Biomedical subjects

Xin Tian

Publications and source records attributed to Xin Tian.

At least 19 recordsLinked to original sources

PubMed2026

Distress Intolerance, Social Anxiety, and Depressive Symptoms in Adolescents: Evidence from Random-Intercept Cross-Lagged Panel and Cross-Lagged Panel Network Analyses.

Social anxiety and depressive symptoms frequently co-occur during adolescence, yet the mechanisms underlying their longitudinal associations remain insufficiently understood. Distress intolerance has been proposed as a transdiagnostic risk factor implicated across internalizing symptoms. However, it remains unclear whether distress intolerance is predicted by social anxiety and depressive symptoms, as well as the underlying mechanisms among these three constructs. The specific symptoms most centrally involved in these cross-domain associations remain poorly understood. The present study investigated the longitudinal associations among distress intolerance, social anxiety, and depressive symptoms using a dual-method framework combining random-intercept cross-lagged panel models (RI-CLPM) and cross-lagged panel network (CLPN) analyses. A total of 1,378 Chinese adolescents (Mage = 12.57, SDage = 0.63; 50.4% female) were assessed at three time points with six-month intervals between waves. The RI-CLPM analyses revealed that higher distress intolerance prospectively predicted subsequent increases in both social anxiety and depressive symptoms, whereas elevated social anxiety and depressive symptoms in turn predicted subsequent increases in distress intolerance. Moreover, distress intolerance mediated the longitudinal associations between social anxiety and depressive symptoms. Additionally, distress intolerance was also indirectly associated with its own subsequent levels through social anxiety and depressive symptoms. The CLPN analyses revealed that fear of negative evaluation and fatigue were the strongest predictors of other network nodes from T1 to T2 and from T2 to T3, respectively. In contrast, distress intolerance symptoms were predominantly predicted by other nodes in both cross-lagged networks. These findings extend prior views of distress intolerance as a unidirectional vulnerability by showing that distress intolerance is also predicted by social anxiety and depressive symptoms and accounts for part of their longitudinal associations across adolescence.

Humans↗

PubMed2025

Donor-Derived Cell-Free DNA Stratifies Risk of Mortality and Graft Dysfunction in Severe Acute Cardiac Allograft Rejection.

BACKGROUND: Cardiac acute rejection (AR) is a risk factor for poor outcomes, however there are limited risk prediction models to stratify patients for death or sustained LV dysfunction. This study assesses the prognostic utility of percentage donor-derived cell-free DNA (%dd-cfDNA) at the diagnosis of AR for poor outcomes. METHODS: The prospective multicenter GRAfT study enrolled heart transplant recipients and collected serial plasma samples to quantitate %dd-cfDNA. AR was defined as acute cellular rejection (ACR), antibody-mediated rejection (AMR), as well as biopsy-negative AMR (donor-specific antibody positivity with LV dysfunction). AR was classified as mild-to-moderate (ACR grade 2 or AMR grade 1) or severe (ACR grade ≥3, AMR grade ≥2, or DSA+/LV dysfunction) and further stratified by a %dd-cfDNA threshold of 0.25%. Regression models assessed the association between AR and %dd-cfDNA levels at the AR diagnosis with the primary composite outcome of sustained LVEF decline <50% and/or death. RESULTS: The study included 275 patients and 3,190 %dd-cfDNA assessments. Over the median of 4.6 (IQR 1.8 - 5.0) years follow-up, 51 patients experienced the composite outcome of death or prolonged EF reduction, and 75 patients developed AR, including 16.2% patients with ACR, 9.4% with pathologic AMR, and 6.6% with DSA+/LV dysfunction. Thirty-two (42.7%) patients had severe AR and 43 (57.3%) had mild-to-moderate AR. Severe-but not mild-to-moderate-AR was associated with an increased risk of the primary composite endpoint (HR = 5.17, 95% CI 2.38 - 11.3, p < 0.001). Among those with severe AR, a %dd-cfDNA level greater than 0.25% at diagnosis was associated with a higher risk of the primary outcome (HR, 6.06, 95% CI, 1.78-20.6; p = 0.004). Percent dd-cfDNA remained elevated in severe AR patients with adverse outcomes. CONCLUSION: Severe AR with high %dd-cfDNA levels is associated with an increased risk of poor outcomes, offering novel prognostic utility.

Acute Rejection↗

PubMed2025

Utility of Plasma Cell-free Chromatin Immunoprecipitation to Detect Cardiac Allograft Rejection.

