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Biomedical subjects

Y M Yang

Publications and source records attributed to Y M Yang.

At least 19 recordsLinked to original sources

Preparation of silica microspheres encapsulating phase-change material by sol-gel method in O/W emulsion.

Spherical silica microcapsules containing phase-change material (PCM) were prepared by the sol-gel method in O/W emulsion. This is the first time that inorganic encapsulation of PCM with core/shell structure has been studied. The results of this synthesis revealed that micron size (4 - 8 microm) silica microspheres encapsulating n-pentadecane can be successfully created from acidic solutions ([H+] > or = 1.44 N) by using cationic surfactants as the emulsifiers. The identification of the mechanisms for the formation of silica shell at the oil-water interface indicates that it should be the charge-controlled mechanism through S+X-I+ (positively charged surfactant-halide ion-positively charged silica species) electrostatic interactions or the reaction rates-controlled mechanism working on cationic emulsifiers.

Drug Compounding↗

An analysis of frequency response for the blood flow of volume pulse in microcirculation.

In this paper, a frequency analysis for the microcirculation model is introduced to find new microcirculation parameters in the frequency domain. By using Bode Plot of transfer function, we found two characteristic parameters of the model: damping ratio xi and break frequency omega(n). By analyzing the variation of xi and omega(n), it enables us to have better understanding of different states of microcirculation. At low damping, 0 or =1, the state of microcirculation will be worse and worse along with the descending of the omega(n). The results of experiments on 120 subjects are consistent with the analytical results of the model.

Analysis of Variance↗

Endophytic naphthopyrone metabolites are co-inhibitors of xanthine oxidase, SW1116 cell and some microbial growths.

Fractionation of the extract of Aspergillus niger. IFB-E003, an endophyte in Cyndon dactylon, gave four known compounds naphtho-gamma-pyrones rubrofusarin B, fonsecinone A, asperpyrone B and aurasperone A, which were further investigated biologically. Rubrofusarin B was shown to be cytotoxic to the colon cancer cell line SW1116 (IC50: 4.5 microgml-1), and aurasperone A inhibitory on XO (xanthine oxidase) (IC50: 10.9 micromoll-1). Moreover, the four naphtho-gamma-pyrones exhibited growth inhibitions against the five test microbes with MICs ranging in between 1.9 and 31.2 microgml(-1). The present recognition of rubrofusarin B and aurasperone A as strong co-inhibitors on XO, colon cancer cell and some microbial pathogens is of significance for the imperative discovery of new relevant therapeutic agents.

Anti-Infective Agents↗

Antibacterial and xanthine oxidase inhibitory cerebrosides from Fusarium sp. IFB-121, an endophytic fungus in Quercus variabilis.

Two antibacterial and xanthine oxidase inhibitory cerebrosides, one of which is chemically new, were characterized from the chloroform-methanol (1:1) extract of Fusarium sp. IFB-121, an endophytic fungus in Quercus variabilis. By means of chemical and spectral methods [IR, electrospray ionization MS (ESI-MS), tandem ESI-MS, 1H and 13C NMR, distortionless enhancement by polarization transfer, COSY, heteronuclear multiple-quantum coherence, heteronuclear multiple-bond correlation, and 2-D nuclear Overhauser effect correlation spectroscopy], the structure of the new metabolite named fusaruside was established as (2S,2'R,3R,3'E,4E,8E,10E)-1-O-beta-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8,10-sphingatrienine, and the structure of the other was identified as (2S,2'R,3R,3'E,4E,8E)-1-O-beta-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine. Both new and known cerebrosides, although inactive to Trichophyton rubrum and Candida albicans, showed strong antibacterial activities against Bacillus subtilis, Escherichia coli, and Pseudomonas fluorescens, with their minimum inhibitory concentrations being 3.9, 3.9, and 1.9 microg/mL, and 7.8, 3.9, and 7.8 microg/mL, respectively. Furthermore, both metabolites were inhibitory to xanthine oxidase, with the IC50 value of fusaruside being 43.8 +/- 3.6 microM and the known cerebroside being 55.5 +/- 1.8 microM.

Anti-Bacterial Agents↗

Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers.

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.

Amino Acid Sequence↗

Conjunctival cul-de-sac reconstruction with radial forearm free flap in anophthalmic orbit syndrome.

