Biomedical subjects

P Yang

Publications and source records attributed to P Yang.

At least 145 records · Page 8Linked to original sources

PubMed2000

[A reflection interference method for determining optical constants and thickness of a thin solid film].

In this paper we report a simple method for deducing optical constants and thickness from the reflection interference spectrum of a thin transparent film which is on a substrate of high reflection coefficient. When a light beam is incident on the surface of the film, the reflection light beams at the front and rear faces are coherent. We calculated the optical constants and thickness of the film from the reflection spectrum. This simple method makes a directly programmable calculation possible.

English Abstract↗

PubMed2000

[Spectroscopy performances of Yb3+ doped YAG crystal].

The absorption and emission properties of Yb:YAG with different Yb3+ doped concentration have been studied systematically. The emission cross section has been evaluated using the absorption cross section and principle of reciprocity, which was consistent with previous reports. The absorption spectra of Yb2+ and color center were observed in as-grown Yb:YAG boules, which are removed by annealing the boules in oxygen at 1,300 degrees C for 24 h. The photon excited and X-ray excited optical luminescence of Yb:YAG were first discussed. The results indicated that Yb:YAG crystal was favourable for high-power diode-pumping.

Chemical Phenomena↗

PubMed1999

Direct activation of the fission yeast PAK Shk1 by the novel SH3 domain protein, Skb5.

The p21-activated kinase (PAK) homolog Shk1 is essential for cell viability in the fission yeast Schizosaccharomyces pombe. Roles have been established for Shk1 in the regulation of cell morphology, sexual differentiation, and mitosis in S. pombe. In this report, we describe the genetic and molecular characterization of a novel SH3 domain protein, Skb5, identified as a result of a two-hybrid screen for Shk1 interacting proteins. S. pombe cells carrying a deletion of the skb5 gene exhibit no discernible phenotypic defects under normal growth conditions, but when subjected to hypertonic stress, become spheroidal in shape and growth impaired. Both of these defects can be suppressed by overexpression of the Shk1 modulator, Skb1. The growth inhibition that results from overexpression of Shk1 in S. pombe cells is markedly suppressed by a null mutation in the skb5 gene, suggesting that Skb5 contributes positively to the function of Shk1 in vivo. Consistent with this notion, we show that Skb5 stimulates Shk1 catalytic function in S. pombe cells. Furthermore, and perhaps most significantly, we show that bacterially expressed recombinant Skb5 protein directly stimulates the catalytic activity of recombinant Shk1 kinase in vitro. These and additional data described herein demonstrate that Skb5 is a direct activator of Shk1 in fission yeast.

Amino Acid Sequence↗

PubMed1999

Short- and long-term outcomes of Wiktor stent implantation at low versus high pressures. Austrian Wiktor Stent Study Group.

A prospective, randomized, multicenter trial was conducted to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure implantation technique. From June 1995 through May 1996, 181 patients were randomly assigned to either low-pressure (6 to 12 atm, group A, n = 94) Wiktor stent placement or to high-pressure postdilation (> or = 13 atm, group B, n = 87) after stent deployment. All patients were followed up clinically for 7 +/- 3 months, with an angiographic follow-up in 154 patients (85%). After stent implantation, neither minimal lumen diameter (MLD) nor percent diameter stenosis (%DS) differed significantly between the 2 groups (MLD, 2.8 +/- 0.5 vs 2.9 +/- 0.5 mm; %DS, 17 +/- 8% vs 16 +/- 9% for groups A and B, respectively). However, a trend toward a larger mean lumen diameter within the stent was observed in group B (3.3 +/- 0.6 vs 3.5 +/- 0.5 mm for groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval -0.01 to 0.29, p = 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 +/- 0.7 vs 2.2 +/- 0.8 mm; %DS, 31 +/- 17% vs 30 +/- 24% for groups A and B, respectively, p = NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (> or = 50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome.

Aged↗

PubMed1999

Genetic dissection of Sle pathogenesis: Sle3 on murine chromosome 7 impacts T cell activation, differentiation, and cell death.

