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Biomedical subjects

D Huang

Publications and source records attributed to D Huang.

At least 37 records · Page 2Linked to original sources

Disruption of the IL-1beta gene diminishes acetylcholine receptor-induced immune responses in a murine model of myasthenia gravis.

Human autoimmune myasthenia gravis (MG) is associated with the IL-1beta TaqI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine receptor (AChR) immunization in wild-type and IL-1beta deficient (-/-) mice. Compared with wild-type mice, IL-1beta-/- mice were relatively resistant to induction of clinical experimental autoimmune myasthenia gravis (EAMG). Draining lymph node cells from IL-1beta-/- mice showed poor proliferative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1beta-/- mice compared to wild-type mice. Taken together, these results reveal a critical role for IL-1beta in the induction of MG in mice, and support a role for IL-1beta in the pathogenesis of MG in man.

Animals↗

Intrastromal corneal ring segments for low myopia: a report by the American Academy of Ophthalmology.

OBJECTIVE: This document describes intrastromal corneal ring segments (Intacs) inserts technology and examines the evidence to answer the key question about whether the treatment is safe and effective in correcting low myopia. METHODS: A literature search that was conducted in September 2000 retrieved 13 relevant citations, and the reference lists of these articles were consulted for additional citations. Panel members reviewed this information and articles were rated according to the strength of evidence. RESULTS: Prospective multicenter phase II and III clinical trials (Level II evidence rating) of Intacs inserts for myopia of -1.00 to -3.00 diopters (D), with a maximum of +1.00 D of astigmatism, enrolled a total of 452 subjects, with a total of 454 surgical attempts. The results from phase II and phase III were pooled for much of the analysis. At 1 year, 97% of patients who completed follow-up had 20/40 or better uncorrected visual acuity (UCVA). Seventy-four percent of patients had 20/20 or better UCVA. Ninety-two percent of eyes were within +/-1 D of intended refractive correction, and 69% were within 0.5 D of intended refractive correction. At 3 months, 90% of patients had less than 1.0 D of change from the previous examination performed at 1 month. The ocular complication rate, which was defined as clinically significant events but not resulting in permanent sequelae, was 11% at 12 months. The adverse event rate was 1.1%, defined as a serious event if untreated. Nearly 9% of patients requested to have their inserts removed and a total of 3.8% of patients required a secondary surgical intervention. CONCLUSIONS: To date, evidence suggests that low myopia (-1 to -3 D) in a well-defined group of patients who have a stable manifest refraction and less than +1.0 D of astigmatism can be treated with Intacs inserts with a reasonable assurance of safety and effectiveness. Additional clinical research is needed to determine the long-term effectiveness of treatment and the comparative safety, effectiveness, and costs with other treatment modalities, including laser-assisted in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK).

Academies and Institutes↗

Anterior chamber stability during bimanual irrigation and aspiration. Theoretical and experimental analysis.

PURPOSE: To determine the requirements for maintaining a stable anterior chamber during bimanual irrigation and aspiration (I/A) using side-port cannulas. SETTING: Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. METHODS: A theoretical fluid dynamic model of the closed I/A system was developed. Model predictions were compared with experimental flow measurements made on the Alcon Legacy 20000 system using a number of commercial and custom I/A cannulas. RESULTS: Bore diameter, length, and orifice size determine the pressure-flow relationship of cannulas. Four of 18 tested irrigation cannulas were able to maintain anterior chamber stability when used with a 23-gauge/0.3 mm orifice aspiration cannula and maximum aspiration settings. All 4 had a 21-gauge lumen diameter. A shorter cannula length also contributed to higher flow. CONCLUSIONS: Anterior chamber stability during bimanual I/A required the irrigation system to have lower flow resistance than the aspiration system, which can be provided by using cannulas with larger lumen diameters and shorter lengths. Special cannula designs can provide these characteristics without requiring larger side-port incisions.

Anterior Chamber↗

Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele.

Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease with both genetic and environmental components. In addition to the human leukocyte antigen (HLA) complex, the single major genetic contributor of susceptibility, an unknown number of other unidentified genes are required to mediate disease. Although many loci conferring susceptibility to T1D have been mapped, their identification has proven problematic due to the complex nature of this disease. Our strategy for finding T1D susceptibility genes has been to test for human homologues of loci implicated in diabetes-prone NOD (non-obese diabetic) mice, together with application of biologically relevant stratification methods. We report here a new susceptibility locus, IDDM18, located near the interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B alleles was observed in affected sibpairs and was confirmed in an independent cohort of simplex families. A single base change in the 3' UTR showed strong linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR alleles showed different levels of expression in cell lines. Variation in IL-12p40 production may influence T-cell responses crucial for either mediating or protecting against this and other autoimmune diseases.

3' Untranslated Regions↗

Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma.

We have previously shown that the introduction of human recombinant wild-type p53 mediated by an adenoviral vector (Ad5CMV-p53), either alone or delivered in combination with ionizing radiation, was cytotoxic to two nasopharyngeal carcinoma (NPC) cell lines. To further explore the potential therapeutic role for gene therapy, the combination of Ad5CMV-p53 and cisplatin was examined in two NPC cell lines, CNE-1 and C666-1. The C666-1 cells are particularly relevant because they express Epstein-Barr virus latent gene products analogous to human NPC in situ. Cells were infected with 5 pfu/cell of Ad5CMV-p53 or Ad5CMV-beta-gal, followed by exposure to increasing doses of cisplatin. Clonogenic and MTT assays were used to assess the sensitivity of cells to these treatments, and apoptosis was also quantified. The combination of Ad5CMV-p53 and cisplatin resulted in approximately 25% greater cytotoxicity compared to that observed with cisplatin alone in either cell line. Apoptosis was induced in approximately 50% of cells following administration of both Ad5CMV-p53 and cisplatin, but was induced in considerably fewer cells following either treatment alone. The two modalities appeared to interact in an additive manner. Ad5CMV-p53 gene therapy resulted in the expression of biologically active p53 protein, shown by induction of p21(WAF1/CIP1). Cisplatin treatment showed little effect on either p53 or p21(WAF1/CIP1) expression. Therefore, both p53 gene therapy and cisplatin chemotherapy demonstrated cytotoxicity mediated by apoptosis despite the presence of EBV gene products in the C666-1 cells, but it appears that the two modalities induce cytotoxicity by independent pathways.

Adenoviridae↗

Cytotoxic T-lymphocyte antigen-4 microsatellite polymorphism is associated with multiple myeloma.

Multiple myeloma (MM) is a B-lineage malignancy with unknown aetiology. It has been considered that predisposing genetic factors might be implicated in the disease. In this study, the microsatellite polymorphism in the exon 3 of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene was analysed in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), together with ethnically matched healthy controls. The results showed that frequencies of the genotype 86/86 and of the allele 86 were significantly decreased in MM and MGUS compared with matched healthy controls, indicating that the CTLA-4 microsatellite polymorphism might represent a susceptibility locus for MM and MGUS.

Abatacept↗

Pathogenesis: immunogenetic factors.

The occurrence, albeit infrequent, of systemic vasculitis in closely related family members suggests that both environmental and genetic factors may play a role in the pathogenesis of these diseases. Malfunction of immune regulation in the systemic vasculitides may indicate a role for genes that encode molecules critical to the immune responses. The extremely polymorphic sequences of MHC molecules may provide a structural basis for associations of MHC genes and systemic vasculitis. This review summarizes recent reports of MHC associations, mechanisms by which MHC may play a role in certain vasculitides, and also examines the role for genes encoding non-MHC molecules, such as Fcgamma receptors, cytokines and T cell co-stimulators. Data suggest that the pathogenesis of systemic vasculitides such as giant-cell arteritis, Takayasu's arteritis and Wegener's granulomatosis might be governed by multiple genes encoding host defence molecules, in conjunction with environmental factors.

Cluster Analysis↗

UPBEAT: the impact of a psychogeriatric intervention in VA medical centers. Unified Psychogeriatric Biopsychosocial Evaluation and Treatment.