Contracted eye socket is a constant cosmetic embarrassment to the patient. It not only renders patients unable to maintain an eye prosthesis, but it becomes a source of chronic discharge and irritation. Eye socket reconstruction with free skin, mucous membrane, cartilage, or dermis-fat usually remains unsatisfactory in many cases, due to secondary graft contracture. Traumatic injuries to the orbit and neighboring soft tissue frequently lead to a contracted eye socket. This condition results from the need for removal of the traumatized conjunctiva at the time of the enucleation, along with the traumatized eyeball, for satisfactory wound closure. In traumatic anophthalmos patients, a radial forearm free flap was used for conjunctival cul-de-sac reconstruction. Eye socket beds were developed as hinge-shaped flaps and used as lining for the upper and lower palpebrae. The authors conclude that the radial forearm flap is a useful alternative in the treatment of traumatic anophthalmos.

Adult↗

Beta-chemokine induction of activation protein-1 and cyclic AMP responsive element activation in human myeloid cells.

Chemokines effect leukocyte chemotaxis and activation through their binding to specific G protein-coupled receptors. Although early steps in chemokine signal transduction pathways have been characterized, there is relatively limited information available at the transcription factor level. To that end, we have examined the binding activity on activation protein-1 (AP-1) and cyclic AMP responsive element (CRE) target sequences in human THP-1 myeloid cells after treatment with the beta-chemokine macrophage inflammatory protein (MIP-1alpha). MIP-1alpha induced both AP-1 and CRE activation. Although inhibition of protein kinase C blocked the AP-1 activity induced by this chemokine, there was no decrease in CRE activation in the presence of a protein kinase A inhibitor. Using kinase assays, it appeared that mitogen-activated protein kinase pathways were involved in CRE activation. In addition, HIV-1 infection of THP-1 cells resulted in constitutive activation of AP-1 and CRE elements but no further response to MIP-1alpha treatment. These results suggest that beta-chemokines act via protein kinase C-dependent pathways and mitogen-activated protein kinase pathways to modulate the host transcriptional response in myeloid cells, and that this response is altered by HIV infection.

Cell Line↗

[Gene point mutation in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum].

OBJECTIVE: To investigate the gene point mutation in the dihydrofolate reductase-thymidylate synthase(dhfr) gene of Plasmodium falciparum isolate from Yunnan Province strongly associated with pyrimethamine and cycloguanil resistance. METHODS: Nested PCR and restriction endonuclease digestion were applied to detect the gene mutation using dried blood filter paper collected from the fields in Yunnan Province. RESULTS: Different mutations were found in 4 amino acids at positions 16, 51, 108 and 164 of dhfr gene, particularly, Asn-108 and Ile-51, the mutation frequency being 94.1% and 90.1%, respectively. The frequency of the wild-type genotype (3D7-type) Ser-108 appeared lower (9.1%), while the frequency of the Ala-16 was high(61.8%); the mutation-type was very high, the ratio of HB3-type, 7G8-type/FCR3-type and Cambodian-type was 1:21:7.5. CONCLUSION: The investigation first demonstrated that Plasmodium falciparum Yunnan isolate dihydrofolate reductase-thymidylate synthase gene (dhfr) at positions 16, 51, 108 and 164 exhibited different degrees of point mutation. The frequency of mutation of the 7D8-type involved in pyrimethamine resistance was higher, while that of the FCR3-type involved in cycloquanil resistance was lower.

Animals↗

Immunohistochemical study of nucleoporin p62 in the hippocampus and hypothalamus of the rat brain.

We immunohistochemically studied the distribution of nucleoporin p62 in the hippocampus and hypothalamus of rat brain. Previous reports have shown the presence of p62-immunoreactivity (ir) in the nuclear rim in the non-neuronal cells, but the present study showed that of p62-ir within the nucleus in addition to the nuclear rim in the neuronal cells of the hippocampus and hypothalamic nuclei; in these areas the glucocorticoid receptor (GR) undergoes nucleocytoplasmic translocation determined by ligand. We analyzed the expression of p62-ir after adrenalectomy (ADX). ADX changed the localization of GR-ir from the nucleus to the cytoplasm, but did not change the localization or immunoreactivity of p62, suggesting that nucleoporin p62 is stable regardless of intracellular signal transduction between the cytoplasm and the nucleus.

Animals↗

Mechanism for fetal hemoglobin induction by hydroxyurea in sickle cell erythroid progenitors.

