Search PubMed⌕ Search

Biomedical subjects

A Nguyen

Publications and source records attributed to A Nguyen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Stabilization of the N-terminal residues of luteinizing hormone-releasing hormone agonists and the effect on pharmacokinetics.

To stabilize leuprolide (1) against chymotrypsin and intestinal degradation several agonists of LHRH (2-12), modified at position 1, 2, or 3 and/or containing N-alpha-methyl at positions 1, 2, or 4, were synthesized by SPPS. These agonists were tested in vitro for (a) rat pituitary LHRH receptor binding, (b) LH release from rat pituitary cells, (c) stability against chymotrypsin, and (d) stability against rat intestinal degradation. The clearances of the compounds in the rat were determined using a RIA. Complete stabilization against chymotrypsin (t1/2) and lumenal degradation (T1/2) was achieved with substitution of NMe-Ser4 in leuprolide; however, with an increase in clearance. Substitution with 1-Nal3 increased both t1/2 and T1/2, while substitution with NAc-Sar1 increased only T1/2. [NAcSar1,NMeSer4,D-Trp6,Pro9NHEt]LHRH (12), the doubly stabilized analogue, was tested in the rat by both iv and id administrations, and its bioavailabilities were measured. No significant improvement in id absorption over leuprolide was observed.

Amino Acid Sequence↗
PubMed1992

Effect of stem cell factor with and without granulocyte colony-stimulating factor on neonatal hematopoiesis: in vivo induction of newborn myelopoiesis and reduction of mortality during experimental group B streptococcal sepsis.

Neonatal hematopoiesis and host defense are developmentally immature and under states of increased demand predispose the newborn to peripheral cytopenias and depletion of bone marrow storage pool reserves. We have previously demonstrated that recombinant human granulocyte colony-stimulating factor (rhG-CSF) can significantly modulate neonatal rat granulopoiesis and act synergistically with antibiotic therapy to reduce the mortality rate during experimental group B streptococcal sepsis. Stem cell factor (SCF) has been shown to stimulate early hematopoietic progenitor cells and, in the presence of lineage-specific CSFs, enhance committed progenitor cell proliferation. In the present study we examined the in vivo neonatal hematologic effects of recombinant rat (rr) SCF (14 days), simultaneous rrSCF + rhG-CSF (14 days), and sequential combination of rrSCF (7 days) + rhG-CSF (7 days). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneal (IP) x 14 days with the above combinations. rrSCF (0 to 200 micrograms/kg/d) had a negligible effect on the peripheral platelet count and absolute neutrophil count (ANC) but the diminution in the hematocrit during the first 10 days of treatment was less pronounced (P = .0001). However, the simultaneous use of rrSCF + rhG-CSF synergistically increased the circulating day 6 to 13 ANC (P = .001). Similarly, sequential rrSCF + rhG-SCF also had a synergistic significant effect during the second week of therapy on the circulating ANC (P = .01). The bone marrow neutrophil storage and proliferative pools were also significantly increased in newborn rats treated with rrSCF + rhG-CSF versus rhG-CSF (P = .02). The bone marrow and liver/spleen CFU-GM pool was unchanged; however, the CFU-GM proliferative rates were significantly increased in the rrSCF + rhG-CSF group (P = .04). rrSCF also induced a significant increase in the bone marrow and liver/spleen mast cell pool (P = .002). Lastly, rrSCF x 14 days +/- rhG-CSF significantly reduced the mortality rate at 48 and 120 hours after experimental group B streptococcus sepsis (P = .03 and .05, respectively). These data suggest that combination SCF + G-CSF therapy compared with G-CSF alone significantly increases the neonatal rat peripheral neutrophil count, bone marrow myeloid pools and proliferative rates, and induces a reduction in the mortality rate during experimental bacterial sepsis. SCF therapy may have future potential applications in the modulation of human neonatal hematopoiesis and host defense.

Animals↗
PubMed1992

Left ventricular pseudoaneurysm associated with mitral regurgitation.

A patient with a large posterolateral left ventricular pseudoaneurysm flush with the posterior papillary muscle and associated with mitral regurgitation was successfully treated surgically. The operation consisted of opening the sac of the aneurysm, dissecting the wall of the left ventricle from the fibrous wall of the sac, leaving a cuff of fibrous tissue suitable to hold sutures, and closing the defect with a Dacron patch.

Echocardiography↗
PubMed1992

Metabolic effects of adenosine in the isolated perfused rat heart.

The effects of adenosine on myocardial substrate utilization were assessed in isolated Langendorff-perfused rat hearts. In unpaced hearts perfused at constant flow with insulin, adenosine inhibited oxidation of both glucose and palmitate with similar dose-dependency, without significant effects on effluent lactate+pyruvate. Significant effects of adenosine were observed at 0.1 microM adenosine. In a second series of paced hearts, perfusion pressure was kept constant during adenosine infusion by increasing the flow rate from 10 to 16.3 +/- 0.6 ml/min. Under these conditions, oxidation of both substrates was increased to a similar extent. Lactate+pyruvate output and total glycolytic flux were also increased. At zero or low insulin concentrations, the increases in substrate oxidation were similar to those seen at high insulin, but increases in lactate and pyruvate output and total glycolytic flux were abolished. It is concluded that adenosine does not preferentially increase glucose oxidation in this model.

