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Biomedical subjects

K R Stewart

Publications and source records attributed to K R Stewart.

At least 19 recordsLinked to original sources
PubMed2001

Molecular basis for enantioselectivity of lipase from Chromobacterium viscosum toward the diesters of 2,3-dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol.

2,3-Dihydro-3-(4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol, 1, is a chiral bisphenol useful for preparation of polymers. Previous screening of commercial hydrolases identified lipase from Chromobacterium viscosum (CVL) as a highly regio- and enantioselective catalyst for hydrolysis of diesters of 1. The regioselectivity was > or =30:1 favoring the ester at the 5-position, while the enantioselectivity varied with acyl chain length, showing the highest enantioselectivity (E = 48 +/- 20 S) for the dibutanoate ester. In this paper, we use a combination of nonsymmetrical diesters and computer modeling to identify that the remote ester group controls the enantioselectivity. First, we prepared nonsymmetrical diesters of (+/-)-1 using another regioselective, but nonenantioselective, reaction. Lipase from Candida rugosa (CRL) showed the opposite regioselectivity (>30:1), allowing removal of the ester at the 4'-position (the remote ester in the CVL-catalyzed reaction). Regioselective hydrolysis of (+/-)-1-dibutanoate (150 g) gave (+/-)-1-5-dibutanoate (89 g, 71% yield). Acylation gave nonsymmetrical diesters that varied at the 4'-position. With no ester at the 4'-position, CVL showed no enantioselectivity, while hindered esters (3,3-dimethylbutanoate) reacted 20 times more slowly, but retained enantioselectivity (E = 22). These results indicate that the remote ester group can control the enantioselectivity. Computer modeling confirmed these results and provided molecular details. A model of a phosphonate transition state analogue fit easily in the active site of the open conformation of CVL. A large hydrophobic pocket tilts to one side above the catalytic machinery. The tilt permits the remote ester at the 4'-position of only the (S)-enantiomer to bind in this pocket. The butanoate ester fits and fills this pocket and shows high enantioselectivity. Both smaller and larger ester groups show low enantioselectivity because small ester groups cannot fill this pocket, while longer ester groups extend beyond the pocket. An improved large-scale resolution of 1-dibutanoate with CVL gave (R)-(+)-1-dibutanoate (269 g, 47% yield, 92% ee) and (S)-(-)-1-4'-monobutanoate (245 g, 52% yield, 89% ee). Methanolysis yielded (R)-(+)-1 (169 g, 40% overall yield, >97% ee) and (S)-(-)-1 (122 g, 36% overall yield, >96% ee).

Chromobacterium↗
PubMed2001

Arsenic extraction and speciation in carrots using accelerated solvent extraction, liquid chromatography and plasma mass spectrometry.

Arsenic present in freeze-dried carrots was extracted using accelerated solvent extraction (ASE). Several parameters, including selection of the dispersing agent, extraction time, number of extraction cycles, particle size and extraction temperature, were evaluated to optimize the ASE method. Filtering and treatment with C-18 SPE cartridges were also evaluated as part of the sample preparation procedure before speciation analysis. The method was validated by spiking single arsenical and mixed arsenical standards on the dispersing agent and on portions of freeze-dried carrot prior to extraction. LC-ICP-MS was used to determine individual arsenic species in the carrot extracts. A weak anion-exchange column was used for the separation of As(III), As(v), monomethylarsonic acid (MMA), dimethylarsinic acid and arsenobetaine. Optimized sample preparation conditions were applied to the extraction of arsenic in nine freeze-dried carrot samples. Total arsenic concentration in the carrot samples ranged from less than 20 ng g(-1) to 18.7 microg g(-1), dry mass. Extraction efficiency, defined as the ratio of the sum of individual arsenic species concentrations to total arsenic, ranged from 80 to 102% for freeze-dried carrots with arsenic concentrations greater than the limit of quantitation. Inorganic As(III) and As(v) were the only species found in samples that contained less than 400 ng g(-1) total arsenic. MMA and an unidentified arsenic compound were present in some of the samples with higher total arsenic content.

Arsenic↗
PubMed1999

Evaluation of ENCOREplus. A community-based breast and cervical cancer screening program.

