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Biomedical subjects

Y Cao

Publications and source records attributed to Y Cao.

At least 325 records · Page 18Linked to original sources

Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways.

The switch from a quiescent tumor to an invasive tumor is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires a change in the balance of angiogenic stimulators and angiogenic inhibitors. The nature of the angiogenic switch is not known. Here, we show that introduction of activated H-ras into immortalized endothelial cells is capable of activating the angiogenic switch. Angiogenic switching is accompanied by up-regulation of vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity and downregulation of tissue inhibitor of MMP. Furthermore, we show that inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor angiogenesis, thus demonstrating that activated H-ras activates tumor angiogenesis through two distinct pathways. Finally, we show evidence for two forms of tumor dormancy.

Androstadienes↗

Effect of atmosphere on phase transformation in plasma-sprayed hydroxyapatite coatings during heat treatment.

The purpose of this study was to evaluate the effect of atmosphere on the phase transformation in hydroxyapatite (HA) coatings during heat treatment by varying the atmosphere in the furnace pipe. Heat treatment always increased the crystallinity of HA coatings regardless of the kind of atmosphere. Water molecules in atmosphere further promoted HA recrystallization during heat treatment. In a dry atmosphere, tricalcium phosphate (TCP) and tetracalcium phosphate (TTCP) were more stable than HA, so heat treatment could not convert them into HA. However, in a humid atmosphere, heat treatment would transform TCP and TTCP into HA by hydrolytic reactions.

Atmosphere↗

Effect of water vapor pressure and temperature on the amorphous-to-crystalline HA conversion during heat treatment of HA coatings.

X-ray diffraction was used to characterize the increment of crystallinity of HA coatings after heat treatment. Coatings were heated over the temperature (T) interval of 300 degrees-460 degrees C with a partial water vapor pressure of 0.01 MPa and 0.001 MPa. Heat treatment also was done in air, as a contrast. It was found that the ratio (n) of the increment of crystallinity to the crystallinity of the as-received HA coatings was more significant for the coatings heated in atmosphere with water vapor than for those heated in air. This ratio also increased with water vapor pressure. The logarithm of the ratio increased linearly with 1/T, indicating that the ratio is exponential to T. The reason might be that recrystallization of the amorphous phase is a diffusion controlled process; the nucleation rate and growth velocity of the crystallites are in proportion to the diffusion coefficient, which is exponential to the temperature (T). Incorporation of water vapor in the atmosphere during heat treatment may decrease the activation energy for diffusion, which helps raise the diffusion coefficient of the atoms. Thus recrystallization of the amorphous phase can be accelerated.

Biocompatible Materials↗

The origin of chlorarachniophyte plastids, as inferred from phylogenetic comparisons of amino acid sequences of EF-Tu.

A molecular phylogenetic analysis of elongation factor Tu (EF-Tu) proteins from plastids was performed in an attempt to identify the origin of chlorarachniophyte plastids, which are considered to have evolved from the endosymbiont of a photosynthetic eukaryote. Partial sequences of the genes for plastid EF-Tu proteins (1,080-1,089 bp) were determined for three algae that contain chlorophyll b, namely, Gymnochlora stellata (Chlorarachniophyceae), Bryopsis maxima (Ulvophyceae), and Pyramimonas disomata (Prasinophyceae). The deduced amino acid sequences were used to construct phylogenetic trees of the plastid and bacterial EF-Tu proteins by the maximum likelihood, the maximum parsimony, and the neighbor joining methods. The trees obtained in the present analysis suggest that all plastids that contain chlorophyll b are monophyletic and that the chlorarachniophyte plastids are closely related to those of the Ulvophyceae. The phylogenetic trees also suggest that euglenophyte plastids are closely related to prasinophycean plastids. The results indicate that the chlorarachniophyte plastids evolved from a green algal endosymbiont that was closely related to the Ulvophyceae and that at least two secondary endosymbiotic events have occurred in the lineage of algae with plastids that contain chlorophyll b.

Amino Acid Sequence↗

Profilin gene expression and regulation in a temperature-sensitive breast cancer cell line: tsFT101.

