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Biomedical subjects

B D Nguyen

Publications and source records attributed to B D Nguyen.

At least 19 recordsLinked to original sources

Mapping of genes controlling aluminum tolerance in rice: comparison of different genetic backgrounds.

Aluminum toxicity is the main factor limiting the productivity of crop plants in acid soils, particularly in the tropics and subtropics. In this study, a doubled-haploid population derived from the rice ( Oryza sativa L.) breeding lines CT9993 and IR62266 was used to map genes controlling Al tolerance. A genetic linkage map consisting of 280 DNA markers (RFLP, AFLP and SSR) was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Al tolerance. Three characters - control root length (CRL), Al-stressed root length (SRL) and root length ratio (RR) - were evaluated for the DH lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs controlling root growth under Al stress and control conditions were detected and distributed over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. The two QTLs of largest effect, qALRR-1-1 and qALRR-8 for root length ratio (a measurement of Al tolerance) were localized on chromosomes 1 and 8, respectively. Three other QTLs in addition to qALRR-8 were apparently unique in the CT9993 x IR62266 mapping population, which may explain the high level of Al tolerance in CT9993. Comparative mapping identified a conserved genomic region on chromosome 1 associated with Al tolerance across three rice genetic backgrounds. This region provides an important starting point for isolating genes responsible for different mechanisms of aluminum tolerance and understanding the genetic nature of this trait in rice and other cereals.

Aluminum↗

De novo establishment and cost-effectiveness of Papanicolaou cytology screening services in the Socialist Republic of Vietnam.

BACKGROUND: Cervical carcinoma is the leading cause of cancer-related death among women in the developing world. The absence of cervical screening in Vietnam and other developing countries is due in large part to the perceived expense of implementing Papanicolaou cytology screening services, although, to the authors' knowledge, the cost-effectiveness of establishing such services has never been studied in a developing country. METHODS: Using decision analytic methods, the authors assessed cost-effectiveness of Pap screening from a societal perspective in Vietnam, the world's 9th most populous developing country (estimated 1999 population, 79 million). Outcomes measured included life expectancy, cervical carcinoma incidence, cost per woman, and cost-effectiveness. RESULTS: Total costs to establish a nationwide 5-year interval Pap screening program in Vietnam will average less than $148,400 annually during the 10-year time period assumed necessary to develop the program and may be considerably lower if only high risk geographic areas are targeted. Maintenance costs will average less than $0.092 annually per woman in the target screening population. Assuming 70% program participation, cervical carcinoma incidence will decrease from 26 in 100,000 to 14.8 in 100,000, and cost-effectiveness will be $725 per discounted life-year. Several assumptions used in this analysis constitute biases against the effectiveness of Pap screening, which in reality may be significantly more cost-effective than reported here. CONCLUSIONS: Contrary to widespread belief, Pap screening in developing countries such as Vietnam is extraordinarily inexpensive and appears to be cost-effective. Because prospects are uncertain regarding useful alternatives to the Pap test, the evidence-based argument for establishing conventional Pap screening services in developing countries such as Vietnam is compelling. Population-based conventional Pap screening services have been established de novo in Vietnam and are now operational.

Adult↗

Decreases in dilated pupil size in depressed patients with age may reflect adrenergic changes.

Some studies have suggested that noradrenergic activity may decrease with age in depressed patients. Pupil size is regulated by a balance between norepinephrine and acetylcholine. The present study compares pupil size in 10 unmedicated patients with unipolar depression (296. 3) and in 16 normal controls. Pupil size after dilation with tropicamide, a cholinergic antagonist, was inversely related to age in the patients (r=-0.87), but did not diminish with age in controls. The results suggest that pupil size may provide an index of diminished noradrenergic function with age in patients with major depression.

Acetylcholine↗

Solution (1)H NMR study of the influence of distal hydrogen bonding and N terminus acetylation on the active site electronic and molecular structure of Aplysia limacina cyanomet myoglobin.

The sea hare Aplysia limacina possesses a myoglobin in which a distal H-bond is provided by Arg E10 rather than the common His E7. Solution (1)H NMR studies of the cyanomet complexes of true wild-type (WT), recombinant wild-type (rWT), and the V(E7)H/R(E10)T and V(E7)H mutants of Aplysia Mb designed to mimic the mammalian Mb heme pocket reveal that the distal His in the mutants is rotated out of the heme pocket and is unable to provide a stabilizing H-bond to bound ligand and that WT and rWT differ both in the thermodynamics of heme orientational disorder and in heme contact shift pattern. The mean of the four heme methyl shifts is shown to serve as a sensitive indicator of variations in distal H-bonding among a set of mutant cyanomet globins. The heme pocket perturbations in rWT relative to WT were traced to the absence of the N-terminal acetyl group in rWT that participates in an H-bond to the EF corner in WT. Analysis of dipolar contacts between heme and axial His and between heme and the protein matrix reveal a small approximately 2 degrees rotation of the axial His in rWT relative to true WT and a approximately 3 degrees rotation of the heme in the double mutant relative to rWT Mb. It is demonstrated that both the direction and magnitude of the rotation of the axial His relative to the heme can be determined from the change in the pattern of the contact-dominated heme methyl shift and from the dipolar-dominated heme meso-H shift. However, only NOE data can determine whether it is the His or heme that actually rotates in the protein matrix.

