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H Dang

Publications and source records attributed to H Dang.

At least 19 recordsLinked to original sources
PubMed2007

The postnatal maternal environment influences diabetes development in nonobese diabetic mice.

When nonobese-diabetic (NOD) mouse embryos were implanted into pseudopregnant mothers of a nonautoimmune mouse strain, the progeny had a reduced type 1 diabetes (T1D) incidence, suggesting that transmission of maternal autoantibodies is important for T1D development. Whether eliminating islet autoantibody transmission in utero, or postnatally (through milk), prevented T1D is unknown. Herein, we show that fostering newborn NOD mice on B-cell deficient NOD.Igmu-/- dams does not prevent T1D, demonstrating that postnatally transmitted islet autoantibodies are not required for disease pathogenesis. Additionally, NOD.Igmu-/- mice reared on NOD dams did not develop T1D, indicating that autoantibody transmission to B-cell deficient NOD neonates is insufficient to trigger T1D. Interestingly, newborn NOD mice that were reared by ICR (but not NOD or C57BL/6) dams had reduced T1D incidence, although not as reduced as that reported after embryo transfer to ICR mice, suggesting that both prenatal and postnatal factors contribute to the observed reduction in T1D incidence. Thus, NOD mice have different risks for developing T1D depending on the strain of their foster mother, and both prenatal and postnatal maternal factors, other than islet autoantibodies, influence their T1D incidence. The results may be relevant for understanding the increasing incidence of T1D and designing interventions.

Animals↗
PubMed2006

Identification of distal KIR promoters and transcripts.

A more complete understanding of the transcriptional control of the human and murine class I MHC receptors will help to shed light on the mechanism of selective, stochastic, gene activation that operates in these gene families. Studies of the murine Ly49 class I MHC receptor genes have revealed an important role for distal transcripts originating upstream of the proximal promoter. To date, there have been no reports of distal promoters within the functionally analogous human KIR family of class I MHC receptors. In the current study, reverse transcriptase-polymerase chain reaction (RT-PCR) and RNase protection assays were used to reveal the presence of distal KIR transcripts initiating upstream of the previously characterized proximal KIR promoter. The intergenic promoter elements detected were associated with repetitive elements of the Alu and L1 families. Unlike the proximal KIR promoter, the distal promoter regions were not NK cell-specific. KIR genes expressed in a variegated manner produced a low level of distal transcripts containing a large 5' untranslated region. In contrast, the highly expressed KIR2DL4 gene possessed a higher level of spliced distal transcripts that were capable of producing KIR2DL4 protein. The identification of distal KIR promoter elements suggests that intergenic transcripts may influence the expression of KIR genes.

Cell Line↗
PubMed2002

Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for Sjögren's syndrome.

OBJECTIVE: Apoptosis is an organized energy-dependent process of cellular self-destruction carried out by proteolytic enzymes such as the caspases. These enzymes may play a role in epithelial cell apoptosis in Sjögren's syndrome (SS). A classical caspase substrate is poly(ADP-ribose)polymerase (PARP), a DNA repair enzyme. To elucidate the molecular mechanisms responsible for salivary gland dysfunction in SS, we studied the expression of caspase and PARP in SS salivary gland biopsies. METHODS: The presence of activated caspases (caspases 3 and 9) and cleaved PARP (85 kDa) in SS biopsies was demonstrated by immunohistochemistry using specific polyclonal antibodies. RESULTS: Initial studies performed with an antibody reagent that recognizes both active and inactive forms of caspase 3 identified this enzyme in SS salivary ductal and acinar cells. Activated caspase 3 and cleaved PARP were strongly expressed in ductal and acinar cells in SS salivary glands (13/15). Ductal and acinar cells from normal salivary glands (n=5) stained with less intensity compared with SS tissue. Staining for activated caspase 9 was negative in all samples. Likewise, infiltrating lymphocytes were negative for caspase 3, caspase 9 and cleaved PARP. CONCLUSION: This study shows that caspase 3 is important in the salivary dysfunction of SS, while caspase 9 appears not to be involved.

Apoptosis↗
PubMed2001

Steps to demarcate the effects of chromophore aggregation and planarization in poly(phenyleneethynylene)s. 2. The photophysics of 1,4-diethynyl-2-fluorobenzene in solution and in crystals.

