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Article ; Online: Response to COVID-19: The Outpatient Dialysis Setting.

Silberzweig, Jeffrey / Wu, Sylvia / Sinclair, Matthew / Watson, Thomas / Welder, Nancy / Concepcion, Danilo / Yee, Jerry / Speed, Felicia / Cukor, Daniel / Schiller, Brigitte / Weiner, Daniel

Clinical journal of the American Society of Nephrology : CJASN

2023

Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.0000000000000091
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Article ; Online: A Distinct Nasal Microbiota Signature in Peritoneal Dialysis Patients.

Khan, Iman / Wu, Sylvia / Hudson, Anika / Hughes, Clayton / Stryjniak, Gabriel / Westblade, Lars F / Satlin, Michael J / Tedrow, Nicholas / Uhlemann, Anne-Catrin / Kraft, Colleen / Dadhania, Darshana M / Silberzweig, Jeffrey / De Vlaminck, Iwijn / Li, Carol / Srivatana, Vesh / Lee, John Richard

Kidney360

2023 Volume 4, Issue 10, Page(s) 1419–1429

MeSH term(s)	Humans ; Nose ; Peritoneal Dialysis ; Microbiota
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000249
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Article: A Distinct Nasal Microbiota Signature in Peritoneal Dialysis Patients.

medRxiv : the preprint server for health sciences

2023

Abstract: Rationale & objective: The nasal passages harbor both commensal and pathogenic bacteria. In this study, we sought to characterize the anterior nasal microbiota in PD patients using 16S rRNA gene sequencing.: Study design: Cross-sectional.: Setting & ...

Abstract	Rationale & objective: The nasal passages harbor both commensal and pathogenic bacteria. In this study, we sought to characterize the anterior nasal microbiota in PD patients using 16S rRNA gene sequencing. Study design: Cross-sectional. Setting & participants: We recruited 32 PD patients, 37 kidney transplant (KTx) recipients, 22 living donor/healthy control (HC) participants and collected anterior nasal swabs at a single point in time. Predictors: We performed 16S rRNA gene sequencing of the V4-V5 hypervariable region to determine the nasal microbiota. Outcomes: Nasal microbiota profiles were determined at the genus level as well as the amplicon sequencing variant level. Analytical approach: We compared nasal abundance of common genera among the 3 groups using Wilcoxon rank sum testing with Benjamini-Hochberg adjustment. DESeq2 was also utilized to compare the groups at the ASV levels. Results: In the entire cohort, the most abundant genera in the nasal microbiota included: Limitations: 16S RNA gene sequencing provides taxonomic information to the genus level. Conclusions: We find a distinct nasal microbiota signature in PD patients compared to KTx recipients and HC participants. Given the potential relationship between the nasal pathogenic bacteria and infectious complications, further studies are needed to define the nasal microbiota associated with these infectious complications and to conduct studies on the manipulation of the nasal microbiota to prevent such complications.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.23.23286379
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Article ; Online: Early outcome of patients undergoing transcatheter aortic valve implantation (TAVI): The Auckland City Hospital experience 2011-2015.

Wu, Sylvia S Y / Wang, Tom Kai Ming / Nand, Parma / Ramanathan, Tharumenthiran / Webster, Mark / Stewart, Jim

The New Zealand medical journal

2016 Volume 129, Issue 1428, Page(s) 47–55

Abstract: Aims: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in high-risk patients. We report the initial TAVI experience at Auckland City Hospital.: Methods: The records of patients undergoing ... ...

Abstract	Aims: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in high-risk patients. We report the initial TAVI experience at Auckland City Hospital. Methods: The records of patients undergoing TAVI between 2011 and 2015 at Auckland City Hospital were reviewed. We report the procedural success and outcome, including major adverse events (death, stroke, myocardial infarction, bleeding, vascular complications and rehospitalisations), degree of aortic regurgitation and symptom status up to 1-year follow-up. Results: Mean age was 80.7 years and mean Euroscore II and Society of Thoracic Surgeons' scores were 8.2% and 6.3% respectively; 50% had undergone previous cardiac surgery. Successful deployment of the valve was achieved in all patients. The cumulative mortality rates at 30 days, 6 months and 1 year were 2.4%, 6.1% and 12.2% and cumulative stroke rates 1.2%, 3% and 8.2% respectively. Severe aortic regurgitation occurred in 2.3% Conclusion: TAVI is available in the New Zealand public hospital system for patients who are high-risk candidates for AVR. Early results are excellent and indicate that the technology is being used appropriately, according to current access criteria. If the early cost effectiveness data are confirmed, the indications for TAVI may widen.
MeSH term(s)	Acute Kidney Injury/epidemiology ; Aged, 80 and over ; Aortic Valve Stenosis/mortality ; Aortic Valve Stenosis/surgery ; Clinical Audit ; Female ; Follow-Up Studies ; Hospital Mortality ; Hospitals, Public ; Humans ; Male ; New Zealand/epidemiology ; Patient Readmission/statistics & numerical data ; Postoperative Complications/epidemiology ; Severity of Illness Index ; Transcatheter Aortic Valve Replacement
Language	English
Publishing date	2016-01-08
Publishing country	New Zealand
Document type	Journal Article ; Observational Study
ZDB-ID	390590-1
ISSN	1175-8716 ; 0028-8446 ; 0110-7704
ISSN (online)	1175-8716
ISSN	0028-8446 ; 0110-7704
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Ua VI Zs.396: Show issues

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Article: The removal of pyroglutamic acid from monoclonal antibodies without denaturation of the protein chains.

