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Biomedical subjects

Y Yang

Publications and source records attributed to Y Yang.

At least 1,027 records · Page 57Linked to original sources

Functional magnetic resonance neuroimaging data acquisition techniques.

Functional MRI studies of human brain require rapid data acquisition techniques, to map dynamic changes with sufficient anatomical coverage. In addition, task activation studies employing functional MRI require a high scan sensitivity, in order to discriminate the small, activation-related signal changes from background noise. An overview is given of current fast scan methods, which are sensitized to detect susceptibility changes related to task-induced changes in blood oxygenation. Sources of artifacts are discussed, as well as their effect on image quality.

Artifacts↗

Autonomic and behavioral thermoregulation in golden hamsters exposed perinatally to dioxin.

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause s a permanent change in thermoregulatory control of male offspring of the rat, characterized by a reduced core temperature (Tc over a wide range of ambient temperatures (Ta). To examine the similarities in this effect across species, the thermoregulatory effects of perinatal TCDD were evaluated in the golden hamster, a species which is very resistant to the lethal effects of TCDD. Adult male hamsters exposed on Gestational Day 11.5-11.75 to 2.0 microgram TCDD/kg by gavage were subjected to a variety of behavioral and autonomic thermoregulatory measurements. Nocturnal Tc of TCDD-treated animals was 0.4 to 1.0 degrees C below that of controls over a Ta range of 14 to 34 degrees C. Hypothermia persisted in spite of normal metabolic responses to cold exposure. The hypothermic effect of perinatal TCDD exposure was found to persist over a 24-hr period in unrestrained hamsters monitored by radiotelemetry. The TCDD-treated hamster offspring placed in a temperature gradient exhibited a preference for warm Ta's for 2 to 3 hr; however, when maintained over a 22-hr period in the gradient there was no effect of TCDD on behavioral thermoregulation. TCDD had no effect on motor activity measured over a 24-hr period. TCDD resulted in an approximately 30% reduction in body weight compared to controls; however, this weight loss appeared to have no bearing on the thermoregulatory deficiencies of the TCDD-treated animals. TCDD-treated hamsters displayed a normal metabolic response to cold exposure; thus, it would appear that perinatal exposure to TCDD leads to a dysfunction in the central control of body temperature. The perinatal effects of TCDD on thermoregulation in the rat and hamster appear to be similar.

Animals↗

Abnormal expression of MDM-2 in breast carcinomas.

MDM-2 is a cellular oncoprotein that binds to the p53 protein and abrogates its growth-suppressing function. At least seven MDM-2 mRNAs and five proteins (p90, p85, p76, p74, and p57) have been reported in tissue culture. MDM-2 gene amplification occurs in human sarcomas and high-grade gliomas. MDM-2 overexpression without gene amplification has been reported in leukemias and lymphomas. Here we report MDM-2 mRNA overexpression in 24 (73%) out of 33 cases of human breast carcinoma as compared with normal breast tissue. The MDM-2 overexpression was seen in the absence of MDM-2 gene amplification. MDM-2 protein expression was studied by western blot analysis in 21 of these cases of carcinoma. We found complete concordance between MDM-2 mRNA overexpression and MDM-2 protein levels. MDM-2 proteins were overexpressed in 15 of 21 breast carcinoma tissue samples but not in normal breast tissue controls. Ten of these fifteen cases overexpressed MDM-2 p57 protein, two cases overexpressed both p57 and p90, and three cases overexpressed only p90. MDM-2 overexpression was confirmed by immunohistochemistry. p53 overexpression was also studied by immunohistochemistry, 69% of breast carcinomas that overexpressed the MDM-2 mRNA had detectable nuclear p53 protein. These findings demonstrate that MDM-2 oncoprotein expression is altered in primary human breast carcinomas at both mRNA and protein levels. In addition, our results suggest that MDM-2 p57 protein represents the main MDM-2 protein altered in breast carcinomas.

Blotting, Western↗

Kinetics of modification of the mitochondrial succinate-ubiquinone reductase by 5,5'-dithiobis-(2-nitro-benzoic acid).

