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Biomedical subjects

Y Jiang

Publications and source records attributed to Y Jiang.

At least 289 records · Page 16Linked to original sources

Lipid peroxidation and antioxidant activities in rat testis after chronic cocaine administration.

OBJECTIVES: Our recent study has shown that cocaine has adverse action on spermatogenesis and fertility in male rats. Adverse effects of cocaine on the testes may be mediated by oxidative damage and subsequent lipid peroxidation. Glutathione is a cellular antioxidant and is found in high concentrations in the rat testes. In this study, the effects of chronic cocaine administration on the activities of glutathione peroxidase, the level of testicular reduced glutathione, and lipid peroxidation were investigated. METHODS: Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg/kg body weight) subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed at 15, 30, 60, and 90 days after cocaine injection. Tissues were washed and homogenized in ice-cold metaphosphoric acid solution or Tris-HCI buffer. Reduced glutathione, glutathione peroxidase, and malonaldehyde levels were determined by colorimetric assay. Statistical analysis was performed using analysis of variance. RESULTS: Testicular reduced glutathione and glutathione peroxidase were significantly decreased in the treatment testes 15, 30, 60, and 90 days after chronic cocaine injection compared with controls (P <0.05). The testicular malonaldehyde level was 20.8% (P <0.05), 22.1% (P <0.05), 31.2% (P <0.05), and 24.7% (P <0.05) above the control value on days 15, 30, 60, and 90, respectively. CONCLUSIONS: Our findings demonstrate that chronic administration of cocaine to male rats induces a depletion of reduced glutathione and glutathione peroxidase. Adverse effects of cocaine on the testes are at least in part due to impairment of the function of the antioxidant defense and further enhancement of lipid peroxidation.

Animals↗

Computer-aided diagnosis in radiology: potential and pitfalls.

Computer-aided diagnosis (CAD) may be defined as a diagnosis made by a physician who takes into account the computer output as a second opinion. The purpose of CAD is to improve the diagnostic accuracy and the consistency of the radiologists' image interpretation. This article is to provide a brief overview of some of CAD schemes for detection and differential diagnosis of pulmonary nodules and interstitial opacities in chest radiographs as well as clustered micro-calcifications and masses in mammograms. ROC analysis clearly indicated that the radiologists' performances were significantly improved when the computer output was available. An intelligent CAD workstation was developed for detection of breast lesions in mammograms. Results obtained from the first 10,000 cases indicated the potential of CAD in detecting approximately one-half of 'missed' breast cancer.

Breast Neoplasms↗

Effect of reflection of arterial pressure on carotid circulation in essential hypertension.

Pressure wave reflection plays a pivotal role in the augmentation of systolic blood pressure. In the present study, the association between reflection of pressure wave and structural and functional alteration, including blood flow, in the common carotid artery was investigated in 70 hospitalized essential hypertensive patients. The reflection of pressure was estimated by the "augmentation index" of the carotid arterial pressure waveform. The carotid augmentation index was significantly related to age (r = 0.36), body height (r = -0.30), intima-media thickening (r = 0.28), number of plaques (r = 0.44), stiffness of the carotid artery (r = 0.38), diastolic carotid flow velocity (r = -0.31), and left ventricular mass index (r = 0.33). Furthermore, the reflection of arterial pressure showed a significant negative correlation with diastolic/systolic ratio of blood flow velocity in the carotid artery (r = -0.41, P = .0005). Stepwise regression analysis revealed that age and left ventricular mass index were independent determinants for the carotid augmentation index. These findings indicate that the reflection of arterial pressure is related to morphological and functional alterations of the carotid artery, including a relative reduction of diastolic blood flow.

Adult↗

Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.

Mutant ataxin-1, the expanded polyglutamine protein causing spinocerebellar ataxia type 1 (SCA1), aggregates in ubiquitin-positive nuclear inclusions (NI) that alter proteasome distribution in affected SCA1 patient neurons. Here, we observed that ataxin-1 is degraded by the ubiquitin-proteasome pathway. While ataxin-1 [2Q] and mutant ataxin-1 [92Q] are polyubiquitinated equally well in vitro, the mutant form is three times more resistant to degradation. Inhibiting proteasomal degradation promotes ataxin-1 aggregation in transfected cells. And in mice, Purkinje cells that express mutant ataxin-1 but not a ubiquitin-protein ligase have significantly fewer NIs. Nonetheless, the Purkinje cell pathology is markedly worse than that of SCA1 mice. Taken together, NIs are not necessary to induce neurodegeneration, but impaired proteasomal degradation of mutant ataxin-1 may contribute to SCA1 pathogenesis.