Werner, William E / Wu, Sylvia / Mulkerrin, Michael

Analytical biochemistry

2005 Volume 342, Issue 1, Page(s) 120–125

Abstract: Typically, the removal of pyroglutamate from the protein chains of immunoglobulins with the enzyme pyroglutamate aminopeptidase requires the use of chaotropic and reducing agents, quite often with limited success. This article describes a series of ... ...

Abstract	Typically, the removal of pyroglutamate from the protein chains of immunoglobulins with the enzyme pyroglutamate aminopeptidase requires the use of chaotropic and reducing agents, quite often with limited success. This article describes a series of optimization experiments using elevated temperatures and detergents to denature and stabilize the heavy chains of immunoglobulins such that the pyroglutamate at the amino terminal was accessible to enzymatic removal using the thermostable protease isolated from Pyrococcus furiosus. The detergent polysorbate 20 (Tween 20) was used successfully to facilitate the removal of pyroglutamate residues. A one-step digestion was developed using elevated temperatures and polysorbate 20, rather than chaotropic and reducing agents, with sample cleanup and preparation for Edman sequencing performed using a commercial cartridge containing the PVDF membrane. All of the immunoglobulins digested with this method yielded heavy chain sequence, but the extent of deblocking was immunglobulin dependent (typically>50%).
MeSH term(s)	Antibodies, Monoclonal/chemistry ; Detergents ; Enzyme Stability ; Hot Temperature ; Humans ; Polysorbates ; Protein Denaturation ; Pyroglutamyl-Peptidase I/metabolism ; Pyrrolidonecarboxylic Acid/chemistry ; Sequence Analysis, Protein/methods
Chemical Substances	Antibodies, Monoclonal ; Detergents ; Polysorbates ; Pyroglutamyl-Peptidase I (EC 3.4.19.3) ; Pyrrolidonecarboxylic Acid (SZB83O1W42)
Language	English
Publishing date	2005-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2005.04.012
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Zs.A 389: Show issues

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Article: Pediatric drugs--a review of commercially available oral formulations.

Strickley, Robert G / Iwata, Quynh / Wu, Sylvia / Dahl, Terrence C

Journal of pharmaceutical sciences

2008 Volume 97, Issue 5, Page(s) 1731–1774

Abstract: Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral ... ...

Abstract	Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral formulations. The physicochemical and organoleptic properties of the active drug substance such as solubility, chemical stability, and taste along with the intended dose can determine which formulations are feasible to develop. Oral pediatric formulations are available in 17 different varieties and can be either a ready-to-use formulation such as a solution, syrup, suspension, tablet, scored tablet, chewable tablet, orally disintegrating tablet, or thin strip, or can also be a formulation that requires manipulation such as a powder for constitution to a suspension, tablet for constitution to a suspension, powder for constitution to a solution, drops for reconstitution to a suspension, concentrated solution for dilution, effervescent tablet, bulk oral granules, bulk oral powder, or solid in a capsule to mix with food or drink. Recently there has been an increase in pediatric formulation development inspired by increased regulatory incentives. The intent of this review is to educate the reader on the various types of formulations administered orally to pediatrics, the rationale in deciding which type of formulation to develop, the excipients used, development challenges, the in-use handling of oral pediatric formulations, and the regulatory incentives.
MeSH term(s)	Administration, Oral ; Chemistry, Pharmaceutical ; Child ; Humans ; Pediatrics ; Suspensions ; Tablets
Chemical Substances	Suspensions ; Tablets
Language	English
Publishing date	2008-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1002/jps.21101
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Article ; Online: GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions.

Wolfgang, Grushenka H I / Shibata, Riri / Wang, Jianying / Ray, Adrian S / Wu, Sylvia / Doerrfler, Edward / Reiser, Hans / Lee, William A / Birkus, Gabriel / Christensen, Neil D / Andrei, Graciela / Snoeck, Robert

Antimicrobial agents and chemotherapy

2009 Volume 53, Issue 7, Page(s) 2777–2784

Abstract: GS-9191 is a novel double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine (PMEG) designed as a topical agent to permeate skin and be metabolized to the active nucleoside triphosphate analog in the epithelial layer. The prodrug was ... ...

