Clinical pharmacy and pediatrics: why focus on antibiotics?
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Anti-Bacterial Agents↗
Biomedical subjects
B T Nguyen
Publications and source records attributed to B T Nguyen.
Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.
Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.
Algorithms↗
An association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome.
PURPOSE: To describe an association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome. METHODS: Case series, describing three patients. RESULTS: In two patients, the disorders had their onsets within 2 weeks of each other; in the third patient, Vogt-Koyanagi-Harada disease occurred after 3 months, as Guillain-Barré syndrome resolved. All three patients had bilateral panuveitis typical of Vogt-Koyanagi-Harada disease. Each also developed well-accepted manifestations of Guillain-Barré syndrome, including paresis of the lower extremities (all patients), paresis of the upper extremities (two patients), paresis of cranial nerves (two patients), areflexia (all patients), and abnormal electromyography findings (two patients). CONCLUSIONS: Vogt-Koyanagi-Harada disease may follow or occur simultaneously with Guillain-Barré syndrome. The fact that these two autoimmune disorders occur together in some patients suggest that they may share common disease mechanisms.
Adult↗
Computed tomography diagnosis of thoracic aortic aneurysms.
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Aneurysm, False↗
Tissue-specific expression of antisense and sense transcripts at the imprinted Gnas locus.
The mouse Gnas gene encodes an important signal transduction protein, the alpha subunit of the stimulatory G protein, G(s). In humans, partial deficiency of G(s)alpha, the alpha subunit of G(s), results in the hormone-resistance syndrome pseudohypoparathyroidism type 1a. The mouse Gnas (and the human GNAS1) locus is transcribed from three promoter regions. Transcripts from P1, which encode Nesp55, are derived from the maternal allele only. Transcripts from P2 encode Xlalphas and are derived only from the paternal allele, while transcripts from P3 encode the alpha subunit and are from both parental alleles. The close proximity of reciprocal imprinting suggests the presence of important putative imprinting elements in this region. In this report, we demonstrate that the reciprocal imprinting occurs in normal tissues of interspecific (Mus spretus x C57BL/6) mice. Transcripts from P1 are most abundant in CNS (pons and medulla) in contrast to the more ubiquitous expression from P2 and P3. In the P1-P2 genomic region, we have identified an antisense transcript that starts 2.2 kb upstream of the P2 exon and spans the P1 region. While the P1 transcript is derived from the maternal allele, the P1-antisense (Gnas-as) is derived only from the paternal allele in most but not all tissues. Although both the Nesp55 region and the Gnas-as transcripts are present in cerebral cortex, adrenal, and spleen, Gnas-as is abundant in some tissues in which transcription from the Nesp55 region is negligible. Furthermore, the Nesp55 region transcripts remain strictly imprinted in tissues that lack Gnas-as. Our results suggest that multiple imprinting elements, including the unique Gnas-as, regulate the allelic expression of the Nesp55 region sense transcript.
Animals↗
Symmetric and asymmetric DNA methylation in the human IGF2-H19 imprinted region.
The two contiguous IGF2 (human insulin-like growth factor II) and H19 genes are reciprocally imprinted in both human and mouse. In most tissues, IGF2 is transcribed only from the paternal chromosome while H19 is transcribed only from the maternal allele. The presence of a differential methylation region (DMR) on the two parental alleles at the 5' flanking region of H19 has been proposed to constitute the gametic imprint, which controls the reciprocal allelic expression of the two genes. Using bisulfite genomic sequencing, we have assessed the methylation status of cytosine (including 154 CpG sites) in six CpG-rich regions of the human IGF2-H19 genes. In a CpG island near promoter P3 of the IGF2 gene, more than 99.8% of all cytosines were converted to thymidine by sodium bisulfite mutagenesis, indicating that none of the CpGs was methylated. In the IGF2 exon 8-9 region, mosaic methylation of 56 CpG sites was observed in fetal tissues and in adult blood DNA. In contrast to the mosaic methylation of IGF2, the allelic methylation of the human H19 DMR was uniform. In the CpG region located 2 kb upstream (-2362 to -1911) of the H19 transcription site, all 25 CpG sites were completely methylated on only one parental allele. Uniform allele-specific methylation was also observed in the CpG island proximal to the H19 promoter (-711 to -290) with complete methylation of all 25 CpG sites in one parental allele. In contrast, the CpG region in the H19 promoter (-292 to +15) was mosaically methylated in all tissues. In addition, cytosine was methylated at three CpNpG and GpNpC sites on the top DNA strand and one CpNpG site on the bottom DNA strand from the fetal brain. The cytosines at CpG sites were methylated on both DNA strands (symmetric methylation) while cytosines at the CpNpG and GpNpC sites were methylated on only one DNA strand (asymmetric methylation). The asymmetric methylation was associated with tissue-specific disruption of H19 genomic imprinting in fetal brain.