Crystals of 1,4-bis(2-hydroxy-2-methyl-3-butynyl)-2-fluorobenzene 4 have a rich packing structure with four distinct molecules in the unit cell. A complex hydrogen bonding network results in the formation of cofacial trimers, cofacial dimers, and monomers within the same unit cell. Given a remarkable opportunity to investigate the effect of aggregation on the photophysics of 1,4-diethynylbenzenes, we analyzed the absorption, diffuse reflectance, and emission spectra of compound 4 in solutions and in crystals. Diffuse reflectance and fluorescence excitation revealed a red-shifted absorption that is absent in dilute solution but becomes observable at high concentrations and low temperatures. The fluorescence emission in the solid state is dual with components assigned to monomers and aggregates. The excitation and emission assigned to the monomer are nearly identical in crystals and dilute solutions. The absorption and emission bands assigned to aggregates are broad and red-shifted by 60--80 nm. As expected for a sample with absorbers and emitters with different energies and incomplete equilibration, efficient monomer-to-aggregate energy transfer was observed by a proper selection of excitation wavelengths. The fluorescence quantum yield of 4 in solution is relatively low (Phi(F) = 0.15) and the singlet lifetime short (tau(F) = 3.8 ns). A lower limit for the triplet yield of Phi(T) = 0.64 was determined indirectly in solution by (1)O(2) sensitization, and a relatively strong and long-lived phosphorescence was observed in low-temperature glasses and in crystals at 77 K.

Journal Article↗
PubMed2001

Functional pleiotropy of an intramolecular triplex-forming fragment from the 3'-UTR of the rat Pigr gene.

A microsatellite-containing 359-bp restriction fragment, isolated from the rat Pigr gene (murine polymeric immunoglobulin receptor gene) 3'-untranslated region (3'-UTR) and inserted into 3'-UTR or 3' flanking positions in transcription units of supercoiled plasmids, attenuates luciferase reporter gene expression in orientation- and position-dependent ways following transient transfection of human 293 cells. The same fragment stimulates orientation-dependent gene expression in a 5' flanking position. Plasmid linearization abrogates both orientation- and position-dependent responses. Cell-free translation reveals that 5' and 3' flanking expression responses are proportional to increased and decreased luciferase mRNA levels, whereas 3'-UTR expression is associated with control mRNA levels. Hypersensitivity to nucleases S1 and P1, gel mobility differences between supercoiled plasmids carrying opposing microsatellite orientations, and anomalous melting profiles of this fragment are also observed. These results suggest that functional pleiotropy of this fragment depends on the DNA context of its purine-rich microsatellite strand and on DNA supercoiling. Intramolecular triplexes stabilized by supercoiling and secondary structures of purine repeat-rich mRNAs may also confer regulatory properties to similar genomic elements.

3' Untranslated Regions↗
PubMed2001

Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

Animals↗
PubMed2001

Elevated proapoptotic Bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome.

OBJECTIVE: Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NODscid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-xL, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. METHODS: Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohistochemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. RESULTS: Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. CONCLUSION: These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.

Animals↗
PubMed2001

Fas-mediated apoptosis in a rat acinar cell line is dependent on caspase-1 activity.

Apoptosis plays an important role in the dysfunction of exocrine glands. Fas is a death-inducing receptor found on many types of cells including epithelial acinar cells. To elucidate the intracellular mechanism of Fas-mediated cell death in exocrine glands, an epithelial acinar cell line, SMG-C6, was studied. Caspase-1, -3, -8, and -9 activities were elevated in SMG-C6 cells after the induction of apoptosis by soluble Fas ligand (FasL). The activation of caspase-1 and -8 occurred prior to caspase-3 and -9 activation. The caspase-1 inhibitor, zYVAD-fmk, was effective in preventing cell death, whereas the caspase-3 and -8 inhibitors (ac-DEVD-CHO and ac-IETD-CHO, respectively) were not. zYVAD-fmk was able to inhibit caspase-3 activation indicating that caspase-1 is upstream to caspase-3. Furthermore, kinetic studies show that caspase-1 is an early event in the Fas apoptotic pathway. This study shows that caspase-1 participates in Fas-mediated apoptosis of epithelial cells by initiating the caspase cascade.

Animals↗
PubMed2001

TGF-beta1 null mutation leads to CD154 upregulated expression in affected tissues.

The TGF-beta1(-/-) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-beta1(-/-) mice. Heart, lung, liver, and salivary gland from TGF-beta1(-/-) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-beta1(-/-) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-beta1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.