Abstract	GS-9191 is a novel double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine (PMEG) designed as a topical agent to permeate skin and be metabolized to the active nucleoside triphosphate analog in the epithelial layer. The prodrug was shown to be metabolized intracellularly to 9-(2-phosphonylmethoxyethyl)-N(6)-cyclopropyl-2,6,diaminopurine (cPrPMEDAP) and subsequently deaminated to PMEG. The active form, PMEG diphosphate, was shown to be a potent inhibitor of DNA polymerase alpha and beta while showing weaker activity against mitochondrial DNA polymerase gamma (50% enzyme inhibition observed at 2.5, 1.6, and 59.4 microM, respectively). GS-9191 was markedly more potent than PMEG or cPrPMEDAP in a series of human papillomavirus (HPV)-positive cell lines, with effective concentrations to inhibit 50% cell growth (EC(50)) as low as 0.03, 207, and 284 nM, respectively. In contrast, GS-9191 was generally less potent in non-HPV-infected cells and primary cells (EC(50)s between 1 and 15 nM). DNA synthesis was inhibited by GS-9191 within 24 h of treatment; cells were observed to be arrested in S phase by 48 h and to subsequently undergo apoptosis (between 3 and 7 days). In an animal model (cottontail rabbit papillomavirus), topical GS-9191 was shown to decrease the size of papillomas in a dose-related manner. At the highest dose (0.1%), cures were evident at the end of 5 weeks, and lesions did not recur in a 30-day follow-up period. These data suggest that GS-9191 may have utility in the treatment of HPV-induced lesions.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Cell Cycle/drug effects ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cells, Cultured ; Female ; Guanine/analogs & derivatives ; Guanine/pharmacology ; Guanine/therapeutic use ; Humans ; Male ; Nucleic Acid Synthesis Inhibitors ; Phenylalanine/analogs & derivatives ; Phenylalanine/pharmacology ; Phenylalanine/therapeutic use ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; Rabbits ; Uterine Cervical Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents ; Antiviral Agents ; GS-9191 ; Nucleic Acid Synthesis Inhibitors ; Prodrugs ; Phenylalanine (47E5O17Y3R) ; Guanine (5Z93L87A1R)
Language	English
Publishing date	2009-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00103-09
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Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: GS-9219--a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma.

Clinical cancer research : an official journal of the American Association for Cancer Research

2008 Volume 14, Issue 9, Page(s) 2824–2832

Abstract: Purpose: GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG), was designed as a cytotoxic agent that preferentially targets lymphoid cells. Our objective was to characterize the antiproliferative activity, ... ...

Abstract	Purpose: GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG), was designed as a cytotoxic agent that preferentially targets lymphoid cells. Our objective was to characterize the antiproliferative activity, pharmacokinetics, pharmacodynamics, and safety of GS-9219. Experimental design: GS-9219 was selected through screening in proliferation assays and through pharmacokinetic screening. The activation pathway of GS-9219 was characterized in lymphocytes, and its cytotoxic activity was evaluated against a panel of hematopoietic and nonhematopoietic cell types. To test whether the prodrug moieties present in GS-9219 confer an advantage over PMEG in vivo, the pharmacokinetics, pharmacodynamics (lymph node germinal center depletion), and toxicity of equimolar doses of GS-9219 and PMEG were evaluated after i.v. administration to normal beagle dogs. Finally, proof of concept of the antitumor efficacy of GS-9219 was evaluated in five pet dogs with spontaneous, advanced-stage non-Hodgkin's lymphoma (NHL) following a single i.v. administration of GS-9219 as monotherapy. Results: In lymphocytes, GS-9219 is converted to its active metabolite, PMEG diphosphate, via enzymatic hydrolysis, deamination, and phosphorylation. GS-9219 has substantial antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. In contrast, resting lymphocytes and solid tumor lines were less sensitive to GS-9219. GS-9219, but not PMEG, depleted the germinal centers in lymphoid tissues of normal beagle dogs at doses that were tolerated. In addition, GS-9219 displayed significant in vivo efficacy in five dogs with spontaneous NHL after a single administration, with either no or low-grade adverse events. Conclusion: GS-9219 may have utility for the treatment of NHL.
MeSH term(s)	Alanine/administration & dosage ; Alanine/adverse effects ; Alanine/analogs & derivatives ; Alanine/pharmacokinetics ; Alanine/therapeutic use ; Animals ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dogs ; Guanine/analogs & derivatives ; Guanine/therapeutic use ; Lymphoid Tissue/cytology ; Lymphoid Tissue/drug effects ; Lymphoid Tissue/metabolism ; Lymphoma, Non-Hodgkin/drug therapy ; Organophosphorus Compounds/therapeutic use ; Prodrugs/adverse effects ; Prodrugs/chemistry ; Prodrugs/pharmacokinetics ; Prodrugs/therapeutic use ; Purines/administration & dosage ; Purines/adverse effects ; Purines/pharmacokinetics ; Purines/therapeutic use ; Tissue Distribution
Chemical Substances	Antineoplastic Agents ; Organophosphorus Compounds ; Prodrugs ; Purines ; rabacfosadine ; 9-((2-phosphonylmethoxy)ethyl)guanine (114088-58-3) ; Guanine (5Z93L87A1R) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2008-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-07-2061
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