Hydroxyurea (HU) is a widely used cytotoxic agent that is known to induce fetal hemoglobin (HbF) production and is presently used to ameliorate the severity of pain episodes in patients with sickle cell anemia (HbSS). Previously we have shown that HU inhibits growth of burst forming unit-erythroid (BFU-E) colonies in a dose-dependent manner, while fetal hemoglobin levels were increased. In the present report, we extended our analysis demonstrating the number of S phase cells is significantly higher for HbSS patients that respond to HU therapy. Studies were completed in vitro using erythroid progenitors derived from umbilical cord samples or peripheral blood from patients with HbS-hereditary persistence of fetal hemoglobin (HbS-HPFH) or HbSS disease. The effect of HU on (a) S phase erythroid progenitors, (b) BFU-E colony growth, (c) HbF levels in BFU-E colonies, and (d) total cellular RNA synthesis was analyzed in vitro for the three groups. The level of S phase erythroid progenitors was similar for all three groups and BFU-E colony growth was inhibited 92-94% for all samples in a dose-dependent manner. The HbF levels were increased in BFU-E colonies from HbSS patients (control, 4.0% +/- 1.15% vs. +HU, 22.67% +/- 2.03%) whereas HbF levels were decreased in BFU-E colonies derived from umbilical cord samples (control, 80% +/- 9.07% vs. +HU, 35.7% +/- 4.81%) or HbS-HPFH patients (control, 49.67% +/- 3.84% vs. +HU, 23.3% +/- 0.88%). Total RNA synthesis measured by 3H-uridine incorporation increased with increasing concentrations of HU; however, actinomycin D inhibited HU-induced RNA synthesis. These results suggest that HU can inhibit an active globin gene without preference and that newly synthesized RNA is under transcriptional control mechanisms.

Adolescent↗

Prenatal sickle cell screening education effect on the follow-up rates of infants with sickle cell trait.

OBJECTIVE: To assess the effect of prenatal education about newborn sickle cell screening on parents' compliance with the follow-up for infants with sickle cell trait. SUBJECTS: Expectant mothers whose prenatal education included information about newborn sickle cell screening were the study group, and those whose prenatal education did not include such information were the control group. METHODS: Mothers of infants with sickle cell trait were given the opportunity for in-person notification of screening results and follow-up counseling/education. Follow-up rates, anxiety and retention of information were assessed for the case-control study. RESULTS: There were a total of 15,670 infants born in the region, and 647 infants were identified with sickle cell trait. The follow-up rate for parents of infants with sickle cell trait was significantly higher (76%) for study group than the control group (49%) (P = 0.0006). Parents whose prenatal education included sickle cell hemoglobinopathy information retained significantly more of the information given during the post-natal education than did controls. CONCLUSION: Our data suggest that prenatal education for expectant mothers which includes information about newborn sickle cell screening significantly increases the follow-up rate for infants with sickle cell trait and contributes to a greater retention of information.

Adult↗

Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption.

The causes for the propensity of metastasized prostate cancer cells to grow in bone and to induce osteoblastic lesions remain unresolved. Co-culture of human prostate cancer cell lines with bone slices was determined to increase the level of endothelin-1 (ET-1) mRNA and its production. ET-1 is an ejaculate protein that also stimulates osteoblasts. Osteoclastic bone resorption was significantly blocked by the presence of androgen-independent prostate cancer cells in a dose-dependent manner as that of synthetic ET-1. The inhibition could be neutralized by specific ET-1 antibody, indicating the association of prostate cancer-derived ET-1 with inhibition of bone resorption. The combined ET-1 activity on osteoclasts and osteoblasts disrupts bone remodelling. ET-1 production is also elevated in the presence of prostate-specific antigen (PSA). ET-1 in turn enhances DNA synthesis of prostate cancer cells. Interactions among cancer cells, bone, ET-1 and PSA may be critical in cancer growth and lesions in bone.

Analysis of Variance↗

Physical growth, sexual maturation, body image and sickle cell disease.

PURPOSE: This study assessed delays in physical growth and sexual maturation, self-esteem and body image in youth with homozygous sickle hemoglobin disease (HgbSS). METHOD: A consecutive sample of 30 subjects age 8 through 19 with homozygous sickle cell disease (hemoglobin SS) and a similar number of control subjects matched for age, race, gender and socioeconomic status and free of chronic illness were examined for height, weight and Tanner staging of sexual development. Subjects also completed the Body Cathexis Scale and Piers-Harris Self-Concept Scale. Assessments were with paired samples t-tests. RESULTS: The subjects with sickle cell disease had significantly lower weights and were shorter than matched control subjects. Sexual development (physical) was also delayed in the sickle cell subjects. The study failed to find significant differences for either body image or self-esteem. CONCLUSIONS: The latency age and adolescent subjects with sickle cell disease had significant delays in physical (height, weight, secondary sexual characteristics) maturation. The study failed to find significant differences in either self-esteem or body image between the two groups. Theoretical constructs from the literature were presented which questioned the belief that these expected delays in physical growth and sexual maturation have an adverse effect upon self-esteem and body image.

