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Biomedical subjects

M T Nguyen

Publications and source records attributed to M T Nguyen.

At least 19 recordsLinked to original sources

Nitrous oxide as a 1,3-dipole: a theoretical study of its cycloaddition mechanism.

The 1,3-dipolar cycloadditions of nitrous oxide and substituted alkynes have been studied at the B3LYP/6-31G(d,p) level. The reaction is controlled by LUMO (dipole)--HOMO (dipolarofile) and involves aromatic transition structures. The shape of the potential energy surface and the regioselectivity are not affected by the polarity of the solvents, except in the case of N2O + HC triple bond CSiH3. Different reactivity criteria including FMO coefficients product C, local softness differences Delta, magnetic susceptibility anisotropy chi(anis), and nucleus-independent chemical shifts NICS were used to predict the regioselectivity in all studied cases; the C, Delta criteria turn out to give the best results among them. The aromaticity of the transition structure is not a factor in determining the regiochemistry of the cycloaddtition reactions.

Alkynes↗

Mechanism of the ring-chain rearrangement in phosphiranes: hydrogen versus halogen migration.

Ab initio quantum chemical calculations including HF, MP2, CCSD(T), CASSCF(10,10)/CASPT2, and B3LYP methods with the 6-31G(d,p) basis set were used to probe the mechanism of the ring-chain rearrangement of halogeno-phosphiranes. It is confirmed that the lowest energy interconversion between C-halogenated-(X)-phosphiranes and vinylphosphines, with X = H, F, Cl, and Br, is a one-step process in which the C-P bond cleavage and X-sigmatropic migration from C to P occur in a concerted manner in a single transition structure. The migration of a hydrogen from CH(H) is slightly favored over that of CX(H), and thus, the cleavage of the C(X)-P bond is preferred. The energy barrier for the whole process involving hydrogen migration in the parent phosphirane is calculated to be about 45 +/- 5 kcal/mol. The migratory aptitude of the atoms X in the uncomplexed species is found as follows: H > Br > Cl > F, either in the gaseous phase or in aqueous and DMSO solutions. The solvation enthalpies that were estimated using a polarizable continuum model (PCM) are rather small and do not modify the relative ordering of the energy barriers. Such a trend is at variance with recent experimental findings on metal-phosphinidene complexes in which only halogen migration was observed. This might arise from a peculiar effect of the metal fragments W(CO)(5) used in the experimental studies to stabilize the phosphorus species that induce a quite different mechanism. Calculations of the (31)P chemical shifts using the GIAO/B3LYP/6-311+G(d,p) method show a remarkable correlation between the delta(31)P(X) chemical shifts of X-phosphiranes and those of X-phosphines (XCH(2)PH(2)), suggesting that the large beta substituent effect is not inherent to the small rings.

Journal Article↗

Theoretical Study of [2 + 1] cycloaddition of CO and CS to acetylenes forming cyclopropenones and cyclopropenethiones.

The [2 + 1] cycloadditions of carbon monoxide and carbon monothioxide CX (X = O, S) to acetylenes (R1C triple bond CR2 with R1 = H, OH and R2 = CH3, OH, NH2, C6H5) have been studied at the B3LYP/6-311G(d,p) level. It has been shown that the reaction proceeds in two steps forming first an intermediate having the properties of both a carbene and a zwitterion followed by a ring closure leading to cyclopropenones or cyclopropenethiones. The solvent effect does not play an important role in the course of the cycloaddition. The estimation of the first vertical excitation energies by CIS and TD-B3LYP methods shows that the reactions likely take place in the ground state rather than in an excited state. All the studied cyclopropenones and cyclopropenethiones are aromatic as shown by their NICS values and confirmed by calculated and experimental NMR chemical shifts. Different reactivity criteria including HOMO coefficient, local softness, hardness, polarizability, and NICS are used to predict the site selectivity in all studied cases, and the NICS criterion seems to yield the best results among them.

