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Biomedical subjects

D Nguyen

Publications and source records attributed to D Nguyen.

At least 91 records · Page 5Linked to original sources

Oscillating balloon angioplasty: does pressure oscillation reach the balloon?

Oscillating pressure inflations may minimize trauma to the coronary artery during coronary angioplasty. We measured in vitro diameters of polyolepin copolymer compliant angioplasty balloons (as a surrogate for pressure) during pressure oscillation at the inflator to determine if pressure oscillations at the inflator were conducted to the balloon. Balloon diameter oscillation increased as cycle length and inflator pressure amplitude increased. Currently practiced oscillating inflation (cycle length 2-3 sec, amplitude 2-3 atm) did not effectively transmit oscillation to the balloon. Clinically feasible optimal balloon oscillation was achieved at a cycle length of 6 sec and pressure amplitude of about 3 atm.

Angioplasty, Balloon, Coronary↗

Acculturation style and psychological functioning in children of immigrants.

Thirty-four immigrants, predominantly Asian, and their 48 children were assessed for relationship of acculturation style to children's psychological functioning. Children of parents accepting the majority culture scored higher in social competence. Many of the children reported as having extreme behavioral problems had rejected their ethnic culture.

Acculturation↗

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.

A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Aged↗

Demonstration of thyromimetic effects of 3,5,3'-triiodothyronine sulfate (T3S) in euthyroid rats.

We have previously demonstrated that T3 sulfate (T3S) exhibits thyromimetic effects in hypothyroid rats and that, on a molar basis, its activity approximates 20% that of T3. Since T3S is avidly deiodinated by 5'-deiodinase, type I (5'-DI) and 5'-DI activity is markedly reduced in hypothyroidism, it seemed possible that T3S is active only in hypothyroidism and not in the euthyroid state wherein normal tissue 5'-DI activity will rapidly degrade T3S and little T3S will be left for metabolism (desulfation) to biologically active T3. This study was undertaken to test this possibility. We studied the effect of T3S (4.6, 14, or 42 nmol/day for 7 days, ip) and T3 (1.0, 3.0 or 9.0 nmol/day for 7 days, ip) in groups of male Sprague-Dawley rats (5-6/group); the control group was treated with saline ip. Treatment with both T3 and T3S caused a significant (p < 0.05) increase in hepatic and renal 5'-DI. Similarly, both treatments caused a significant reduction in serum total T4 and TSH levels. In these effects, T3S was approximately one-fifth as potent as T3 on a molar basis. Interestingly, changes in body weight during treatment with T3 and T3S suggested that at doses that caused a comparable tissue or pituitary effect, T3S treatment permitted a significantly greater weight gain than treatment with T3. We conclude that T3S exhibits thyromimetic effects in euthyroid rats in a manner comparable to that in hypothyroid rats. The biological effects of T3S may be due to T3 generated in tissues by desulfation of T3S.

Animals↗

A study of the effects of epinephrine infiltration on delayed bleeding in a rat flap model.

Infiltrating the operative site prior to incision with an epinephrine solution will provide vasoconstriction and a dryer operative field. However, some surgeons fear that as the vasoconstrictive effects of the epinephrine subside, smaller vessels will rebleed and a hematoma may result. In this study, 51 rats were operated with two flaps. The ventral pedicled flap, based on the inferior superficial epigastric arteries, and the McFarlane dorsal skin flap were utilized. The perimeter of all flaps was infiltrated with one of the following test infusions: (1) no infiltrate (control group), (2) 1% lidocaine hydrochloric acid (HCl), (3) 2% lidocaine HCl, (4) 1% lidocaine HCl and epinephrine 1:100,000, and (5) 0.5% lidocaine HCl and epinephrine 1:200,000. Flaps were replaced in their beds. Animals were sacrificed 24 hours postoperatively. Flaps were raised at 26 hours and the coagulum weighed. No statistically significant difference was found between the weights of the coagulum of the infiltrated flaps versus the noninfiltrated flaps. Statistical power calculations on the main study flap yielded values greater than 80%. This suggests that the difference in delayed bleeding between noninfiltrated flaps and flaps infiltrated with various combinations of lidocaine and epinephrine was insignificant.

Anesthesia, Local↗

Body mass index and body fat distribution in newly-arrived Vietnamese refugees in Sydney, Australia.

