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Biomedical subjects

J Yang

Publications and source records attributed to J Yang.

At least 631 records · Page 35Linked to original sources
PubMed1999

Sjögren's syndrome in mice carrying the Ipr(cg) gene and the therapeutic efficacy of an immunosuppressive agent FK506.

The influence of the Ipr(cg) gene on the development of Sjögren's syndrome was followed up to 5 months of age in male and female mice of MRL, CBA and C3H strains. In MRL-Ipr(cg) mice, focal mononuclear cell infiltration started at 2 months and became conspicuous after 3 months of age in the lacrimal and submandibular glands but was minimal in the parotid and sublingual glands, even at 5 months of age, without any apparent sex effects found. In CBA and C3H mice carrying the Ipr(cg) gene, this manifestation of Sjögren's syndrome was much less prominent, indicating that the participation of some genes of the MRL strain may be indispensable for the development of Sjögren's syndrome in mice carrying this gene. In MRL-Ipr(cg) mice, an immunosuppressive agent, FK506, improved the serological abnormalities (decreased levels of anti-double-stranded DNA antibody of IgG2a and IgG3 subclasses) and proteinuria. It also reduced the manifestations of Sjögren's syndrome when it was intraperitoneally administered three times weekly at a dose of 2 mg/kg from 6 weeks (before disease onset) until 5 months of age (the termination of the experiment). Although VP8.2+ T cells have been demonstrated to be responsible for causing several autoimmune diseases, the selective deletion of Vp8.2+ T cells with the superantigen encoded by mouse mammary tumor virus did not affect the disease severity at all, suggesting that this T cell repertoire may not play a crucial role in induction of Sjögren's syndrome.

Animals↗
PubMed1999

Substitution of surface-exposed framework residues alters secretion of recombinant fusion protein Fv/tumor necrosis factor in Escherichia coli.

Substitution of hydrophobic residues with hydrophilic ones at surface-exposed positions may influence the yield of antibody fragment expression in Escherichia coli by reducing its aggregation potential. We introduced such substitutions at 8 surface-exposed framework region residues of a fusion protein Fv/Tumor Necrosis Factor, which resulted in the expression of 10 mutant fusion proteins (Mut 1-10) in E. coli. Our results showed that expression levels of Mut 1-3, with mutations of A9S, T18K, and G41D, respectively, decreased by 4- to 8-fold, whereas expression levels of Mut 4, 9, and 10, with mutations of S60D/S70D, T28D, and G65D, respectively, were not affected. In contrast, mutation of F83A at light-chain residue 83, which is usually buried at the variable/constant domain interface of antibody molecules but becomes surface-exposed in recombinant Fv molecules, increased the expression level of Mut 5 by 4-fold. Our results suggest that this important substitution of a hydrophobic residue with a hydrophilic one may also be applied to increase the secretion of other recombinant Fv molecules in E. coli periplasm.

Escherichia coli↗
PubMed1999

The isoprostanes: unique prostaglandin-like products of free-radical-initiated lipid peroxidation.

The discovery of IsoPs as products of nonenzymatic lipid peroxidation has opened up new areas of investigation regarding the role of free radicals in human physiology and pathophysiology. The quantification of IsoPs as markers of oxidative stress status appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease. An important need in the field of free-radical medicine is information regarding the clinical pharmacology of antioxidant agents. Because of the evidence implicating free radicals in the pathogenesis of a number of human diseases, large clinical trials are planned or underway to assess whether antioxidants can either prevent the development or ameliorate the pathology of certain human disorders. However, data regarding the most effective doses and combination of antioxidant agents to use in these clinical trials is lacking. As mentioned previously, administration of antioxidants suppresses the formation of IsoPs, even in normal individuals. Thus, measurement of IsoPs may provide a valuable approach to define the clinical pharmacology of antioxidants. In addition to being markers of oxidative stress, several IsoPs possess potent biological activity. The availability of additional IsoPs in synthetic form should broaden our knowledge concerning the role of these molecules as mediators of oxidant stress. Despite the fact that considerable information has been obtained since the initial report of the discovery of IsoPs [6], much remains to be understood about these molecules. With continued research in this area, we believe that much new information will emerge that will open up additional important new areas for future investigation.