Journal Article↗

High-energy collisional activation of the molecular ions of thiophene-2-one with different target gases.

Collisional activation of keV thiophene-2-one radical cations 1(+*) with O(2) or NO(*) as the target gas leads to a desulfuration reaction. This peculiar reaction is insignificant or absent with other targets such as helium, argon, methane or nitrogen. The radical cations produced in this desulfuration reaction are most probably vinylketene ions, as indicated by a triple mass spectrometric (MS/MS/MS) experiment performed on a 'hybrid' tandem mass spectrometer of sector--quadrupole--sector configuration. Tentatively, it is proposed that population of an excited state accounts for the non-ergodic behavior of 1(+*) upon collision with oxygen or nitric oxide. Ab initio molecular orbital calculations using molecular orbital theory (UMP2, UCCSD(T)) and density functional theory (B3LYP) with 6--31G(d,p) and 6--311++G(d,p) basis sets were used to evaluate the relative energy of the excited quartet state of 1(+*) radical cations. This quartet state is calculated to lie about 3.6 eV above the (2)A(") ground state and 0.9 eV above the C(4)H(4)O(+*)+S dissociation products. It is proposed that the quartet ion serves as the precursor for the spontaneous desulfuration.

Journal Article↗

Pediatric imaging: sedation with an injection formulation modified for rectal administration.

PURPOSE: To determine if rectal sedation with thiopental sodium produced for intravenous administration provides safe and effective sedation for children undergoing diagnostic imaging. MATERIALS AND METHODS: Five hundred twenty-five consecutive children (mean age, 2.7 years +/- 2.2 [SD]) underwent magnetic resonance imaging (n = 425), computed tomography (n = 89), and nuclear medicine (n = 11) examinations after rectal administration of thiopental sodium injection solution. The solution was prepared from thiopental sodium powder mixed with sterile water to create a concentration of 100 mg/mL. The dose ranged from 25 to 40 mg per kilogram of body weight, with a total dose limit of 1.5 g. The percentages of successful sedations and adverse reactions were evaluated on the basis of data collected at the time of the sedation. RESULTS: Sedation was successful in 504 (96%) children. Ten (2%) children experienced desaturation, but only three of the 10 experienced sedation failure. All cases of desaturation were treated successfully with head repositioning, administration of supplemental oxygen, or both. No children experienced vomiting, acute rectal irritation, paradoxical hyperactivity, or prolonged sedation. CONCLUSION: Thiopental sodium sedation for pediatric imaging, with use of a rectal solution prepared from thiopental sodium preparation for intravenous injection, is safe and effective.

Administration, Rectal↗

Siderotic nodules in the cirrhotic liver at MR imaging with explant correlation: no increased frequency of dysplastic nodules and hepatocellular carcinoma.

PURPOSE: To determine the sensitivity of magnetic resonance (MR) imaging for detection of siderotic nodules in patients with cirrhosis and whether the frequency of hepatocellular carcinoma (HCC) and dysplastic nodules is greater if siderotic nodules are present. MATERIALS AND METHODS: MR imaging (1.5 T) was performed within 0-117 days (mean, 30 days) before liver transplantation in 77 patients. Two readers retrospectively evaluated gradient-echo (GRE) (echo time [TE], > or = 9 and 4-5 msec) and turbo short inversion time inversion-recovery or T2-weighted images for low-signal-intensity nodules. Whole-explant pathologic correlation was available in every case. RESULTS: At explantation, 28 (36%) of 77 patients had HCC, 25 (32%) had dysplastic nodules, and nine (12%) had both; 35 (45%) patients had siderotic nodules. The sensitivity of GRE imaging with 9-msec or longer TE for the detection of siderotic nodules was 80% (28 of 35) but decreased to 31% (11 of 35) with 4-5-msec TE. Frequency of HCC was not significantly higher (P =.27) in patients with (43% [15 of 35]) than in patients without (31% [13 of 42]) siderotic nodules. Frequency of dysplastic nodules also was not significantly higher (P =.42) in patients with (37% [13 of 35]) than in patients without (29% [12 of 42]) siderotic nodules. CONCLUSION: Sensitivity of MR imaging for the detection of siderotic nodules was improved with use of GRE pulse sequences with longer TEs of 9 msec or greater (80%) versus 4-5 msec (31%); however, there was no significant increased frequency of HCC or dysplastic nodules in patients with pathologically proved siderotic nodules.