Body mass index (BMI), body fat distribution and some behavioural variables were examined in an ethnic Vietnamese population newly arrived in Australia. The age range was 23 to 74 years for males (n = 246, mean = 38.8) and 24 to 66 for females (n = 165, mean = 36.4). Mean BMI was 20.62 +/- 2.65 (male) and 21.25 +/- 3.16 (female). Waist-to-hip ratio (WHR) was 0.844 (males) v 0.802 (females), p < 0.0001: waist was 73.7 cm (males) v 71.7 cm (females), (p = 0.007). Male smoking was 69%, female, 1%; the BMI of male non-smokers was higher than that of smokers 21.22 v 20.35 (p = 0.0017). Exercise patterns, diet or alcohol intake did not appear to affect BMI. The mean BMI of this refugee Vietnamese population is low by comparison with the Australian population. Vietnamese females although of lower mean BMI, have higher WHR than Australian females.

Adipose Tissue↗

Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation.

Wild-type p53 gene transfer into the SW620 colorectal carcinoma cell line was performed using the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effect of wild-type p53 expression on radiation sensitivity. The results indicated that infection with Ad5/CMV/p53 sensitized the cells. The survival at 2 Gy was reduced from 55 to 23%. Flow cytometric analysis of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-labeled cells and in situ TUNEL staining of xenograft tumors demonstrated an increase in labeled cells with combination treatment, indicating increased apoptosis in cells treated with Ad5/CMV/p53 before irradiation. A significant enhancement of tumor growth suppression by this combination strategy was observed in a s. c. tumor animal model compared to p53 gene therapy alone. The delay in regrowth to control tumor size of 1000 mm3 was 2 days for 5 Gy, 15 days for Ad5/CMV/p53, and 37 days for Ad5/CMV/p53 + 5 Gy, indicating synergistic interactions. These data indicate that the delivery of wild-type p53 to cells with p53 mutations increases their radiation sensitivity, and this may be accomplished by adenoviral-mediated gene therapy.

Adenoviridae↗

The minimal gene complement of Mycoplasma genitalium.

The complete nucleotide sequence (580,070 base pairs) of the Mycoplasma genitalium genome, the smallest known genome of any free-living organism, has been determined by whole-genome random sequencing and assembly. A total of only 470 predicted coding regions were identified that include genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. Comparison of this genome to that of Haemophilus influenzae suggests that differences in genome content are reflected as profound differences in physiology and metabolic capacity between these two organisms.

Antigenic Variation↗

Cell cycle arrest and inhibition of tumor cell proliferation by the p16INK4 gene mediated by an adenovirus vector.

The p16INK4 (MTS1) gene has many features of a tumor suppressor gene. It maps to 9p21, a region of frequent loss of heterozygosity in a variety of tumor types. It encodes an inhibitor of cyclin-dependent kinase 4, and its homozygous deletion is common in tumor-derived cell lines. To examine its tumor suppressive function and its potential in cancer gene replacement therapy, wild-type p16INK4 was expressed in an adenovirus-derived gene delivery system and introduced into lung cancer cell lines that do not express p16INK4. Expression of the introduced p16INK4 blocked tumor cell entry into S phase of the cell cycle and inhibited tumor proliferation both in vitro and in vivo. These observations strongly support that p16INK4 is a tumor suppressor gene and is a candidate for cancer gene replacement therapy.

Adenoviridae↗

Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease.

A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease has been designed by using the three-dimensional structure of the enzyme as a guide. By employing iterative protein cocrystal structure analysis, design, and synthesis the binding affinity of the lead compound was incrementally improved by over four orders of magnitude. An inversion in inhibitor binding mode was observed crystallographically, providing information critical for subsequent design and highlighting the utility of structural feedback in inhibitor optimization. These inhibitors are selective for the viral protease enzyme, possess good antiviral activity, and are orally available in three species.

Administration, Oral↗

Strychnine-insensitive glycine site antagonists attenuate a cardiac arrest-induced movement disorder.

Male Sprague-Dawley rats underwent experimentally induced cardiac arrest and resuscitation, subsequently exhibiting involuntary jerking movements (myoclonus) with salient features similar to the human form of the disorder. The novel strychnine-insensitive glycine site antagonists ACEA-1011 (5-chloro-7-trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-2,3,-dio ne) and ACEA-1021 (5-nitro-6,7-dichloro-quinoxalinedione) significantly attenuated the myoclonus in cardiac-arrested rats. (+)-HA-966, (+/-)-HA-966 (3-amino-1-hydroxy-2-pyrrolidinone), and felbamate (2-phenyl-1,3-propanediol dicarbamate) were also effective. Although the drugs vary in their selectivity for strychnine-insensitive glycine sites, they all possess antagonist activity at these sites. Vehicle injections (saline, dimethyl sulfoxide, water) were without effect and no obvious side effects were observed with any of the ligands tested in this study. Since hyperexcitability in the central nervous system is thought to underlie myoclonus, the attenuation of excitatory amino acid neurotransmission through antagonism of strychnine-insensitive glycine sites provides a logical mechanism of action for the antimyoclonic effects observed herein.