BACKGROUND: Minority women and women with low income levels are significantly less likely to practice appropriate mammography and Pap test screening. ENCOREplus is a health promotion program that provides outreach, education, referral, and other service that facilitate breast and cervical cancer screening for medically underserved women. The program is delivered through a network of community-based nonprofit organizations (YWCA of the U.S.A). The purpose of this study was to assess the effectiveness of ENCOREplus in promoting mammography and Pap test screening among women who were nonadherent to screening guidelines. METHODS: Baseline data were collected from women participating in the program. Follow-up occurred within six months of baseline to assess whether or not enrollees received recommended screenings. Screening-completion rates were compared to rates from other published intervention studies. RESULTS: Data from the program's second implementation year show that 27,494 women participated in the ENCOREplus program. Over half the women were racial/ethnic minorities, over 75% reported annual incomes under $15,000, and 49% reported no insurance. Among women 40 and over, 69.7% were nonadherent to ACS mammography screening guidelines at baseline. Among participants 18 and older, 68.9% were nonadherent to Pap test screening guidelines. Of nonadherent participants, 57.8% received mammograms and 36.5% received Pap tests. Both mammography and Pap test screening-completion rates compared favorably with other programs. CONCLUSION: This study demonstrates that programs implemented through community-based organizations can be successful in increasing mammography and Pap test screening among low-income and minority women.

Adolescent↗
PubMed1995

Mutagenicity of tetranitroazoxytoluenes: a preliminary screening in Salmonella typhimurium strains TA100 and TA100NR.

Tetranitroazoxytoluenes are polynitroaromatic compounds that can be produced during the microbial reduction of the explosive, 2,4,6-trinitrotoluene (TNT). The three major tetranitroazoxytoluenes were synthesized and tested in Salmonella typhimurium strains TA100 and TA100NR. All compounds were mutagenic in TA100 but not in TA100NR, indicating the need for nitroreductase activity to induce mutagenicity. The most active chemical was 4,4',6,6'-tetranitro-2,2'-azoxytoluene (2735 rev/mumol) followed by 2',4,6,6'-tetranitro-2',4-azoxytoluene (929 rev/mumol) and 2,2'-6,6'-tetranitro-4,4'-azoxytoluene (320 rev/mumol). These chemicals were more active than the aminodinitrotoluenes (298 rev/mumol for 2-amino-4,6-dinitrotoluene and 115 rev/mumol for 4-amino-2,6-dinitrotoluene) and only 4,4',6,6'-tetranitro-2,2'-azoxytoluene was more active than the parent compound, TNT (1022 rev/mumol).

Azo Compounds↗
PubMed1994

Combating pharmacist shortage through labor certification.

Several solutions, ranging from increased technician duties to salary raises, automation, and increasing job satisfaction, have been presented in the literature as methods of assuaging the pharmacist shortage. Although a significant portion of pharmacy graduates from American pharmacy colleges are foreign nationals, no marketing strategies have been elucidated in the retention and recruitment of foreign nationals through labor certification. Labor certifications are generally approved by the Secretary of Labor if the following factors have been verified: 1) there are not sufficient United States workers who are able, willing, qualified, and available for employment; and 2) the employment of the foreign national will not adversely affect the wages and working conditions of U.S. workers similarly employed. When properly understood, the labor certification process is a test of the job market where foreigners, by virtue of their skills and qualifications, attain certification which subsequently leads to permanent residency (green card). The objective of this report is to elucidate the tedious yet effective method of retaining American-educated foreign nationals through labor certification.

Documentation↗
PubMed1989

Immunoenzyme techniques in dermatopathology.

The advantages and disadvantages of the immunofluorescence and immunoperoxidase techniques and an introductory description of the major variations of the basic immunoperoxidase method are discussed. The ability to identify intermediate filaments, T and B lymphocyte cell markers, S-100 proteins, myelin basic protein, and carcinoembryonic antigen in tissue sections can assist the dermatopathologist in classifying undifferentiated or histologically similar-appearing tumors. A systematic approach to the diagnosis of a majority of these tumors with the use of immunoenzyme staining is provided.

Antigens, Differentiation↗
PubMed1988

Mutagenic activities of fecapentaene derivatives in the Ames/Salmonella test system.