The kinetic theory of the substrate reaction during modification of enzyme activity previously described by Tsou [Tsou (1988), Adv. Enzymol. Relat. Areas Mol. Biol. 61, 381-436] has been applied to a study of the kinetics of the course of inactivation of the mitochondrial succinate-ubiquinone reductase by 5,5'-dithiobis-(2-nitro-benzoic acid) (DTNB). The results show that the inactivation of this enzyme by DTNB is a conformation-change-type inhibition which involves a conformational change of the enzyme before inactivation. The microscopic rate constants were determined for the reaction of the inactivator with the enzyme. The presence of the substrate provides marked protection of this enzyme against inactivation by DTNB. The modification reaction of the enzyme using DTNB was shown to follow a triphasic course by following the absorption at 412 nm. Among these reactive thiol groups, the fast-reaction thiol group is essential for the enzyme activity. The results suggest that the essential thiol group is situated at the succinate-binding site of the mitochondrial succinate-ubiquinone reductase.

Animals↗

The value of perioperative echocardiography in percutaneous balloon mitral valvuloplasty.

In order to investigate the value of perioperative echocardiography in percutaneous balloon mitral valvuloplasty (PBMV), two-dimensional echocardiography (2-DE), Doppler echocardiography and color Doppler flow imaging (CDFI) were employed prior to PBMV in 52 patients and during or after PBMV in 15 patients. The results showed that TTE and TEE were helpful in the selection of candidates for 2-DE transseptal and balloon dilation procedures. Continuous monitoring of 2-DE, Doppler echocardiography and CDFI during PBMV could make this procedure safer and more effective, reduce X-ray exposure and avoid complications. Echocardiography was useful in fluoroscopy and could be used for evaluation of the effects of operation.

Adult↗

Molecular mechanisms of class I major histocompatibility complex antigen processing and presentation.

The presentation of antigenic peptides by class I major histocompatibility complex molecules plays a central role in the cellular immune response, since immune surveillance for detection of viral infections or malignant transformations is achieved by CD8+ T lymphocytes which inspect peptides, derived from intracellular proteins, bind to class I molecules on the surface of most cells. The transporter associated with antigen processing selectively translocates cytoplasmically derived peptides of appropriate sequence and length into the lumen of the endoplasmic reticulum where they associate with newly synthesized class I molecules. The translocated peptides are generated by multicatalytic and multisubunit proteasomes which degrade cytoplasmic proteins in a ATP-ubiquitin-dependent manner. This review discusses our current molecular understanding of class I antigen processing and presentation.

Amino Acids↗

The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon gamma and interleukin-10.

The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA-4 on T cells has been shown to play an important role in the induction of T-cell-mediated immunity against tumors. In the present study, we examined the expression of CD80 and CD86 in the cell lines derived from human gastric, esophageal and colorectal carcinomas at the mRNA level, by means of a reverse transcriptase/polymerase chain reaction analysis and, for their surface expression, using a flow-cytometric analysis with monoclonal antibodies (mAb). The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested, except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these cell lines expressed the surface CD80 or CD86 molecule, detected with the respective mAb. The surface expression of CD80 or CD86 was increased in four to five of the six cell lines tested after a culture with interferon gamma (IFN gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma was inhibited by interleukin-10 (IL-10). These results indicated that, in the cell lines derived from human gastrointestinal carcinoma, both the costimulatory molecules CD80 and CD86 were detectable in the majority of the cell lines examined at the mRNA and protein levels, and could be regulated with the cytokine IFN gamma or IL-10.

Antigens, CD↗

Interleukin-2 and interleukin-7 augment the cytolytic activity and expand the antitumor killing spectrum of alpha CD3-induced activated killer cells: potential use in the immunotherapy of non-immunogenic tumors.