The temperature-sensitive mutant cells (tsFT101) derived from a mouse mammary carcinoma cell line, FM3A, become multinucleated at a non-permissive temperature of 39 degrees C. To further understand the molecular mechanism of such cytokinetic disturbance, we examined the expression of profilin, the main regulator of the transition of globular actin (G-actin) to filamentous actin (F-actin). RT-PCR analysis of mouse profilin cDNA from tsFT101 showed a point mutation (177 A two head right arrow G) which was a wobble mutation causing no change in the encoded amino acid. The expression level of profilin mRNA was, however, diminished in cultured tsFT101 cells under non-permissive temperatures compared with wild-type FM3A cells in association with multinucleation. A stable transfection of profilin cDNA expression vector to tsFT101 cells prevented multinuclear cell formation when cultured at 39 degrees C. In contrast, antisense profilin cDNA expression vector did not alter multinuclear cell formation. The primary cause of the cytokinetic disturbance of tsFT101 cells may be due to the diminished level of profilin gene expression.

Animals↗

Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: apolar localization corresponds to malignant transformation.

Epithelial mucins are present at the apical membranes of gastrointestinal epithelial cells or in their secretions. In this study, we examined the occurrence of peptide epitopes of the mucins MUC1 and MUC3 and of three mucin-associated glycotopes (TF, Tn, and s-Tn) in a series of colorectal tissue samples (normal colon, adenomas with different grades of dysplasia, carcinoma in situ, and invasive carcinomas). A new monoclonal antibody to a conformation-dependent peptide epitope of MUC1 was employed, which does not react with the fully glycosylated mucin as found in normal gastrointestinal mucosa. We found that adenomas acquired the ability to expose Tn, s-Tn, TF and MUC1 epitopes, and this correlated with increasing malignant potential. The secretory mucin, MUC3, revealed a different pattern: it was detectable in all sections, with maximum expression in adenomas and decrease in carcinomas. Most importantly, normal mucosa and benign lesions showed supra-nuclear and/or apical distribution of these antigens, but malignant lesions and lesions with a very high risk of malignancy revealed diffuse cytoplasmic and basolateral membrane localization. The immunohistological response to a combination of MUC1-related antibodies may assist in assessing the malignant potential and status of lesions of the colon.

Adenoma↗

Using prior knowledge of human anatomy to constrain MR image acquisition and reconstruction: half k-space and full k-space techniques.

In this note, we demonstrate how to utilize prior knowledge of human cranial anatomy to constrain full k-space and half k-space acquisition and reconstruction of 128 times 128 images. We used a database of magnetic resonance head images to derive new basis functions which represent the most important features of the head. the "training" images were also used to derive formulas for reconstructing head images from a subset of the usual 128 phase-encoded signals and to determine the optimal k-space locations of those signal measurements. We used this algorithm, called Feature-Recognizing MRI, to reconstruct 128 times 128 head images from 50-60% of the signals filling the full k-space. Furthermore, we combined the algorithm with a conventional half k-space technique to create 128 times 128 images from only 60% of the 80 signals required by the usual unconstrained half k-space imaging. Thus, the prior knowledge represented by the image database, together with a half k-space technique, made it possible to construct accurate magnetic resonance images from only 30-40% of the complete set of 128 signals. In other words, a database of head images was used to devise a 1/3 k-space method for imaging the head.

Adult↗

Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant.

Most HIV-1 infections of children result from mother-to-infant transmission, which may occur perinatally or postnatally, as a consequence of breast feeding. In this study, the influence of maternal viral load on transmission of infection to infants from non-breast-feeding mothers was examined using samples of plasma and peripheral blood mononuclear cells (PBMCs) collected at several time points during pregnancy and the 6-month period after delivery. These samples were analyzed by several quantitative methods, including virus cultures of PBMCs and polymerase chain reaction (PCR) assays for HIV-1 RNA in plasma and DNA in PBMCs. The risk of transmission increased slightly with a higher viral load, but transmission and nontransmission occurred over the entire range of values for each assay. No threshold value of virus load was identified which discriminated between transmitters and nontransmitters. We also noted a significant rise in viral load and a decline in CD4+ lymphocytes in the six months after delivery. These findings suggest that a high maternal viral load is insufficient to fully explain vertical transmission of HIV-1. Additional studies are needed to examine the post-partum increase in viremia.

Anti-HIV Agents↗

Prophylaxis against HIV-1 infection in chimpanzees by nevirapine, a nonnucleoside inhibitor of reverse transcriptase.

Chimpanzees were challenged with HIV-1IIIB while receiving a short regimen of nevirapine (Viramune), a nonnucleoside inhibitor of HIV-1 reverse transcriptase. The untreated, control chimpanzee developed an infection characterized by seroconversion, viremia in peripheral blood mononuclear cells (PBMCs), and plasma positive for viral RNA. In contrast, the three nevirapine-treated chimpanzees remained negative for all viral markers with the exception of nested polymerase chain reaction (PCR) analysis of PBMCs for viral DNA. Although PBMCs from the three nevirapine-treated chimpanzees tested intermittently positive for viral DNA, this PCR signal disappeared and remained negative for the final five months of the study. These data indicate that orally administered nevirapine provided protection from HIV-1 infection in the chimpanzee model.

