HIV type 1 subtype E in commercial sex workers and injection drug users in southern Vietnam.
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Biomedical subjects
Publications and source records attributed to H T Nguyen.
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MEF2 (myocyte-specific enhancer factor 2) is a MADS box transcription factor that is thought to be a key regulator of myogenesis in vertebrates. Mutations in the Drosophila homologue of the mef2 gene indicate that it plays a key role in regulating myogenesis in Drosophila. We show here that the Drosophila tropomyosin I (TmI) gene is a target gene for mef2 regulation. The TmI gene contains a proximal and a distal muscle enhancer within the first intron of the gene. We show that both enhancers contain a MEF2 binding site and that a mutation in the MEF2 binding site of either enhancer significantly reduces reporter gene expression in embryonic, larval, and adult somatic body wall muscles of transgenic flies. We also show that a high level of proximal enhancer-directed reporter gene expression in somatic muscles requires the cooperative activity of MEF2 and a cis-acting muscle activator region located within the enhancer. Thus, mef2 null mutant embryos show a significant reduction but not an elimination of TmI expression in the body wall myoblasts and muscle fibers that are present. Surprisingly, there is little effect in these mutants on TmI expression in developing visceral muscles and dorsal vessel (heart), despite the fact that MEF2 is expressed in these muscles in wild-type embryos, indicating that TmI expression is regulated differently in these muscles. Taken together, our results show that mef2 is a positive regulator of tropomyosin gene transcription that is necessary but not sufficient for high level expression in somatic muscle of the embryo, larva, and adult.
Excitation-contraction coupling in skeletal muscle involves a voltage sensor in the plasma membrane which, in response to depolarization, causes an intracellular calcium-release channel to open. The skeletal isoform of the ryanodine receptor (RyR-1) functions as the Ca2+-release channel and the dihydropyridine receptor (DHPR) functions as the voltage sensor and also as an L-type Ca2+ channel. Here we examine the possibility that there is a retrograde signal from RyR-1 to the DHPR, using myotubes from mice homozygous for a disrupted RyR-1 gene (dyspedic mice). As expected, we find that there is no excitation-contraction coupling in dyspedic myotubes, but we also find that they have a roughly 30-fold reduction in L-type Ca2+-current density. Injection of dyspedic myotubes with RyR-1 complementary DNA restores excitation-contraction coupling and causes the density of L-type Ca2+ current to rise towards normal. Despite the differences in Ca2+-current magnitude, measurements of charge movement indicate that the density of DHPRs is similar in dyspedic and RyR-1-expressing myotubes. Our results support the possibility of a retrograde signal by which RyR-1 enhances the function of DHPRs as Ca2+ channels.
One of the first target cells at the site of inoculation with an alphavirus may be monocytes or macrophages. The replication kinetics of virulent and attenuated molecularly cloned Venezuelan equine encephalitis virus (VEE) in murine macrophages were therefore compared. Infection of both quiescent and activated mouse primary peritoneal macrophages with a molecularly cloned, virulent VEE termed V3000 resulted in peak virus titres of 10(4) plaque forming units (PFU)/ml supernatant by 24 h post-infection (pi), followed by rapidly decreasing virus titres. In contrast, a molecularly cloned attenuated VEE mutant, V3032, that differs from V3000 by a single amino acid at E2 glycoprotein position 209 (glu-->lys) replicated more slowly and to higher titres (10(8) PFU/ml supernatant) that peaked at 72 h pi. Replication of V3032, but not V3000, was sharply restricted by prior activation of macrophages with lipopolysaccharide or interferon-gamma. These results indicate that virulent V3000 and attenuated V3032 differ in their growth kinetics in both quiescent and activated macrophages. Thus, macrophages, and their specific activation state, may play a major role in virulent and attenuated VEE replication and pathogenesis.
Isolation of cDNAs encoding individual members of a gene family is essential for assessing their role in a biological phenomenon. However, this process is often laborious and slow due to highly conserved protein-coding region that interferes with the isolation of the individual members. Identification of gene-specific probes from 3' non-coding regions of different members can assist in the fast retrieval and characterization of individual members of a multigene family. We used the recent technique of differential display for the same purpose. As an example of a multigene family in plants, we selected a heat shock protein gene family, HSP16.9 from wheat, with estimated 12 members. We modified the original differential display technique for selective amplification of the 3' non-coding regions of different wheat HSP16.9 genes by replacing the random 10-mer in the original method with a conserved HSP16.9 gene family-specific primer. Sixteen cDNA fragments from these experiments were sequenced and they represent 8 different members of a 12 member gene family. Our success can be attributed to shorter 3' non-coding regions that are typical of higher-plant genes and use of highly conserved gene family-specific primer in these experiments. This modified differential display technique can be of general application to other plant systems where cloning of the different members of a gene family is desired.