Animals↗
PubMed2001

Effects of radiation on Ca2+ signaling in salivary epithelial cell lines transfected with Bcl-2 and Bcl-XL.

The effects of radiation on the Ca2+ signaling system in HSY cells transfected with the Bcl-2 or Bcl-XL gene were studied. Bcl-2 overexpression did not alter carbachol (CCh)-elicited initial increase in cytosolic free Ca2+ concentrations ([Ca2+]i), but Bcl-XL overexpression dramatically reduced this response. Exposure to 10 Gy gamma-ray did not alter basal [Ca2+]i. By contrast, the CCh-stimulated initial [Ca2+]i increase was reduced at 0.5 and 4 h post-irradiation in all cell types and remained decreased at 24 h in wild-type and control-transfected cells, but recovered in Bcl-2- and Bcl-XL-transfectants. The formation of inositol 1,4,5-trisphosphate (IP3) in response to CCh at 4-h post-irradiation was decreased in wild-type and control-transfected cells, but not in Bcl-2 and Bcl-XL transfectants. The capacity of the IP3-sensitive Ca2+ store was significantly reduced by radiation in all cells except Bcl-XL transfectants. Ca2+ influx after stimulation with CCh was suppressed by exposure to radiation in wild-type and control-transfected cells, but not in Bcl-2- and Bcl-XL-transfectants. However, radiation enhanced Ca2+ influx activated by thapsigargin in all cell types. These results suggest that 1) radiation diminishes IP3 formation and Ca2+ release in response to CCh, but potentiates the store-operated Ca2+ influx; and 2) overexpression of Bcl-2 or Bcl-XL partially protects cells from radiation-induced inhibition of Ca2+ signaling.

Adenocarcinoma↗
PubMed2001

[On cleanliness of hands in diminution of Ascaris lumbricoides infection in children].

OBJECTIVE: To study the relationship between cleanliness of children's hands and diminution of Ascaris lumbricoides infection. METHODS: Before the study all persons positive for ascaris eggs in the preliminary survey were treated with albendazole. Hand-washing habit before meal and after defecation was kept in children of experimental group, but not in the control group. Kato thick smear stool examination was done once every two months for one year to compare the new infection rates in children without ascaris infection in the two groups, and the reinfection rates in the cured negative cases were also compared between them in half a month after chemotherapy. RESULTS: All the new infection rates as well as reinfection rates of each reexamination in the experimental group were significantly lower than that of the control group (P < 0.001). Reexamination one year later showed that the ascaris infection rate of the experimental group was 35.2%, reducing by 48.5% as compared with 68.3% before the operation of the project; while ascaris infection rate of the control group was 73.7%, increasing by 78.0% as compared with 41.4% before the operation of the project. CONCLUSION: Washing hands with toilet soap to keep hands clean can significantly reduce ascaris infection rate.

Ascariasis↗
PubMed2000

The status of immunization measurement and feedback in the United States.

BACKGROUND: A large body of scientific and programmatic data has demonstrated that provider measurement and feedback raises immunization coverage. Starting in 1995, Congress required that all states measure childhood immunization coverage in all public clinics, and federal grant guidelines encourage private practice measurements. OBJECTIVES: To determine state immunization measurement rates and examine risk factors for high rates. METHODS: Review of 1997 state reports, with correlation of measurement rates to birth cohort and provider numbers, public/private proportions, and vaccine distribution systems. RESULTS: Of the 9505 public clinics, 48% were measured; 4 states measured all clinics; 29 measured a majority. Measurement rates were highest for Health Department clinics (67%), lower for community/migrant health centers (39%), and lowest for other clinics (22%). Rates were highly correlated among categories of clinics (r>+0.308, P<.03), and the fewer the clinics, the higher the measurement rates (r = -0.351, P =. 01), but other factors were not significant. Of the 41,378 private practices, 6% were measured; no state measured all its practices; 1 measured a majority. Private practice measurement rates were not correlated to public clinic measurement rates or other factors examined. Of the 50,883 total providers, 14% were measured; no state measured all providers; 2 measured a majority. A trend toward higher measurement rates was found in states with fewer providers (r = -0. 266, P =.06). CONCLUSIONS: Three years after the congressional mandate, only a minority of public clinics and very few private practices had their immunization coverage measured. Greater efforts will be needed to assure implementation of the intervention. Arch Pediatr Adolesc Med. 2000;154:832-836

Child↗
PubMed2000

G-protein signaling abnormalities mediated by CD95 in salivary epithelial cells.