Animals↗

Vaccination with a multi-epitopic recombinant allergen induces specific immune deviation via T-cell anergy.

Prophylactic vaccination has recently emerged as a major paradigm toward the prevention and therapy of allergies and asthma; however, the immunological basis of this approach remains to be elucidated. We examined the potential and mechanism of prophylaxis of allergic response in B6D2F1 mice with a multi-epitopic recombinant allergen, rKBG8.3 (MERA-8.3), which represents a major group of allergens of grass pollens, used herein as a model of MERA vaccine. Vaccination (subcutaneous) with soluble MERA-8.3, prior to immunization with the MERA-8.3 in alum, led to suppression of the IgE antibody response and a concomitant increase in IgG2a antibody response specific to the MERA-8.3 in a dose-dependent manner. Analysis of cytokine patterns in spleen and lymph node cells revealed a marked decrease of interleukin-2 (IL-2) and IL-4 production and to a lesser extent a decrease of interferon-gamma (IFN-gamma) synthesis, resulting in an increased ratio of IFN-gamma: IL-4 in vaccinated-immunized mice compared with untreated-immunized control mice. Furthermore, splenocytes of mice treated with the MERA-8.3 alone proliferated to MERA-8.3 in vitro with reduced capacity compared with the splenocytes of MERA-8.3-alum immunized mice, owing to a markedly reduced level of IL-2 production in the former. Collectively, these results suggest that vaccination with the MERA-8.3 induces T-cell anergy, which is pivotal to deviation of specific immunity from Th2- to Th1-like, and may serve as an important approach to prevention and therapy of allergic disorders.

Allergens↗

Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear.

This study evaluates the feasibility of growing tissue-engineered cartilage in the shape of a human ear using chondrocytes seeded onto a synthetic biodegradable polymer fashioned in the shape of a 3-year-old child's auricle. A polymer template was formed in the shape of a human auricle using a nonwoven mesh of polyglycolic acid molded after being immersed in a 1% solution of polylactic acid. Each polyglycolic acid-polylactic acid template was seeded with chondrocytes isolated from bovine articular cartilage and then implanted into subcutaneous pockets on the dorsa of 10 athymic mice. The three-dimensional structure was well maintained after removal of an external stent that had been applied for 4 weeks. Specimens harvested 12 weeks after implantation and subjected to gross morphologic and histologic analysis demonstrated new cartilage formation. The overall geometry of the experimental specimens closely resembled the complex structure of the child's auricle. These findings demonstrate that polyglycolic acid-polylactic acid constructs can be fabricated in a very intricate configuration and seeded with chondrocytes to generate new cartilage that would be useful in plastic and reconstructive surgery.

Animals↗

Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1.

We have studied the antibody responses to Env and Gag antigens of human immunodeficiency virus type 1 (HIV-1) in several cohorts of HIV-1-infected individuals: long-term nonprogressors, progressors to disease, acute seroconvertors, and recipients of HIV-1 protease inhibitors. We conclude that the antibody responses to Env and Gag antigens are differentially regulated and that changes in the plasma viral load in the measurable range (500 to 10(8) RNA copies per ml) do not directly affect the antibody responses to these HIV-1 proteins. We provide quantitative estimates of HIV-1-specific immunoglobulin G concentrations in plasma, which can be in excess of 1 mg/ml for both anti-gp120 and anti-p24 once the immune response to HIV-1 has stabilized after seroconversion. We discuss the apparent paradox that the absence of anti-Gag antibodies (which have, at best, limited antiviral activity) is indicative of disease progression, while the retention of anti-Env antibodies (which do have antiviral activity) is of limited (or no) prognostic value. We show that the disappearance of anti-Gag antibodies during disease progression is highly unlikely to be due to immune complexing; instead, we believe that it reflects the loss of T-cell help that is more necessary for the anti-Gag than the anti-Env response.

AIDS Vaccines↗

Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell cycle progression.

Several eukaryotic multiprotein complexes, including the Saccharomyces cerevisiae Snf/Swi complex, remodel chromatin for transcription. In contrast to the Snf/Swi proteins, Sfh1p, a new Snf5p paralog, is essential for viability. The evolutionarily conserved domain of Sfh1p is sufficient for normal function, and Sfh1p interacts functionally and physically with an essential Snf2p paralog in a novel nucleosome-restructuring complex called RSC (for remodels the structure of chromatin). A temperature-sensitive sfh1 allele arrests cells in the G2/M phase of the cell cycle, and the Sfh1 protein is specifically phosphorylated in the G1 phase. Together, these results demonstrate a link between chromatin remodeling and progression through the cell division cycle, providing genetic clues to possible targets for RSC function.