Adenosine↗
PubMed1991

Inhibitors of urokinase and thrombin in cultured neural cells.

Recent studies have suggested important roles for certain proteases and protease inhibitors in the growth and development of the CNS. In the present studies, inhibitors of urokinase or thrombin in cultured neural cells and serum-free medium from the cells were identified by screening for components that formed sodium dodecyl sulfate-stable complexes with 125I-urokinase or 125I-thrombin. Rinsed glioblastoma possessed two components that complexed 125I-urokinase. One was type 1 plasminogen activator inhibitor (PAI-1), because the 125I-urokinase-containing complexes were immunoprecipitated with anti-PAI-1 antibodies. The other component formed complexes with 125I-urokinase that were not recognized by antibodies to PAI-1 or protease nexin-1 (PN-1). Its identity is unknown. In addition to these cell-bound components, the glioblastoma cells also secreted two inhibitors that formed complexes with 125I-urokinase; one was PAI-1, and the other was PN-1. The secreted PN-1 also formed complexes with 125I-thrombin. It was the only thrombin inhibitor detected in these studies. Human neuroblastoma cells did not contain components that formed detectable complexes with either 125I-urokinase or 125I-thrombin. However, human neuroblastoma cells did contain very low levels of PN-1 mRNA and PN-1 protein. Added PN-1 bound to the surface of both glioblastoma and neuroblastoma cells. This interaction accelerated the inhibition of thrombin by PN-1 and blocked the ability of PN-1 to form complexes with 125I-urokinase. Thus, cell-bound PN-1 was a specific thrombin inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Protein Precursor↗
PubMed1991

Decreased stimulated GM-CSF production and GM-CSF gene expression but normal numbers of GM-CSF receptors in human term newborns compared with adults.

We investigated cord and adult production of granulocyte-macrophage colony-stimulating factor (GM-CSF), expression of GM-CSF mRNA from unstimulated and activated mononuclear cells, and the affinity and presence of GM-CSF receptors on mature effector cells in an attempt to better understand the underlying pathophysiology of altered neonatal host defense. Utilizing 125I-GM-CSF as a ligand, Scatchard analysis revealed the presence of a single class affinity GM-CSF receptor with similar binding characteristics on both cord and adult peripheral PMN (kd = 44 and 39 pM) for adult and cord, respectively. Additionally, there was no significant difference in the number of GM-CSF receptors on cord versus adult neutrophils. Using a sandwich ELISA for measuring GM-CSF levels, we found nondetectable levels from supernatants of unstimulated cord and adult mononuclear cells and serum from cord and adult peripheral blood. However, there was a significant difference between cord and adult GM-CSF production from stimulated phytohemagglutinin and phorbol-12-myristate-6-acetate mononuclear cells (p less than 0.02). Additionally, GM-CSF mRNA expression from activated cord mononuclear cells was significantly reduced after 6 h of stimulation compared with adults. Nuclear run-on experiments revealed no difference in transcriptional activation from activated cord and adult mononuclear cells. Actinomycin D transcriptional decay studies, however, demonstrated reduced GM-CSF half-life from activated cord versus adult mononuclear cells (t1/2 30 versus 100 min). These results suggest normal affinity and numbers of GM-CSF receptors on peripheral mature effector cells but decreased GM-CSF production and GM-CSF mRNA expression from activated cord versus adult mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis.

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques.

In recent years, adipocytes obtained by suction-assisted lipectomy have been used for implantation by injection methods. This study is designed to assess the appearance of suctioned and excised adipose tissue and its survival after being injected or implanted into different tissues (0.5 cc into the rectus muscle and 0.5 cc into the dorsal ear skin) of New Zealand White rabbits. The results showed that significant numbers of adipocytes were ruptured after suction procedures. The intact cells represented approximately 10 percent of the fat cell population. Fat cells in aspirated and excised samples remained intact and did not differ histologically. After being injected into tissue, adipocytes appeared to survive better for a short term in a more vascularized bed (rectus muscle) than in a low vascular area (ear dermis). Long-term studies at 6- to 9-month intervals revealed transplanted adipose tissue, taken by suction or excision, being replaced with fibrosis, although cystic spaces and only a small number of surviving adipocytes were still present. Insulin did not show any protective effects on survival of the adipocytes during their transplantation.

Adipose Tissue↗
PubMed1989

Production of growth factors by malignant lymphoma cell lines.

Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi-solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

Cell Division↗
PubMed1989

Brain leukotriene C4 binding sites are S-alkylglutathione binding sites.

Leukotriene C4 binding to mouse brain membranes was readily displaced by S-alkylglutathione derivatives, with the affinity of the test compound increasing as the alkyl chain length increases. S-decylglutathione was as potent as leukotriene C4. These data suggest that brain membrane leukotriene C4 binding sites are S-alkylglutathione binding sites, possibly microsomal glutathione transferase.