Adolescent↗

Nitric oxide triggers programmed cell death (apoptosis) of adult rat ventricular myocytes in culture.

Excessive nitric oxide (NO) production within the heart is implicated in the pathogenesis of myocyte death, but the mechanism whereby NO kills cardiac myocytes is not known. To determine whether NO may trigger programmed cell death (apoptosis) of adult rat ventricular myocytes in culture, the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was shown to kill purified cardiac myocytes in a dose-dependent fashion. In situ analysis of ventricular myocytes plated on chamber slides using nick-end labeling of DNA demonstrated that SNAP induces cardiac myocyte apoptosis, which was confirmed by the identification of oligonucleosomal DNA fragmentation on agarose gel electrophoresis. Similarly, treatment of cardiac myocytes with cytokines that induce inducible NO synthase was shown to cause an NO-dependent induction of apoptosis. Addition of reduced hemoglobin to scavenge NO liberated by SNAP extinguished both the increase in percentage of apoptotic cells and the appearance of DNA ladders. Treatment with SNAP (but not with N-acetylpenicillamine or SNAP + hemoglobin) not only induced apoptosis but resulted in a marked increase in p53 expression in cardiac myocytes detected by Western blotting and immunohistochemistry. These data indicate that NO has the capacity to kill cardiac myocytes by triggering apoptosis and suggest the involvement of p53 in this process.

Animals↗

Regulation of growth and apoptosis of breast cancer cells by a 54 kDa lymphokine.

A normal human lymphocyte-derived 54 kDa polypeptide, capable of regulating cell growth has been identified as an isoform variant (abbreviated as NP54) of protein neuroleukin-phosphoglucose isomerase (PGI). Since distinct PGI variants undetectable in normal tissues had been identified in breast cancer tissues, the effect of NP54 on the growth of human breast cancer cells SK-Br-3 in cultures was analyzed. Exposure to NP54 caused a dose-dependent growth modulation. Approximately 40% reduction of cell density was detected at 40 pM of NP54, along with a blocking of G1 cells entering into S phase. The growth modulation was correlated with a significantly reduced expression of epidermal growth factor receptor (EGF-R) gene transcript, supporting the interpretation that the level of EGF-R expression and cell growth are related mechanisms. NP54 treatment also significantly increased cells with apoptotic morphological feature and fragmented DNA. Incubation with a monoclonal anti-NP54 antibody negated NP54 activity, confirming a regulatory activity in cell growth and apoptosis.

Antibodies, Monoclonal↗

Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer.

We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.

AMP-Activated Protein Kinase Kinases↗

ATF2 confers radiation resistance to human melanoma cells.

We have previously identified a U.V.-response element (URE; TGACAACA) and its bound proteins, members of the AP1 and ATF transcription factor families, in melanoma cells. Using a mutant form of cylic AMP response element binding (CREB), we found that CREB-associated-URE-bound proteins conferred characteristic melanoma phenotypes, including radiation resistance (Oncogene 12: 2223, 1996). In the present study we sought to determine which of the CREB-associated proteins confers radiation resistance on human melanoma cells. To this end we purified and identified via microsequencing ATF2 as a major URE- bound and CREB-associated protein in MeWo cells--a late stage human melanoma cell line. To determine the contribution of ATF2 to radiation resistance, MeWo cells were transfected with ATF2 cDNA lacking the trans-activation domain (ATF2(delta1-195)). MeWo cells that stably express ATF2(delta1-195) showed weaker transcriptional activities and an altered pattern of homo/hetero dimers. ATF2(delta1-195) clones exhibited up to tenfold lower resistance to irradiation by either U.V. or X-rays. The degree of resistance to radiation in the ATF2(delta1-195)-expressing clones could be increased upon transient transfection with ATF2(wt), but not with phosphorylation-defective mutant ATF2(69,71). Similarly, transfection of ATF2(wt) to WM3211, an early stage human melanoma cells line, increased resistance to radiation. Finally, changes elicited through ATF2(delta1-195) also led to reduced drug resistance, as shown for MMC, araC and cisplatinum. Our results suggest that ATF2 is a regulator of radiation and drug resistance in melanomas, and that tumor targeted ATF2 modulators may be useful sensitizers in the treatment of tumors of this type.

Activating Transcription Factor 2↗