Polyclonal, generalized T cell defects, as well as Ag-specific Th clones, are likely to contribute to pathology in murine lupus, but the genetic bases for these mechanisms remain unknown. Mapping studies indicate that loci on chromosomes 1 (Sle1), 4 (Sle2), 7 (Sle3), and 17 (Sle4) confer disease susceptibility in the NZM2410 lupus strain. B6.NZMc7 mice are C57BL/6 (B6) mice congenic for the NZM2410-derived chromosome 7 susceptibility interval, bearing Sle3. Compared with B6 controls, B6.NZMc7 mice exhibit elevated CD4:CD8 ratios (2.0 vs 1.34 in 1- to 3-mo-old spleens); an age-dependent accumulation of activated CD4+ T cells (33.4% vs 21.9% in 9- to 12-mo-old spleens); a more diffuse splenic architecture; and a stronger immune response to T-dependent, but not T-independent, Ags. In vitro, Sle3-bearing T cells show stronger proliferation, increased expansion of CD4+ T cells, and reduced apoptosis (with or without anti-Fas) following stimulation with anti-CD3. With age, the B cells in this strain acquire an activated phenotype. Thus, the NZM2410 allele of Sle3 appears to impact generalized T cell activation, and this may be causally related to the low grade, polyclonal serum autoantibodies seen in this strain. Epistatic interactions with other loci may be required to transform this relatively benign phenotype into overt autoimmunity, as seen in the NZM2410 strain.

Animals↗

PubMed1999

Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells.

Autocrine interaction of Fas and Fas ligand leads to apoptosis of activated T cells, a process that is critical for the maintenance of peripheral T cell tolerance. Paracrine interactions of Fas ligand with T cells also may play an important role in the maintenance of tolerance, as Fas ligand can create immune-privileged sites and prevent graft rejection by inducing apoptosis in T cells. We surmised that APCs that express Fas ligand might directly induce apoptosis of T cells during presentation of Ag to the T cells, thus inducing Ag-specific, systemic T cell tolerance. Here, we show that profound, specific T cell unresponsiveness to alloantigen was induced by treatment of H-2k mice with H-2b APCs that expressed Fas ligand and that profound T cell unresponsiveness specific for the H-Y Ag was induced by treatment of H-2Db/H-Y TCR transgenic female mice with H-2Db/H-Y APCs that expressed Fas ligand. The induction of this systemic T cell tolerance required the expression of Fas ligand on the APCs as well as the expression of Fas on the T cells. The tolerance was restricted to the Ag presented by the APCs. The rapid and profound clonal deletion of the Ag-specific, peripheral T cells mediated by the Fas ligand-expressing APCs contributed to the induction of tolerance. These findings demonstrate that Ag-specific T cell tolerance can be induced by APCs that express Fas ligand and suggest a novel function for APCs in the induction of T cell apoptosis. Furthermore, they indicate a novel immunointervention strategy for treatment of graft rejection and autoantigen-specific autoimmune diseases.

Animals↗

PubMed1999

Ischemia/reperfusion-induced arrhythmias in anaesthetized rats: a role of Na+ and Ca2+ influx.

We hypothesized that by limiting the Na+ and Ca2+ loading by a blocker/inhibitor of the Na+ channel (lidocaine), Na+ overload (R56865: N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine), Ca2+ channel (verapamil), Na+ -H+ exchange (ethylisobutyl amiloride) or of Na+ -Ca2+ exchange (No. 7943: 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), it should be possible to reduce ischemia/reperfusion-induced arrhythmias. To test this hypothesis, we used anaesthetized rats subjected to 5 min of coronary artery occlusion followed by 10 min of reperfusion to study antiarrhythmic effects of above compounds on reperfusion-induced ventricular premature beats, ventricular tachycardia, and reversible and irreversible ventricular fibrillation. Compound or saline was administered as an intravenous bolus injection at 5 min before ischemia. Pretreatment with lidocaine (5 mg/kg), verapamil (0.63 mg/kg), R56865 (0.63 mg/kg) or ethylisobutyl amiloride (1.25 mg/kg) significantly reduced or abolished all types of ventricular arrhythmias. However, pretreatment with verapamil was associated with second or third degree heart block in 3 out of 12 animals. Pretreatment with No. 7943 did not significantly influence the ischemia/reperfusion-induced ventricular arrhythmias. The present results suggest that both intracellular Na+ -and Ca2+ -loading play important roles in reperfusion-induced ventricular arrhythmias and the inhibition of Na+ -Ca2+ exchange to limit Ca2+ loading probably does not play any important role in ischemia/reperfusion-induced arrhythmias in anaesthetized rats.

Amiloride↗

PubMed1999

Increased cancer risk among relatives of nonsmoking lung cancer cases.