BACKGROUND: Antibody-mediated rejection (AMR) remains the major risk factor for allograft loss across all solid organ transplantation. Unfortunately, its diagnosis relies on biopsy, an invasive gold standard that often sample unaffected allograft tissue leading to missed diagnosis. Plasma donor-derived cell-free DNA (dd-cfDNA) is noninvasive biomarker that has high sensitivity but low specificity for AMR diagnosis. This proof-of-concept study assessed the utility of cell-free chromatin immunoprecipitation (cfChIP) as a surrogate for gene expression to detect cardiac AMR and the associated pathobiology. METHODS: The discovery GRAfT multicenter cohort of heart transplant patients (NCT02423070) identified AMR, acute cellular rejection (ACR), and stable controls based on biopsy and ddcfDNA results. Plasma cfChIP-sequencing was performed to identify peaks, associated genes and pathobiological pathways. Plasma from an external cohort (GTD, NCT01985412) was also analyzed to verify pathways identified. Digital droplet PCR (ddPCR) assays targeting differential regions were constructed to test the diagnostic performance of cfDNA to detect AMR/ACR from stable controls (rejection-specific assays) or AMR from ACR (AMR-specific assays). RESULTS: The cohort included 21 AMR, 28 ACR, and 45 stable controls from GRAfT and GTD, and 23 healthy controls. cfChIP detected expected active genes, including housekeeping genes and gene targets of transplant immunosuppressive drugs but not inactive genes. Unsupervised clustering of the discovery GRAfT cohort assigned 95% of samples correctly as AMR, ACR or stable control. Differential analysis identified pathobiological pathways of AMR such as neutrophil degranulation and complement activation. The pathways were consistent in GTD samples. Rejection-specific assays detected AMR/ACR from controls with AUC of 0.78 - 0.95. AMR-specific assays detected AMR from ACR with AUC of 0.71 - 0.85, sensitivities of 0.73 - 0.94 and specificities of 0.73 - 0.80. CONCLUSION: This study provides valuable preliminary data supporting the use of cfChIP to detect AMR and the associated pathobiological pathways.

Allograft rejection↗

PubMed2007

Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients.

OBJECTIVE: Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy. METHODS: One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type -1082 G/A and -819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants. RESULTS: Compared with control subjects and patients with negative-specific IgE, there were significantly lower levels of IL-10 in patients with positive-specific IgE (P < 0.05). Similarly, there were significantly lower levels of IL-10 in patients with positive-specific IgG compared with normal controls and allergic patients with negative-specific IgG (P < 0.05). The visible negative correlations existed between IL-10 and four types of specific IgE [benzylpenicilloyl (BPO), phenoxomethylpenicilloyl (PVO), benzylpenicillanyl (BPA), amoxicillanyl (AXA)], and patients with three or more positive-specific IgE had significantly lower IL-10 levels than normal controls (P < 0.01). There was a declining trend for IL-10 level in serum with the increase in types of positive-specific IgE. But there was no significant difference in serum IL-10 level between the positive skin-test group and the allergic-history group. Compared with controls and patients with negative antibodies, a significantly decreased frequency of the -1082 G allele was present in patients with positive antibodies (P < 0.01). The allele T and TT genotype at -819 C/T position had lower frequency in the negative-specific IgG group than that in the positive group and controls (P < 0.01). CONCLUSIONS: Positive specific IgE and IgG are associated with decreased IL-10 level in allergic reaction to penicillins. The distributions of genotype and frequency of allele at the -1082 G/A position may be associated with the production of both specific IgE and IgG antibodies.

Adolescent↗

PubMed2006

Robust trend tests for genetic association using matched case-control design.

Trend tests for genetic association using a matched case-control design are studied, which allows for a variable number of controls per case. However, the tests depend on the scores based on the underlying genetic model, thus it may result in substantial loss of power when the model is misspecified. Since the mode of inheritance may be unknown for complex diseases, robust trend tests in matched case-control studies are developed. Simulation is conducted to compare the trend tests and the robust trend tests under various genetic models. The results are applied to detect candidate-gene association using an example from a case-control aetiologic study of sarcoidosis.

Black People↗

PubMed2006

[Significance of citrullinated collagen type II and its antibodies in rheumatoid arthritis].