Animals↗

Improving breast cancer diagnosis with computer-aided diagnosis.

RATIONALE AND OBJECTIVES: The purpose of this study was to test whether computer-aided diagnosis (CAD) can improve radiologists' performance in breast cancer diagnosis. MATERIALS AND METHODS: The computer classification scheme used in this study estimates the likelihood of malignancy for clustered microcalcifications based on eight computer-extracted features obtained from standard-view mammograms. One hundred four histologically verified cases of microcalcifications (46 malignant, 58 benign) in a near-consecutive biopsy series were used in this study. Observer performance was measured on 10 radiologists who read the original standard- and magnification-view mammograms. The computer aid provided a percentage estimate of the likelihood of malignancy. Comparison was made between computer-aided performance and unaided (routine clinical) performance by using receiver operating characteristic (ROC) analysis and by comparing biopsy recommendations. RESULTS: The average ROC curve area (Az) increased from 0.61 without aid to 0.75 with the computer aid (P < .0001). On average, with the computer aid, each observer recommended 6.4 additional biopsies for cases with malignant lesions (P = .0006) and 6.0 fewer biopsies for cases with benign lesions (P = .003). This improvement corresponded to increases in sensitivity (from 73.5% to 87.4%), specificity (from 31.6% to 41.9%), and hypothetical positive biopsy yield (from 46% to 55%). CONCLUSION: CAD can be used to improve radiologists' performance in breast cancer diagnosis.

Area Under Curve↗

Perspectives on bone mechanical properties and adaptive response to mechanical challenge.

The bones of the human skeleton serve a mechanical function besides providing a reservoir for calcium and hematopoietic homeostatis. When mechanically challenged, they usually respond and adapt; failure to do so can result in fracture. The mechanical behavior of bone is determined by bone mass and its material properties and by its geometry and architecture. Therefore, in vivo noninvasive measurements of bone mass, geometry, and structure can predict bone strength and are usually employed as a useful-if not always reliable-way to estimate bone fragility, whereas direct bone biomechanical testing in vitro can provide detailed information about mechanical strength. Because bone strains are likely to be regulators of bone mass and strength, exercise protocols designed to counteract the effects of osteoporosis should load the target bone with repeated high peak forces and high strain rates or high impacts on a long-term basis. Such a protocol creates varied strain distributions throughout the bone structure, producing short, repeated strains on the bone in directions to which it is unaccustomed. Exercise in this manner can maintain and perhaps increase bone mass and improve mechanical properties and neuromuscular competency, reducing skeletal fragility and the predisposition to falls.

Adaptation, Physiological↗

The impact of visual exploration of judgments of whether a gap is crossable.

When observers look down into a gap in the ground plane, their judgments of the widest gap they can step across (gapmax) decrease as gap depth increases (Y. Jiang & L. S. Mark, 1994). This study investigated the possibility that Jiang and Mark's viewing conditions did not afford observers a sufficient opportunity to perform exploratory movements needed to detect information about gap width. Experiment 1 showed that the gap depth by gaze interaction disappeared only when restrictions were not imposed on observers' exploratory activities (eye, head, and body movements). Experiment 2 showed that observers tended to see the vertical surface as slanted away from them, which made the bottom of the surface appear farther away from them than the top. Only when observers were able to view the gap binocularly under conditions that did not restrict exploratory activity did their slant perception improve and their gapmax judgments no longer covary with gap depth. The data indicate that the exploratory movements of prospective actors are essential for the pickup of information about their action capabilities.

Adult↗

Age-related reduction in 3-D visual motion priming.

In 3 experiments, younger and older adults judged the perceived motion of three-dimensional (3-D) figures that rotated in depth either unambiguously or ambiguously. Both groups were found to be equivalent in judging the direction of single rotations of the simulated 3-D objects (Experiment 1). In Experiments 2 and 3, a single unambiguous rotation (prime) was followed 0-3200 ms later by an ambiguous rotation (target). Motion priming was indicated by the disambiguation of the second rotation by the first rotation. 3-D motion priming was initially found to be similar in young and old, but it rapidly reduced in the older participants compared to the younger ones. Using a nonluminance depth cue--occlusion--to induce 3-D motion, diminished contrast sensitivity in the elderly was ruled out as a cause of the reduced priming. The results show that 3-D motion priming exhibits robust age-related decline. An age-related decrease in temporal persistence may account for the reduction in 3-D motion priming in older adults.

