Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

At least 181 records · Page 10Linked to original sources

PubMed1994

Hypertonic saline/dextran for cardiopulmonary bypass reduces gut tissue water but does not improve mucosal perfusion.

Gut mucosal ischemia has been associated with cardiopulmonary bypass (CPB) and may contribute to postoperative systemic inflammatory response and multiorgan dysfunction. Hypertonic saline/dextran (HSD) has been previously shown to selectively increase mucosal blood flow in circulatory shock. To determine whether adding HSD to the prime solution for CPB improves gut mucosal blood flow and oxygenation, we performed normothermic, non-cross-clamped CPB in pigs with 1 ml/kg of HSD (25% NaCl/24% dextran 70) (HSD group, n = 9) or lactated Ringer's solution (LRS group, n = 9) as control added to a standard prime. Animals were instrumented with ultrasonic flow probes on the superior mesenteric artery (SMA), laser Doppler mucosal flow probes in the ileum, and indwelling portal vein catheters and tonometers for mucosal hydrogen ion measurements and pH calculations in the stomach, ileum, and rectum. The total infused volume and net fluid balance was significantly lower in the HSD than in the LRS group (649 +/- 171 ml vs 2075 +/- 385 ml and 502 +/- 182 ml vs 1891 +/- 363 ml, respectively, P < 0.01). SMA flow in the LRS group increased to 110-123% of baseline during CPB and was significantly higher than that in the HSD group which remained unchanged. Ileal mucosal blood flow decreased significantly to 70-50% of baseline in both groups with no difference between groups. Gut oxygen (O2) delivery decreased during CPB in both groups, but O2 consumption remained unchanged. Gastric, ileal, and rectal mucosal pH decreased progressively, and portal venous blood pH also decreased in both groups, but there was no significant difference between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Selectively 13C-enriched DNA: 13C and 1H assignments of a triple helix by two-dimensional relayed HMQC experiments.

We present NMR studies of an intramolecular triple helix, the three strands of which have been linked by a hexaethylene glycol chain. To overcome the generally encountered difficulties of assignment in the homo-pyrimidine strands, the carbon Cl' of the pyrimidines were selectively 13C-enriched. Assignments of the aromatic and sugar protons were obtained from NOESY-HMQC and TOCSY-HMQC spectra. We show that the recognition of a DNA duplex by a third strand via triplex formation is easily carried out in solution by observing the changes of the 1Hl'-13Cl' connectivities as a function of pH. Furthermore, the conformation of the sugars has been found to be C2'-endo, on the basis of the coupling constant values directly measured in an HSQC spectrum.

Base Sequence↗

PubMed1994

Performance of an intravenous gas exchanger (IVOX) in a venovenous bypass circuit.

To analyze quantitatively the performance of the intravenacaval blood gas exchanger (IVOX), we developed a right atrium-pulmonary artery venovenous extracorporeal bypass circuit. Oxygen transfer and carbon dioxide removal were calculated at different blood flow rates, different hemoglobin levels, and during permissive hypercapnia. Oxygen transfer increased linearly with blood flow up to 41 mL/min. Likewise, O2 transfer increased linearly with hemoglobin levels up to 7.5 g/dL, but no further increases were achieved above this level. Carbon dioxide removal increased linearly as flow increased from 1.0 to 3.0 L/min but did not increase further for higher flows. Carbon dioxide removal was 45 mL/min at blood carbon dioxide tension of 42 mm Hg but increased to a maximum of 81 mL/min at a carbon dioxide tension of 90 mm Hg. We conclude that IVOX is a diffusion-limited device dependent on blood flow, hemoglobin content, and the gas pressure gradient across the membrane. Further engineering improvements are needed to improve the gas exchange performance of IVOX.

Animals↗

PubMed1994

Effects of systemic delivery of insulin on plasma lipids and lipoprotein concentrations in pancreas transplant recipients.

OBJECTIVE: To determine whether pancreas transplantation alters lipid and lipoprotein concentrations and whether peripheral hyperinsulinemia is always associated with altered lipid levels. DESIGN: We assessed the lipid profiles of seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven kidney recipients without diabetes who received the same immunosuppressive agents, and eight normal subjects. MATERIAL AND METHODS: In the three study groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol, triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III concentrations were determined. RESULTS: Fasting and postprandial glucose concentrations did not differ between the two transplant groups; however, peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas-kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53 +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion of a meal. Preprandial and postprandial insulin levels in both transplant groups also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and 40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in insulin concentrations, no differences were noted in total cholesterol, high-density or low-density lipoprotein cholesterol, plasma free fatty acids, or apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups. Plasma triglyceride concentrations in the two transplant groups were similar (114 +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal subjects (80 +/- 7 mg/dL). CONCLUSION: Despite peripheral hyperinsulinemia, pancreas transplantation can result in normal or near-normal lipid and lipoprotein concentrations. Thus, systemic delivery of insulin does not invariably produce an atherogenic lipid profile.