Acetylation↗

The use of chemical shift temperature gradients to establish the paramagnetic susceptibility tensor orientation: implication for structure determination/refinement in paramagnetic metalloproteins.

The use of dipolar shifts as important constraints in refining molecular structure of paramagnetic metalloproteins by solution NMR is now well established. A crucial initial step in this procedure is the determination of the orientation. of the anisotropic paramagnetic susceptibility tensor in the molecular frame which is generated interactively with the structure refinement. The use of dipolar shifts as constraints demands knowledge of the diamagnetic shift. which, however, is very often not directly and easily accessible. We demonstrate that temperature gradients of dipolar shifts can serve as alternative constraints for determining the orientation of the magnetic axes, thereby eliminating the need to estimate the diamagnetic shifts. This approach is tested on low-spin, ferric sperm whale cyanometmyoglobin by determining the orientation, anisotropies and anisotropy temperature gradients by the alternate routes of using dipolar shifts and dipolar shift gradients as constraints. The alternate routes ultimately lead to very similar orientation of the magnetic axes, magnetic anisotropies and magnetic anisotropy temperature gradients which, by inference, would lead to an equally valid description of the molecular structure. It is expected that the use of the dipolar shift temperature gradients, rather than the dipolar shifts directly, as constraints will provide an accurate shortcut in a solution structure determination of a paramagnetic metalloprotein.

Animals↗

1H NMR investigation of the distal hydrogen bonding network and ligand tilt in the cyanomet complex of oxygen-avid Ascaris suum hemoglobin.

The O(2)-avid hemoglobin from the parasitic nematode Ascaris suum exhibits one of the slowest known O(2) off rates. Solution (1)H NMR has been used to investigate the electronic and molecular structural properties of the active site for the cyano-met derivative of the recombinant first domain of this protein. Assignment of the heme, axial His, and majority of the residues in contact with the heme reveals a molecular structure that is the same as reported in the A. suum HbO(2) crystal structure (Yang, J., Kloek, A., Goldberg, D. E., and Mathews, F. S. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 4224-4228) with the exception that the heme in solution is rotated by 180 degrees about the alpha,gamma-meso axis relative to that in the crystal. The observed dipolar shifts, together with the crystal coordinates of HbO(2), provide the orientation of the magnetic axes in the molecular framework. The major magnetic axis, which correlates with the Fe-CN vector, is found oriented approximately 30 degrees away from the heme normal and indicates significant steric tilt because of interaction with Tyr(30)(B10). The three side chain labile protons for the distal residues Tyr(30)(B10) and Gln(64)(E7) were identified, and their relaxation, dipolar shifts, and nuclear Overhauser effects to adjacent residues used to place them in the distal pocket. It is shown that these two distal residues exhibit the same orientations ideal for H bonding to the ligand and to each other, as found in the A. suum HbO(2) crystal. It is concluded that the ligated cyanide participates in the same distal H bonding network as ligated O(2). The combination of the strong steric tilt of the bound cyanide and slow ring reorientation of the Tyr(30)(B10) side chain supports a crowded and constrained distal pocket.

Animals↗

Symptoms associated with oophorectomy and tamoxifen treatment for breast cancer in premenopausal Vietnamese women.

There are very few data about the efficacy and toxicity of adjuvant systemic therapies for breast cancer in non-western populations. In 1993 in Vietnam we began a randomized controlled clinical trial on premenopausal women with operable breast cancer comparing adjuvant surgical oophorectomy plus tamoxifen with observation and this same combined hormonal treatment on recurrence. We evaluated the symptoms reported at regular follow-up visits by the first 482 premenopausal women entered in this clinical trial and treated with surgical oophorectomy plus tamoxifen or observation. Hot flash frequency and intensity, vaginal discharge, and genital pruritus were the only symptoms to occur more frequently in oophorectomy and tamoxifen-treated subjects. Seventy-seven percent of oophorectomy/tamoxifen subjects reported grade 1 or more and 44% grade 2 or more hot flash frequency symptoms in the first 12 months, versus 9% and 1% of observation subjects, respectively. Twenty percent of oophorectomy/tamoxifen subjects had grade 2 or greater intensity of hot flashes some time in the first 12 months versus 0% in observation subjects. Through three years, vasomotor symptoms were reported more frequently in oophorectomy/tamoxifen-treated women (in 23% vs. 3% at three years, mostly grade 1 toxicities). While noted and persistent vasomotor symptoms were found with oophorectomy plus tamoxifen in this population of Vietnamese women, these were of lower grades and tolerable. This adjuvant treatment may be widely accepted if it is demonstrated to be effective in this population.

Adult↗

Somatostatin receptor scintigraphy and somatostatin therapy in the evaluation and treatment of malignant thymoma.

PURPOSE: This report illustrates the potential diagnostic and therapeutic utility of somatostatin receptor scintigraphy and therapy with somatostatin. METHODS: In-111 pentetreotide (In-111 octreotide), a somatostatin analog, was used to define the receptor status and the extent of disease in a case of malignant thymoma. RESULTS: Subsequent treatment with nonradioactive somatostatin inhibited tumor growth. CONCLUSION: In-111 octreotide may be useful to define tumor receptor status and may provide prognostic information useful in determining subsequent therapy.

Adult↗