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Biomedical subjects

R Yang

Publications and source records attributed to R Yang.

At least 163 records · Page 9Linked to original sources

Redistribution of platelet membrane glycoprotein IV and release of intracellular alpha-granule thrombospondin in patients with chronic myelogenous leukemia.

The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular alpha-granule thrombospondin (TSP) were examined and the inhibition of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of beta-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080 +/- 17010 molecules/platelet as compared with 13190 +/- 4810 from the controls (P < 0.01). No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/IIIa (P > 0.05). The GPIV redistribution on active platelet membrane induced thrombin (IU/ml) from CML and healthy donors was 44320 +/- 32310 and 22800 +/- 12700 molecules/platelet respectively (P < 0.01). The difference in the release of intracellular alpha-granule TSP between CML and the control group was not found (P > 0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high levels of beta-TG and PF4 in sera inhibited release of intracellular alpha-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of internal TSP pools is hindered by either beta-TG or PF4 in sera.

CD36 Antigens↗

Mechanism of the morphological changes induced by staurosporine in rat osteoblasts.

Protein kinase C (PKC) plays an important role in the differentiation of cells, however, little is known about its relationship to bone metabolism. We have previously demonstrated that staurosporine concentration dependently transformed the cultured rat osteoblasts into stellate cells. In this study, we further investigated the possible mechanisms and significance of the morphological changes of osteoblasts induced by staurosporine. The morphological changes induced by staurosporine were inhibited by microtubule depolymerizers or elevated intracellular calcium, however, actin depolymerizers enhanced the effects of staurosporine. Fluorescence labeling showed that staurosporine caused the dissolution of the actin microfilaments, but left the microtubules and vimentin filaments intact. PKC activators partially antagonized the morphological changes induced by staurosporine. Inhibition of protein kinase A or calmodulin-dependent kinase is less effective in the induction of stellate cell formation. These results suggest that the morphological changes of osteoblasts induced by staurosporine may be partly due to PKC inhibition, but other mechanisms may also be involved.

Actin Cytoskeleton↗

Symmetry of bone mineral density at the proximal femur with emphasis on the effect of side dominance.

The symmetry and effect of side dominance on the bone mineral density (BMD) of proximal femur was evaluated in 266 normal Chinese women with a dual photon absorptiometer (DPA, Norland 2600). The BMDs of the femoral neck, trochanter, and Ward's triangle at the proximal femur in the dominant leg (BMDd) were compared with those of the nondominant side (BMDn). The linear regression of BMDd and BMDn of the corresponding regions at the proximal femur showed a good correlation (r = 0.893-0.941, SEE = 0.052-0.062 g/cm2). The paired difference of proximal femoral BMD was -0.002 +/- 0.062 g/cm2 for the femoral neck, 0.003 +/- 0.054 g/cm2 for the trochanter, and 0.008 +/- 0.062 g/cm2 for the Ward's triangle. The ratio of asymmetry for femoral neck BMD was mean +/- SD = -0.4 +/- 7.8%, for trochanter 0.6 +/- 8.1%, and for the Ward's triangle 1.3 +/- 9.7%. Both paired difference and ratio of asymmetry between BMDd and BMDn were approximately normally distributed, with a mean +/- 2 SD ranging from -0.126 to 0.122 g/cm2 for paired difference and -16.0% to 15.2% for the ratio of asymmetry in the femoral neck. These data revealed that dominance had little effect on the proximal femur BMDs. However, the wide range of paired difference and ratio of asymmetry of the proximal femur BMD in the normal individuals should be considered in the interpretation of the proximal femoral BMD.

Adolescent↗

Histology of rat small bowel transplants: cyclosporine A ameliorates features of rejection including apoptosis and ganglion cell reduction.