Adult↗

PubMed1994

Lipids and Lp(a) lipoprotein levels and coronary artery disease in subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether increased Lp(a) lipoprotein levels are associated with either non-insulin-dependent diabetes mellitus (NIDDM) or coronary artery disease (CAD) in patients with NIDDM and to examine the relationship between Lp(a) levels and glycemic control. DESIGN: We conducted a cross-sectional study of subjects with NIDDM who were participants in the Rochester Diabetic Neuropathy Study and healthy control subjects from the population of Rochester, Minnesota. MATERIAL AND METHODS: Lipids and Lp(a) lipoprotein levels were compared in 227 subjects with NIDDM and 163 control subjects and, among the subjects with NIDDM, in those with (N = 96) and without (N = 131) CAD. The correlation between Lp(a) levels and glycosylated hemoglobin was investigated. RESULTS: Subjects with NIDDM had higher triglyceride and lower high-density lipoprotein cholesterol levels than did control subjects. Subjects with NIDDM and CAD had higher total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and lower high-density lipoprotein cholesterol levels than did subjects with NIDDM without CAD. Subjects with NIDDM had significantly higher Lp(a) levels than did control subjects, but subjects with NIDDM and CAD did not have significantly higher Lp(a) levels than did those without CAD. Among subjects with NIDDM, the level of Lp(a) was not significantly correlated with glycosylated hemoglobin. CONCLUSION: Although subjects with NIDDM have higher Lp(a) levels than do control subjects, Lp(a) does not seem to be associated with CAD in subjects with NIDDM. In this study, no association was found between Lp(a) level and glycemic control.

Adult↗

PubMed1994

Light modulation of ferredoxin mRNA abundance requires an open reading frame.

Ferredoxin I (Fed-1) mRNA abundance is modulated by an internal light regulatory element that includes sequences both 5' and 3' of the translational initiation site. To test the hypothesis that the light response mediated by this element might be coupled to translation, we transformed tobacco plants with gene constructs blocked in translational initiation or elongation. Here, we report that such mutations abolish the light response in vivo. A nonsense mutation could be rescued by restoring the open reading frame with a different sequence, even when the new codon caused an amino acid substitution. Our data establish that the light response requires a translatable reading frame and thus provide strong circumstantial evidence for post-transcriptional modulation of Fed-1 mRNA levels. The Fed-1 system is presently the only higher plant example of a developmentally regulated change in mRNA abundance that requires translation of the affected mRNA.

Ferredoxins↗

PubMed1994

Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness.

In the absence of antibiotics, carriage of pACYC184 reduces the competitive fitness of an Escherichia coli B genotype that was not previously selected for plasmid carriage, relative to that of an isogenic plasmid-free competitor. However, a host genotype propagated with the plasmid for 500 generations evolved an unexpected competitive advantage from plasmid carriage, relative to its own isogenic plasmid-free segregant. We manipulated the pACYC184 genome in order to identify the plasmid-encoded function that was required for the enhancement of the coevolved host genotype's competitive fitness. Inactivation of the plasmid-encoded tetracycline resistance gene, by deletion of either the promoter region or the entire gene, eliminated the beneficial effect of plasmid carriage for the coevolved host. This beneficial effect for the coevolved host was also manifest with pBR322, which contains a tetracycline resistance gene identical to that of pACYC184 but is otherwise heterologous.

Biological Evolution↗

PubMed1994

Direct measurement of whole body thyroid hormone pool sizes and interconversion rates in fasted rats: hormone regulation implications.