Adult↗

Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse.

Production of prostaglandin E(2) (PGE(2)) is enhanced during inflammation, and this lipid mediator can dramatically modulate immune responses. There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways. To identify the EP receptors that regulate cellular immune responses, we used mouse lines in which the genes encoding each of the four EP receptors were disrupted by gene targeting. Using the mixed lymphocyte response (MLR) as a model cellular immune response, we confirmed that PGE(2) has potent antiproliferative effects on wild-type responder cells. The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE(2) in the MLR. In contrast, when responder cells lacked the EP2 receptor, PGE(2) had little effect on proliferation. Modest resistance to PGE(2) was also observed in EP4-/- responder cells. Reconstitution experiments suggest that EP2 receptors primarily inhibit the MLR through direct actions on T cells. Furthermore, PGE(2) modulates macrophage function by activating the EP4 receptor and thereby inhibiting cytokine release. Thus, PGE(2) regulates cellular immune responses through distinct EP receptors on different immune cell populations: EP2 receptors directly inhibit T cell proliferation while EP2 and EP4 receptors regulate antigen presenting cells functions.

Animals↗

Magnification views of mammography decrease biopsy rates.

Mammography is a valuable tool for screening and has increased early detection of breast cancer. Magnification views are commonly used to further elucidate suspicious changes seen on routine mammograms. The effect of magnification views and their utility have not been studied regarding the influence on treatment strategies. All patients who had magnification views performed along with their mammogram at Tulane University Medical Center over a one-year period were included. Patient charts were reviewed for mammogram readings, recommendations, and any biopsy results. The original mammograms without the magnification views were given to a physician who was blinded to the final results of the magnification views for a recommendation of whether or not to biopsy the lesion. These recommendations were compared with the results with actual recommendations. Magnification views were performed on 127 patients. After the additional magnification views were taken 27 per cent (34 of 127) of patients had biopsies performed. Biopsy results revealed benign findings in 71 per cent and nonbenign findings (lobular carcinoma in situ, ductal carcinoma in situ, or carcinoma) in 29 per cent. On the basis of the recommendations without magnification views 64 per cent of patients would have had biopsies performed. Magnification views decreased the biopsy rates by 58 per cent (P < 0.001; chi2 tests). Magnification views can help decrease the number of biopsies performed for suspicious small areas on mammograms. Their judicious use can help decrease unnecessary procedures, patient anxiety, and cost. Magnification views are useful to help surgeons and radiologists best screen for breast cancer.

Biopsy↗

Dissociation of IGF2 and H19 imprinting in human brain.

The human IGF2 and H19 genes are imprinted in most normal tissues. Alterations of genomic imprinting or loss of imprinting (LOI) have been observed in a number of malignant tumors. Although LOI has been linked to tumorigenesis, loss of IGF2 imprinting has also been observed in choroid plexus and leptomeninges in normal mouse brain. We have therefore analyzed the allelic expression of both IGF2 and H19 in human fetal brain and in different regions of human adult brain. In the brains of fetuses of 6-12 weeks gestation, both IGF2 and H19 were transcribed from both parental alleles. In contrast, strictly monoallelic expression of both IGF2 and H19 was observed in all other fetal tissues, suggesting a tissue-specific LOI in the central nervous system. In adult brain, LOI of IGF2 was region-specific. IGF2 was expressed from both parental alleles in the pons, but not in globus palludus, Raphe nucleus and hypothalamus. H19 expression was drastically reduced in adult brain compared to fetal brain, and was detectable only in the pons and globus palludus. In contrast to IGF2, the expression of H19 in adult pons was monoallelic. Examination of IGF2 promoter usage indicated predominant utilization of promoter P3 in all fetal and adult brain tissues. The LOI of IGF2 therefore reflects biallelic expression from the predominant promoter. IGF2 transcripts derived from the less abundant promoter P1, however, showed monoallelic expression in the adult pons. Our results suggest that IGF2 and H19 undergo ontogenetic changes in allelic expression and that there is dissociation of IGF2 and H19 imprinting in both fetal and adult human brain.

