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Biomedical subjects

Karen Wright

Publications and source records attributed to Karen Wright.

15 recordsLinked to original sources
PubMed2006

Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine.

Protection against reinfection with noncapsulated Gram-negative bacteria, such as Shigella, an enteroinvasive bacterium responsible for bacillary dysentery, is mainly achieved by Abs specific for the O-Ag, the polysaccharide part of the LPS, the major bacterial surface Ag. The use of chemically defined glycoconjugates encompassing oligosaccharides mimicking the protective determinants carried by the O-Ag, thus expected to induce an efficient anti-LPS Ab response, has been considered an alternative to detoxified LPS-protein conjugate vaccines. The aim of this study was to identify such functional oligosaccharide mimics of the S. flexneri serotype 2a O-Ag. Using protective murine mAbs specific for S. flexneri serotype 2a and synthetic oligosaccharides designed to analyze the contribution of each sugar residue of the branched pentasaccharide repeating unit of the O-Ag, we demonstrated that the O-Ag exhibited an immunodominant serotype-specific determinant. We also showed that elongating the oligosaccharide sequence improved Ab recognition. From these antigenicity data, selected synthetic oligosaccharides were assessed for their potential to mimic the O-Ag by analyzing their immunogenicity in mice when coupled to tetanus toxoid via single point attachment. Our results demonstrated that induction of an efficient serotype 2a-specific anti-O-Ag Ab response was dependent on the length of the oligosaccharide sequence. A pentadecasaccharide representing three biological repeating units was identified as a potential candidate for further development of a chemically defined glycoconjugate vaccine against S. flexneri 2a infection.

Amino Acid Sequence↗
PubMed2006

Peripheral cannabinoid receptor, CB2, regulates bone mass.

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2(-/-) phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-kappaB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.

Animals↗
PubMed2005

Induced axial chirality in the biphenyl core of the proatropoisomeric, C alpha-tetrasubstituted alpha-amino acid residue Bip in peptides.

An induced axial chirality in the biphenyl core of the 2',1':1,2;1'',2'':3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid (Bip) residue, a conformationally labile, atropoisomeric, C(alpha)-tetrasubstituted alpha-amino acid, was observed by CD and (1)H NMR spectroscopic techniques in the linear dipeptides Boc-Bip-Xaa*-OMe where Boc=tert-butoxycarbonyl, OMe=methoxy, and Xaa*=D- and/or L-Ala, -Val, -Leu, -Phe, -(alphaMe)Val and -(alphaMe)Leu. Chiral induction was significantly lower in the isomeric dipeptides Boc-Xaa*-Bip-OMe, with the Xaa* residue located at the N-terminus of Bip, as well as in the cyclic dipeptide cyclo-[Bip-L-Ala]. The results obtained in solution were confirmed by X-ray diffraction analysis of a crystalline sample of Boc-(R)-Bip-D-Ala-OMe.

Amino Acids↗
PubMed2005

Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing.

BACKGROUND & AIMS: Two G-protein-coupled cannabinoid receptors, termed CB1 and CB2, have been identified and several mammalian enteric nervous systems express CB1 receptors and produce endocannabinoids. An immunomodulatory role for the endocannabinoid system in gastrointestinal inflammatory disorders has been proposed and this study sought to determine the location of both cannabinoid receptors in human colon and to investigate epithelial receptor function. METHODS: The location of CB1 and CB2 receptors in human colonic tissue was determined by immunohistochemistry. Primary colonic epithelial cells were treated with both synthetic and endogenous cannabinoids in vitro, and biochemical coupling of the receptors to known signaling events was determined by immunoblotting. Human colonic epithelial cell lines were used in cannabinoid-binding studies and as a model for in vitro wound-healing experiments. RESULTS: CB1-receptor immunoreactivity was evident in normal colonic epithelium, smooth muscle, and the submucosal myenteric plexus. CB1- and CB2-receptor expression was present on plasma cells in the lamina propria, whereas only CB2 was present on macrophages. CB2 immunoreactivity was seen in the epithelium of colonic tissue characteristic of inflammatory bowel disease. Cannabinoids enhanced epithelial wound closure either alone or in combination with lysophosphatidic acid through a CB1-lysophosphatidic acid 1 heteromeric receptor complex. CONCLUSIONS: CB1 receptors are expressed in normal human colon and colonic epithelium is responsive biochemically and functionally to cannabinoids. Increased epithelial CB2-receptor expression in human inflammatory bowel disease tissue implies an immunomodulatory role that may impact on mucosal immunity.

Biomarkers↗
PubMed2005

Transforming hope: how elderly palliative patients live with hope.

Hope is important to palliative patients; however, the process by which these patients live with hope is unknown. The purpose of this study was to describe, using a grounded theory approach, the processes by which palliative patients live with hope. Sixteen interviews were conducted with 10 home-care palliative patients (mean age 75 years) in their homes using open-ended questions. The participants defined their hope as expectations such as not suffering more and having a peaceful death. They described their main concern as wanting to "live with hope" and they achieved this through the basic social process of transforming hope. Transforming hope involved acknowledging "life the way it is," searching for meaning, and positive reappraisal. The results of this study provide a foundation for future research and the development of interventions to engender hope in older palliative patients.