Food deprivation markedly reduces thyroid hormone levels in mammalian plasma, but existing data are incomplete and equivocal regards extrathyroidal hormone production and other indices of overall hormone economy. We have used a novel experiment design and analysis to directly measure the whole-body rate of conversion of T4 into T3 and several other steady-state whole organism parameters, in 4-day fasted and fed control rats. Trace amounts of 125I-labeled T3 (T3) or T4 (T*4) were infused for 7 days from osmotic minipumps implanted sc. On day 7, rats were anesthetized, bled, and killed and carcasses were frozen in liquid N2, pulverized, homogenized, and extracted. Extracts and plasma samples were chromatographed on both Sephadex and HPLC. Tracer infusion rates, whole rat tissue weights, and steady state tissue, blood, and plasma T*3, T*4, and total radioactivity concentrations provided all kinetic parameters of interest from simple steady state computations. T4 secretion (SR4) and whole body pool sizes were reduced 49-55% in fasted rats. But the most notable results were that the percent of available extrathyroidal T4 converted to T3 in fasted [41.6 +/- 7.9% (SD)] was 87% greater than that in the fed (22.3 +/- 7.69%) rats and this, in turn, generated an absolute rate of production of T3 from T4 not significantly different in fasted vs. fed controls (7.17 +/- 2.40 vs. 7.54 +/- 3.10 ng/h.100 g BW). The surprisingly high 42% conversion ratio in fasting is explained in part by larger T3 blood pools (which are not sites of T3 production from T4) relative to tissue T3 pools in fasted rats, not accounted for in earlier whole-body studies. In contrast with this finding of an increased T4 to T3 conversion ratio in fasted rats, based on whole body measurements, T3 plasma concentrations (Cp3), clearance rates (PCR3), appearance rates (PAR3 = PCR3Cp3), and more conventional indirect estimates of the T4 to T3 conversion ratio (100 PAR3/SR4) were all substantially reduced, consistent with reports in fasting humans limited to measurements of T3 and T3 turnover in plasma and interpreted as indicative of reduced whole body T4 or T3 conversion. Directly measured total T3 extrathyroidal distribution volumes, reduced 55% in the fasted group from 241 +/- 19.5 to 109 +/- 8.14 ml/100 g BW, are also of interest because fed rat values are 27-61% greater than virtually all previous estimates of this index of total body T3.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

A fluorescence-conjugated immunobinding assay for the detection of P-selectin on platelets.

P-selectin (GMP-140 or PADGEM) is translocated to the plasma membrane of platelets after platelet activation. P-selectin, therefore, may be a potential marker for evaluating platelet activation. A fluorescence-conjugated immunobinding assay (FCIBA) has been developed to detect specifically P-selectin on platelets. Platelets were isolated from fresh blood by centrifugation and stimulated with various doses of ADP before being fixed with 1% of paraformaldehyde. Fixed platelets were incubated with fluorescence-conjugated anti-P-selectin monoclonal antibody in the wells of fluoricon microtiter plates, and the fluorescence intensity was read on a fluorescence concentration analyzer. Once platelets were fixed, the procedures were completed in < 2 hours. The intra-assay coefficient of variation (CV) was 6.97% (n = 40), the time-based interassay CV was 8.11% (n = 16), and the sample-based inter-assay CV was 6.17% (n = 16). The FCIBA had an excellent correlation (r = 0.936, p < 0.001) with flow cytometry in the measurement of expressed P-selectin in platelets of 20 normal donors. Translocation of P-selectin in plasma-suspended platelets in response to increasing doses of adenosine diphosphate (ADP) occurred in a dose-dependent manner and correlated positively with ADP-induced platelet aggregation in terms of both stimulating doses of ADP (r = 0.99, p < 0.01) and time intervals (r = 0.92, p < 0.05). The findings show that FCIBA is a fast and convenient assay with good precision for the determination of P-selectin expression of human platelets.

Adenosine Diphosphate↗

PubMed1994

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.

Bacteremia↗

PubMed1994

Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke.

PURPOSE: To evaluate safety and efficacy of delayed intraarterial urokinase therapy with mechanical disruption of clot to treat thromboembolic stroke. METHODS: Thirteen patients with cerebral thrombolic disease (10 carotid territory, 3 basilar territory) were treated with catheter-directed intraarterial urokinase therapy with mechanical disruption of the clots. All patients were excluded from a 6-hour multicenter thrombolytic trial by either time, recent surgery, age, seizure, or myocardial infarction. Time elapsed before treatment ranged from 3.5 to 48 hours (12 +/- 13 hours), with 200,000 to 900,000 U of urokinase used. RESULTS: Ten patients had successful vessel recanalization, confirmed by repeat angiography. Cases with distal branch vessel occlusions were less likely to recanalize. Asymptomatic hemorrhagic conversion occurred in 2 patients on repeat scans. Both acute neurologic and functional outcomes were assessed with significant improvement occurring in 9 (69%) of 13 patients at 48 hours (greater than four-point change on the National Institutes of Health scale) and in 100% of 3-month survivors. All patients who improved had normal initial CT scans. CONCLUSIONS: Intraarterial cerebral thrombolysis with mechanical disruption of clot seems to be a useful therapy in selected stroke cases even after 6 hours.