The histology of rat small bowel transplants (SBT) was examined in orthotopic isografts and allografts with and without immunosuppression. Lewis to Lewis isografts were examined 7 days after transplant, and LBNF1 to Lewis allografts were examined 2, 4, 7, and 10 days after transplant; one group received cyclosporine A (CyA), and their allografts were examined 7 days after transplant. Compared with similar intestinal segments from unoperated animals, allografts at 4, 7, and 10 days after surgery showed progressive inflammation, cryptitis, villous atrophy, and transmural necrosis. In contrast, SBT in animals given CyA did not significantly differ from normal in any histological parameter. The number of apoptotic structures per 100 crypts in SBT at day 4 (58.25 +/- 32.98) and day 7 (31.86 +/- 27.63) after transplant were significantly increased compared with unoperated bowel (5.23 +/- 13.41) (P < .05); the number in CyA-treated allografts (11.57 +/- 29.56) did not differ significantly from normal. The number of intermyenteric ganglion cells was significantly reduced (P< .05) in allografts 7 and 10 days after transplant (mean and [range] = 31 [18 to 38] and 25 [23 to 27], respectively) but the number in allografts from CyA-treated animals (47 [24 to 72]) did not differ from unoperated bowels (52 [30 to 88]). We conclude that CyA treatment significantly reduces the histological abnormalities associated with transplant rejection including adverse effects on epithelial and ganglion cells; therefore, the absorptive capacity and motility characteristics of the CyA-treated SBT should be preserved compared with untreated allograft controls.

Animals↗

C/EBP-epsilon: chromosomal mapping and mutational analysis of the gene in leukemia and preleukemia.

We and others have cloned a novel human gene CCAAT/enhancer-binding protein epsilon (C/EBP-epsilon) encoding a member of the C/EBP gene family. It is exclusively expressed in myeloid and T-lymphoid cells and appears to have an important role in inducing expression of several myeloid-specific genes. We used a polymerase chain reaction (PCR)-based technique to examine DNA from 93 hamster/human radiation hybrid clones in order chromosomally to map C/EBP-epsilon to 14q11.2 (between D14S264 and D14S275) which is telomeric to the T-cell receptor alpha and delta genes and centromeric to several other myeloid gene products including Cathepsin G (CTSG) and Chymase-1 (CMA1). To determine whether C/EBP-epsilon behaves as an altered tumor-suppressor gene, samples from patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) evolving to AML were studied for loss of heterozygosity (LOH) using microsatellite sequences that we identified within 0.2 kb of the amino-terminus of the human C/EBP-epsilon gene. Allelic loss of the C/EBP-epsilon gene was detected in four out of 20 (20%) evolving MDS cases and in none of the 17 AML and 17 T-cell leukemia cases. Mutational analysis of the gene was performed using PCR-SSCP on 37 AML and 40 MDS cases including those with LOH at the gene. No abnormalities were found suggesting that the altered gene in this region is not C/EBP-epsilon. Also, C/EBP-epsilon was examined by Southern blot analysis on DNA samples from 20 AML patients and 10 AML cell lines. No rearrangements or amplifications of the gene were detected. Taken together, we have mapped C/EBP-epsilon to 14q11.2, a region containing other myeloid and T-lymphoid specific genes. Furthermore, no structural alterations were detected in the C/EBP-epsilon gene.

Acute Disease↗

DNA based biosensors.

Compared to advances in enzyme sensors, immunosensors, and microbial biosensors, relatively little work exists on DNA based biosensors. Here we review the DNA based biosensors that rely on nucleic acid hybridization. Major types DNA biosensors--electrochemical, optical, acoustic, and piezoelectric--are introduced and compared. The specificity and response characteristics of DNA biosensors are discussed. Overall, a promising future is foreseen for the DNA based sensor technology.

Journal Article↗

Destruction of a cyropreserved meniscal allograft: a case for acute rejection.

A cryopreserved nontissue-antigen-matched medial meniscus was transplanted arthroscopically into the knee of a 33-year-old cyclist. The patient had previously had an open medial menisectomy 19 years earlier and had significant symptoms. Ten weeks postoperatively, the patient underwent a second-look arthroscopy for a persistent effusion. Intraoperative cultures were obtained and all ultimately tested negative. The graft was found to be frayed throughout its length and significantly decreased in size. Its central portion had become detached from the peripheral repair while both the anterior and posterior bone blocks remained intact. Dense, inflammatory, hypertrophic synovium enveloped the entire joint. Histologically, the graft was found to be necrotic and acellular centrally, whereas the periphery was infiltrated with inflammatory leukocytes and giant cells. This histologic appearance is classical for an acute or subacute type rejection of allograft tissue.