Dinoprost↗
PubMed1999

An extreme-sib-pair genome scan for genes regulating blood pressure.

Hypertension, a risk factor for many cardiovascular, cerebrovascular, and renal diseases, affects one in four Americans, at an annual cost of>$30 billion. Although genetic mutations have been identified in rare forms of hypertension, including Liddle syndrome and glucocorticoid-remediable aldosteronism, the abundance of plausible candidate genes and potential environmental risk factors has complicated the genetic dissection of more prevalent essential hypertension. To search systematically for chromosomal regions containing genes that regulate blood pressure, we scanned the entire autosomal genome by using 367 polymorphic markers. Our study population, selected from a blood-pressure screen of >200,000 Chinese adults, comprises rare but highly efficient extreme sib pairs (207 discordant, 258 high concordant, and 99 low concordant) and all but a single parent of these sibs. By virtue of the sampling design, the number of sib pairs, and the availability of genotyped parents, this study represents one of the most powerful of its kind. Although no regions achieved a 5% genomewide significance level, maximum LOD-score values were >2.0 (unadjusted P<.001) for regions containing five markers (D3S2387, D11S2019, D15S657, D16S3396, and D17S1303), in our primary analysis. Other promising regions identified through secondary analyses include loci near D4S3248, D7S2195, D10S1423, D20S470, D20S482, D21S2052, PAH, and AGT.

Adolescent↗
PubMed1999

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗
PubMed1999

The removal of human breast cancer cells from hematopoietic CD34+ stem cells by dielectrophoretic field-flow-fractionation.

Dielectrophoretic field-flow-fractionation (DEP-FFF) was used to purge human breast cancer MDA-435 cells from hematopoietic CD34+ stem cells. An array of interdigitated microelectrodes lining the bottom surface of a thin chamber was used to generate dielectrophoretic forces that levitated the cell mixture in a fluid flow profile. CD34+ stem cells were levitated higher, were carried faster by the fluid flow, and exited the separation chamber earlier than the cancer cells. Using on-line flow cytometry, efficient separation of the cell mixture was observed in less than 12 min, and CD34+ stem cell fractions with a purity >99.2% were obtained. The method of DEP-FFF is potentially applicable to many biomedical cell separation problems, including microfluidic-scale diagnosis and preparative-scale purification of cell subpopulations.

Bone Marrow Purging↗
PubMed1999

Protective effects of pregnancy and lactation against N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats.

The role of parity before and after N-methyl-N-nitrosourea (MNU) treatment in protection against mammary carcinogenesis was investigated. The effect of lactation on reduction in the incidence of mammary carcinoma was also examined. Parous rats were compared with respective age-matched virgins (AMVs). Pregnancy and lactation prior to MNU exposure significantly reduced both the incidence of mammary carcinoma (22 versus 72%) and the average number of mammary carcinomas per rat (0.22 versus 0.86) and significantly prolonged the latency of the carcinomas (247 versus 215 days). Pregnancy and lactation following MNU exposure also significantly reduced both the incidence of mammary carcinoma (25 versus 94%) and the average number of mammary carcinomas per rat (0.25 versus 1.50) and significantly prolonged the latency (240 versus 155 days). Lactation showed an additive effect on the reduction in mammary cancer. Pregnancy suppressed the number of estrogen receptor (ER)- and progesterone receptor (PgR)-positive cells and lowered the cell proliferation rate in the non-tumoral mammary glands. Since the majority (>76%) of the mammary carcinomas was hormone dependent in both the parous and AMV rats, pregnancy and lactation appear to decrease the ER- and/or PgR-positive cells presumed to be the progenitors of hormone-dependent carcinomas and they lowered the cell turnover necessary for tumor promotion in parous rats, resulting in a lower mammary carcinoma yield.

Animals↗
PubMed1999

Induction of mammary carcinomas by N-methyl-N-nitrosourea in ovariectomized rats treated with epidermal growth factor.