Adolescent↗

PubMed1994

Complications of neonatal extracorporeal membrane oxygenation. Collective experience from the Extracorporeal Life Support Organization.

Since 1973, 7667 neonates have been treated with extracorporeal membrane oxygenation for severe respiratory failure and their cases reported to the Extracorporeal Life Support Organization Registry. The overall survival was 81% in these neonates, who were thought to have a survival of 20% without extracorporeal membrane oxygenation. A total of 4322 mechanical complications (0.56 +/- 0.84 per case) and 13,827 patient complications (1.80 +/- 2.12 per case) were reported overall. The most common mechanical complications included clots in the circuit (19%), cannula placement (9%), oxygenator failure (4%), and others (9%). Common patient complications included cardiopulmonary (43%), neurologic (35%), bleeding (35%), metabolic (32%), renal (25%), and renal (25%), and infectious (9%). From the initial experience to 1988 the average number of mechanical complications per case was 0.27 per case and this significantly increased during 1990 to 1992 to 0.75 per case (p < 0.05). Likewise, from 1973-1985 to 1988 the average patient complications per case were 1.44 per case and this significantly increased during 1990 to 1992 to 2.10 per case. During the same periods, patient survival significantly decreased from 84% (1973-1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005). Venovenous double-lumen single cannula extracorporeal membrane oxygenation had a higher survival than venoarterial extracorporeal membrane oxygenation (91% versus 81%) and a lower rate of major neurologic complications. The incidence and survival with seizures (6% and 89% venovenous versus 13% and 61% venoarterial) or cerebral infarction (9% and 69% venovenous versus 14% and 46% venoarterial) was significantly lower with the venovenous method and appeared to have a substantial impact on overall survival. The correlation of patient complication rate and total complication rate with survival was highly significant, however, causality cannot be established. Explanations for the increase in complications, relative to a decrease in survival, despite a growing nationwide experience include (1) increased complexity of cases as many programs expand entry criteria (more premature infants, infants with grade 1 or 2 intracranial hemorrhage, and complex congenital diaphragmatic hernia), (2) a growing number of programs with fewer cases per program, yet greater accessibility, (3) less reluctance to report complications encountered during extracorporeal membrane oxygenation as group experience grows, and (4) changes in the Extracorporeal Life Support Organization data form to be more inclusive of more minor complications.

Equipment Failure↗

PubMed1993

A novel series of selective, non-peptide inhibitors of angiotensin II binding to the AT2 site.

The availability of peptide and non-peptide Ang II receptor antagonists has permitted the study of Ang II receptor heterogeneity. It is now widely recognized that there are at least two distinct Ang II receptor subtypes. AT1 receptors are selective in their recognition of agents such as losartan, DuP 532, L-158,809, SK&F108566, and similar non-peptides. To date, all of the well-known actions of Ang II in mammals are blocked by the AT1 selective antagonists such as losartan and are thus designated as being mediated by the AT1 receptor. Although there have been reports of functional activity mediated through AT2 sites, the pharmacological role for the AT2 receptor has not yet been elucidated. Herein, we report the chemistry and SAR on a novel series of 1,2,3,4-tetrahydrosioquinoline-3-carboxylic acids which have selective affinity for AT2 receptors. The most potent of which (19) has an IC50 of 30 nM for the AT2 receptor in the rat adrenal radioligand binding assay.

Angiotensin II↗

PubMed1993

Antihyperglycemic activity of novel naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides.

A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. Substitution at the 1-, 5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4-[(5-Chloronaphthalen-2-yl)methyl]-3H-1,2,3,5-oxathiadiazole++ + 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation.

Animals↗

PubMed1993

Co-regulation of the mitogen-activated protein kinase, extracellular signal-regulated kinase 1, and the 90-kDa ribosomal S6 kinase in PC12 cells. Distinct effects of the neurotrophic factor, nerve growth factor, and the mitogenic factor, epidermal growth factor.