This study investigates the effect of different cytokines on the growth and antitumor activity of the alpha CD3-induced killer cells CD3-AK, and the potential of the use of CD3-AK cells in cancer immunotherapy. Eight cytokines were tested. Only three (interleukin-2, -4 and -7) were able to support the growth of CD3-AK cells, which selectively killed different tumor targets of diversified origin. Culturing in interleukin-4 (IL-4) or IL-7 alone could maintain the growth of CD3-AK cells for 6-8 days. Only IL-2 could maintain long-term growth, but further addition of IL-4 exerted an inhibitory effect, which terminated the cell growth in 2 weeks. In contrast, despite the fact that IL-7 inhibited the proliferation of CD3-AK cells cultured in IL-2, as determined by [3H]thymidine uptake, the recovery of viable cells was not reduced. In 10 days, CD3-AK cells cultured in IL-2 alone or IL-2 plus IL-7 increased 160- or 176-fold respectively. There is an inverse relationship between the in vitro growth ability and Fas expression on the CD3-AK cells. Further, IL-7 increased the cytolytic activity of the CD3-AK cells two- to threefold. CD3-AK cells could be maintained in IL-2 or IL-2 plus IL-7 for 60-240 days or more. The long-term-cultured CD3-AK cells not only possessed a high level of cytolytic activity, but also showed a wide spectrum of killing with different tumor targets; the normally "resistant" targets, such as EL-4 lymphoma, fibrosarcoma, or melanoma, became susceptible. When the in vivo antitumor activity of the CD3-AK cells against a non-immunogenic tumor. EL-4, was tested by tumor-neutralization experiments, we found that only the long-term-cultured cells gave significant protection, with those maintained in both IL-2 and IL-7 giving the highest degree of protection. Thus, these long-term-cultured CD3-AK cells may have the potential to be used for immunotherapy of a variety of tumors whatever their immunogenicity.

Animals↗

An analysis of statistical term strength and its use in the indexing and retrieval of molecular biology texts.

The biological literature presents a difficult challenge to information processing in its complexity, diversity, and in its sheer volume. Much of the diversity resides in its technical terminology, which has also become voluminous. In an effort to deal more effectively with this large vocabulary and improve information processing, a method of focus has been developed which allows one to classify terms based on a measure of their importance in describing the content of the documents in which they occur. The measurement is called the strength of a term and is a measure of how strongly the term's occurrences correlate with the subjects of documents in the database. If term occurrences are random then there will be no correlation and the strength will be zero, but if for any subject, the term is either always present or never present its strength will be one. We give here a new, information theoretical interpretation of term strength, review some of its uses in focusing the processing of documents for information retrieval and describe new results obtained in document categorization.

Abstracting and Indexing↗

Theoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols.

Pharmaceutical inhalation aerosols intended to deliver drugs to the lungs may be sampled by inertial devices, that divide particle distributions into pre-calibrated diameters. A characteristic particle diameter (D50) is prescribed, below which the aerosol mass is designated the 'respirable fraction'. The following studies compare designated respirable fractions with predicted lower lung deposition. Designated respirable fractions (% of particulate matter < 6.4 microns or alternatively < 9.8 microns) of 30, 40 and 50% were selected to represent typical inhalation aerosols. The compendial inertial samplers used to aerodynamically characterize the particle size of pharmaceutical aerosols operate at approximately 30 or 60 l/min. These values were selected as the volumetric flow rates (Qv) for a mathematical model of lung deposition. The model was employed to predict the lung deposition of particle size distributions giving rise to each designated respirable fraction. Nominal tidal volumes (Tv) of 500 and 1622 ml were adopted at appropriate breathing frequencies to accommodate the designated Qv. Predicted lung depositions (+/- range due to particle size) of 1.4 +/- 0.6%, at a respirable fraction of 30% (Qv = 60 l/min, Tv = 500 ml, D50 = 9.8 microns), and 20.9 +/- 3.6%, at a respirable fraction of 50% (Qv = 30 l/min., Tv = 1622 ml, D50 = 6.4 microns) illustrate the range of results obtained. Under well defined conditions there appeared to be a qualitative correlation between respirable fraction and predicted lower lung deposition. However, this was influenced by the aerosol particle size distribution and breathing parameters.

Aerosols↗

Inhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide.