OBJECTIVE: To investigate the significance of citrullinated collagen type II and its antibodies in the pathogenesis and diagnosis of rheumatoid arthritis (RA). METHODS: Serum samples were obtained from 175 patients with RA, 112 patients with systemic lupus erythematosus (SLE), 37 patients with osteoarthritis (OA), and 160 healthy controls. Arginine residues of bovine collagen type II (bCII) were converted to citrulline residues by peptidylarginine deiminase (PAD). The presence of antibodies against citullinated bCII (Cit-bCII) and bCII, a substrate protein of PAD, were examined by using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The levels of anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) in the above patients were detected. RESULTS: The positive rate of anti-CitbCII antibodies of the RA patients was 50.3% (88/175), significantly higher than those of the SLE patients (17.9%, 20/112), OA patients (18.9%, 7/37), and healthy controls (2.5%, 4/160). The positive rate of anti-b of the RA patients was 33.7% (59/175), significantly lower than that of the CII antibodies. The levels of anti-CitbCII and anti-bCII antibodies were not statistically different from SLE and OA patients. There was a close correlation between anti-CitbCII and anti-CCP antibodies. Spearman correlation analysis showed that anti-CitbCII antibodies were positively correlated with anti-CCP antibodies, and CRP, ESR, RF, X ray imaging, course of disease, and age were not associated with anti-CitbCII antibodies. CONCLUSION: Anti-citrullinated bCII antibody is relatively RA-specific. Citrullination appears to be important in RA.

Adult↗

PubMed2006

Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system.

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1-7). We hypothesized that ACE2 is part of the brain renin-angiotensin system, and its expression is regulated by the other elements of this system. ACE2 immunostaining was performed in transgenic mouse brain sections from neuron-specific enolase-AT(1A) (overexpressing AT(1A) receptors), R(+)A(+) (overexpressing angiotensinogen and renin), and control (nontransgenic littermates) mice. Results show that ACE2 staining is widely distributed throughout the brain. Using cell-type-specific antibodies, we observed that ACE2 staining is present in the cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical organ, an area lacking the blood-brain barrier and sensitive to blood-borne angiotensin II, ACE2 was significantly increased in transgenic mice. Interestingly, ACE2 mRNA and protein expression were inversely correlated in the nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the ventrolateral medulla, when comparing transgenic to nontransgenic mice. These results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the brain and that ACE2 levels appear highly regulated by other components of the renin-angiotensin system, confirming its involvement in this system. Moreover, ACE2 expression in brain structures involved in the control of cardiovascular function suggests that the carboxypeptidase may have a role in the central regulation of blood pressure and diseases involving the autonomic nervous system, such as hypertension.

Angiotensin-Converting Enzyme 2↗

PubMed2006

[Diagnostic values of antibody to citrullinated human fibrinogen in rheumatoid arthritis].

OBJECTIVE: To study the prevalence of antibody to citrullinated human fibrinogen (ACF) in rheumatic diseases and the diagnostic values in rheumatoid arthritis. METHODS: Human fibrinogen was deiminated by the peptidylarginine deiminase (PAD) in the presence of Ca2+ in vitro. ACF was detected by ELISA in 352 patients with rheumatic diseases (183 RA, 121 SLE and 48 OA) and 108 healthy controls. The sensitivity and specificity in RA were calculated and the correlations between ACF and the clinical and laboratory parameters were analysed by SPSS statistical software. RESULTS: Compared with SLE (25.62%), OA (18.75%) and healthy control (2.78%) respectively, the patients with RA had a significantly higher level of ACF (67.21%, P<0.001). ACF had a sensitivity of 67.21% and a specificity of 84.84% for RA. In the investigated clinical and laboratory parameters of RA, the significant correlations were found between ACF and ESR (r=0.386, P<0.001), anti-CCP antibody (r=0.288, P<0.05) and AKA (r=0.288, P<0.05), respectively. Abnormalities in ESR, radiographic progression, IgM-RF, anti-CCP, AKA and APF were more often in ACF positive patients than in ACF negative patients. Moreover, ACF was positive in 38.00% of IgM-RF negative, 59.81% of AKA negative and 68.22% of APF negative patients, respectively. CONCLUSION: ACF is a sensitive and specific antibody in diagnosing RA. The ACF test is also very useful in diagnosing RA with other autoantibodies negative.

Adolescent↗

PubMed2006

Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin II-induced cardiomyocyte hypertrophy.