Adult↗

Genetic polymorphism of murine tissue plasminogen activator associated with antiphospholipid syndrome.

In a subset of patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome characterized by thrombocytopenia, thrombosis, recurrent abortion and antiphospholipid antibodies develops. Male (NZW x BXSB) F1 mice are widely used as a model for SLE-associated antiphospholipid syndrome. Our earlier genetic studies showed that one susceptibility allele for thrombocytopenia and associated IgG platelet-binding autoantibodies in male (NZW x BXSB) F1 mice was linked to the BXSB-type polymorphic microsatellite D8Mit96, located in proximity to the gene Plat for tissue-type plasminogen activator (t-PA). In the present studies, sequence analyses for structural and promoter regions of Plat revealed a single nucleotide polymorphism encoding a catalytic domain of t-PA, with an amino acid substitution of anionic Glu366 in NZW for a cationic Lys in BXSB. Progeny studies using NZW x (NZW x BXSB) F1 male backcross mice showed that the BXSB Plat allele was significantly associated with high levels of both platelet-binding antibodies and thrombocytopenia. Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen. Thus, the BXSB-type Plat may be one susceptibility allele for the multigenic antiphospholipid syndrome seen in (NZW x BXSB) F1 mice. Potential mechanisms are discussed.

Amino Acid Sequence↗

Induction of selected lipid metabolic enzymes and differentiation-linked structural proteins by air exposure in fetal rat skin explants.

The epidermal permeability barrier of premature infants matures rapidly following birth. Previous studies suggest that air exposure could contribute to this acceleration, because: (i) development of a structurally and functionally mature barrier accelerates when fetal rat skin explants are incubated at an air-medium interface, and (ii) occlusion with a water-impermeable membrane prevents this acceleration. To investigate further the effects of air exposure on epidermal barrier ontogenesis, we compared the activities of several key enzymes of lipid metabolism and gene expression of protein markers of epidermal differentiation in fetal rat skin explants grown immersed versus air exposed. The rate-limiting enzymes of cholesterol (HMG CoA reductase) and ceramide (serine palmitoyl transferase) synthesis were not affected. In contrast, the normal developmental increases in activities of glucosylceramide synthase and cholesterol sulfotransferase, responsible for the synthesis of glucosylceramides and cholesterol sulfate, respectively, were accelerated further by air exposure. Additionally, two enzymes required for the final stages of barrier maturation and essential for normal stratum corneum function, beta-glucocerebrosidase, which converts glucosylceramide to ceramide, and steroid sulfatase, which desulfates cholesterol sulfate, also increased with air exposure. Furthermore, filaggrin and loricrin mRNA levels, and filaggrin, loricrin, and involucrin protein levels all increased with air exposure. Finally, occlusion with a water-impermeable membrane prevented both the air-exposure-induced increase in lipid enzyme activity, and the expression of loricrin, filaggrin, and involucrin. Thus, air exposure stimulates selected lipid metabolic enzymes and the gene expression of key structural proteins in fetal epidermis, providing a biochemical basis for air-induced acceleration of permeability barrier maturation in premature infants.

Acyltransferases↗

Fetal epidermal differentiation and barrier development In vivo is accelerated by nuclear hormone receptor activators.