The importance of epidermal growth factor (EGF) in both normal and malignant mammary gland development are presented in these studies. Initial findings demonstrated that in the absence of ovarian hormones, EGF had a significant proliferative effect on mammary epithelial cells. To determine whether mammary epithelial cells grown with EGF, in the absence of ovarian hormones, could be transformed by N-methyl-N-nitrosourea (MNU), female ovariectomized Lewis rats were implanted with pellets containing EGF for 1 week and then treated with MNU for initiation. Two days after MNU treatment, ovaries were implanted and EGF pellets were removed from all ovariectomized groups in order to promote carcinogenesis. The mammary carcinoma incidence of the EGF-stimulated group (90%) was not significantly different from the intact group (100%). The mammary cancer morphology of EGF-treated carcinomas was either ductal carcinoma or cribriform adenocarcinoma, whereas intact animals developed mainly papillary and occasional cribriform carcinomas. Fifty-eight percent of the carcinomas from the EGF group were ovarian hormone-independent compared with 10% of carcinomas from the intact group. These results demonstrate that EGF-induced proliferation during initiation with MNU was sufficient to induce the transformation of mammary carcinomas in the absence of ovarian hormones. The hormonal dependency of these EGF-induced carcinomas were different compared with MNU-initiated mammary carcinomas in intact rats.

Adenocarcinoma↗
PubMed1999

Mapping of a blood pressure quantitative trait locus to chromosome 15q in a Chinese population.

Blood pressure is a complex trait of pivotal biological importance, in which 20-50% of interindividual variation is genetically determined. Whereas genes have been identified in several rare Mendelian forms of hypertension, little progress has been made in understanding the genetics of blood pressure variation in the general population. Recently, we screened the human genome using rural Chinese sibling pairs with extreme blood pressure and identified suggestive linkage for two chromosomal regions. By refining the trait definition and genotyping additional markers, we detected significant linkage (maximum lod score = 3.77) near D15S203 in lower extreme diastolic blood pressure sibling pairs. Using a second independent data set from the same geographical area, we marginally replicated ( P = 0.05) this result, suggesting that this locus is very likely to be involved in the regulation of diastolic blood pressure.

Adult↗
PubMed1999

The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis.

Expansions of an intronic GAA repeat reduce the expression of frataxin and cause Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease. Frataxin is a mitochondrial protein, and disruption of a frataxin homolog in yeast results in increased sensitivity to oxidant stress, increased mitochondrial iron and respiration deficiency. These previous data support the hypothesis that FRDA is a disease of mitochondrial oxidative stress, a hypothesis we have tested in cultured cells from FRDA patients. FRDA fibroblasts were hypersensitive to iron stress and significantly more sensitive to hydrogen peroxide than controls. The iron chelator deferoxamine rescued FRDA fibroblasts more than controls from oxidant-induced death, consistent with a role for iron in the differential kinetics of death; however, mean mitochondrial iron content in FRDA fibroblasts was increased by only 40%. Treatment of cells with the intracellular Ca2+chelator BAPTA-AM rescued both FRDA fibroblasts and controls from oxidant-induced death. Treatment with apoptosis inhibitors rescued FRDA but not control fibroblasts from oxidant stress, and staurosporine-induced caspase 3 activity was higher in FRDA fibroblasts, consistent with the possibility that an apoptotic step upstream of caspase 3 is activated in FRDA fibroblasts. These results demonstrate that FRDA fibroblasts are sensitive to oxidant stress, and may be a useful model in which to elucidate the FRDA mechanism and therapeutic strategies.

Apoptosis↗
PubMed1999

Ontogeny of luteinizing hormone and estradiol secretion in turkey hens exposed to different photoperiods from hatch to sixty weeks of age.