Angiotensin II (ANG II) has profound effects on the development and progression of pathological cardiac hypertrophy; however, the intracellular signaling mechanisms are not fully understood. In this study, we used genetic tools to test the hypothesis that increased formation of superoxide (O2-*) radicals from a Rac1-regulated Nox2-containing NADPH oxidase is a key upstream mediator of ANG II-induced activation of serine-threonine kinase Akt, and that this signaling cascade plays a crucial role in ANG II-dependent cardiomyocyte hypertrophy. ANG II caused a significant time-dependent increase in Rac1 activation and O2-* production in primary neonatal rat cardiomyocytes, and these responses were abolished by adenoviral (Ad)-mediated expression of a dominant-negative Rac1 (AdN17Rac1) or cytoplasmic Cu/ZnSOD (AdCu/ZnSOD). Moreover, both AdN17Rac1 and AdCu/ZnSOD significantly attenuated ANG II-stimulated increases in cardiomyocyte size. Quantitative real-time PCR analysis demonstrated that Nox2 is the homolog expressed at highest levels in primary neonatal cardiomyocytes, and small interference RNA (siRNA) directed against it selectively decreased Nox2 expression by >95% and abolished both ANG II-induced O2-* generation and cardiomyocyte hypertrophy. Finally, ANG II caused a time-dependent increase in Akt activity via activation of AT(1) receptors, and this response was abolished by Ad-mediated expression of cytosolic human O2-* dismutase (AdCu/ZnSOD). Furthermore, pretreatment of cardiomyocytes with dominant-negative Akt (AdDNAkt) abolished ANG II-induced cellular hypertrophy. These findings suggest that O2-* generated by a Nox2-containing NADPH oxidase is a central mediator of ANG II-induced Akt activation and cardiomyocyte hypertrophy, and that dysregulation of this signaling cascade may play an important role in cardiac hypertrophy.

Adenoviridae↗

PubMed2006

HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins.

BACKGROUND: Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin. METHODS: Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction. RESULTS: Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, chi(2) = 4.057, P = 0.044). CONCLUSION: HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

Adolescent↗

PubMed2006

Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif.

Primary cilia play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The affected proteins, polycystin-1 (PC1) and polycystin-2 (PC2), interact with each other and are expressed in cilia. We found that COOH-terminal truncated PC2 (PC2-L703X), lacking the PC1 interaction region, still traffics to cilia. We examined PC2 expression in several tissues and cells lacking PC1 and found that PC2 is expressed in cilia independently of PC1. We used N-terminal deletion constructs to narrow the domain necessary for cilia trafficking to the first 15 amino acids of PC2 and identified a conserved motif, R6VxP, that is required for cilial localization. The N-terminal 15 amino acids are also sufficient to localize heterologous proteins in cilia. PC2 has endogenous cilia trafficking information and is present in cilia of cells lining cysts that result from mutations in PKD1.

Amino Acid Motifs↗

PubMed2006

NAD(P)H oxidase-induced oxidative stress in sympathetic ganglia of apolipoprotein E deficient mice.

Superoxide anion (O2*-) is increased throughout the arterial wall in atherosclerosis. The oxidative stress contributes to lesion formation and vascular dysfunction. In the present study, we tested the hypothesis that NAD(P)H oxidase-derived O2*- is increased in nodose sensory ganglia and sympathetic ganglia of apolipoprotein E deficient (apoE-/-) mice, an established animal model of atherosclerosis. O2*- measured ex vivo by L-012-enhanced chemiluminescence was increased by 79+/-17% in whole sympathetic ganglia from apoE-/- mice (n=5) compared with sympathetic ganglia from control mice (n=5) (P<0.05). In contrast, O2*- was not elevated in nodose ganglia from apoE-/- mice. Dihydroethidium staining confirmed the selective increase in O2*- in sympathetic ganglia of apoE-/- mice, and revealed the contribution of both neurons and non-neuronal cells to the O2*- generation. We investigated the enzymatic source of increased O2*- in sympathetic ganglia of apoE-/- mice. The mRNA expression of gp91phox, p22phox, p67phox, and p47phox subunits of NAD(P)H oxidase measured by real time RT-PCR was increased approximately 3-4 fold in sympathetic ganglia of apoE-/- mice (n=5) compared with control ganglia (n=5). NADPH oxidase activity measured by lucigenin chemiluminescence was increased by 68+/-12% in homogenates of sympathetic ganglia from apoE-/- mice (n=7) compared with control ganglia (n=7) (P<0.05). The results identify sympathetic ganglia as a novel site of oxidative stress in atherosclerosis, and suggest that upregulation of NAD(P)H oxidase is the source of increased O2*- generation. We speculate that oxidative stress in sympathetic ganglia may contribute to impaired baroreflex control of sympathetic nerve activity.

Analysis of Variance↗

PubMed2006

Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype.