BACKGROUND: The Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) program provides individualized interdisciplinary mental health treatment and care coordination to elderly veterans whose comorbid depression, anxiety, or alcohol abuse may result in overuse of inpatient services and underuse of outpatient services. OBJECTIVES: To determine whether proactive screening of hospitalized patients can identify unrecognized comorbid psychiatric conditions and whether comprehensive assessment and psychogeriatric intervention can improve care while reducing inpatient use. DESIGN: Randomized trial. SUBJECTS: Veterans aged 60 and older hospitalized for nonpsychiatric medical or surgical treatment in 9 VA sites (UPBEAT, 814; usual care, 873). MEASURES: The Mental Health Inventory (MHI) anxiety and depression subscales, the Alcohol Use Disorder Identification Test (AUDIT) scores, RAND 36-Item Health Survey Short Form (SF-36), inpatient days and costs, ambulatory care clinic stops and costs, and mortality and readmission rates. RESULTS: Mental health and general health status scores improved equally from baseline to 12-month follow-up in both groups. UPBEAT increased outpatient costs by $1,171 (P <0.001) per patient, but lowered inpatient costs by $3,027 (P = 0.017), for an overall savings of $1,856 (P = 0.156). Inpatient savings were attributable to fewer bed days of care (3.30 days; P = 0.016) rather than fewer admissions. Patients with 1 or more pre-enrollment and postenrollment hospitalizations had the greatest overall savings ($6,015; P = 0.069). CONCLUSIONS: UPBEAT appears to accelerate the transition from inpatient to outpatient care for acute nonpsychiatric admissions. Care coordination and increased access to ambulatory psychiatric services produces similar improvement in mental health and general health status as usual care.

Aged↗

Temporal gene regulation during HIV-1 infection of human CD4+ T cells.

CD4(+) T-cell depletion is a characteristic of human immunodeficiency virus type 1 (HIV-1) infection. In this study, modulation of mRNA expression of 6800 genes was monitored simultaneously at eight time points in a CD4(+) T-cell line (CEM-GFP) during HIV infection. The responses to infection included: (1) >30% decrease at 72 h after infection in overall host-cell production of monitored mRNA synthesis, with the replacement of host-cell mRNA by viral mRNA, (2) suppression of the expression of selected mitochondrial and DNA repair gene transcripts, (3) increased expression of the proapoptotic gene and its gene p53-induced product Bax, and (4) activation of caspases 2, 3, and 9. The intense HIV-1 transcription resulted in the repression of much cellular RNA expression and was associated with the induction of apoptosis of infected cells but not bystander cells. This choreographed host gene response indicated that the subversion of the cell transcriptional machinery for the purpose of HIV-1 replication is akin to genotoxic stress and represents a major factor leading to HIV-induced apoptosis.

CD4-Positive T-Lymphocytes↗

[Significance of detection of transfusion transmitted virus in extrahepatic tissues].

OBJECTIVE: To investigate the location and distribution of transfusion transmitted virus (TTV) in the liver and extrahepatic tissues. METHODS: TTV DNA was detected in paraffin-embedded autopsy liver and extrahepatic tissues, including liver, pancreas, kidney, spleen, testicle, and heart from 13 patients with non A-G hepatitis by nested-PCR and in situ hybridization (ISH) techniques. RESULTS: Positive hybridization signals of TTV nucleus acid were observed in 5 liver, 3 kidney, 2 pancreas and spleen tissues, respectively. TTV DNA was detected in one from each two samples of testicle and heart. Positive signal was mainly located in nucleoli of the liver and extrahepatic parenchymal cells. There was not obvious pathological damage in those extrahepatic tissues. The positive rate of PCR approximately corresponded to ISH. CONCLUSIONS: TTV can infect hepatic and extrahepatic tissues and its infection in extrahepatic tissues might be responsible for a state of reinfection and higher prevalence in different population.

Adult↗

Application of autologous peripheral blood stem cell transplantation in children with malignant tumor.