Changes in concentrations of plasma luteinizing hormone (LH) and estradiol-17beta in turkey hens were measured during development utilizing stimulatory and nonstimulatory lighting treatments. All hens were maintained under 24 h light (L) from hatch to 3 wk of age, then 16L:8 dark (D) to 10 wk of age. From 10 wk of age, three lighting treatments were used: 1) 16L:8D from 10 to 60 wk of age (Treatment LD); 2) 6L:18D from 10 to 60 wk of age (Treatment SD); and 3) 16L:8D from 10 to 20 wk of age, 6L:18D from 20 to 30 wk of age, and then 16L:8D from 30 to 60 wk of age (Treatment SD-LD). Measurements of plasma LH and estradiol-17beta concentrations were based on weekly blood samples. Similar patterns of LH were observed in all treatments before 24 wk of age. The concentrations of LH were high at hatch then declined to low levels at 10 wk of age and rebounded to high levels at 18 wk of age before declining to low levels at about 24 wk of age. Low concentrations of LH were then maintained for hens on all treatments but were slightly higher in hens on Treatment SD from 35 to 60 wk of age. A transitory increase in LH, lasting about 3 wk, occurred for hens on Treatment SD-LD after photostimulation. The concentrations of estradiol-17beta were low and stable for hens on all treatments when they were not laying but were elevated about 2 wk prior to and during egg laying. All hens on Treatments LD and SD-LD laid eggs; no hens on Treatment SD laid eggs to 60 wk of age. It was concluded that 1) changes in plasma LH and estradiol-17beta were age related before about 24 wk of age, 2) turkey hens may not be photorefractory at hatch and can lay without juvenile exposure to SD photoperiods, and 3) LD photoperiods after about 20 wk of age are necessary for initiation of egg production in turkey hens before 60 wk of age.

Aging↗
PubMed1999

Protein markers in colorectal cancer: predictors of liver metastasis.

OBJECTIVE: To assess the significance of the expression of five protein markers (nm23, p53, c-erbB-2, u-PA, and VEGF) to the development of metastasis in colorectal cancer. SUMMARY BACKGROUND DATA: The metastatic cascade is a complex multistep process involving several genetic alterations, angiogenesis activation, and tissue proteolysis. Although the prognosis of colorectal cancer depends on the stage of the tumor, the development of metastasis is difficult to predict. METHODS: Paraffin-embedded specimens of 58 patients who underwent surgery for colorectal cancer were retrospectively analyzed by immunohistochemistry, and the coexpression of these protein markers was related to patient outcome. RESULTS: The risk of developing liver secondaries was correlated with the expression of nm23 protein (p < 0.0001); this was also the case in those patients with Dukes' stage B showing positive nm23 immunostaining (p = 0.006). The determination of the number of positive markers or the cumulative intensity score did not improve the predictive value over and above that of nm23 protein alone. CONCLUSION: Expression of nm23 protein is correlated with the risk of developing liver metastasis. Its evaluation alone may help to determine which patients who have undergone apparently curative resection of a colorectal cancer have an increased risk of liver recurrence, especially those with Dukes' stage B tumors who might be considered for adjuvant chemotherapy.

Adult↗
PubMed1999

Krill protease effects on wound healing after corneal alkali burn.

PURPOSE: To study the effect of a novel protease in the development and progression of corneal ulceration secondary to alkali burning. METHODS: By using a 4N alkali burn model of corneal ulceration in rabbits, the effects and efficacy of topical application of a novel protease (PHM-101) capable of degrading metalloproteinases was studied for 28 days of treatment and 7 days off treatment for its effect on corneal ulceration and recurrent erosion. RESULTS: At day 28, both the protease- and placebo-treated groups had different numbers of eyes showing reepithelialization (nine (45%) of 20 and six (33%) of 18, respectively]. By day 35 the protease-treated group had significantly fewer recurrent epithelial defects [two (13%) of 15 vs. eight (61%) of 13; p = 0.02]. Similarly, at day 35 the protease-treated group showed significantly less corneal ulceration [two (13%) of 15 vs. six (46%) of 13; p = 0.02], and those ulcers were of a lesser severity (three units vs. 17.76 units). No difference was found in the degree of stromal edema or neovascularization, nor was there any difference in histopathologic characteristics of inflammatory cell infiltration and corneal scarring. CONCLUSION: We conclude that this novel protease is efficient in reducing recurrent corneal epithelial defects and stromal ulceration after alkali burning.

Alkalies↗
PubMed1999

Effect of radiochemical purity of 99Tcm-Q12 on myocardial SPET image quality.