Attitude to Death↗
PubMed2004

Induced axial chirality in the biphenyl core of the Calpha-tetrasubstituted alpha-amino acid residue Bip and subsequent propagation of chirality in (Bip)n/Val oligopeptides.

In the dipeptides Boc-Bip-L-Val-OMe and Boc-Bip-D-Val-OMe, an induced axial chirality in the biphenyl core of the Bip residue, a conformationally labile, proatropoisomeric C(alpha,alpha)-disubstituted glycine, was observed by electronic CD and (1)H NMR. Chiral induction is significantly higher when the Val residue is located at the C-terminal position of Bip. An outstanding phenomenon of propagation of chirality was demonstrated to occur in the related 3(10)-helical -(Bip)n-L-Val (n = 2-6) oligopeptides by CD and vibrational CD techniques.

Amino Acids↗
PubMed2004

Preparation of synthetic glycoconjugates as potential vaccines against Shigella flexneri serotype 2a disease.

The synthesis of three neoglycopeptides incorporating carbohydrate haptens, differing in length, covalently linked to a non natural universal T helper peptide is disclosed. They were synthesized according to a blockwise strategy based on the condensation of appropriate di-, tri-, and tetrasaccharide trichloroacetimidate donors onto an azidoethyl 2-acetamido-2-deoxybeta-D-glucopyranoside acceptor. Use of thiol-maleimide coupling chemistry allowed site-selective efficient conjugation.

Acetylglucosamine↗
PubMed2004

Blockwise approach to fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a: convergent Synthesis of a decasaccharide representative of a dimer of the branched repeating unit.

The D'A'B'(E')C'DAB(E)C decasaccharide representative of a dimer of a frame-shifted pentasaccharide repeating unit of the O-specific polysaccharide of Shigella flexneri 2a was synthesized as its methyl glycoside by condensing a pentasaccharide donor (D'A'B'(E')C') and a pentasaccharide acceptor (DAB(E)C-OMe). Several convergent routes to these two building blocks, involving either the AB linkage or the BC linkage as the disconnection site, were evaluated in comparison to the linear strategy. The latter was preferred. It is based on the use of the trichloroacetimidate chemistry. The target branched oligosaccharide was designed to probe the recognition at the molecular level of the natural polysaccharide by protective monoclonal antibodies.

Molecular Structure↗
PubMed2004

Understanding the breast cancer experience of women: a qualitative study of African American, Asian American, Latina and Caucasian cancer survivors.

Breast cancer is the most common form of cancer in American women across most ethnic groups. Although the psychosocial impact of breast cancer is being studied, there is little information on women from diverse ethnic and socioeconomic backgrounds. We conducted a qualitative study with breast cancer survivors (BCS) of various ethnicities. A total of 102 BCS participated in focus group interviews (24 African Americans, 34 Asians, 26 Latinas and 18 Caucasians); 20 health professionals participated in key informant interviews. Important ethnic differences in type of treatment were noted, Asians and Latinas were more likely to receive mastectomies and African American BCS were least likely to receive adjuvant therapies, including radiation and chemotherapy. These BCS enjoyed a fairly good overall health-related quality of life (HRQOL) with some persistent concerns. The prevailing concerns among all women included overall health, moderate physical concerns, cancer recurrence or metastases, psychosocial concerns related to worry about children and burdening the family, and body image and sexual health concerns. Additional challenges included: lack of knowledge about breast cancer; medical care issues such as insurance, cost and amount of time spent with physician; cultural sensitivity of providers, language barriers, cultural factors related to beliefs about illness, gender role and family obligations (e.g. self-sacrifice). These BCS, particularly the women of color, voiced that their spiritual beliefs and practices are central to their coping. This study accomplishes two goals; it adds to the sparse literature concerning the psychosocial sequelae of breast cancer among women of color, and it increases our knowledge of specific cultural influences (e.g. dietary practices, coping) and socio-ecological factors on HRQOL. More importantly, the study addressed areas that have not been studied before, specifically, an in-depth study on BCS QOL comparing multiple ethnic groups in the US. The results of this investigation will provide preliminary information to survivors and health-care providers about the impact of culture and socio-ecological contexts on survivorship. Among women of all major ethnic groups, breast cancer is the most common form of cancer and the second leading cause of cancer death (American Cancer Society (ACS), 2002). In 2002, over 203,000 women in the United States will be diagnosed with breast cancer (ACS, 2002). Ethnic disparities exist for cancer stage, diagnosis, survival, morbidity and mortality. In general, ethnic minority women are diagnosed with more advanced disease and experience greater morbidity and mortality (Haynes & Smedley, 1999; Miller et al., 1996; Ries et al., 2000; Shinagawa, 2000). In general, increases in survival rates have prompted greater interest in the quality of life (QOL) of breast cancer survivors (BCS) over the past two decades. Additionally, the QOL of cancer survivors from diverse ethnic, cultural and socioeconomic backgrounds is an emerging priority area for studies on survivorship research and clinical care (Haynes and Smedley, 1999; National Cancer Institute (NCI), 2002; President's Cancer Panel, 2000).