PURPOSE: The authors tested the antiangiogenic properties of intravitreally administered triamcionolone acetonide in a pig model of preretinal neovascularization to determine the effectiveness of this therapy in preventing neovascularization. METHODS: In 14 eyes of seven pigs, branch retinal vein occlusions were created in a standardized manner using photodynamic thrombosis with rose bengal dye and thermal burns from the argon green laser. Intravitreal injection of approximately 4 mg of triamcinolone acetonide was performed in one eye of each animal, and eyes were followed clinically for 12 weeks with ophthalmoscopy and fundus photography. A standardized grading system was developed to permit masked assessment of disc proliferations from fundus stereophotographs. After death, all neovascularization was confirmed histopathologically and a final grade was assigned to each eye. Statistical analysis employed use of a nonparametric test of the paired data. RESULTS: Significant inhibition of neovascularization was observed in triamcinolone-treated eyes (P = 0.0156). Although none of the steroid-injected eyes demonstrated clinically evident new vessels, histopathologic and photographic analysis results demonstrated fine new vessels on the optic disc in four eyes. In all of the untreated eyes, neovascularization of a moderate (II) to high (III to IV) grade developed. CONCLUSIONS: Intravitreal triamcinolone acetonide effectively inhibited preretinal and optic nerve head neovascularization in the pig model. The grading system used permitted masked assessment of outcome and paired analysis allowed a conclusion to be drawn from a relatively small number of eyes. The mechanisms by which triamcinolone acetonide inhibits neovascularization remain to be elucidated.

Animals↗

Propofol inhibits epileptiform activity in rat hippocampal slices.

Propofol (2,6 di-isopropylphenol) is an intravenous general anesthetic used widely in neuroanesthesia, as a sedative in intensive care units, and has successfully aborted refractory status epilepticus. We investigated the effects of propofol on epileptiform activity in rat hippocampal slices. Interictal epileptiform activity was produced by bath applying one of the following: picrotoxin (PTX; 10 and 50 microM), bicucculine methiodide (BMI; 10 and 50 microM), 4-aminopyridine (4-AP; 50 microM), 8.5 mM [K+]o or 0 [Mg2+]o artificial cerebrospinal fluid. Propofol was then added in increasing concentrations and the effect on the rate of extracellular field epileptiform discharges was measured. Ictal-like discharges (> 2 Hz for > 2 s) were produced by 7.5 mM [K+]o and pilocarpine (10 microM). Propofol (30 micrograms/ml, 168 microM) completely abolished discharges induced by 8.5 mM [K+]o and at 60 micrograms/ml (337 mM) completely suppressed discharges induced by 4-AP and 0 [Mg2+]o. Propofol was less effective in reducing discharges produced by GABAA/Cl- receptor complex antagonists. Propofol at a concentration of 300 micrograms/ml (1.7 mM) was needed to reduce BMI-induced (50 microM) discharges by 77% and only reduced PTX-induced (50 microM) discharges by 20%. Ictal-like discharges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 micrograms/ml, 16.9-56.2 microM) and the duration of the ictal-like discharge period was significantly reduced. We found that propofol has significant in vitro antiepileptic effects. Additionally, propofol was less effective against GABAA antagonists suggesting that the GABAA receptor complex is the site of its action.

Analysis of Variance↗

Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2.

The segment polarity gene dishevelled (dsh) of Drosophila is required for pattern formation of the embryonic segments and the adult imaginal discs. dsh encodes the earliest-acting and most specific known component of the signal transduction pathway of Wingless, an extracellular signal homologous to Wnt1 in mice. We have previously described the isolation and characterization of the Dvl1 mouse dsh homolog. We report here the isolation of a second mouse dsh homolog, Dvl2, which maps to chromosome 11. The Dvl2 amino acid sequence is equally related to the dsh sequence as is that of Dvl1, but Dvl2 is most similar to the Xenopus homolog Xdsh. However, unlike the other vertebrate dsh homologs. Like the other genes, Dvl2 is ubiquitously expressed throughout most of embryogenesis and is expressed in many adult organs. We have developed an assay for dsh function in fly embryos, and show that Dvl2 can partially rescue the segmentation defects of embryos devoid of dsh. Thus, Dvl2 encodes a mammalian homolog of dsh which can transduce the Wingless signal.

Adaptor Proteins, Signal Transducing↗

Monoclonal T cells identified in early NOD islet infiltrates.