Lung cancer has been shown to aggregate in families of nonsmoking lung cancer cases with an earlier age at onset. The current study evaluates whether relatives of nonsmoking lung cancer cases are at increased risk of cancers at sites other than lung. Families were identified through 257 population-based, nonsmoking lung cancer cases and 277 population-based, nonsmoking controls residing in metropolitan Detroit. Data were collected for 2,252 relatives of cases and 2,408 relatives of controls. First-degree relatives of nonsmoking lung cancer cases were at 1.52-fold (95% CI, 1.02-2.27) increased risk of cancer of the digestive system after adjustment for each relative's age, race, sex, and smoking status. Relative risk estimates also were elevated, but not significantly, for tobacco-related cancers (RR = 1.39) and breast cancer (RR = 1.72). Among first-degree relatives of younger probands (age 40-59), risk was non-significantly increased 72% (95% CI 0.95-3.10) for all cancers combined and 3.14-fold for cancers of the digestive system (95% CI 0.76-12.9). Nonsmoking relatives of cases were at increased risk of all cancer sites combined (RR = 1.32; 95% CI 1.003-1.73), cancers other than lung (RR = 1.37; 95% CI 1.03-1.82), and digestive system cancers (RR = 2.01; 95% CI 1.20-3.37). These findings of moderate familial aggregation for cancers of the lung, digestive system, breast, and tobacco-related sites suggest that common susceptibility genes may act to increase risk for a variety of cancers in families.

Adult↗

PubMed1999

Lung cancer risk in families of nonsmoking probands: heterogeneity by age at diagnosis.

In an earlier investigation, we did not detect a major genetic component to lung cancer in families of nonsmoking lung cancer probands. However, heterogeneity with respect to familial aggregation, based on probands' age at diagnosis, was evident. We reanalyzed our previously collected data of 257 families, stratified by age at diagnosis of the probands, using complex segregation analysis. We specifically tested the effects of a Mendelian diallelic gene, history of tobacco use, and history of selected chronic lung diseases in families with a proband diagnosed at the age of 60 years or older and in families with a younger proband (i.e. , under 60 years of age). Cases were identified from the Metropolitan Detroit Cancer Surveillance System. Information on lung cancer occurrence, smoking history, and chronic respiratory diseases in first-degree relatives was obtained for 210 older probands and for 47 younger probands. In older probands' families, no evidence of a major genetic effect was detected. A history of emphysema and tobacco-smoke exposure were found to be significant risk factors. In younger probands' families, a Mendelian codominant model with significant modifying effects of smoking and chronic bronchitis best explained the observed data. Our results suggest the presence of a high-risk gene contributing to early-onset lung cancer in a population where the probands are nonsmokers.

Adult↗

PubMed1999

Cigarette smoking among medical college students in Wuhan, People's Republic of China.

BACKGROUND: This study examined cigarette smoking among a sample of medical college students in Wuhan, People's Republic of China. Specific cultural factors associated with cigarette smoking in China were discussed and issues which need to be studied in the future are presented. METHODS: A self-administrated questionnaire was administered to a sample of 1,611 medical students in 1995. Smoking status was based on self-reported use of cigarettes within the preceding 180 days. Information about demographic characteristics, home residence, annual family income, and smoking status of family members was also obtained. RESULTS: A total of 1,540 (1,201 males and 339 females) completed and returned the questionnaires (response rate 95.6%). None of the 339 female students surveyed reported cigarette smoking. A total of 37.7% (95% confidence interval (CI) = 35.0-40.5%) of the male medical students were current smokers, and 5. 3% (95% CI = 4.0-6.6%) were former smokers. The mean age of beginning to smoke was 16.5 years (95% CI = 8.7-24.3 years). The major reasons for first smoking were stress (42.8%, 95% CI = 38.2-47. 4%), curiosity (34.4%, 95% CI = 29.6-38.4%), and loneliness (33.7%, 95% CI = 28.7-37.4%). Multivariate analyses suggested that age, college year, and having a family member who smoked were significantly associated with cigarette smoking. CONCLUSIONS: The results indicated a need to provide comprehensive tobacco use prevention programs among medical students.

Adolescent↗

PubMed1999

Bisindolylmaleimide VIII facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases.