Nuclear receptors which interact with the retinoid X receptor are involved in the regulation of epidermal differentiation and development. We have recently shown that activators of the peroxisome proliferator-activated receptor and of the farnesoid X-activated receptor accelerate epidermal barrier maturation in fetal rat skin in vitro. In this study we asked whether cutaneous development in utero was affected by peroxisome proliferator-activated receptor or farnesoid X-activated receptor activators, or by an activator of another retinoid X receptor partner, liver X receptor. Activators of the peroxisome proliferator-activated receptor (clofibrate or linoleic acid), farnesoid X-activated receptor (farnesol or juvenile hormone III), or liver X receptor (22R-hydroxycholesterol), were injected into the amniotic fluid of fetal rats on gestational day 17. Fetal epidermal barrier function and morphology was assessed on day 19. Whereas vehicle-treated fetal rats displayed no measurable barrier (transepidermal water loss > 10 mg per cm2 per h), a measurable barrier was induced by the intra-amniotic administration of all activators tested (transepidermal water loss range 4.0-8.5 mg per cm2 per h). By light microscopy, control pups lacked a well-defined stratum corneum, whereas a distinct stratum corneum and a thickened stratum granulosum were present in treated pups. By electron microscopy, the extracellular spaces of the stratum corneum in control pups revealed a paucity of mature lamellar unit structures, whereas these structures filled the stratum corneum interstices in treated pups. Additionally, protein and mRNA levels of loricrin and filaggrin, two structural proteins of stratum corneum, were increased in treated epidermis, as were the activities of two lipid catabolic enzymes critical to stratum corneum function, beta-glucocerebrosidase and steroid sulfatase. Finally, peroxisome proliferator-activated receptor-alpha and -delta and liver X receptor-alpha and -beta mRNAs were detected in fetal epidermis by reverse transcriptase-polymerase chain reaction and northern analyses. The presence of these receptors and the ability of their activators to stimulate epidermal barrier and stratum corneum development suggest a physiologic role for peroxisome proliferator-activated receptor and liver X receptor and their endogenous ligands in the regulation of cutaneous development.

Amnion↗

Linkage detection adaptive to linkage disequilibrium: the disequilibrium maximum-likelihood-binomial test for affected-sibship data.

It has been demonstrated in the literature that the transmission/disequilibrium test (TDT) has higher power than the affected-sib-pair (ASP) mean test when linkage disequilibrium (LD) is strong but that the mean test has higher power when LD is weak. Thus, for ASP data, it seems clear that the TDT should be used when LD is strong but that the mean test or other linkage tests should be used when LD is weak or absent. However, in practice, it may be difficult to follow such a guideline, because the extent of LD is often unknown. Even with a highly dense genetic-marker map, in which some markers should be located near the disease-predisposing mutation, strong LD is not inevitable. Besides the genetic distance, LD is also affected by many factors, such as the allelic heterogeneity at the disease locus, the initial LD, the allelic frequencies at both disease locus and marker locus, and the age of the mutation. Therefore, it is of interest to develop methods that are adaptive to the extent of LD. In this report, we propose a disequilibrium maximum-binomial-likelihood (DMLB) test that incorporates LD in the maximum-binomial-likelihood (MLB) test. Examination of the corresponding score statistics shows that this method adaptively combines two sources of information: (a) the identity-by-descent (IBD) sharing score, which is informative for linkage regardless of the existence of LD, and (b) the contrast between allele-specific IBD sharing score, which is informative for linkage only in the presence of LD. For ASP data, the proposed test has higher power than either the TDT or the mean test when the extent of LD ranges from moderate to strong. Only when LD is very weak or absent is the DMLB slightly less powerful than the mean test; in such cases, the TDT has essentially no power to detect linkage. Therefore, the DMLB test is an interesting approach to linkage detection when the extent of LD is unknown.

Alleles↗

Genetically determined aberrant down-regulation of FcgammaRIIB1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multigenic disease associated with IgG hypergammaglobulinemia, IgG anti-nuclear antibodies and immune complex (IC)-type glomerulonephritis. In both human and murine SLE, one susceptibility allele has been mapped to the interval linked to the IgG Fc receptor II (FcgammaRII) gene on chromosome 1. In spontaneous SLE models of NZB and (NZB x NZW) F(1) mice, expression of FcgammaRIIB1, which acts as a negative regulator for B cells, was abnormally down-regulated in follicular germinal center B cells from aged mice, compared to findings in non-SLE NZW, while levels in non-germinal center B cells were practically identical. Such strain differences were also evident in young mice upon in vivo stimulation with foreign antigens. In the FcgammaRIIB promoter region, the NZB allele has two deletion sites, including transcription factor-binding sites. Analyses using (NZB x NZW) F(1) x NZW backcross mice showed that this NZB allele was significantly linked to hyper-IgG, irrespective of the MHC haplotype, while high levels of IgG antibodies specific for DNA were regulated by a combinatorial effect of the F(1)-unique MHC haplotype and the NZB FcgammaRIIB allele. Therefore, the FcgammaRIIB promoter polymorphism may possibly predispose to SLE through germinal center B cells abnormally down-regulating FcgammaRIIB1 expression upon autoantigen stimulations and thus escaping negative signals for IgG production.

Age Factors↗

IL-2 may be a limiting factor precluding lymphocytes from genetically resistant mice from responding to HgCl2.

