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Biomedical subjects

M T Nguyen

Publications and source records attributed to M T Nguyen.

At least 37 records · Page 2Linked to original sources

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↗

Variations in Vietnamese marriages, births and infant deaths by months of the Julian calendar and years of the Vietnamese and Chinese astrological calendars.

The timing of births and marriages in Vietnam appears to have some statistically significant relationships with the signs of the Chinese and Vietnamese astrological calendars. Years considered to be good years have significantly more births and marriages than years that are not considered as desirable. Births and marriages also have some significant variations with seasons of the year. Infant deaths do not appear to have any significant relationships with the astrological signs although infant mortality has some significant relationships with seasons of the year. The findings indicate that there is some purposeful planning for marriages and births to coincide with optimal times defined in the astrological calendars.

Astrology↗

Demographic trends in Vietnam.

"Asia's four ¿little dragons' (South Korea, Hong Kong, Singapore and Taiwan) have in common not only an economic boom, but also the same rapid demographic transition. How does Vietnam, whose economy is poised for a take-off, stand in this respect? In an attempt to answer this question, [the authors] study the growing corpus of information which a number of ad hoc surveys have added to the 1979 and 1989 population censuses."

Asia↗

Two-day oral desensitization to trimethoprim-sulfamethoxazole in HIV-infected patients.

OBJECTIVE: To establish whether an outpatient, 2-day oral desensitization protocol would be both safe and effective in HIV-infected patients with previous trimethoprim-sulfamethoxazole (TMP-SMX) intolerance. DESIGN: A single center trial of TMP-SMX desensitization in HIV-infected patients with prior TMP-SMX hypersensitivity reactions. METHODS: HIV-infected patients with CD4 lymphocyte counts < 250 x 10(6)/l cells or CD4% < 20% with previous non-life-threatening hypersensitivity reactions to TMP-SMX were eligible. The desensitization protocol utilized 40 graduated doses over 36 h; the first 28 doses (7.5 h) of the protocol were given in an outpatient clinic with the remaining doses taken at home. RESULTS: Twenty-seven (60%) of the 45 subjects completed the protocol and were subsequently maintained on daily TMP-SMX without adverse reactions (mean follow-up, 9 months; range, 4-16 months). Patients with CD4 counts < 100 x 10(6)/l cells were just as likely as patients with higher CD4 counts to tolerate the desensitization. No patient required hospitalization for treatment of an adverse reaction. CONCLUSION: Oral desensitization to TMP-SMX in HIV-infected patients is a useful option in the management of patients with advanced HIV disease and prior intolerance to TMP-SMX.

AIDS-Related Opportunistic Infections↗

Factors influencing infant mortality in Vietnam.

Selected determinants of overall infant mortality in Vietnam were examined using data from the 1988 Vietnam Demographic and Health Survey, and factors underlying neonatal and post-neonatal mortality were also compared. Effects of community development characteristics, including health care, were studied by logistic regression analysis in a subsample of rural children from the 1990 Vietnam Accessibility of Contraceptives Survey. Infant neonatal and post-neonatal mortality rates showed comparable distributions by birth order, maternal age, pregnancy intervals, mother's education and urban-rural residence. Rates were highest among first order births, births after an interval of less than 12 months, births to illiterate mothers and to those aged under 21 or over 35 years of age. Logistic regression analysis showed that the most significant predictor of infant mortality was residence in a province where overall infant mortality was over 40 per 1000 live births. In the rural subsample, availability of public transport was the most persistent community development predictor of infant mortality. Reasons for the low infant mortality rates in Vietnam compared to countries with similar levels of economic development are discussed.

Adolescent↗

Selected determinants of fertility in Vietnam: age at marriage, marriage to first birth interval and age at first birth.

Data from the 4172 women aged 15-49 interviewed in the 1988 Vietnamese Demographic and Health Survey were used to examine age at marriage, marriage to first birth intervals and age at first birth. Differences between urban and rural areas, northern and southern provinces and by education of the women were analysed. The majority of the women had their first birth before age 20, but women with secondary education had a significantly higher age at first birth than those with little or no education, and women from the north had a significantly higher age at first birth than women from the south. Rural women and those with little or no education married at significantly younger ages than urban women and those with secondary education; these education effects were confirmed in a rural subsample of women. Women from rural areas and from the north had significantly shorter marriage to first birth intervals than urban women and those from the south, but there were no significant effects related to education.

Adolescent↗