Fas-mediated apoptosis is essential for the elimination of cells, and impaired apoptosis can have severe detrimental consequences. Bisindolylmaleimide VIII potentiated Fas-mediated apoptosis in human astrocytoma 1321N1 cells and in Molt-4T cells, both of which were devoid of apoptosis induced by anti-Fas antibody in the absence of bisindolylmaleimide VIII, and in Jurkat and CEM-6 T cells, which showed slight and moderate apoptotic responses, respectively, to low levels of Fas stimulation. Potentiation of Fas-mediated apoptosis by bisindolylmaleimide VIII was selective for activated, rather than non-activated, T cells, and was Fas-dependent, as it was not observed in T cells from Fas-deficient lpr/lpr mice. Administration of bisindolylmaleimide VIII to rats during autoantigen stimulation prevented the development of symptoms of T cell-mediated autoimmune diseases in two models, the Lewis rat model of experimental allergic encephalitis and the Lewis adjuvant arthritis model. Thus, the use of agents such as bisindolylmaleimide VIII may be therapeutically useful for supporting more effective elimination of detrimental cells through enhancement of Fas-dependent apoptosis signaling.

Animals↗

PubMed1999

Increased TNF-alpha, IL-1 beta and IL-6 levels in the bronchoalveolar lavage fluid with the upregulation of their mRNA in macrophages lavaged from patients with active pulmonary tuberculosis.

SETTING: We hypothesized that patients with active pulmonary tuberculosis (TB) have tubercular pneumonitis and that alveolar macrophages at these sites release proinflammatory cytokines, resulting in high levels of cytokines in alveolar epithelial lining fluid. OBJECTIVE: To measure cytokine levels in bronchoalveolar lavage fluid (BALF) and to confirm the source of any cytokines by examination of alveolar macrophage cytokine mRNA. DESIGN: Seventeen active pulmonary TB patients and 15 healthy controls were prospectively studied. Bronchoalveolar lavage (BAL) was performed, proinflammatory cytokine levels were determined and alveolar macrophages isolated from BALF were prepared for RNA extraction and Northern blot analysis. RESULTS: Compared with healthy controls, TNF-alpha, IL-1 beta and IL-6 in BALF were all significantly higher in patients with active pulmonary TB, 298.7 +/- 85.9 vs. 8.9 +/- 2.7 (P = 0.0001); 164.4 +/- 67.5 vs. 8.9 +/- 2.7 (P = 0.003); 969.2 +/- 214.2 vs. 86.4 +/- 17.0 (mean +/- SE pg/ml) (P = 0.0001), respectively. Only TNF-alpha and IL-6 levels were significantly higher in sera of active pulmonary TB patients, 92.3 +/- 28.7 vs. 3.5 +/- 1.2; 15.2 +/- 5.4 vs. 2.1 +/- 2.1, respectively. Northern blot analysis revealed increased gene expression of these alveolar macrophage cytokines in patients with active pulmonary TB compared healthy controls. CONCLUSION: Significantly higher levels of TNF-alpha, IL-1 beta and IL-6 were found in BALF from patients with active pulmonary TB, and were released by alveolar macrophages in the TB lesions.

Adult↗

PubMed1999

Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis.

The replication initiation protein Cdc6p forms a tight complex with Cdc28p, specifically with forms of the kinase that are competent to promote replication initiation. We now show that potential sites of Cdc28 phosphorylation in Cdc6p are required for the regulated destruction of Cdc6p that has been shown to occur during the Saccharomyces cerevisiae cell cycle. Analysis of Cdc6p phosphorylation site mutants and of the requirement for Cdc28p in an in vitro ubiquitination system suggests that targeting of Cdc6p for degradation is more complex than previously proposed. First, phosphorylation of N-terminal sites targets Cdc6p for polyubiquitination probably, as expected, through promoting interaction with Cdc4p, an F box protein involved in substrate recognition by the Skp1-Cdc53-F-box protein (SCF) ubiquitin ligase. However, in addition, mutation of a single, C-terminal site stabilizes Cdc6p in G2 phase cells without affecting substrate recognition by SCF in vitro, demonstrating a second and novel requirement for specific phosphorylation in degradation of Cdc6p. SCF-Cdc4p- and N-terminal phosphorylation site-dependent ubiquitination appears to be mediated preferentially by Clbp/Cdc28p complexes rather than by Clnp/Cdc28ps, suggesting a way in which phosphorylation of Cdc6p might control the timing of its degradation at then end of G1 phase of the cell cycle. The stable cdc6 mutants show no apparent replication defects in wild-type strains. However, stabilization through mutation of three N-terminal phosphorylation sites or of the single C-terminal phosphorylation site leads to dominant lethality when combined with certain mutations in the anaphase-promoting complex.