We have modified the differential display technique to isolate 3' regions from different members of the wheat HSP70 gene family. An HSP70 gene family-specific degenerate primer was used as a 5' primer in place of the arbitrary primer used in the original technique. We cloned and sequenced three cDNA fragments that were differentially expressed in heat stressed wheat seedlings. Based on the high similarity between predicted translation products of these three sequences and known members of the HSP70 family from plants, these cDNAs were identified as members of the HSP70 gene family. Two of these members appeared distinct in the 3' non-coding region with only 48% identity. Therefore differential display could successfully be used to isolate 3' regions of different members of a multigene family in a relatively short period, even if the members had highly similar protein-coding regions.
A major issue for health reform is the equitable distribution of health services. Equity in the use of services depends in large part on the distribution of need for services, in addition to availability, accessibility, affordability, and acceptability of the services. The present paper focuses on one set of indicators of need, the disability data reported in the 1990 U.S. Census of Population and Housing for 14 southern states. The Census data on work limitation, inability to work, physical mobility, and ability to perform routine personal care show differentials for subpopulations defined by rural versus urban areas within levels of poverty, age, sex, education, and ethnic group. Highest rates of work disability are found for rural, female, elderly, less educated, African-American, and below poverty level populations. The implications of such findings for health care reform suggest that there should be greater access to services by populations of greater identified need. Historically, the opposite has been true, perhaps exacerbating the observed differentials in need.
PURPOSE: W examined the anatomy of the ejaculatory ducts in normal men and correlated findings with theories of ejaculatory duct obstruction. MATERIALS AND METHODS: Gross and microscopic anatomical studies were performed on cadaveric and operative specimens derived from radical prostatectomy. RESULTS: Histologically, the ejaculatory ducts are a continuation of the seminal vesicles. However, the thick muscle wall of the seminal vesicle is not present within the ejaculatory duct. Normal ejaculatory duct luminal and wall dimensions are remarkably uniform among men. A luminal diameter of greater than 2.3 mm. defines a dilated system statistically. CONCLUSIONS: The largely collagenous ejaculatory ducts may serve as simple semen conduits instead of muscular tubes with spasmodic, sphincteric or peristaltic properties. The anatomical findings presented suggest several possible mechanisms for the prevention of urinary reflux into the ejaculatory ducts.
The reliability of diagnosing mood disorders is reviewed for previous and current versions of the American Psychiatric Association's DMS. Reliability is shown to improve with the increasing specificity of diagnostic criteria. The new specifiers for the course of major depression in relation to dysthymia also are shown to be reliable.
mef2 encodes the only apparent Drosophila homolog of the vertebrate myocyte-specific enhancer factor 2 (MEF2). We show herein that the Drosophila MEF2 protein is expressed throughout the mesoderm following gastrulation. Later in embryogenesis, its expression is maintained in precursors and differentiated cells of the somatic and visceral musculature, as well as the heart. We have characterized genetic deficiencies and EMS-induced point mutations that result in complete loss of MEF2 protein in homozygous mutant embryos. These embryos exhibit a dramatic absence of myosin heavy chain (MHC)-expressing myoblasts and lack differentiated muscle fibers. Examination of earlier events of muscle development indicates that the specification and early differentiation of somatic muscle precursors are not affected because even-skipped-, nautilus-, and beta 3-tubulin-expressing myoblasts are present. However, these partially differentiated cells are unable to undergo further differentiation to form muscle fibers in the absence of mef2. The later aspects of differentiation of the visceral mesoderm and the heart are also disrupted in mef2 mutant embryos, although the specification and early development of these tissues appear unaffected. Midgut morphogenesis is disrupted in the mutant embryos, presumably as a consequence of abnormal development of the visceral mesoderm. In the heart, the cardial cells do not express MHC. These results indicate that MEF2 is required for later aspects of differentiation of the three major types of musculature, which include body wall muscles, gut musculature, and the heart, in the Drosophila embryo.
5' untranslated leaders (5' UTLs) are suggested to play a crucial role in the selective translation of their eukaryotic mRNAs encoding heat shock proteins (HSP) during heat stress conditions. However, the structural features of the HSP mRNAs which cause this effect are mostly unknown. We have compiled the 5' UTLs from about 140 eukaryotic HSP mRNAs including vertebrates, invertebrates, higher and lower plants. A detailed analysis of these sequences according to length, A+T content, context of functional ATGs and presence of upstream non-functional ATGs was made. We observed that all these features were similar to the earlier studies in the literature based on data from HSP as well as non-HSP mRNAs. These observations were reconfirmed by intra-specific comparison of 5' UTLs from HSP and non-HSP genes. Similar to the translation element involved in the selective translation of mRNAs in polioviruses, a search for a short sequence motif complementary to highly conserved 18S rRNA was performed using a HSP mRNA database. The majority of the HSP mRNA sequences (77%) contained one or more small sequence motifs suggesting that they may function as internal ribosome entry sites for selective initiation of translation during heat stress.