In myocardial perfusion SPET studies with 99Tcm-Q12, we observed that some patients had high liver uptake that interfered significantly in the assessment of the inferior wall. The aim of this study was to assess the effects of the radiochemical purity of 99Tcm-Q12 on liver uptake. Thirty-one patients undergoing routine myocardial infarction perfusion studies were evaluated. The radiochemical purity of 99Tcm-Q12 was determined using HPLC. Venous blood samples taken 50 min after injection of 99Tcm-Q12 during peak exercise were also analysed. Liver uptake was expressed as the liver-to-heart ratio. In addition, the SPET images were classified by two experienced nuclear medicine specialists into three groups representing high-quality images (n = 7), images with high general background activity (n = 13) and images with high liver and/or intestinal uptake (n = 11). The liver-to-heart ratio correlated inversely with the radiochemical purity of 99Tcm-Q12 (r = -0.65, P < 0.001) and unchanged 99Tcm-Q12 in plasma (r = -0.44, P < 0.02). The radiochemical purity of 99Tcm-Q12 was significantly lower in the group with high liver uptake (60.1 +/- 4.2%) than in the group with good-quality images (81.8 +/- 5.6%, P < 0.01) or with high background activity (82.3 +/- 2.5%, P < 0.01). In conclusion, the radiochemical purity of 99Tcm-Q12 has a significant inverse correlation with the liver-to-heart ratio; thus, the high radiochemical purity of 99Tcm-Q12 should be confirmed to prevent interference by liver uptake.

Chromatography, High Pressure Liquid↗
PubMed1999

Generation of soliton oscillations in nonlinear quadratic materials.

We show analytically and numerically that the generation of long-lasting soliton oscillations in resonant chi(2) optical materials possesses a threshold for the amplitude of a fundamental wave. The persistent oscillations of solitary waves reported by Etrich et al. [Phys. Rev. E 54, 4321 (1996)] are found to appear for finite values of the wave amplitude.

Journal Article↗
PubMed1999

Structure of the Rhizomucor miehei aspartic proteinase complexed with the inhibitor pepstatin A at 2.7 A resolution.

Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with pepstatin A grew in the orthorhombic space group P212121 and were isomorphous to native RMP crystals. The unit-cell dimensions are a = 41.52, b = 50.82, c = 172.71 A. There is one RMP-pepstatin A complex per asymmetric unit. The structure of the RMP-pepstatin A complex has been refined to a crystallographic R value of 19.3% and an Rfree value of 28.0% at 2.7 A resolution. A pepstatin A molecule fits into the large substrate-binding cleft between the two domains of RMP in an extended conformation up to the alanine residue at the P2' position. The dipeptide analogue statine residue at the P3'-P4' position forms an inverse gamma-turn (P3'-P1') with the statine residue at the P1-P1' position and its leucyl side chain binds back into the S1' subsite. The inhibitor interacts with the residues of the substrate-binding pocket by both hydrogen bonds and hydrophobic interactions. The hydroxyl group of the statine residue at the P1-P1' position forms hydrogen bonds with both catalytic aspartate residues (Asp38 and Asp237). This conformation mimics the expected transition state of the enzyme-substrate interaction. The binding of the inhibitor to the enzyme does not produce large distortions of the active site. No domain movement was observed compared with the native enzyme structure. However, the surface-flap region (residues 82-88) undergoes a conformational change, moving toward the inhibitor and becoming rigid owing to the formation of hydrogen bonds with the inhibitor. B-factor calculations of the two domains suggest that the C-terminal domain becomes more rigid in the complex than in the native structure.

Aspartic Acid Endopeptidases↗
PubMed1999

A novel and efficient regimen for producing chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) in SJL mice.

We report that SJL mice developed chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) when injected with a mixture of mouse spinal cord homogenate (MSCH), killed mycobacteria tuberculosis (M. tb), and mycobacteria butyricum (M. b) in PBS 2 months before a conventional acute experimental autoimmune encephalomyelitis (EAE) induction injection. The altered progression of the disease involved an accelerated but less severe acute attack and development of a chronic course with relapsing-remitting episodes. Histological examination revealed inflammatory cell infiltration and demyelination in the brain. The dose of neuroantigen as well as the anatomical sites of injections were found to be crucial for the development of the disease.

Animals↗