Adenosine Triphosphatases↗

Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication in the lung.

We investigated the in vivo effect of coinfection of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) replication using bronchoalveolar lavage (BAL) of 11 HIV-1-infected patients with pulmonary tuberculosis and 10 patients with no lung disease. Lung segments involved with pulmonary tuberculosis had significantly elevated HIV-1 branched DNA (bDNA) levels and p24 in BAL compared with lung segments uninvolved with tuberculosis or with BAL from patients with no lung disease. The BAL viral burden was higher than plasma HIV-1 in tuberculosis patients, indicating local production of virus. BAL HIV-1 bDNA declined over the course of treatment for tuberculosis in three patients who underwent serial bronchoscopies. Tumor necrosis factor-alpha (TNF-alpha) and HIV-1 bDNA particles were strongly correlated (r2 = 0.9, p < 0.01) in lung segments involved with tuberculosis. The deduced amino acid sequence of HIV-1 gp120 V3 region from involved segments of three patients with pulmonary tuberculosis showed basic substitutions associated with altered viral phenotype. Phylogenetic analysis of V3 sequences demonstrated that BAL HIV-1 RNA had diverged from plasma. These data support the conclusion that pulmonary tuberculosis enhances local HIV-1 replication in vivo.

Adult↗

Mucins (MUC1 and MUC3) of gastrointestinal and breast epithelia reveal different and heterogeneous tumor-associated aberrations in glycosylation.

In a comprehensive study, we examined the expression of the membrane and secretory mucins MUC1 and MUC3, respectively, in normal and neoplastic gastrointestinal and breast epithelia before and after specific alterations of their glycan structures by neuraminidase, alpha-fucosidase, or carbohydrate-specific periodate oxidation. MUC1 mRNA was also identified in normal colorectal tissues by in situ hybridization. The data revealed that normal colorectal epithelia express both MUC1 mRNA and protein, which were detectable after periodate oxidation with all tested MUC1-specific antibodies. During tumorigenesis in the colon, MUC1 became recognizable without periodate treatment concomitantly with highly dysplastic lesions and the malignant state. In the breast, in which MUC1 is detectable with most antibodies in normal epithelium as well as in carcinomas, staining could be enhanced by pretreatment with periodate and casually by enzyme treatments. MUC3 was detectable in normal and neoplastic colorectal tissues and was more intensely stained after periodate oxidation. It was absent in normal breast even after pretreatment but was expressed in seven of 20 breast carcinomas. Therefore, incomplete glycosylation, abnormal distribution, and ectopic expression of mucins are characteristics of malignancy. Periodate oxidation may be widely applicable to immunohistochemistry for examining changes in glycosylation and for detecting antigens masked by glycans.

Biomarkers, Tumor↗

[Effect of vagi excitation on HRV and the exploration of its mechanism].

The experiments were performed on rabbits anaesthetized with urethane and chloralose. The ECG heart rate and blood pressure were recorded. The power spectrum analysis of R-R interval (RRI) was done by computer. Electrical stimulation of nucleus ambiguus (NA), depressor nerve (DN) and the peripheral end of right vagus (RV) all evoked a decrease in heart rate and blood pressure (P < 0.001), and an increase in LF, HF, LF/HF, TV and VLF (P < 0.05-0.001); The LF, HF, LF/HF, TV and VLF were significantly decreased (P < 0.05-0.01) by pretreatment with intravenous injection of atropine. The enhancement of LF during stimulating DN and NA were attenuated (P < 0.05) by prior intravenous injection of propranolol. It is suggested that vagus activity is one of the major regulator of HRV and mediates VLF. The HF is mediated only by vagi, while the LF is mediated by both vagi and sympathetic system.

Animals↗

[Quantitative change of glucagon and insulin immunoreactivities in the pancreas of fasting rats].

In this study, the glucagon and insulin immunoreactivities in the fasting rat pancreas were quantitated by image analysis. The results showed that the glucagon immunoreactivity significantly decreased in fasting rats and that of insulin increased, as compared with that in normal rats. The glucagon immunoreactivity significantly increased after intravenous injection of glucose but no marked difference was found in insulin. These results suggest that the A cells of pancreas may be directly stimulated by nutrients, and the B cells in a different way.

Animals↗