Adult↗
PubMed2004

Elderly palliative care cancer patients' descriptions of hope-fostering strategies.

The purpose of this study was to describe perceptions of hope-fostering strategies of elderly patients with advanced cancer receiving palliative home care. Using a qualitative thematic research design, saturation was reached with 10 palliative home care patients (mean age 75 years) (five males and five females). Face-to-face audiotaped interviews were conducted in the participants' homes. Participants described hope for: "not suffering more", "living life to the fullest in the little time I have left", a peaceful death, life after death and "hope for a better life in the future" for their family. Using Lubrosky's thematic analysis, themes of fostering their hope were: leaving a legacy, achieving short-term goals, "turn your mind off", supportive family and friends, symbols of hope, positive thoughts, honest information and symptom control.

Adaptation, Psychological↗
PubMed2003

Liquid chromatographic enantioseparation of spin-labelled beta-amino acids.

Direct and indirect high-performance liquid chromatographic (HPLC) methods were developed for the enantioseparation of spin-labelled, cyclic, chiral beta-amino acids containing nitroxide free radicals, trans-3-amino- 1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (trans-POAC), cis-4-amino-1-oxyl-2,2,6,6-tetramethylpiperidine-3-carboxylic acid (cis-beta-TOAC) and their N-Fmoc-protected analogues, synthesized in racemic and enantiomerically pure forms. The direct method involved the use of a Chiralcel OD-RH column, while indirect separation was carried out by application of either 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate or (S)-N-(4-nitrophenoxycarbonyl)-phenylalanine methoxyethyl ester as chiral derivatizing agent. Use of 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (Marfey's reagent) as chiral derivatizing agent failed because of the low of yield of the derivatization reaction. Selection and variation of the mobile phase was restricted by the sensitivity of the spin-labelled amino acids to acidic conditions. Conditions affording the best resolution were found and the differences in separation capability of the methods were noted. The sequence of elution of the enantiomers was determined by different methods and, in the case of the beta-TOAC analogues, the absolute configurations of the enantiomers corresponding to each peak were identified.

Amino Acids↗
PubMed2003

New tools for the control of peptide conformation and supramolecular chemistry: crown-carrier, C(alpha)-methyl L-DOPA amino acids.

The preferred conformation of five, terminally protected, model peptide series to the hexamer level, based on three novel crowned, C(alpha)-methyl L-DOPA amino acids combined with either L-Ala/Aib or Gly/Aib, were assessed in structure supporting solvents using FT-IR absorption, (1)H NMR, and CD techniques. The FT-IR absorption spectra strongly suggest that the contribution of the crowned C(alpha)-tetrasubstituted residue to intramolecular H-bonding is equivalent to that of Aib and is much more significant than that of either L-Ala or Gly. In addition, the (1)H NMR titrations and the CD patterns resemble those typically exhibited by (right-handed) 3(10)-helical structures.

Alanine↗
PubMed2002

Synthesis, conformational analysis, and spectroscopic characterization of peptides based on Daf, the first rigid transition-metal receptor, cyclic C(alpha,alpha)-disubstituted glycine.

Three series of terminally protected model oligopeptides to the nonamer level, based on 9-amino-4,5-diazafluorene-9-carboxylic acid, the first rigid bipyridine-type C(alpha,alpha)-disubstituted glycine, and either Gly, L-Ala, or Aib residues were synthesized by solution methods and fully characterized. The molecular structures of two derivatives and one tripeptide were determined in the crystal state by x-ray diffraction. Moreover, the solution preferred conformations of these peptides were assessed by Fourier transform infrared absorption and (1)H-NMR techniques. A comparison with the known structural tendencies of the strictly related C(alpha,alpha)-disubstituted glycyl residues 1-aminocyclopentane-1-carboxylic acid and 9-aminofluorene-9-carboxylic acid is made, and the implications for the use of the 9-amino-4,5-diazafluorene-9-carboxylic acid residue in conformationally constrained analogs of bioactive peptides are briefly examined. A spectroscopic (uv absorption, fluorescence, CD) characterization of this novel heteroaromatic C(alpha,alpha)-disubstituted glycine is also reported. Finally, preliminary conformational data and membrane activity measurements are discussed for an analog of the lipopeptaibol antibiotic [L-Leu(11)-OMe] trichogin GA IV in which a 9-amino-4,5-diazafluorene-9-carboxylic acid residue was synthetically incorporated in position 1 (replacing the original Aib residue).

Aza Compounds↗
PubMed1997

Patent medicine.

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Breast Neoplasms↗