To examine the hypothesis that a single initiating antigen was recognized by a monoclonal T cell population leading to subsequent inflammatory insulitis in non-obese (NOD) mouse islets, we examined the T cell receptor TCR V beta repertoire of islet-infiltrating T cells in very young (2-week-old) NOD mice. In independent experiments, we repeatedly identified one monoclonal TCR V-beta 8.2 gene product expressed by T lymphocytes infiltrating the islets of NOD mice at 2 weeks of age. The resultant inflammatory response quickly obscures the monoclonal nature of the initiating event. These data suggest that autoimmune diabetes in NOD mice may be initiated by recognition of a single autoantigen.

Age Factors↗

Ascaris, people and pigs in a rural community of Jiangxi Province, China.

A longitudinal investigation on natural populations of Ascaris in humans and pigs and an investigation of soil contamination with Ascaris eggs were carried out from June 1993 to June 1994 in 2 villages, Manhu area, Xinjian County, Jiangxi Province, China. Results from these studies indicate that although human ascariasis is endemic there is significant fluctuation in both prevalence and the mean number of eggs/g faeces (epg) of the communities. Fluctuation of age-stratified prevalence and mean epg was detected in children but not in most adult groups. Most cases of human ascariasis were judged to involve low intensities of infection and a typical overdispersion distribution pattern was observed through the year. It was estimated that during the year, nearly half of the eggs discharged in the environment came from infections in children aged between 2 and 15 years which accounted for about 30% of the total population. Soil in and around houses and in vegetable gardens was found to be contaminated by Ascaris eggs and this situation remained relatively stable throughout the year. Monthly developmental rate of Ascaris eggs in soil was detected and the results suggest that the fluctuation in prevalence observed during the year should be directly attributed to the effect of seasonality of egg development. Features of Ascaris infection in pigs were found to be similar to those in humans except for a lower mean intensity of infection. The possibility of cross-infection of Ascaris between human and pig hosts is discussed.

Adolescent↗

Interaction of monocytoid cells with the mucosal addressin MAdCAM-1 via the integrins VLA-4 and LPAM-1.

The differentiation of myeloid cells into macrophages and granulocytes is accompanied by marked changes in adhesive phenotype. Here we seek to understand the regulation of expression and functionality of the VLA-4 (alpha 4 beta 1), LPAM-1 (alpha 4 beta 7) and HML-1 (alpha E beta 7) integrins on monocytes/macrophages and granulocytes, given that these integrins including LFA-1 (alpha L beta 2) mediate the entry, retention and signalling events of pathogenic leucocytes within chronically inflamed tissues. Phorbol ester-induced monocytic differentiation of the promyelocyte cell line HL60 led to increases in the steady-state levels of beta 2 and beta 7 mRNA transcripts, requiring a period of 10 and 24 h, respectively, of de novo protein synthesis. There was a parallel de novo expression of LPAM-1 on the cell surface, despite the fact that alpha 4 mRNA transcripts were rapidly down-regulated. At 72 h, HML-1 was not coexpressed with LPAM-1 on HL60 cells, although it was weakly expressed on peripheral blood monocytes/macrophages after a prolonged period of in vitro culture. Retinoic acid-induced granulocytic differentiation of HL60 cells led to the appearance of low levels of LPAM-1 at the cell surface. LPAM-1 was not found expressed on peripheral blood neutrophils, raising the possibility that it is transiently expressed during granulocyte differentiation. In accord with the above findings, differentiated monocytes and HL60 cells bound to recombinant MAdCAM-1 in an alpha 4- and beta 7-integrin-dependent fashion, whereas a population of undifferentiated HL60 cells and Mn(+2)-activated monocytes bound in an alpha 4-integrin-dependent beta 7-integrin-independent manner via VLA-4 expressed abundantly at all stages of differentiation. Four h after attachment, some of these VLA-4+ LPAM-1- HL60 cells could be seen to start spreading. These finding suggest that MAdCAM-1 can bind to VLA-4 when LPAM-1 is absent, and thus has the potential to recruit both VLA-4-bearing monocytes and VLA-4+ LPAM-1+ macrophages into chronically inflamed tissues.

Antigens, CD↗

A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Chromosomes, Human, Pair 2↗