It is unclear how HgCl2 causes autoimmune disorders in genetically predisposed rodents. We investigated the cytokine profile induced by HgCl2 in vitro, and found a high frequency of IL-2-secreting cells in splenocytes from susceptible A.SW and BALB/c mice, whereas the frequency was low in cells from resistant DBA/2 mice. More IL-2-secreting cells were induced in splenocytes from the high responder A.SW mice than in cells from the intermediate responder BALB/c mice. Unexpectedly, a similar level of IL-4 production was induced in splenocytes from BALB/c and DBA/2 mice. IL-4 production was high in unstimulated cells from A.SW mice and was further increased by HgCl2. IFN-gamma-secreting cells were detectable in splenocytes from all three strains after activation by HgCl2. The highest frequency of IL-10-secreting cells was found in splenocytes from A.SW mice after activation, whereas the frequency was lower in cells from BALB/c mice, followed by cells from DBA/2 mice. We showed that neutralizing anti-IL-2 antibody profoundly inhibited the in vitro response to HgCl2. In contrast, antibodies against IL-4, IFN-gamma and IL-10 did not significantly affect the response of splenocytes from either A.SW or DBA/2 mice. The addition of IL-2 into cultures enhanced the proliferative response to HgCl2 in splenocytes from DBA/2 mice to a level comparable with that in cells from BALB/c mice. We found no evidence for the suggestion that HgCl2 induces a Th1/Th2 imbalance in resistant/susceptible strains. We conclude that IL-2 may be a limiting factor precluding lymphocytes from resistant mice from responding to HgCl2.

Animals↗

Cocaine induced apoptosis in rat testes.

PURPOSE: Exposure of rats to chronic cocaine results in disruption of spermatogenesis including reduction of germ cells. However, the cellular mechanism responsible for the testicular damage in testes is still unknown. We have studied the role of apoptosis in cocaine induced testicular damage. MATERIALS AND METHODS: Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg./kg. body weight) subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed at 15, 30, 60, and 90 days of cocaine administration. In situ detection of germ cells with DNA strand breaks in paraffin-embedded testicular section (5 microm.) was achieved by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labeling (TUNEL) method. DNA fragmentation was also determined by gel electrophoresis. RESULTS: Apoptotic cells were found in the spermatocytes and spermatogonia of germinal epithelium. Less than 7% of seminiferous tubule cross sections showed a high level of apoptosis (> or =3 apoptotic cells per tubule) in control animals compared with experimental group where 25% of the tubules showed a high level of apoptosis (p<0.05). The number of apoptotic cells was significantly increased by 15 days, peaked at 30 days and persisted up to 90 days of cocaine exposure when compared with controls (p<0.05). DNA isolated from the cocaine treated testes displayed a clear ladder pattern whereas the DNA from controls did not. CONCLUSIONS: The experimental results presented here suggest that cocaine exposure leads to significant apoptosis in rat testes and the mechanism of cocaine induced testicular injury may be related to the induction of apoptosis.

Animals↗

Hysteresis and avalanches in two-dimensional foam rheology simulations.

Foams have unique rheological properties that range from solidlike to fluidlike. We study two-dimensional noncoarsening foams of different disorder under shear in a Monte Carlo simulation, using a driven large-Q Potts model. Simulations of periodic shear on an ordered foam show several different response regimes. At small strain amplitudes, bubbles deform and recover their shapes elastically, and the macroscopic response is that of a linear elastic cellular material. For increasing strain amplitude, the energy-strain curve starts to exhibit hysteresis before any topological rearrangements occur, indicating a macroscopic viscoelastic response. When the applied strain amplitude exceeds a critical value, the yield strain, topological rearrangements occur, the foam starts to flow, and we observe macroscopic irreversibility. We find that the dynamics of topological rearrangements depend sensitively on the structural disorder. Structural disorder decreases the yield strain; sufficiently high disorder changes the macroscopic response of a foam from a viscoelastic solid to a viscoelastic fluid. This wide-ranging dynamical response and the associated history effects of foams result from avalanchelike rearrangement events. The spatiotemporal statistics of rearrangement events do not display long-range correlations for ordered foams or at low shear rates, consistent with experimental observations. As the shear rate or structural disorder increases, the topological events become more correlated and their power spectra change from that of white noise toward 1/f noise. Intriguingly, the power spectra of the total stored energy also exhibit this 1/f trend.

Journal Article↗