Aging↗

The nucleus: a target site for parathyroid hormone-related peptide (PTHrP) action.

It is becoming increasingly apparent that parathyroid hormone-related peptide (PTHrP) modulates cellular function in a dual mode of action: first, by binding and activating its cognate cell surface G-protein-coupled receptor and, second, by direct intracellular effects following translocation to the nucleus and/or nucleolus of the target cell. Little is presently known about the mechanisms and events that determine the timing and degree of PTHrP nuclear translocation or the role it may serve in normal or dysregulated cellular function. Clarifying the nuclear actions of PTHrP would add significantly to our present understanding of this protein as a signaling molecule during embryonic development and as an oncoprotein whose expression in many tumors correlates with increased tumor aggressiveness and propensity for metastasis.

Amino Acid Sequence↗

Mutations in microphthalmia, the mouse homolog of the human deafness gene MITF, affect neuroepithelial and neural crest-derived melanocytes differently.

The mouse microphthalmia (Mitf) gene encodes a basic-helix-loop-helix-zipper transcription factor whose mutations are associated with abnormalities in neuroepithelial and neural crest-derived melanocytes. In wild type embryos, Mitf expression in neuropithelium and neural crest precedes that of the melanoblast marker Dct, is then co-expressed with Dct, and gradually fades away except in cells in hair follicles. In embryos with severe Mitf mutations, neural crest-derived Mitf-expressing cells are rare, lack Dct expression, and soon become undetectable. In contrast, the neuroepithelial-derived Mitf-expressing cells of the retinal pigment layer are retained, express Dct, but not the melanogenic enzyme genes tyrosinase and Tyrp1, and remain unpigmented. The results show that melanocyte development critically depends on functional Mitf and that Mitf mutations affect the neural crest and the neuroepithelium in different ways.

Animals↗

Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia.

A single homozygous nucleotide exchange in exon E3 of the gene encoding the parathyroid hormone receptor type 1 (PTHR1) was identified in an infant with Blomstrand chondrodysplasia born to consanguineous parents. This alteration changes a strictly conserved proline residue at position 132 in the receptor's amino terminal extracellular domain to leucine. COS-1 cells expressing the mutant receptor did not accumulate cyclic adenosine 3',5'-monophosphate in response to PTH or PTH-related peptide (PTHrP) and did not bind the radiolabeled ligand. Expression of the mutant protein on the cell surface of transiently transfected COS-1 cells and in growth plate chondrocytes derived from the affected infant suggests that proline 132 is critical for the receptor's intrinsic binding activity. These findings suggest that the Blomstrand form of human short-limbed dwarfism arises from defective PTHR1 signaling in the developing cartilaginous skeleton.

Amino Acid Sequence↗

Effect of cow milk on pulmonary function in atopic asthmatic patients.