We recently characterized the association of the 44-kDa mitogen-activated protein kinase, also known as extracellular-regulated kinase 1 (ERK1), with the 90-kDa ribosomal S6 kinase (pp90rsk), one of its putative substrates in intact PC12 cells. Using antibodies to ERK1 that precipitate a functional ERK1.pp90rsk phosphoprotein complex, we demonstrate here the regulation of both kinases by various stimuli. In mouse fibroblasts expressing human insulin receptors, insulin and vanadate swiftly stimulated ERK1 activity within 5 min. While the hormonal effect was short-lived, vanadate led to a first peak followed by a progressively increasing second phase. In PC12 cells, epidermal growth factor, which is a growth promoting factor, provokes a rapid but evanescent activation of ERK1. In contrast, nerve growth factor (NGF), which acts as a neuronal differentiation factor for PC12 cells, induced a swift monophasic response followed by a sustained second phase. This strikingly different pattern of ERK1 stimulation by NGF and epidermal growth factor was associated to a contrasting effect on ERK1 cellular translocation. Thus, NGF induced a nuclear translocation of ERK1, while epidermal growth factor was without noticeable effect on ERK1 localization. In both cell systems all effectors tested stimulated ERK1 phosphorylation on both threonine and tyrosine residues in an 1:1 ratio. During ERK1 inactivation, phosphothreonine and phosphotyrosine were dephosphorylated in a similar fashion. Concurrent with ERK1 activation was the de novo appearance of phosphothreonine and an increase in phosphoserine on pp90rsk. The pp90rsk phosphothreonine content paralleled the ERK1 activity more closely than the phosphoserine level. These results provide compelling evidence that in fibroblasts and PC12 cells ERK1 plays a direct role in the phosphorylation of pp90rsk and that pp90rsk represents a physiologically relevant substrate of extracellular-regulated kinases. Finally, we would like to suggest that the differentiating action of NGF in PC12 cells might be due, at least in part, to the conjunction of its sustained and robust stimulation of ERK1 and pp90rsk, and of its induction of ERK1 nuclear translocation.

Amino Acids↗

PubMed1993

Separation of high-density lipoproteins into apolipoprotein E-poor and apolipoprotein E-rich subfractions by fast protein liquid chromatography using a heparin affinity column.

The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E-rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions.

Apolipoproteins↗

PubMed1993

Inactivation of the recA protein by mutation of histidine 97 or lysine 248 at the subunit interface.

We have used site-directed mutagenesis to prepare two new mutant recA proteins, one in which histidine 97 has been replaced by alanine, and another in which lysine 248 has been replaced by alanine. Although these mutant proteins were originally designed from different considerations, they turned out to have remarkably similar properties. Both the [H97A]recA protein and the [K248A]recA protein bind poorly to single-stranded DNA, have no single-stranded DNA-dependent ATP hydrolysis activity, and do not promote renaturation of complementary single-stranded DNA molecules or the ATP-dependent three-strand exchange reaction. Furthermore, both mutant proteins are defective in Mg(2+)-induced helical filament formation. To account for these results, we propose that the mutation of either histidine 97 or lysine 248 alters subunit interactions between recA monomers and that this leads to the loss of cooperative single-stranded DNA binding and DNA pairing activities. This proposal is consistent with the recently determined x-ray structure of the recA protein, which shows that although histidine 97 and lysine 248 are distant from one another in the monomer structure, these two residues are on the opposing complementary faces of the recA subunit and pack against each other at the interface between adjacent recA monomers in the helical filament (Story, R. M., Weber, I. T., and Steitz, T. A. (1992) Nature 355, 318-325).

Adenosine Triphosphate↗

PubMed1993

Growth factors. Local and systemic.

Growth factors that are produced locally at the wound site and systemically from distant sources may elicit inhibitory or stimulatory responses depending on interactions with other factors and the cellular environment into which they are liberated. Growth factors released from macrophages, neutrophils, lymphocytes, platelets, and fibroblasts bind to target cells via specific cell-surface receptors inducing cells to migrate, divide, or produce other factors required for wound healing. Structural similarities between cell receptors may explain cross-reactivity between substances. Systemic growth factors, such as growth hormone and local epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, and transforming growth factor beta have all been shown to enhance wound healing. Further, growth factors have been shown to have a distinct role in catabolic and malnourished patients as well as in patients with cancer. Clinical trials with growth factors have demonstrated efficacy, and specific uses for those particular factors may become an accepted mode of therapy producing important differences in outcome.

Blood Platelets↗