Adult↗
Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation.
Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala (BLA) block the enhancing effects of posttraining systemic or intrahippocampal glucocorticoid administration on memory for inhibitory avoidance training. The present study further examined the basis of this permissive influence of the BLA on hippocampal memory functioning. Immediate posttraining unilateral infusions of the specific glucocorticoid receptor agonist RU 28362 (11beta,17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20-yn-3-one; 3.0, 10.0, or 30.0 ng in 0.5 microliter) administered into the dorsal hippocampus of male Sprague-Dawley rats induced dose-dependent enhancement of 48-h inhibitory avoidance retention. Infusions of the beta-adrenoceptor antagonist atenolol (0.5 microgram in 0.2 microliter) into the ipsilateral, but not the contralateral, BLA 10 min prior to training blocked the hippocampal glucocorticoid effects on memory consolidation. Infusions of the muscarinic cholinergic antagonist atropine (0.5 microgram in 0.2 microliter) into either the ipsilateral or contralateral BLA before training did not block the hippocampal glucocorticoid effects. These findings provide further evidence that beta-adrenergic activity in the BLA is essential in enabling glucocorticoid-induced modulation of memory consolidation and are consistent with the hypothesis that the BLA regulates the strength of memory consolidation in other brain structures. The ipsilateral nature of the BLA-hippocampus interaction indicates that BLA influences on hippocampal memory processes are mediated through neural pathways rather than by influences by means of the activation of peripheral stress responses.
Amygdala↗
Lack of reciprocal genomic imprinting of sense and antisense RNA of mouse insulin-like growth factor II receptor in the central nervous system.
Two models have been proposed to account for the molecular mechanism underlying genomic imprinting of the insulin-like growth factor II receptor gene (Igf2r): expression-competition and promoter DNA methylation. To examine which model best explains the regulation of Igf2r imprinting, we examined the allelic expression of endogenous Igf2r sense and antisense RNAs in mice. In peripheral tissues, Igf2r sense and antisense RNAs show a reciprocal pattern of imprinting and DNA methylation between the two parental alleles: the sense RNA is monoallelically expressed only from the maternal promoter which is unmethylated in region 1, and the antisense RNA is derived solely from the paternal promoter which is unmethylated in region 2. The paternal promoter of sense Igf2r and the maternal promoter of antisense Igf2r are hypermethylated and are transcriptionally suppressed. In CNS, the genomic imprinting of Igf2r sense and antisense RNAs is uncoupled: both parental promoters of Igf2r gene coding for sense RNA are unmethylated and are biallelically used for transcription. In contrast, antisense RNA of Igf2r is derived only from the paternal allele that is unmethylated in region 2, while the methylated maternal allele is silent. Uncoupling of genomic imprinting of Igf2r sense and antisense RNAs in CNS correlates with DNA methylation of the appropriate promoter region, thus favoring the model of DNA methylation over that of antisense as the chief regulator of Igf2r genomic imprinting.
Alleles↗
[Hematopoietic recovery as a function of the number of autografted CD34+ cells: a retrospective study of 66 patients with malignant hematologic diseases].
Engraftment in relation to infused CD34+ cell number was retrospectively analysed in 66 patients with hematological diseases: non-Hodgkin's lymphoma (n = 33), multiple myeloma (n = 21), acute myelogenous leukemia (n = 7), Hodgkin's disease (n = 4) and myelodysplastic syndrome (n = 1). Progenitor cells were mobilized with rhG-CSF, alone or in association with chemotherapy. The cells were harvested by leukapheresis until at least 2 x 10(6) CD34+/kg body weight were obtained. A total of 194 leukaphereses were performed (median = 3 per patient, range 1-9). A median of 3.40 x 10(8) nucleated cells/kg (range 0.31-27.59) and a median of 7.15 x 10(6) CD34+ cell/kg (range 1.31-115.70) were transplanted. Regardless of transfusional support or patient diagnosis, engraftment was rapid in patients who had received > or = 5 x 10(6) CD34+ cell/kg. In this case, absolute neutrophil blood count > or = 0.5 x 10(9)/l was obtained on day 12 post graft (range 7-19) and platelet count > or = 20 x 10(9)/l was also reached after the same median time interval (range 8-121). From the present results, a minimal threshold of 5 x 10(6) CD34+ cell/kg appears to be suitable for providing rapid and complete hematopoieitc reconstitution in patients exposed to high doses of chemotherapy with or without total body irradiation. Furthermore, administration of rhG-CSF during post-graft period significantly decreased the neutrophil time recovery (P = 0.002) but not that of platelets (P > 0.05).