Acute Disease↗

Structure optimization of a leukotriene D4 antagonist by combinatorial chemistry in solution.

Structure optimization of the leukotriene D4 antagonist Ro24-5913 was attempted by combinatorial chemistry. Three segments in its N-succinyl-3-(2-thiazolylethenyl)anilide skeleton, designated as A, B, and C coincided with the thiazolyl, aniline, and N-acyl moieties, respectively, and were selected for variations in a synthesis involving the sequences A + B-->AB and AB + C-->ABC to furnish the library (10A 7B 10C) containing 700 compounds. Lead candidates were identified by the LTD4-induced muscle-contraction assay. Assays of the C-partition 10(10A 7B C) of the set led to a subset of C elements associated with significant bioactivities, ic = {C1, C2, C3}, from which the preferred element C1 was selected. Incorporating this selection into the synthesis of the first reduced set gave the partition 7(10A B C1) whose assay revealed the set iB = {B1, B6} and hence the preferred B element B1. The second reduced set, 10(A B1 C1) incorporating the selected C1 and B1 moieties, revealed iA = {A1, A3, A4, A6, A7, A8, A9} In the resulting combinatiorial product iA x iB x iC, comprising 42 elements, A1 B1 C1 appears on top of the list. Thus, 4-[[3-[2-[4-(2,2-dimethyl ethyl)cyclobutyl-2-thiazolyl]ethenyl] phenyl]amino]-2,2-diethyl-4-oxobutanoic acid (Ro24-5913) was confirmed as the structure with the highest bioactivity. Analogues obtained by replacement of the cyclobutyl group in Ro24-5913 with 4-fluorophenyl and t-butyl were the runners-up. Of these, the former exhibited bioactivity comparable to that of Ro24-5913.

Animals↗

Cancer incidence in the Hmong of Central California, United States, 1987-94.

The Hmong are an ethnic minority in China, some of whom migrated to the mountainous areas of North Vietnam, Laos, and Thailand in the 19th and 20th centuries. Because of their support for the United States during the Vietnam war, many Laotian Hmong fled to Thailand and eventually were re-settled in the US after the end of that conflict. Approximately 100,000 Hmong currently live in the US, of whom about half reside in the Central Valley of California. The purpose of this study was to measure cancer incidence in this unique new immigrant population. Using the resources of the Cancer Registry of Central California (CRCC), a population-based cancer registry, cancer incidence in the Hmong was evaluated by calculating age-adjusted incidence rates as well as by calculating proportional incidence ratios. Compared with all races combined, elevated rates of cancer in the Hmong were observed for the following sites: nasopharynx, stomach, liver, pancreas, leukemia, and non-Hodgkin's lymphoma. Cervical cancer incidence overall was elevated, but more noteworthy, invasive cervix cancer rates were much higher than expected. Lower cancer rates were found for breast, prostate, and colorectal cancer. Hmong also experienced advanced stage and grade of disease at diagnosis for many cancer sites in addition to cervical cancer, which may be explained by cultural factors, including avoidance of Western medical care and low rates of participation in screening programs. This population should be followed closely and monitored for patterns of cancer incidence in the future since it provides a natural laboratory for studies of cancer etiology as this population gradually becomes acculturated to the Western lifestyle.

Adolescent↗

Inhibition of growth of human leukemia cell lines by retrovirally expressed wild-type p16INK4A.