Salivary epithelial cells from patients with primary Sjögren's syndrome (SS) undergo Fas-mediated apoptosis. Bcl-2 and Bcl-xL are apoptosis suppressing oncogenes. Very little is known about the role of these oncogene molecules in salivary epithelial cells. To investigate the possible prevention of salivary glandular destruction in SS by Bcl-2 and Bcl-xL, stable transfectants expressing these molecules were made from HSY cells, a human salivary epithelial cell line. HSY cells were transfected with an expression vector for human Bcl-2 or Bcl-xL. Stable transfectants were selected and apoptosis was induced by anti-Fas antibody. Apoptosis was quantified by propidium iodide staining followed by flow cytometry. Caspase activity was detected by immunohistochemical analysis and enzyme cleavage of DEVD-AMC, a fluorescent substrate. Response to carbachol, a muscarinic receptor agonist, and EGF was measured by Ca2+ mobilization and influx. Fas-mediated apoptosis was significantly inhibited in Bcl-2 and Bcl-xL transfectants compared to wild-type and control transfectants (empty vector). Surprisingly, caspase activity was not inhibited in Bcl-2 and Bcl-xL transfectants. Activation of the Fas pathway in the Bcl-2 and Bcl-xL transfectants by antibody also inhibited carbachol and EGF responsiveness (i.e., Ca2+ mobilization and/or influx) by 50-60%. This Fas-mediated inhibition of cell activation was partially or completely restored by specific peptide interference of caspase enzyme activity. The prevention of Fas-mediated apoptosis by the overexpression of Bcl-2 and Bcl-xL in salivary gland epithelial cells results in injured cells expressing caspase activity and unable to respond normally to receptor agonists. Such damaged cells may exist in SS patients and could explain the severe dryness out of proportion to the actual number of apoptotic cells seen on salivary gland biopsy.

Apoptosis↗
PubMed2000

Mice homozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor show increased neuronal apoptosis and die within 1 day of birth.

The alpha7 nicotinic acetylcholine receptor (nAChR) has been implicated in modulating neurotransmitter release and may play a role in the regulation of neuronal growth and differentiation. A threonine for leucine 247 substitution in the channel domain of the chick alpha7 nAChR increases agonist affinity and decreases the rate of desensitization, creating a "gain of function" model for this receptor. We have generated mice that express the analogous mutation (L250T) in the alpha7 nAChR using the techniques of homologous recombination and here report their characteristics. Mice heterozygous (+/T) for the L250T mutation are viable, fertile, and anatomically normal compared with wild-type littermates. In contrast, homozygous (T/T) L250T mice die within 2-24 h of birth. Brains of T/T mouse pups exhibit a marked reduction in alpha7 nAChR protein levels and show extensive apoptotic cell death throughout the somatosensory cortex. Furthermore, alpha7 L250T nAChRs are functionally expressed on neurons within the brains of T/T neonatal mice and have properties that are consistent with those observed for the rat alpha7 L250T and the chick alpha7 L247T mutant nAChRs expressed in oocytes. These findings indicate that neurons in the developing brain expressing only alpha7 L250T mutant nAChRs are susceptible to abnormal apoptosis, possibly due to increased Ca2+ influx.

Animals↗
PubMed2000

Bacterial primary colonization and early succession on surfaces in marine waters as determined by amplified rRNA gene restriction analysis and sequence analysis of 16S rRNA genes.