Acute Disease↗
Multiple brain atlas database and atlas-based neuroimaging system.
For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.
Anatomy, Artistic↗
Inhibition of junction assembly in cultured epithelial cells by hepatocyte growth factor/scatter factor is concomitant with increased stability and altered phosphorylation of the soluble junctional molecules.
Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived glycoprotein with a strong scattering effect on epithelial cells. A receptor tyrosine kinase encoded by the met proto-oncogene has been identified as the cellular receptor for HGF/SF. Following stimulation with HGF/SF, cell scattering occurs concurrent with decreased cell-cell adhesion and disassembly of junctional components. In culture, junction formation is cell-cell contact dependent and can be regulated by modulating the Ca2+ concentrations of the growth media. Decreasing the Ca2+ concentrations below 50 microM causes rapid disassembly of junctions, whereas increasing the Ca2+ concentrations to 1.8 mM induces cell-cell contact and junction assembly. Although associated with decreased cell-cell adhesion and disassembly of the junctional complex, HGF/SF-induced scattering occurs under high extracellular Ca2+ concentrations. To gain insight into the mechanisms of HGF/SF-induced scattering of epithelial cells, we have studied the effect(s) of HGF/SF on junction assembly by examining the solubility, stability, phosphorylation, and subcellular localization of the major components of the adhering junctions, plakoglobin (Pg) and E-cadherin, in Madin-Darby canine kidney (MDCK) epithelial cells and in a MDCK cell line expressing an exogenous chimeric met receptor (CSF-MET) that scatters in response to colony-stimulating factor 1 (CSF-1). The results have shown that in HGF/SF-stimulated MDCK cells, adhering junctions were not assembled upon induction of cell-cell contact. Immunofluorescence analyses showed that larger amounts of Pg and E-cadherin were Triton X-100 extractable, and more significantly, these proteins were homogeneously distributed along the membrane and were not concentrated at the areas of cell-cell contact. Similar results were obtained for CSF-MET expressing MDCK cells in response to CSF-1. In contrast, none of the above effects were detected in MDCK cells expressing a mutant CSF-MET chimera containing a phenylalanine substitution at tyrosine 1356 in met, which fails to scatter in response to CSF-1. When compared with the unstimulated cells, the inhibition of cell adhesion promoted by HGF/SF correlated with an increased stability of the newly synthesized soluble E-cadherin and Pg and an altered phosphorylation pattern of E-cadherin, as determined by partial proteolytic peptide mapping.
Animals↗
Human T-lymphotropic virus type II infection in Vietnamese thalassemic patients.
Anti-human T-lymphotropic virus type I/II (HTLV-I/II) antibodies were screened by particle agglutination test in a total of 66 patients with thalassemia major who received multiple transfusion from paid donors at the Blood Transfusion Hematology Center of Ho Chi Minh City in South Vietnam. HTLV-II infection was confirmed in 6 patients (9.1%) by Western blot analysis and/or polymerase chain reaction. Phylogenetic analysis revealed that long terminal repeat sequences of HTLV-II proviruses from 5 thalassemic patients in Vietnam belonged to the same phylogenetic subgroup of HTLV-IIb as those from intravenous drug abusers in North America and Europe. These data shed light on the route of introducing HTLV-II into Vietnam.
Adolescent↗
In situ hybridization to chromosomes stabilized in gel microdrops.
Conventional chromosome in situ hybridization procedures rely on fixation to glass slides followed by microscopic evaluation. This report describes the development of a microdrop in situ hybridization to chromosomes in suspension. Chromosomes encapsulated in gel microdrops (GMDs) composed of an agarose matrix withstood stringent hybridization and denaturation conditions. Because of the increased stability, hybridization to encapsulated chromosomes was detected by flow cytometry as well as conventional microscopy. Thus, the MISH method offers a means for chromosome hybridization without slides and may enable identification and isolation of chromosome using hybridization rather than nucleic acid binding dyes.