BACKGROUND: There is a perception by some asthmatic patients that stimulation of respiratory mucous production by cow milk may worsen airway obstruction. OBJECTIVE: To determine whether cow milk ingestion reduces bronchial airflow in asthmatic patients as measured by standard spirometry. METHODS: Twenty-five atopic adults with mild asthma but no history of cow milk allergy or lactose intolerance participated in a prospective, randomized, double-blind, placebo-controlled crossover study. Subjects were randomly assigned to ingest either a solution containing cow milk powder or a placebo solution, received neither during a 14-day washout period, then ingested the alternate solution. Forced vital capacity (FVC), forced expiratory volume in 1 second (s) (FEV1), and FEV1/FVC were measured at 30 minutes, 1 hour (h), and 7 hours after challenge. A > or = 20% decrease in FEV1 or FEV1/FVC was considered clinically significant. RESULTS: FEV1 was slightly lower at 30 minutes than the baseline value (mean change, .6% to 3.3%) for both challenges. None of the subjects experienced any adverse symptoms, acute or delayed, after cow milk or placebo challenges. Statistically significant changes in FEV1 were reached 30 minutes after cow milk challenge (P = .0007) and at one hour after placebo (P = .0027). These changes are not clinically significant. CONCLUSION: Although this study disclosed no acute or delayed asthmatic symptoms or deterioration of pulmonary function detected by using conventional spirometry, methacholine inhalation before and after cow milk challenge may be more sensitive for evaluation of cow milk-induced bronchial hyperreactivity.

Adult↗

A Schwann cell matrix component of neuromuscular junctions and peripheral nerves.

Molecules localized to the synapse are potential contributors to processes unique to this specialized region, such as synapse formation and maintenance and synaptic transmission. We used an immunohistochemical strategy to uncover such molecules by generating antibodies that selectively stain synaptic regions and then using the antibodies to analyse their antigens. In this study, we utilized a monoclonal antibody, mAb 6D7, to identify and characterize an antigen concentrated at frog neuromuscular junctions and in peripheral nerves. In adult muscle, immunoelectron microscopy indicates that the antigen is located in the extracellular matrix around perisynaptic Schwann cell at the neuromuscular junction and in association with myelinated and nonmyelinated axons in peripheral nerves. The maintenance of the mAb 6D7 epitope is innervation-dependent but is muscle-independent; it disappears from the synaptic region within 2 weeks after denervation, but persists after muscle damage when the nerve is left intact. mAb 6D7 immunolabelling is also detected at the neuromuscular junction in developing tadpoles. Biochemical analyses of nerve extracts indicate that mAb 6D7 recognizes a glycoprotein of 127 kDa with both N- and O-linked carbohydrate moieties. Taken together, the results suggest that the antigen recognized by mAb 6D7 may be a novel component of the synaptic extracellular matrix overlying the terminal Schwann cell. The innervation-sensitivity of the epitope at the neuromuscular junction suggests a function in the interactions between nerves and Schwann cells.

Animals↗

Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor.

The more than 20 different Mitf mutations in the mouse are all associated with deficiencies in neural crest-derived melanocytes that range from minor functional disturbances with some alleles to complete absence of mature melanocytes with others. In the trunk region of wild-type embryos, Mitf-expressing cells that coexpressed the melanoblast marker Dct and the tyrosine kinase receptor Kit were found in the dorsolateral neural crest migration pathway. In contrast, in embryos homozygous for an Mitf allele encoding a non-functional Mitf protein, Mitf-expressing cells were extremely rare, no Dct expression was ever found, and the number of Kit-expressing cells was much reduced. Wild-type neural crest cell cultures rapidly gave rise to cells that expressed Mitf and coexpressed Kit and Dct. With time in culture, Kit expression was increased, and pigmented, dendritic cells developed. Addition of the Kit ligand Mgf or endothelin 3 or a combination of these factors all rapidly increased the number of Dct-positive cells. Cultures from Mitf mutant embryos initially displayed Mitf-positive cells similar in numbers and Kit-expression as did wild-type cultures. However, Kit expression did not increase with time in culture and the mutant cells never responded to Mgf or endothelin 3, did not express Dct, and never showed pigment. In fact, even Mitf expression was rapidly lost. The results suggest that Mitf first plays a role in promoting the transition of precursor cells to melanoblasts and subsequently, by influencing Kit expression, melanoblast survival.

Amino Acid Sequence↗