OBJECTIVE: To investigate if low dose total body irradiation (TBI, 6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation results in better survival in children with refractory leukemia or solid tumors. METHODS: Twenty-one children with malignant tumors were included in this study. There were 14 males and 7 females aged 3.5-12 years. Underlying disease included high-risk acute lymphoblastic leukemia (ALL, CR1 in 3 children and CR2 in 5 children), acute myeloblastic leukemia (AML, 9 children), non-Hodgkin's lymphoma stage IV (2 children), and neuroblastoma stage IV (2 children). The peripheral hematopoietic stem cells were collected six to eleven months after complete response, mobilized with high dose chemotherapy alone or combined with GM-CSF or G-CSF. The conditioning regimen consisted of chemotherapy with two to three combinations of the following drugs: cyclophosphamide, arabinosylcytosine, McNU, etopside, and ldarubicin on the basis of TBI (6.0-9.0 Gy). A mean of (1.8 +/- 0.5) x 10(8)/kg autologous mononuclear cells were transplanted. The patients were followed up after transplantation. RESULTS: Severe bone marrow suppression occurred in all patients around day +7. Peripheral white blood cell count decreased to 0 in all patients at day +4.8 +/- 2.9, and platelet count decreased to less than 20 x 10(9)/L at day +9.0 +/- 2.6. Successful engraftment was achieved in 21 patients, but four died of infection at day +17, +20, +31 and +67, respectively. Recovery of white blood cell (WBC) to 10 x 10(9)/L, absolute neutrophil count to 0.5 x 10(9)/L, platelet count to 20 x 10(9)/L occurred on 21 +/- 12, 26 +/- 13, and 27 +/- 10 days, respectively. During the follow up period, three patients relapsed at months, +1.5 years, and +2 years 10 months, respectively. One patient died of intracranial hemorrhage at +8 months. Thirteen patients had event-free survival for 2-12 years, with a mean of 6.7 +/- 3.4 years. CONCLUSION: Our preliminary data suggest that myeloablative therapy with low dose TBI (6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation might be associated with favorable results in children with refractory leukemia or solid tumors.

Child↗

Nationality differences in distributions of serum lipids, lipoproteins and apolipoproteins levels in Xinjiang China.

OBJECTIVE: To reveal the distribution characteristics of serum lipids, lipoproteins, and apolipoproteins levels in different nationalities. METHODS: Quantitative levels of those traits mentioned above were determined and body height (H), weight (W) and body mass index (BMI = W/H2) were assessed in 773 Kazaks (men 360 and women 413) and 911 Han nationality (men 466 and women 445) from the Xinjiang Autonomous Region of China. RESULTS: Kazaks men and women, respectively, had significantly higher serum levels of HDL-c and ApoA1 (all P < 0.001) and significantly lower serum levels of TG (men P < 0.01, women P < 0.001), Lp(a) (all P < 0.005), ApoB (men P < 0.005, women P < 0.001) and ApoB/A1 (men P < 0.01, women P < 0.001) than their Han nationality controls. The threshold points of ApoA1 (< 1.2 g/L) and ApoB (> 1.2 g/L) are higher in Hans than in Kazaks for ApoA1 (20.7 vs 9.8%) and ApoB (18.6 vs 14.3%); the serum levels of TG, HDL-c, Lp(a), ApoA1 and ApoB/A1 are all closely correlated with nationality (P < 0.001, P = 0.001, and P < 0.05, respectively). CONCLUSION: The results suggest that the nationality differences exist in serum levels of lipids, lipoproteins, and apolipoproteins, and Kazaks have a superior serum lipid pedigree to Hans. This differences may come from genetic differences, which affect the serum levels of lipids, lipoproteins, and apolipoproteins by controlling lipid metabolism patterns. Future study will be needed to dissect to the role of genetic factors on serum lipids.

Apolipoproteins↗

[A study of the effects of basic fibroblast growth factor on fibrovascular ingrowth into hydroxyapatite orbital implants].