Loss of the p16INK4A gene by homozygous deletions or point mutations is attributed to the development of many types of cancers including leukemia. T cell acute lymphoblastic leukemias (T-ALLs) and B-cell ALLs show a remarkable rate of 75 and 20% homozygous deletion of this gene, respectively. Restoration of p16 expression in p16-deficient solid tumor cell lines results in a dramatic reduction of growth and maligant phenotype. To test the hypothesis that p16INK4A suppresses the growth of p16-deficient leukemias, we utilized a retroviral system to restore wild-type (wt) or mutant p16 protein expression. We tested the efficacy of our system by expressing the wt or mutant p16 genes in the osteosarcoma cell line, U20S, which lacks p16 and retains functional retinoblastoma protein (pRb). The wt p16 protein formed complexes with both cyclin-dependent kinases (CDK) 4 and 6 and inhibited U20S growth by 30-fold. The p16 mutants E120K and R144C formed complexes with CDK4 and CDK6 in cells and inhibited cell growth as effectively as wt p16 (20-fold) while the mutant proteins that did not complex with detectable levels of CDK4 or CDK6 only inhibited growth 0.25- and five-fold (G101W and D141, respectively) or not at all (H83Y and DA4). The COOH-terminal 'tail' of the wt p16 protein (amino acid residues 141-156), missing in mutant D141, enhanced the growth suppressive capability of p16. The amino acid substitutions in mutants G101W and H83Y not only disrupted CDK4 and CDK6 binding, but decreased the protein half-lives by two- and three-fold, respectively, compared to wt p16. The wt, but not mutant p16 genes, effectively inhibited the growth of T cell acute lymphoblastic (CEM) and myeloid leukemia (NB-4 and K562) cell lines that lacked the p16 gene, but retained functional pRb. Growth of the T-ALL cell line, HSB-2, which lacked both p16 and pRb, was not inhibited, indicating the growth suppression involved the pRb pathway. These results define regions critical for the function of p16 and demonstrate that restoration of wt p16 expression in p16-deficient leukemias significantly reverted their transformed phenotype and inhibited their growth.

Animals↗

Induction of rabbit cyclooxygenase 2 in the anterior uvea following glaucoma filtration surgery.

PURPOSE: This study was undertaken to evaluate for the presence of cyclooxygenase 2 (COX2) gene expression in the anterior uvea of rabbits following glaucoma filtration surgery. METHODS: One of the following surgical procedures were performed on the right eye of New Zealand white albino rabbits: (1) paracentesis (2.5 mm limbal incision); (2) iridectomy through a 2.5 mm limbal incision; (3) lamellar scleral flap formation or (4) full glaucoma filtration surgery. The animals were sacrificed within 3 hours of post-surgery, and the anterior uveal tissues were isolated. Polymerase chain reaction-based techniques were employed to assay for the presence of COX2 transcript. RESULTS: A partial coding sequence of the previously unreported rabbit COX2 gene was obtained. COX2 mRNA was detected in the operated eyes of animals that underwent either full filtration surgery or iridectomy through a limbal incision. CONCLUSIONS: In normal rabbit anterior uveal tissue, there appears to be minimal expression of COX2 message. After experimental glaucoma filtration surgery, there is rapid induction of COX2 message.

Amino Acid Sequence↗

OVAREX MAb-B43.13:IFN-gamma could improve the ovarian tumor cell sensitivity to CA125-specific allogenic cytotoxic T cells.

Various immunological parameters were studied in 100 ovarian cancer patients injected with the OVAREX therapeutic vaccine (the functional component of which is anti-CA125 MAb-B43.13) to explain the serendipitous observation of prolonged survival after such treatment. In addition to CA125-specific humoral and cellular responses, interferon-gamma (IFN-gamma) was also found to be induced in those patients receiving the vaccine. In vitro studies indicated that the expression of MHC I, MHC II, and ICAM I in ovarian tumor cells were upregulated in response to IFN-gamma. Such tumor cells were also found to be more sensitive to CA125-specific cytotoxic T cells compared to cells that were not incubated with IFN-gamma.

Animals↗

Hemodynamic effects of scatter factor in conscious rats.

Scatter factor (SF), also known as hepatocyte growth factor, is a potent mitogen that has been suggested to exhibit greater efficacy than vascular endothelial growth factor (VEGF) in rabbits with hindlimb ischemia. Our study examined the effects of SF on cardiovascular hemodynamics and compared the responses to VEGF. Hemodynamic parameters were monitored before and after administration of SF or VEGF in conscious, instrumented rats. Intravenous injection of SF produced a dose-related reduction in mean arterial pressure (MAP) and increase in heart rate (HR). These responses were significantly attenuated by pretreatment with N omega-nitro-L-arginine methyl ester a nitric oxide (NO) synthase inhibitor, suggesting the depressor effect of SF may be mediated by NO. SF (250 micrograms/kg) reduced stroke volume and cardiac output, but did not affect the maximal first derivation of left ventricular pressure (dP/dt), suggesting that the reduction in cardiac output is caused by decreased stroke volume that probably results from a reduction in venous return. Compared with SF, VEGF produced greater hypotensive and tachycardic responses and greater reductions in stroke volume and cardiac output, indicating that SF has fewer side effects on hemodynamics. Although both growth factors might reduce venous return, SF decreased hematocrit presumably through venodilation, whereas VEGF increased hematocrit as a result of vascular hyperpermeability.