OBJECTIVE: Omeprazole, lansoprazole and rabeprazole have been widely used as proton pump inhibitors (PPIs). They can be metabolized in the liver by CYP2C19, a polymorphic enzyme, and have a wide inter-individual variability with respect to drug response. In the investigation reported here, we examined the kinetic characteristics of the three PPIs in healthy Chinese subjects in relation to CYP2C19 genotype status. METHODS: Six homozygous extensive metabolizers (homEMs), six heterozygous extensive metabolizers (hetEMs) and six poor metabolizers (PMs) were recruited for the study from a total of 90 healthy Chinese volunteers whose CYP2C19 genotype status was determined by means of PCR-restriction fragment length polymorphism (RFLP). The study was had an open label, randomized, three-way crossover design. After a single oral dose of 40 mg omeprazole, 30 mg lansoprazole or 40 mg rabeprazole, plasma concentrations of the three PPIs were determined by HPLC. RESULTS: There were some differences for the area under the plasma concentration-time curve (AUC), the elimination half-life (t(1/2 ke)) and the maximum plasma concentration (c(max)) in the three groups. In the homEMs, hetEMs and PMs, the relative AUC(0-infinity) values were 1:2.8:7.5 for omeprazole, 1:1.7:4.0 for lansoprazole and 1:1.6:3.7 for rabeprazole, respectively; the relative t(1/2 ke) values were 1:1.02:1.65 for omeprazole, 1:1.08:2.39 for lansoprazole and 1:1.37:1.85 for rabeprazole, respectively; the relative c(max) values were 1:2.09:4.39 for omeprazole, 1:1.34:1.72 for lansoprazole, and 1:1.24:2.04 for rabeprazole, respectively. CONCLUSION: The pharmacokinetic characteristics of the three PPIs are significantly dependent on the CYP2C19 genotype status. These data indicate that individualized dose regimen of the three PPIs, based on identification of genotype, can be of great benefit for ensuring the reasonable use of these drugs.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

Rapid bidirectional allele-specific PCR identification for triazine resistance in higher plants.

Triazine resistance is reported to be due to chloroplast herbicide target insensitivity in most species, and this is most often caused by a Ser(264)-Gly mutation at the D1 protein. In order to ascertain whether this mutation is really predominant amongst resistant plants, and also for gene flow studies, a rapid test is needed that allows the testing of large quantities of plants. Here a bidirectional allele-specific PCR (polymerase chain reaction) identification is proposed. The designed primers were shown to be universal in the three grass and three broadleaf species examined.

Alleles↗

PubMed2006

Diuretic use, progressive heart failure, and death in patients in the DIG study.

BACKGROUND: Nonpotassium-sparing diuretics (NPSDs), have been associated with increased sudden cardiac death (SCD) and progressive heart failure (HF) death in HF patients. METHODS AND RESULTS: In 6797 Digitalis Investigation Group study patients, risk ratios were calculated for death, cardiovascular death (CVD), death from worsening HF, SCD, and HF hospitalization among those taking a potassium-sparing (PSD), NPSD, or no diuretic. Compared with not taking diuretic, risk of death (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17-1.59, P < .0001), CVD (RR = 1.38, 95% CI 1.17-1.63, P = .0001), progressive HF death (RR = 1.41, 95% CI 1.06-1.89, P = .02), SCD (RR = 1.67, 95% CI 1.23-2.27, P = .001), and HF hospitalization (RR = 1.68, 95% CI 1.41-1.99, P < .0001) were increased with NPSD. There was no significant difference in any end point for patients taking only PSD compared to no diuretic. PSD only subjects were less likely than NPSD subjects to be hospitalized for HF (RR = 0.71, 95% CI 0.52-0.96, P = .02). CONCLUSION: NPSDs are associated with increased risk of death, CVD, progressive HF death, SCD, and HF hospitalization. A randomized trial is needed to assess the role of NPSDs versus PSDs in HF patients.

Aged↗

PubMed2006

The lay concept of conduct disorder: do nonprofessionals use syndromal symptoms or internal dysfunction to distinguish disorder from delinquency?