OBJECTIVE: To investigate the effects of different doses of basic fibroblast growth factor (bFGF) on the fibrovascular ingrowth into hydroxyapatite orbital implants. METHODS: Thirty-six New Zealand albino rabbits were divided into 4 groups, and hydroxyapatite orbital spheres were implanted into their orbits. The implants were pretreated with 0.5, 1.5 and 5.0 g/L bFGF solution respectively in 3 groups, the untreated implants were used in the control group. At the postoperative 2, 4 and 6 weeks the implants were harvested. Observers classified the extent of the fibrovascular ingrowth in a blind manner under light microscopy. RESULTS: Histologic studies demonstrated that postoperatively, the rate of vascularization of the implants pretreated with 1.5 and 5.0 g/L bFGF solution was significantly increased at week 2 in comparison with that of the control group. No difference was noted between the group with the implants pretreated with 0.5 g/L bFGF solution and the control group. CONCLUSION: The bFGF 1.5 and 5.0 g/L in concentration may promote the fibrovascular ingrowth into hydroxyapatite orbital implants at week 2 after the implantation.

Animals↗

[Pathogenecity and replication of transfusion transmitted virus in liver tissue by in situ hybridization].

OBJECTIVE: To study its pathogenecity based on infection status and replication of transfusion transmitted virus (TTV) in the liver tissues. METHODS: Using recombinant plasmid as template and symmetrical and asymmetrical polymerase chain reaction (PCR), double-strand and single-strand TTV probes were labeled with digoxigenin. Fifty-six cases of liver biopsy specimens were detected by in situ hybridization, and six positive cases of them were tested further with single-strand probes. RESULTS: TTV DNA was found in 14 of 51 patients with non A and non G hepatitis (27.5%), and five cases in the control group were negative. TTV DNA was mainly observed in the nuclei of hepatocytes and pathologic changes and necrosis in the infected liver cells were not so apparent, but they could be seen in the liver tissues of acute, chronic and severe hepatitis, as well as of liver cirrhosis. TTV genome strand hybridization detected by single-strand probe was consistent with that by double-strand probe. Both TTV genome strand and its complementary strand were present in the two cases of liver specimens, but hybridizational signals were weaker in the latter than those in the former. CONCLUSION: TTV could cause injury and replicate itself in the liver, but no obvious and direct injury to hepatocytes.

DNA, Viral↗

[HCV-PCR-Hybrid.ELISA for the detection of HCV RNA in serum samples from hepatitis patients].

BACKGROUND: To detect HCV RNA in serum samples from hepatitis patients by using the methods of HCV-Reverse transcription polymerase chain reaction and hybrid ELISA. METHODS: HCV RNA in serum samples was amplified by RT-PCR with one of the primer labeled with biotin. PCR amplified products were detected with microtiter plate hybridization with HCV specific probe, then determined with steptavidin-HRP assay. Anti-HCV in these samples was also detected with ELISA simultaneously. RESULTS: The positive rates of HCV RNA were 81.8% (72/88) in anti-HCV positive group and 57.9% (88/152) in the whole patients group. Serum HCV RNA and anti-HCV positive rates were compared and the consistent rate was 78.9% (120/152, P>0.05). The positive rate of HCV RNA was higher in H.ELISA (57.9%, 88/152) than that in electrophoresis (35.5%, 54/152)(P<0.01). CONCLUSIONS: The HCV-PCR-H.ELISA was a sensitive, specific, stable, semi-quantitative and easy to operate method. This HCV RNA detection was especially beneficial to early diagnosis during viramia period and was helpful for the evaluation of anti-HCV therapy.

Adolescent↗

[A study of genetic polymorphism of the STR locus D2S441 in Chinese Han population in Chengdu].

Using PCR and PAG, followed by silver staining, the tetrameric STR D2S441 locus was studied in 260 unrelated Chinese individuals living in Chengdu. 9 alleles and 26 genotypes were observed. The range of fragment size was 131 bp to 155 bp. The genotype distribution of D2S441 locus in Han population was in accordance with Hardy-Weinberg equilibrium. Family survey confirmed Mendelian inheritance of alleles. The discriminating power (Dp), observed heterozygosity (H), polymorphism information content (PIC) and power of exclusion (PE) were 0.9084, 0.7885, 0.7390 and 0.5778 respectively. The results demonstrated that this locus was highly polymorphic and could be used for forensic identification and paternity testing.

Alleles↗