Animals↗

Treatment of acute exacerbation of chronic cor pulmonale with fei xin ling syrup.

30 cases of chronic cor pulmonale with acute exacerbation were treated with Fei Xin Ling Syrup compared with 30 similar cases treated with Western modern drugs as controls. The Chinese herbal drug modality was found to be superior to the administration of modern drugs in the control group in overall therapeutic effects, with regard to the symptoms of coughing, tachypnea, phlegm production, edema, and the prevention of heart and respiratory failure. Rheological studies in part of the patients also indicated that the Chinese herbal prescription improved the blood circulation.

Aged↗

[Evidence for a major role of genetic factors in the etiology of laryngeal and hypopharyngeal carcinomas].

Several investigations revealed that lymphocytes from patients with head and neck cancers showed a high sensitivity to mutagens. However, whether lymphocytes from healthy blood relatives of the patients were sensitive to mutagen or not had not been reported. This study was aimed to investigate the unknown problem. Mutagen sensitivity was investigated in 116 laryngeal and 38 hypopharyngeal cancer patients, 107 healthy controls, and 30 blood relatives of laryngeal or hypopharyngeal cancer patients. Chromosome damage was measured by enumerating mutagen-induced chromatid breaks, the average number of chromatid breaks per cell (b/c value) was used as marker which reflects variable host susceptibility to the action of environmental carcinogens. The b/c values were 0.61 +/- 0.27, 0.66 +/- 0.31, 0.28 +/- 0.12, and 0.45 +/- 0.26 for patients with laryngeal cancer, hypopharyngeal cancer, healthy controls, and blood relatives respectively. A significant difference of b/c value was found between patients and controls (P < 0.01), but not between patients and their blood relatives (P > 0.05). Our findings suggest that genetic predisposition plays an important role in the eitiology of laryngeal and hypopharyngeal cancers. Both patients with laryngeal or hypopharyngeal cancers and their blood relatives should be considered as in high cancer risk.

Aged↗

[Experimental study on erythrocyte of obstructive jaundice patient: its changes of membrane protein and mechanical properties].

The component of the erythrocyte membrane protein under three states obstruction, after surgical relief of obstruction, and normal) were analyzed qualitatively by using SDS-PAGE and the method of thin scanning. The result revealed that the membrane protein band 4.2 was absent under the state of obstruction and it recovered after surgical relief of obstruction. Then the mechanical properties of the above three cases of erythrocytes were tested by the micropipette aspiration system and the data were analyzed by Voigt model. The result showed that the elastic modulus and the coefficient of viscosity of the erythrocytes under the state of obstruction were greater than those of the normal; thus the deformability decreased, but "overcorrection" appeared after surgical relief of obstruction. The possible relations between the mechanical properties and the change of membrane protein were discussed.

Adult↗

[Studies on hydrolysis of anti-HRV IgY and its oral passive immunity effect to human rotavirus].

In this paper, hens of fine breed were immunized with human rotavirus (HRV), and the anti-HRV IgY was isolated and purified from their eggs collected daily. In addition, the resistance of anti-HRV IgY to hydrolysis of gastric juice and proteases in human digestive tract, the safety of IgY and the effectiveness of IgY in clinical use were observed as well. The results showed that anti-HRV IgY has a fairly good resistance to gastroinstestinal proteases. The safety of using anti-HRV IgY was affirmed by oral administration to mice of a solution of IgY. In clinical test the IgY has been proved to be anti-HRV and, therefore, effective against infections of infant diarrhea induced by HRV.

Administration, Oral↗