This article highlights some of the research in cardiac molecular biology in progress in the Department of Cardiology at Children's Hospital. It provides a sampling of investigative approaches to key questions in cardiovascular development and function and, as such, is intended as an overview rather than a comprehensive treatment of these problems. The featured projects, encompassing four different "model" systems, include (1) genetic analysis of the mef2 gene required for fruit fly cardial cell differentiation, (2) cardiac-specific homeobox factors in zebrafish cardiovascular development, (3) mouse transgenic and gene knockout models of cardiac potassium ion channel function, and (4) mapping and identification of human gene mutations causing long QT syndrome.
This study was designed to assess whether the experience of passionate love would change as a consequence of development throughout adulthood and whether highly anxious people would be especially motivated to seek passionate love relationships. The Passionate Love Scale and the State-Trait Anxiety Inventory were administered to a cross-generational sample (total N = 255) of adolescents, young adults, middle-aged adults, and elderly in the United States. Status of past and present relationships was also determined. Contrary to expectations, no age-related differences were found for overall PLS scores. Moreover, the anticipated correlation between anxiety and passionate love was found only in the adolescent sample. A regression analysis revealed that for all age groups, whether or not a person was currently experiencing a passionate love relationship was the best predictor of scores on the PLS. These findings suggest a reconceptualization of passionate love as a life-span construct, rather than as a phenomenon largely confined to the period of adolescence.
A young, otherwise healthy man was hospitalized with clinical findings of acute retroperitoneal hemorrhage. Radiographic evaluation suggested a large bleeding renal mass that was thought to be renal cell carcinoma. Radical nephrectomy was performed after angio-embolization. Final pathological diagnosis was grade III transitional cell carcinoma of the renal pelvis invading the renal parenchyma. Distal ureterectomy was subsequently performed 12 days after nephrectomy. Preoperative or intraoperative diagnosis of transitional cell carcinoma would have spared our patient the morbidity of a delayed second procedure. Transitional cell carcinoma of the renal pelvis should be considered in the differential diagnosis of acute retroperitoneal hemorrhage.
A single honey bee mariner transposon (TnM1a) was sequenced, revealing a transpositionally non-autonomous element of 937 bp delimited by 30 bp perfect inverted terminal repeats. The element is flanked by the TA duplication typical of mariner elements in general. There are approximately 435 copies of TnM1a homologous elements per haploid genome. These elements appear, by Southern blot analysis, to be dispersed throughout the genome. Thirteen individual genomic clones with an average size of 15 kb, were found to contain only a single element each, which also suggests that the elements are not tightly clustered. Finally, mariner elements are neither inactivated by methylation nor sequestered into a methylated fraction of the genome.
The management of blunt renal trauma has evolved due to advances in clinical and radiographic staging. Careful clinical evaluation and the selective use of intravenous urography (IVU) and computed tomography (CT) have allowed many patients with major renal injuries to undergo surveillance, rather than renal exploration, with low morbidity. This article reviews the current diagnosis, staging, and management of adult and pediatric blunt renal trauma and describes the technique for renal exploration and repair.
One-hundred-and-four cases of histopathologically confirmed hydatiform moles were subjected to ultrasound examination at the Hung Vuong Hospital, Ho-Chi-Minh-ville (Vietnam) over a period of 16 months (1988-1989). The diagnosis was confirmed only in some cases on clinical grounds (18%) or by laboratory tests (52%). In contrast, typical ultrasound signs were found in 82% of cases; in the other 18% of cases, other aspects had suggested disorders calling for aspiration (partial mole, clear ovum, pregnancy terminated). Some ultrasound images, highly suggestive of mole, were found in occasional cases of mucoid ovarian cyst, endometrial cancer or cystic necrobiosis of fibroma (HCG tests negative). Despite its limitations in Vietnam ultrasound constitutes the primary method of detecting hydatiform mole, the acquisition of practical experience is facilitated by the high number of cases and the concentration of cases reported.
We have identified a mesoderm-specific Drosophila gene, designated D-mef2. The encoded protein contains the MADS- and MEF2-specific domains, which are characteristic of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. D-mef2 RNA is first detectable in the presumptive mesoderm at late cellular blastoderm stage and is expressed in all mesoderm after invagination. Following the dorsal migration of the mesodermal layer, D-mef2 expression becomes restricted to the primordia for visceral muscle and the heart. In the second phase, D-mef2 expression is first distinct in heart precursors and then becomes prominent sequentially in visceral and somatic muscles. twi activity is required for D-mef2 expression, while sna function may be needed for the maintenance of D-mef2 expression but not its initiation. D-mef expression is not dependent on the function of tin, and embryos that are deficient for the mesodermal gene DFR1 also show normal initiation of D-mef2 expression at blastoderm. These results suggest that D-mef2 could have a function in early mesoderm differentiation and may be required for subsequent cell fate specifications within the somatic and visceral/heart mesodermal layers.