Animals↗

Cytoskeletal regulation of Caco-2 intestinal monolayer paracellular permeability.

An abnormal increase in intestinal paracellular permeability may be an important pathogenic factor in various intestinal diseases. The intracellular factors and processes that regulate and cause alteration of intestinal paracellular permeability are not well understood. The purpose of this study was to examine some of the intracellular processes involved in cytoskeletal regulation of intestinal epithelial paracellular permeability using the filter-grown Caco-2 intestinal epithelial monolayers. Cytochalasin-b and colchicine were used to disrupt the cytoskeletal elements, actin microfilaments, and microtubules. Cytochalasin-b (5 micrograms/ml) and colchicine (2 x 10(-5) M) at the doses used caused marked depolymerization and disruption of actin microfilaments and microtubules, respectively. Cytochalasin-b-induced disruption of actin microfilaments resulted in perturbation of tight junctions and desmosomes and an increase in Caco-2 monolayer paracellular permeability. The cytochalasin-b-induced disruption of actin microfilaments and subsequent changes in intercellular junctional complexes and paracellular permeability were not affected by inhibitors of protein synthesis (actinomycin-D or cycloheximide) or microtubule function (colchicine), but were inhibited by metabolic energy inhibitors (2,4-dinitrophenol or sodium azide). The cytochalasin-b-induced disturbance in Caco-2 actin microfilaments and intercellular junctional complexes and increase in paracellular permeability were rapidly reversed. The paracellular pathway "re-tightening" following cytochalasin-b removal was not affected by actinomycin-D, cycloheximide, or colchicine, but was inhibited by 2,4-dinitrophenol and sodium azide. The colchicine-induced disruption of microtubules did not have significant effect on actin microfilaments, intercellular junctions, or paracellular permeability. These findings suggest that cytochalasin-b-induced increase in Caco-2 monolayer paracellular permeability was due to actin microfilament mediated perturbation of intercellular junctional complexes. The re-tightening of paracellular pathways (following removal of cytochalasin-b) resulted from energy-mediated re-assembly of pre-existing actin microfilaments and intercellular junctional complexes. This re-closure process did not require protein synthesis or microtubule-mediated shuttling process.

Actins↗

Nodal benign and malignant monocytoid B cells with and without follicular lymphomas: a comparative study of follicular colonization, light chain restriction, bcl-2, and t(14;18) in 39 cases.

As part of an effort to develop a better understanding of the relationship between nodal monocytoid B-cell lymphomas (MBCLs) and follicular lymphomas (FLs) when they coexist (MBCL + FL) and to assess the validity of the morphological criteria for the latter diagnosis, we evaluated follicular colonization, bcl-2 reactivity, light chain restriction, and the presence of t(14;18) in 14 benign lymph node specimens containing benign monoclonal B cells (MBCs), in eight nodal specimens of pure MBCL, and in 17 nodal specimens of MBCL coexisting with FL (MBCL + FL). Follicular colonization by malignant MBCs was observed in six specimens of pure MBCL and in 13 specimens of MBCL + FL. Benign MBCs did not express bcl-2 by immunohistological methods in 11 of 12 benign specimens. In contrast, weak reactivity for bcl-2 was detected in malignant MBCs in four of five specimens of pure MBCL and in the MBCL component in 13 of 15 specimens from the MBCL + FL group. In the FL component of 13 specimens, the bcl-2 was strongly positive. Identical light chain restriction was detected by immunohistological methods in both the FL component and the MBCL component in 15 specimens of MBCL + FL. Polymerase chain reaction analysis did not detect the t(14;18) translocation in any of 10 benign specimens or any of six evaluable pure MBCL specimens. In contrast, the translocation was detected in whole sections from eight of 12 specimens of MBCL + FL. Thus, on the one hand, the high incidences of follicular colonization and the coexistence of MBCL and FL as well as the identical light chain restriction in MBCL and FL components of MBCL + FL cases suggest that possibly these are related closely when they coexist. On the other hand, the bcl-2 and t(14;18) data cannot be used as evidence in support of a close relationship.

Chromosomes, Human, Pair 14↗

EEG delta, positron emission tomography, and memory deficit in Alzheimer's disease.

