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Biomedical subjects

E R White

Publications and source records attributed to E R White.

At least 19 recordsLinked to original sources

Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells.

The Insulin-like growth factor-1 receptor (IGF-1R) is overexpressed in a variety of tumors including breast, prostate and myeloma. Thus, IGF-1R and its downstream signaling effectors are good candidates for molecular-based targeted antitumor therapies. Indeed, protein inhibitors of IGF-1R signaling and IGF-1R blocking antibodies are undergoing clinical trials. Herein, the molecular basis for antibody-mediated IGF-1R signal inhibition has been investigated in a hematopoietic cell line model, FDC-P1, that has been rendered interleukin-3 independent in a ligand-dependent manner through retroviral-mediated expression of IGF-1R (FD/IGF-1R). Furthermore, the ability of an anti-IGF-1R antibody to synergize with signal-transduction pathway inhibitors and induce apoptosis was determined. The alphaIGF-1R antibody, A12, was capable of arresting IGF-1 or insulin-induced FD/IGF-1R cell proliferation in the G1 phase of the cell cycle and resulted in apoptotic induction. A12 effectiveness could be potentiated through combination treatment with small molecule inhibitors of the Ras/Raf/MEK/ERK or PI3K/Akt/mTOR pathways. These results validate the use of the FD/IGF-1R cells to evaluate the effectiveness and mechanisms of targeted IGF-1R therapeutic strategies.

Animals↗

Custom made C18 columns for the hydrophobic chromatography of cephalosporin C derivatives.

"Hydrophobic chromatography", which is a variation of reverse phase chromatography, is applicable to the analysis of cephalosporin C derivatives, especially in fermentation broths. Unfortunately, there are no commercial C18 columns which are entirely suitable for this class of compounds. For this reason C18 columns were prepared by an in-situ bonding technique and were optimally designed for cephalosporin C derivatives. Mono-, di- and trifunctional octadecyl bonding agents were used with 10 microns silica of both 60 A and 100 A pore diameter. The best results were obtained with the difunctional agent, methyloctadecyldichlorosilane, and 100 A silica. "Endcapping" of residual silanol groups with a trimethylsilylation agent was optional, since good results were obtained with both a plain C18 column and one that was "endcapped".

Cephalosporins↗

Reverse phase high speed liquid chromatography of antibiotics. III. Use of ultra high performance columns and ion-pairing techniques.

Improved methods for the separation and quantitation of cephalosporin, penicillin, aminoglycoside and anthracycline antibiotics are presented. The use of ultra high performance 5 micrometer phase columns combined with the added dimension of ion-pairing greatly increases the ease of separation and speed of analysis of complex antibiotic mixtures. Antibiotics in a variety of dosage forms and in fermentation broths have been examined in order to provide the maximum data on impurities to meet regulatory requirements for drug safety, purity and efficacy. Mixtures of antibiotics have been analyzed to demonstrate the improved separations, increased efficiency and shortened analysis times possible with ultra thin performance columns. Under these improved conditions, the danger of multiple components in a single peak are markedly reduced.

Aminoglycosides↗

Risk management: preventive medicine for malpractice.

The remedy for malpractice problems hinges on their identification and subsequent prevention. This study was undertaken to ascertain any patterns of medical negligence, as indicated by patients' allegations, so that specific recommendations could be made to health care providers. In general, it was found that most malpractice suits could have been avoided if more diligent patient care had been provided, particularly with regard to patient communication.

Communication↗

The determination of cephradine and cephalexin by reverse phase high-performance liquid chromatography.

The application of reverse phase high-performance liquid chromatography to the separation and analysis of cephradine and cephalexin is demonstrated. The procedure has been applied to chemicals, pharmaceutical formulations and reaction solutions. The preparation of samples is simple and rapid. Chromatographic conditions are described for both pellicular and small particle columns. The feasibility of determing cephradine and cephalexin in physiological fluids has also been demonstrated.

Capsules↗

Reverse phase high speed liquid chromatography of antibiotics. II. Use of high efficiency small particle columns.

Improved methods for the separation and quantitation of cephalosporins, penicillins, tetracyclines and several miscellaneous antibiotics by reverse phase high speed liquid chromatography are presented. The methods have been improved significantly by the substitution of high efficiency, small particle (approximately 10 micrometer reverse phase columns in place of the previously used medium efficiency, pellicular columns. The conditions and procedures described here illustrate that considerable improvements in separation and sensitivity of detection of antibiotics are achieved. Pure compounds, complex mixtures of antibiotics in a variety of dosage forms and fermentation broths are routinely analyzed by the described procedures.

Anti-Bacterial Agents↗

Reverse phase high speed liquid chromatography of antibiotics.

Reverse phase high speed liquid chromatographic methods are presented for the separation and detection of cephalosporins, penicillins, tetracyclines and other miscellaneous antibiotics. The reverse phase approach is superior to ion-exchange liquid chromatography and spectrophotometric, chemical and microbiological procedures currently in use. In addition to being simple and easy to control, the technique is rapid, convenient and precise and provides the basis for the direct analysis of pure compounds, stability samples, complex mixtures and dosage forms of all types. Preparative chromatography has been used in our laboratory for the separation and isolation of up to 500 mg of antibiotics. Using this approach, we have separated and isolated small impurities as well as pure feference compounds. The methodology reported here can be extensively applied to the separation, quantitation and isolation of both naturally occurring and synthetically produced antibiotics in a variety of media including physiological fluids.

Anti-Bacterial Agents↗

Radiation of hemocyanin: inactivation and reactivation of oxygen-carrying capacity.

Oxygen-carrying capacity of hemocyanin from Limulus and Busycotypus (Busycon) decreases with increasing radiation, giving initial yield values for G(-O(2),) of 1.1 and 1.0, respectively. High radiation doses regenerate this capacity of Busycotypus hemocyanin. These effects are attributed largely to the dual nature of hydrogen peroxide, which, at low concentrations, oxidizes protein-bound copper and at high concentrations, that is, at high doses, reduces oxidized copper. The ability of hemocyanin to decompose hydrogen peroxide is relatively unaffected by irradiation, which suggests that copper atoms at the active sites are not all equivalent. The catalase-like activity of Busycotypus hemocyanin can be simulated by amino acid chelates of copper, including arginine, histidine, and glycine.

Animals↗