Anaphase-Promoting Complex-Cyclosome↗

PubMed1999

Secretion of ovarian inhibin and its physiologic roles in the regulation of follicle-stimulating hormone secretion during the estrous cycle of the female guinea pig.

To characterize inhibin secretion during the estrous cycle in guinea pigs, the concentrations of plasma inhibin, estradiol, progesterone, and FSH were determined. A significant positive correlation was observed between inhibin and estradiol throughout the estrous cycle. Plasma inhibin and estradiol started to increase a few days before ovulation (Day 0 = day of estimated ovulation), and decreased after ovulation. These two hormones remained low during the luteal phase. The immunoreactivity of inhibin alpha, betaA, and betaB subunits was colocalized in the granulosa cells of one or two healthy large follicles in the ovary before ovulation. There was no positive reaction of inhibin alpha and beta subunits in the corpora lutea or other follicles. Ovariectomy resulted in an abrupt decrease in plasma inhibin and a significant increase in plasma FSH. Injection of anti-inhibin serum into adult female guinea pigs induced an elevation in plasma FSH in a dose-dependent manner. This report presents the first description of sequential changes in plasma inhibin and estradiol during the estrous cycle of guinea pigs. Results suggest that inhibin is secreted mainly by granulosa cells of a few healthy large follicles in the ovary and that it plays an important role in the regulation of FSH secretion during the estrous cycle in guinea pigs.

Animals↗

PubMed1999

Coronary risk factors influence plaque morphology in patients with unstable angina.

BACKGROUND: The risk of plaque disruption and subsequent thrombosis in patients with unstable angina depends on the plaque type and size. DESIGN: Intravascular ultrasound (IVUS) was employed to illustrate the correlation between risk factors and plaque morphology in patients with unstable angina. METHODS: In a prospective study of 60 of 95 patients consecutively admitted with unstable angina [41 men, aged 61.2 +/- 8.1 years (mean +/- SD)], qualitative (soft and hard plaque, thrombus, calcification, eccentricity, adaptive and constrictive remodeling) and quantitative [lumen, external elastic membrane (EEM) and plaque cross-sectional area (CSA) and plaque burden] IVUS data relating to the target lesion, and proximal and distal reference segments were analyzed and correlated with risk factors. Univariate and multivariate nominal logistic regression analyses and analyses of variance were used to determine the independent predictors for IVUS morphology. RESULTS: For plaque composition univariate analysis showed a younger age (< 60 years) to be a predictor for adaptive remodeling (P = 0.019), and an older age to be a predictor for constrictive remodeling (P = 0.021). Hypercholesterolemia, smoking and sex were associated with a higher frequency of thrombus (P = 0.044, 0.038 and 0.043, respectively). Multivariate analyses revealed that only younger and older ages were independent predictors for adaptive and constrictive remodeling (P = 0.039 and P = 0.045). For plaque size, univariate and multivariate analyses demonstrated that diabetes mellitus and hypercholesterolemia were independent predictors for greater plaque (13.5 +/- 5.72 versus 10.17 +/- 4.6 mm2, P = 0.015, for diabetic versus non-diabetic patients; 12.0 +/- 5.35 versus 9.03 +/- 3.76 mm2, P = 0.010, for hypercholesterolemic versus normocholesterolemic patients) and EEM CSA (17.16 +/- 5.81 versus 14.3 +/- 5.1 mm2, P = 0.033, for diabetic versus non-diabetic patients; 16.57 +/- 5.49 versus 12.25 +/- 3.8 mm2, P = 0.001, for hypercholesterolemic versus normocholesterolemic patients) at the target lesion. Hypercholesterolemia was associated with significantly greater plaque and EEM CSA in both proximal and distal reference segments. CONCLUSIONS: Multivariate analyses indicated that age, diabetes and hypercholesterolemia are independent predictors for plaque morphology in patients with unstable angina.

Aged↗

PubMed1999

Direct binding and In vivo regulation of the fission yeast p21-activated kinase shk1 by the SH3 domain protein scd2.