3T3 Cells↗
Rapid assay for mycobacterial growth and antibiotic susceptibility using gel microdrop encapsulation.
Effective control of tuberculosis transmission in vulnerable population groups is dependent on rapid identification of the infectious agent and its drug susceptibility. However, the slow growth rate of mycobacteria has undermined the ability to quickly identify antimicrobial resistance. These studies describe a mycobacterial growth assay based on microencapsulation technology used in conjunction with flow cytometric analysis. Mycobacteria were encapsulated in agarose gel microdrops approximately 25 microns in diameter, and colony growth was monitored by using flow cytometry to evaluate the intensity of auramine staining after culture for various times at 37 degrees C. By this method, colony growth of Mycobacterium bovis and M. smegmatis could be quantified within 1 to 3 days after encapsulation. Inhibition of growth by rifampin and isoniazid was also evaluated in this time period, and the presence of an isoniazid-resistant subpopulation representing 3% of the total microorganisms could be detected. This use of encapsulation and flow cytometry has the potential to facilitate rapid and automated evaluation of inhibition of growth by antimicrobial agents and shorten the time frame for analysis of clinical specimens.
Bacteriological Techniques↗
Cervical thorium dioxide granuloma ('thorotrastoma').
An elderly woman had an expanding cervical mass that entrapped and compressed the adjacent cranial nerves, blood vessels, and muscles. The mass was dense on radiographs, extended from the skull base to low neck in the prevertebral and parapharyngeal tissues, and showed mixed intensity on MR. A previous direct carotid arteriogram with thorium dioxide as the contrast agent suggested the histologically proved diagnosis of a cervical thorium dioxide granuloma ("thorotrastoma").
Diagnosis, Differential↗
Factors affecting in vitro growth of harvested enterocytes.
Selective enterocyte transplantation may be an alternative to whole organ transplantation for increasing absorptive capacity. Our aim was to determine the effect of initial cell number and viability, proportion of intact crypts, and basement membrane components (BMC) on the in vitro growth of rabbit enterocytes. Enterocytes were harvested using warm trypsinization from ileal segments in 40 rabbits. Initial cell viability was 92 +/- 4% (mean +/- SD), cell yield was 7.7 +/- 3.6 x 10(6) cells/cm, and there were 0.51 +/- 0.33 crypts/100 cells. Initial cell viability correlated with cell yield (r = -0.508, p < 0.001) and % crypts (r = 0.313, p < 0.05). Cell yield also correlated with % crypts (r = -0.645, p < 0.001). Enterocytes (5 x 10(6)) were incubated in growth media in plain or BMC coated growth culture vessels for 14 days. There was a correlation between both number of cells seeded (r = 0.824, p < 0.001) and cell viability (r = -0.696, p < 0.01) and % growth colonies containing epithelial cells at 14 days. Both total growth colonies (r = -0.565, p < 0.05) and colonies with epithelial cells (r = -0.589, p < 0.05) had a negative correlation with % crypts. Incubating cells in BMC coated vessels (n = 6) resulted in significantly more dispase liberated cells after 14 days than in plain vessels (n = 6) (6.6 +/- 1.1 vs. 3.8 +/- 1.0 x 10(6), p < 0.05) but viability was similar (97 +/- 2% vs. 96 +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS)
Amine Oxidase (Copper-Containing)↗
Comparison of appendectomy at a Veterans Administration Medical Center and affiliated university hospital.
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Adolescent↗
Comparison of ulcer surgery at a Veterans Administration and University Hospital.
We compared the patient populations and outcome of surgery for peptic ulcer disease in 81 patients at a Veterans Administration Hospital (OVAH) and 97 patients at an affiliated University Hospital (UNH). The surgeons and choice of operation were comparable at both facilities. Patients were similar with respect to severity of ulcer disease, percentage of elderly patients and distribution of comorbid conditions. There were significantly more female patients (45% vs 2%, P less than 0.05), patients less than 40 years old (22% vs 6%, P less than 0.05), and patients with gastric ulcers (27% vs 12%, P less than 0.05) at UNH. Alcoholism was more prevalent at OVAH (57% vs 22%, P less than 0.05). Postoperative morbidity and mortality rates were 27 per cent and 14 per cent at OVAH and 25 per cent and 16 per cent at UNH. These data suggest that quality of care for surgical therapy of ulcer disease at a VA Hospital is comparable to its tertiary care affiliate with a similar patient population.
Adult↗