Alkylation↗
PubMed1989

Variation in growth and osmotic regulation of roots of water-stressed maritime pine (Pinus pinaster Ait.) provenances.

Hydroponically cultivated Pinus pinaster Ait. seedlings of a drought-sensitive population from France (Landes) and of a more drought-adapted population from Morocco (Tamjoute) were subjected to a progressive increase in water stress by additions of an osmoticum (polyethylene glycol 600) to the nutrient solution. The final osmotic potential (Psi(ms)) of the nutrient solution was achieved over a period of up to 6 days, and ranged from -0.03 (control, no added osmoticum) to -0.8 MPa. In the 6 days during which water stress was imposed, roots elongated faster in the Moroccan provenance than in the French provenance, but the applied water deficits did not inhibit root elongation in either population. Among treatments, root dry weight per unit root length, total root dry weight and root/shoot dry weight ratio increased with decreasing Psi(ms) in both provenances. Both the water potential (Psi(w)) of the roots (apices) and the water potential difference between the roots and the nutrient solution decreased as Psi(ms) decreased. The reduction in Psi(w) was matched by a decrease of comparable magnitude in cell osmotic potential (Psi(pi)) so that root turgor was unaffected by the Psi(ms). Osmotic adjustment was greater, however, in the Moroccan provenance than in the French provenance. Consequently, under the osmotically imposed water stress, the water potential difference between root and nutrient solution was greater in the Moroccan provenance than in the French provenance. Similar changes in plant water relations were observed when seedlings were grown in drying sand.

Journal Article↗
PubMed1989

Frequency analysis of accommodation: single sinusoids.

We present an experimental frequency analysis of a neurological control system, the accommodation system, using single sinusoids. Also, by means of continual experimental calibration full coverage of one subject's dynamic range, we demonstrate an AC nonlinearity saturation, which probably lies in the motor-response portion of the system; in contrast to the switching-mode nonlinearity, which probably lies in the sensory-processing portion. We offer our findings as a basis for further models. In addition, our results can be compared with studies using multiple sinusoids and transients to document how the different aspects of the accommodation system are realized given their different input conditions.

Accommodation, Ocular↗
PubMed1988

Changes in accommodation with age: static and dynamic.

Accommodative amplitude decreases with age, not with aging. The decrease is largely completed by age 40 years; only minor residual accommodation is present in most subjects after the mid-40s. Dynamical measurements show the accommodative response of subjects over 30 years of age to be significantly slowed (time constants of accommodation increases). Accommodation amplitude is less than 3 D by 30 years of age. Thus prepresbyopia is a sign of continual development, not of deterioration of the accommodative mechanism. Accommodation, or the change of clear vision with change in lens power, has been studied by many distinguished scientists including Descartes and Thomas Young. Helmholtz's "Theory of Accommodation" is a dual, indirect, active theory. There are both lenticular, including lens and capsule, and also extralenticular mechanisms, comprised of the zonule of Zinn or suspensory ciliary ligament and the ciliary muscle itself. The ciliary muscle does not act directly on the lens but indirectly through its action on the zonule of Zinn. Active contraction of the ciliary muscle, a unified muscle, produces accommodation; relaxation of the ciliary muscle permits relaxation of accommodation.

Accommodation, Ocular↗
PubMed1988

Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux.

The kinetics of [1-14C]acetate oxidation in isolated perfused rat hearts have been determined over a range of perfusion conditions. Effluent measurements demonstrated that 14CO2 cleared biexponentially over 50 minutes after bolus injection of [1-14C]acetate into normoxic hearts perfused with 5 mM glucose and 10 mU/ml insulin. The clearance half-time (t1/2) for the predominant initial clearance phase was 3.1 +/- 0.5 minutes (n = 4). MVO2 was varied over a fourfold range by hypoxia and phenylephrine stimulation (t1/2, 7.2 +/- 1.2 and 2.2 +/- 0.2 minutes, respectively) and in the presence of alternate substrates (lactate, 2 mM; DL-3-hydroxybutyrate, 20 mM; and palmitate, 0.1 mM), which did not modify either tricarboxylic acid (TCA) cycle flux or acetate kinetics. A good correlation (r = 0.93) was observed between k, the rate constant for the initial phase of 14CO2 clearance, and TCA cycle flux, estimated from oxygen consumption. In contrast to results with [1-14C]acetate, lactate (2 mM) increased t1/2 for 14CO2 clearance from a bolus injection of [1-14C]palmitate from 3.0 +/- 0.4 minutes (n = 3) at control to 4.3 +/- 0.2 minutes (n = 3, p less than 0.01). Addition of acetate in nontracer amounts (0.5 or 5 mM) caused significant underestimation of TCA cycle flux when estimated with [1-14C]acetate. 14CO2 clearance accounted for 88-98% of total effluent 14C between 10 and 20 minutes after [1-14C]acetate bolus injection; rate constants for clearance of 14CO2 and total 14C clearance were very similar during this period, and these two rate constants did not differ significantly from each other under any conditions tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