The nearly universal colonization of surfaces in marine waters by bacteria and the formation of biofilms and biofouling communities have important implications for ecological function and industrial processes. However, the dynamics of surface attachment and colonization in situ, particularly during the early stages of biofilm establishment, are not well understood. Experimental surfaces that differed in their degrees of hydrophilicity or hydrophobicity were incubated in a salt marsh estuary tidal creek for 24 or 72 h. The organisms colonizing these surfaces were examined by using a cultivation-independent approach, amplified ribosomal DNA restriction analysis. The goals of this study were to assess the diversity of bacterial colonists involved in early succession on a variety of surfaces and to determine the phylogenetic affiliations of the most common early colonists. Substantial differences in the representation of different cloned ribosomal DNA sequences were found when the 24- and 72-h incubations were compared, indicating that some new organisms were recruited and some other organisms were lost. Phylogenetic analyses of the most common sequences recovered showed that the colonists were related to organisms known to inhabit surfaces or particles in marine systems. A total of 22 of the 26 clones sequenced were affiliated with the Roseobacter subgroup of the alpha subdivision of the division Proteobacteria (alpha-Proteobacteria), and most of these clones were recovered at a high frequency from all surfaces after 24 or 72 h of incubation. Two clones were affiliated with the Alteromonas group of the gamma-Proteobacteria and appeared to be involved only in the very early stages of colonization (within the first 24 h). A comparison of the colonization patterns on the test surfaces indicated that the early bacterial community succession rate and/or direction may be influenced by surface physicochemical properties. However, organisms belonging to the Roseobacter subgroup are ubiquitous and rapid colonizers of surfaces in coastal environments.

Alphaproteobacteria↗
PubMed2000

Probing the role of a conserved M1 proline residue in 5-hydroxytryptamine(3) receptor gating.

A conserved proline residue is found in the first transmembrane domain (M1) of every subunit in the ligand-gated ion channel superfamily. The position of this proline between the N-terminal extracellular agonist binding and the second transmembrane (M2) channel lining domains in the primary sequence suggests its possible involvement in the gating of the receptor. Replacing this proline with alanine, glycine, or leucine in the 5-hydroxytryptamine (5-HT)(3A) homomeric receptors expressed in Xenopus laevis oocytes resulted in the absence of 5-HT-induced whole-cell currents, although there were normal levels of specific surface [(3)H]granisetron ([(3)H]BRL-43694) binding sites. To determine what properties of the conserved proline are critical for the function of the channel, two imino acids and an alpha-hydroxy acid were incorporated at the proline position using the nonsense suppression method. trans-3-Methyl-proline, pipecolic acid, and leucic acid were able to replace the conserved proline to produce active channels with EC(50) values similar to that for the wild-type receptor. These trends are preserved in the heteromeric receptors consisting of 5-HT(3A) and 5-HT(3B) subunits in oocytes. The prominent common feature among these residues and proline is the lack of hydrogen bond donor activity, potentially resulting in a flexible secondary structure in the M1 region. Thus, lack of hydrogen bond donor activity may be a key element in channel gating and may explain the high degree of conservation of this M1 proline.

Animals↗
PubMed2000

[Clinical results of transmyocardial laser revascularization for 77 patients with coronary artery disease].

OBJECTIVE: To analyses the clinical results of transmyocardial laser revascularization (TMLR) for 77 patients with coronary artery diseases (CAD). METHODS: The mean age of the patients was (65 +/- 7) years. Previous medical record included CABG (6 patients), PTCA (9), AMI (66.2%), hypertension (70.1%), and diabetes mellitus (45.5%). TMLR was performed on the beating heart via a left anterolateral thoracotomy at the fifth intercostal space. Transesophageal echocardiography showed transmyocardial penetration of 23 +/- 6 channels. RESULTS: The hospital mortality was 3.8%, and postoperative complications were AMI (3.8%), left ventricular failure (2.6%), PVC (5.2%). After operation, the mean CCS angina class was improved from the baseline 3.5 +/- 0.7 to 2.1 +/- 0.3 at 3 months, 1.7 +/- 0.3 at 6 months, 1.7 +/- 0.3 at 12 months and 1.8 +/- 0.4 at 24 months. One patient died of AMI and two died not due to cardiac events during a follow-up of 3 to approximately 24 months. Echocardiography showed that the average of left ventricular ejection fractions was improved significantly at 6 months after operation compared with the preoperative value (P = 0.0457). (201)TI-SPECT showed a remarkable improvement in reversible ischemia in 70% patients followed up. Metabolic stress test for 20 patients followed up patients demonstrated an average increase in exercise tolerance from 7.1 +/- 3.2 min at the baseline to 9.6 +/- 1.3 min at 12 months (P = 0.021). Similarly the METs increased from 4.3 +/- 2.1 at the baseline to 5.4 +/- 2.0 at 12 months. CONCLUSIONS: TMLR is a safe and effective procedure for the treatment of end stage coronary artery diseases not amenable to PTCA or CABG. The effect of TMLR is associated with indication, correct evaluation of myocardial ischemia, and management for postoperative complications.

Aged↗