The Ste20/p21-activated kinase homolog Shk1 is essential for viability and required for normal morphology, mating, and cell cycle control in the fission yeast Schizosaccharomyces pombe. Shk1 is regulated by the p21 G protein Cdc42, which has been shown to form a complex with the SH3 domain protein Scd2 (also called Ral3). In this study, we investigated whether Scd2 plays a role in regulating Shk1 function. We found that recombinant Scd2 and Shk1 interact directly in vitro and that they interact in vivo, as determined by the two-hybrid assay and genetic analyses in fission yeast. The second of two N-terminal SH3 domains of Scd2 is both necessary and sufficient for interaction with Shk1. While full-length Scd2 interacted with only the R1 N-terminal regulatory subdomain of Shk1, a C-terminal deletion mutant of Scd2 interacted with both the R1 and R3 subdomains of Shk1, suggesting that the non-SH3 C-terminal domain of Scd2 may be involved in defining specificity in SH3 binding domain recognition. Overexpression of Scd2 stimulated the autophosphorylation activity of wild-type Shk1 in fission yeast but, consistent with results of genetic analyses, did not stimulate the activity of a Shk1 protein lacking the R1 subdomain. Results of additional two-hybrid experiments suggest that Scd2 may stimulate Shk1 catalytic function, at least in part, by positively modulating protein-protein interaction between Cdc42 and Shk1. We propose that Scd2 functions as an organizing center, or scaffold, for the Cdc42 complex in fission yeast and that it acts in concert with Cdc42 to positively regulate Shk1 function.

Binding Sites↗

PubMed1999

Arterial remodelling of native human coronary arteries in patients with unstable angina pectoris: a prospective intravascular ultrasound study.

OBJECTIVE: To investigate the use of intravascular ultrasound (IVUS) in detecting the presence of arterial remodelling in patients with unstable angina. DESIGN: Prospective case study. PATIENTS: 60 of 95 consecutively admitted patients with unstable angina (41 male, 19 female), mean (SD) age 61.2 (8.1) years. INTERVENTIONS: Qualitative and quantitative coronary angiography and IVUS. MAIN OUTCOME MEASURES: Adaptive or constrictive remodelling (AR, CR) was considered present when the cross sectional area of the external elastic membrane at the lesion site was larger than the proximal cross sectional area or smaller than the distal cross sectional area, respectively. RESULTS: 22 of the 60 patients (37%) showed AR and 14 (23%) showed CR. No remodelling was seen in 24 patients (group NR). The plaque contained more thrombus and plaque rupture in group AR than in groups CR and NR (thrombus: 91% v 50% and 67%, respectively, p = 0.023; rupture: 73% v 29% and 42%, p = 0.020). AR was associated with a larger plaque cross sectional area (12.6 (SD 4.6) mm2 v 10.8 (6.3) and 9.2 (3.7) mm2, p = 0.001) and larger external elastic membrane cross sectional area (16.5 (5.8) mm2 v 13.2 (5.2) and 14.4 (3.6) mm2, p = 0.01 in group AR v groups CR and NR, respectively), while the plaque burden was larger in groups AR (74.9 (9.1)%) and CR (72.4 (16.6)%) than in group NR (66.2 (18.1)%, p = 0.005). CONCLUSIONS: IVUS is capable of detecting adaptive and constrictive remodelling of target lesions and its relation to plaque morphology in unstable angina.

Aged↗

PubMed1999

Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies.

Sle1 and Sle3 are 2 loci that confer susceptibility to lupus nephritis in the NZM2410 strain of mice. Our previous work has shown that B6.NZMc1 mice, congenic for Sle1, exhibit loss of tolerance to chromatin but do not develop any pathogenic autoantibodies or disease. B6.NZMc7 mice, congenic for Sle3, exhibit low-grade polyclonal B- and T-cell activation, elevated CD4/CD8 ratios, and mildly penetrant glomerulonephritis. In contrast to these monocongenics, the present study reveals that B6.NZMc1|c7 mice, bicongenic for Sle1 and Sle3, exhibit splenomegaly, significantly expanded populations of activated B and CD4(+) T cells, and a robust, variegated IgG autoantibody response targeting multiple components of chromatin (including double-stranded DNA), intact glomeruli, and basement membrane matrix antigens. As one might predict, these mice, particularly the females, exhibit highly penetrant glomerulonephritis. These findings lend strong support to a two-step epistatic model for the formation of pathogenic, nephrophilic autoantibodies in lupus. Whereas loci such as Sle1 may serve to breach tolerance to chromatin, full-blown pathogenic maturation of the autoantibody response appears to require additional input from other loci (such as Sle3) and gender-based factors.

Animals↗