Quantitative scalp EEG from 32 channels and the cerebral glucose metabolic rate from the 32 underlying cortical positions as assessed by positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) were obtained on 36 patients with mild to moderate senile dementia of the Alzheimer type and 17 age- and sex-matched normal control subjects. Subjects performed a verbal memory task during uptake of FDG. There were significant correlations between both delta amplitude and metabolic rate and memory performance during FDG uptake. Patients with Alzheimer's disease had significantly greater left temporal delta amplitude and lower glucose metabolic rates. Both EEG delta in microvolts and metabolic rate had similar diagnostic sensitivity, but PET had fewer false positives among normals. The left amygdala had the highest sensitivity and percent correct diagnosis of any brain area. Temporal lobe EEG delta activity showed higher correlations with hippocampal metabolic rate than metabolic rate directly under the electrode.

Aged↗

Airway mucus and epithelial function in a canine model of single lung autotransplantation.

Impaired mucociliary function following lung transplantation has been reported in several human and animal studies. This could be a result of altered ciliary function or mucus properties or both. We assessed airway epithelial function by means of transepithelial potential difference (PD) measurements and physical analysis of mucus. Six mongrel dogs underwent single lung autologous transplantation. Measurements were performed preoperatively and 1, 2, 4, and 10 months postoperatively. At 1 and 2 months postoperatively, there was a significant fall in PD for the transplanted, left mainstem bronchus only (-13.5 +/- 1.7 mV at 1 month and -14.6 +/- 1.7 mV at 2 months postoperatively vs -18.6 +/- 2.3 mV preoperatively, baseline; p < 0.001 for both). The PD values in the small airways, right mainstem bronchus, and the trachea remained unchanged. At 2 months postoperation, the mucus collection rate on the left side was increased (p = 0.03), while the mucus viscoelasticity was decreased (p = 0.04). By 4 months postoperation, all epithelial parameters had returned to baseline, and there was no difference in radioaerosol clearance between the two lungs. The PD decrease and alterations in secretion rate and viscoelasticity reflect disturbed epithelial functional integrity at the site of anastomosis still present at 2 months postoperation. Recovery of bronchial epithelial function and clearance in canine studies of lung autotransplantation after healing of the anastomosis area suggest that persistent impairment of lung clearance observed in some long-term human lung transplantation survivors may be due to other mechanisms such as impaired healing or epithelial function or both, during immunosuppressive therapy. Mucociliary function in the anastomosis area is compromised until complete healing ensues; we speculate that chest physiotherapy may aid in overcoming this obstacle.

Animals↗

Determinants of sensitivity to 1-beta-D-arabinofuranosylcytosine in HCT 116 and NCI-H630 human colon carcinoma cells.

The cytotoxicity and metabolism of 1-beta-D-arabinofuranosylcytosine (AraC) and its effects on DNA synthesis and integrity were studied in HCT 116 and NCI-H630 human colon cancer cells. In 116 cells, 0.1 microM AraC decreased colony formation by approximately 50%, whereas 1 microM was required in H630 cells. AraCTP levels after a 24-hr AraC exposure were 2.3- to 3.5-fold lower in H630 cells due to increased ability to deaminate AraCMP. AraC DNA levels increased in proportion to AraCTP pools (r = 0.99) and were 2-fold higher in 116 cells after a 24-hr exposure to 0.1 and 1 microM AraC. Although the half-life of AraCTP was < 1 hr in both lines, > 80% of AraC DNA was retained at 24 hr after drug removal. Clonogenic capacity was inversely related to the extent of AraC DNA incorporation. Interference with nascent DNA chain elongation increased with increasing AraC concentration x time. A 24-hr AraC exposure produced a dramatic shift in the elution profile of nascent DNA during a 15-hr elution at pH 12.1; these effects were greater in 116 cells (DNA retained on filter [percentage of control]): 78%, 23%, and 9% with 0.1, 1, and 10 microM AraC versus 84%, 42%, and 18% in H630 cells, respectively. The extent of nascent DNA damage was proportional to AraC DNA content. Net DNA synthesis was potently inhibited during AraC exposure in both lines. H630 cells had partial recovery of DNA synthesis at 24 hr after drug removal, whereas persistent inhibition was noted in 116 cells. A slight excess of double-strand breaks in parental DNA was detected after a 24-hr exposure to 10 microM AraC in 116 cells. The extent of DNA fragmentation was more pronounced 16 hr after drug removal and was greater in 116 cells: 8.5%, 19%, and 21% with 0.1, 1, and 10 microM AraC DNA content, magnitude of nascent DNA damage, duration of DNA synthetic inhibition, and induction of double-stranded DNA fragmentation appeared to be the crucial determinants of lethality.

Cell Survival↗