SRL), which is a potential targeting signal for import into the glycosomes. A fusion protein of firefly luciferase, without its own C-terminal SKL targeting signal, and T. brucei PEPCK is efficiently imported into the glycosomes when expressed in procyclic trypanosomes. Deletion of the C-terminal SRL tripeptide or the last 29 amino acids of PEPCK reduced the import only by about 50%, while a deletion of the last 47 amino acids completely abolished the import. These results suggest that T. brucei PEPCK may contain a second, internal glycosomal targeting signal upstream of the C-terminal SRL sequence.

Acetyl-CoA C-Acetyltransferase↗

PubMed1994

Pyrido[2,3-d]pyrimidine angiotensin II antagonists.

A series of pyrido[2,3-d]pyrimidine angiotensin II (A II) antagonists was synthesized and tested for antagonism of A II. Compounds with a biphenylyltetrazole pharmacophore and small alkyl groups at the 2- and 4-positions of the pyridopyrimidine ring were found to be the most potent in an AT1 receptor binding assay and in blocking the A II pressor response in anesthetized, ganglion-blocked A II-infused rats. 5,8-Dihydro-2,4-dimethyl-8-[(2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl)methyl]pyrido[2,3-d]pyrimidin-7(6H)-one (4a) was one of the more potent compounds in the binding assay and was the most efficacious compound in the A II-infused rat model. Further study of 4a in Goldblatt (2K-1C) rats showed the compound to have oral bioavailability and to be an efficacious and potent compound in a high renin form of hypertension.

Animals↗

PubMed1994

Lipolysis in burned patients is stimulated by the beta 2-receptor for catecholamines.

OBJECTIVE: To determine if the cardiovascular effects of excessive catecholamines could be selectively blocked in severely burned patients without adversely affecting protein or fat kinetics. DESIGN: Prospective cohort study. SETTING: A large tertiary care referral center in Galveston, Tex. PATIENTS: Sixteen patients with greater than 40% body surface area burns. INTERVENTIONS: Patients were randomly selected to receive propranolol hydrochloride, a nonselective beta 1- and beta 2-blocker, or metoprolol tartrate, a selective beta 1-blocker. MAIN OUTCOME MEASURES: Heart rate; rate-pressure product; rate of appearance of urea, glucose, and leucine; and leucine oxidation were measured before and after selective or nonselective beta-adrenergic blockade. RESULTS: Propranolol and metoprolol caused a significant decrease in heart rate, from a mean (+/- SD) of 143 +/- 15 to 115 +/- 11 and from 147 +/- 17 to 120 +/- 9 beats per minute, respectively, during the 5-day study period. Neither the rate of appearance of urea nor the rate of urea production were significantly altered by propranolol or metoprolol therapy. Only propranolol produced a significant decrease (P < .05) in the rate of appearance of glycerol, from a mean (+/- SD) of 5.54 +/- 0.62 to 3.07 +/- 0.7 mumol/kg per minute. The rate of appearance of leucine, used as an index of total body protein catabolism, was not significantly altered by either beta-blocker. CONCLUSIONS: Selective beta 1-adrenergic blockade did not reduce lipolysis; however, a beta 1- and beta 2-adrenergic blockade significantly reduced lipolysis. Thus, the increased lipolysis, characteristic of severely burned patients, is caused by stimulation of the beta 2-adrenergic receptors for catecholamines.

Adolescent↗

PubMed1994

IVOX with gradual permissive hypercapnia: a new management technique for respiratory failure.

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