BACKGROUND: Conduct disorder (CD) must be distinguished from nondisordered delinquent behaviour to avoid false positives, especially when diagnosing youth from difficult environments. However, the nature of this distinction remains controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria conflict with its definition of mental disorder, which requires that symptoms be considered a manifestation of internal dysfunction to warrant disorder diagnosis. Previous research indicates that professional judgments tend to be guided by the dysfunction requirement, not syndromal symptoms alone. However, there are almost no data on lay conceptualizations. Thus it remains unknown whether judgments about CD are anchored in a broadly shared understanding of mental disorder that provides a basis for professional-lay consensus. OBJECTIVE: The present study tests which conception of CD, syndromal-symptoms or dysfunction-requirement, corresponds most closely to lay judgments of disorder or nondisorder and compares lay and professional judgments. We hypothesized that lay disorder judgments, like professional judgments, tend to presuppose the dysfunction requirement. METHOD: Three lay samples (nonclinical social workers, nonpsychiatric nurses, and undergraduates) rated their agreement that youths described in clinical vignettes have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria. Vignettes were varied to present syndromal symptoms only, symptoms suggesting internal dysfunction, and symptoms resulting from reactions to negative circumstances, without dysfunction. RESULTS: All lay samples attributed disorder more often to youths whose symptoms suggested internal dysfunction than to youths with similar symptoms but without a likely dysfunction. CONCLUSIONS: The dysfunction requirement appears to reflect a widely shared lay and professional concept of disorder.

Attitude to Health↗

PubMed2006

[Downregulation of Bcl-2 and survivin expression and release of Smac/DIABLO involved in bufalin-induced HL-60 cell apoptosis].

OBJECTIVE: To investigate the expression of mitochondria-mediated apoptosis pathway related genes bcl-2, Bax, survivin and Smac/DIABLO in bufalin induced HL-60 cell apoptosis. METHODS: Cell viability was determined by trypan blue exclusion, apoptosis by morphology and flow cytometry, expressions of Bcl-2, Bax, Survivin, Smac/DIABLO and caspase-3 protein by Western blot, and expression of survivin mRNA by RT-PCR. RESULTS: Proliferation of HL-60 cells was inhibited by bufalin and the IC(50) at 24, 48 and 72 h were 25.8, 8.0 and 2.1 nmol/L, respectively. Apoptosis was induced when the cells were treated with bufalin at concentrations of 50.0 nmol/L and higher. Compared with the control, HL-60 cells treated with bufalin at 50.0 nmol/L for 6, 12, 24 and 48 h showed decrease of Bcl-2 protein expression to 88.6%, 53.3%, 19.2% and 9.5%, Bcl-2/Bax ratio (control 2.0) to 1.7, 1.1, 0.4 and 0.2, Survivin protein expression to 75.2%, 54.8%, 37.5% and 20.3%, and survivin mRNA to 85.7%, 39.4%, 12.5%and 0%, respectively. The expression of Smac/DIABLO protein was downregulated to 77.5% (12 h), 21.2% (24 h) and 15.3% (48 h) in mitochondrial fraction and upregulated to 1.4-(12h), 2.0-(24 h) and 3.5- folds (48 h) in cytosolic fraction, respectively. The active subunits of caspase-3 were displayed after treatment for 8 h till 48 h. CONCLUSION: Apoptosis induced by bufalin is related to downregulation of expressions of bcl-2 and survivin, decrease of Bcl-2/Bax ratio, mitochondrial release of Smac/DIABLO, and activation of caspase-3. The mitochondria-mediated apoptotic pathway may be involved in the apoptosis induced by bufalin in HL-60 cells.

Apoptosis↗

PubMed2006

[Enhancement of all-trans retinoic acid-induced differentiation by bufalin in primary culture of acute promyelocytic leukemia cells].

OBJECTIVE: To investigate the effect of bufalin combined with all-trans retinoic acid-induced (ATRA) differentiation of acute promyelocytic leukemia (APL) cells in primary culture. METHODS: Fresh leukemia cells were obtained from heparinized bone marrow aspirations of 12 newly diagnosed APL patients. Cell viability was determined by trypan blue dye exclusion. Apoptosis of APL cell was assessed by morphological analysis. Differentiation of APL cell was also assessed by morphological analysis. Nitro blue tetrazolium (NBT) reduction test and expression of the granulocyte/macrophage-specific antigen CD(11)b was carried out with flow cytometric assay. RESULTS: Bufalin combined with ATRA can induce differentiation of APL cells towards mature stages, NBT reduction was increased 15% - 52% and CD(11)b expression was also increased 16% - 69% in combination of bufalin and ATRA as compared with that of ATRA alone, while the concentration of ATRA needed in the combination group was reduced to 30% and the time of differentiation was reduced from 7 days to 4 days. CONCLUSION: The combination of ATRA with bufalin can significantly enhance the differentiation of acute promyelocytic leukemia cells in primary culture by ATRA.

Antineoplastic Agents↗