The direct mutagenic activities of a pair of naturally-occurring and several synthetic fecapentaenes were measured in the Ames/Salmonella test system. We found that strain TA100 with preincubation was the most sensitive procedure for the naturally-occurring fecapentaene-12 (FP-12). Its natural analog, FP-14, and the synthetic isomer, cis-FP-12, yielded similar mutagenic activities to FP-12 in the range of 1000-2000 TA100 revertants per microgram of compound. The synthetic analogs of FP-12 and FP-14, MFP-12 and MFP-14, wherein the glycerol moiety was replaced by methoxy, exhibited consistently higher mutagenic activities than their parent fecapentaenes (MFP-12 was about 20 times more potent than FP-12; MFP-14 was about twice the potency of FP-14). The standard rat liver metabolizing system (S9) reduced the activities of all the fecapentaenes in a dose-related manner.

Animals↗
PubMed1987

Chemical stability of thiopental sodium injection in disposable plastic syringes.

The chemical stability of thiopental sodium injection (2.5%) when stored at 25 degrees and 5 degrees in disposable plastic syringes of two manufacturers (Monoject and Becton Dickenson and Co.) has been studied using the USP-NF method. The injection appeared to be stable for five days at 25 degrees and 45 days at 5 degrees with a loss in potency of less than 7%. The thiopental sodium did not adsorb on the syringes. The pH values and the physical appearance did not change. An additional peak was obtained in the chromatogram from both the freshly prepared and the assay solution probably due to an impurity in the powder.

Disposable Equipment↗
PubMed1986

Stability of cefuroxime sodium in some aqueous buffered solutions and intravenous admixtures.

Cefuroxime sodium (Zinacef) is a new semisynthetic, broad spectrum cephalosporin antibiotic for parenteral administration which is stable to most of the beta-lactamases. The stability of cefuroxime sodium in aqueous solutions, with or without phosphate buffer, and in 5% dextrose and 0.9% sodium chloride injections was studied using a stability-indicating high-pressure liquid chromatographic method developed in our laboratory. The optimum pH range of stability was determined to be approximately 4.5-7.3. Both buffered and unbuffered solutions followed first-order decomposition. In 5% dextrose and 0.9% sodium chloride injections, cefuroxime was stable for 1 day (more than 90% potent) at 25 degrees C and for at least 30 days at 5 degrees C. At -10 degrees C, there was negligible decomposition after 30 days. The pH values of the solutions stored at 5 degrees C and -10 degrees C remained in the maximum stability range and the solutions were clear even after 30 days of storage. Thawing the frozen solutions in a microwave oven adversely affected the stability.

Buffers↗
PubMed1986

Stability of hydralazine hydrochloride in aqueous vehicles.

The stability of hydralazine hydrochloride in aqueous vehicles which contain either dextrose, fructose, lactose, maltose, mannitol, sorbitol or sucrose has been studied using a stability-indicating high-performance liquid chromatographic method. Dextrose, fructose, lactose and maltose had adverse effects on the stability of hydralazine. In mannitol (better than sorbitol) and sorbitol, hydralazine was stable for about 21 days (loss in potency of less than 10%) and sucrose had an adverse effect only after its hydrolysis to fructose and dextrose. The optimum pH range of stability in dextrose was approximately between 3.2 and 4.4. The first-order rate of decomposition increased with an increase in the concentration of dextrose but not with an increase in the concentration of hydralazine. In the absence of other excipients the phosphate and citrate buffers did not adversely affect the stability of hydralazine hydrochloride.

Chromatography, High Pressure Liquid↗
PubMed1986

Chemical stabilities of lignocaine hydrochloride and phenylephrine hydrochloride in aqueous solution.

The chemical stabilities of lignocaine hydrochloride (lidocaine hydrochloride) and phenylephrine hydrochloride in a combination aqueous solution have been determined using stability-indicating high-performance liquid chromatographic methods. The drugs did not interact and were stable for at least 66 days at room temperature. The pH value changed from 6.0 to 5.8 after 66 days but was still within the optimum pH range for the stabilities of lignocaine and phenylephrine.

Chromatography, High Pressure Liquid↗
PubMed1986

Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections.

The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied. Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL. Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v. bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days. To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days. At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography. Except for the buffered samples, all solutions remained clear and pH was unchanged. Vancomycin concentrations decreased less than 6% during 17 days at room temperature. In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study. Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C.

Chromatography, High Pressure Liquid↗