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Biomedical subjects

B McKibben

Publications and source records attributed to B McKibben.

8 recordsLinked to original sources
PubMed1999

Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays.

Evaluation of a biased "library" of pyrrolo[2,3-d]pyrimidines using yeast-based functional assays expressing human A1- and A2a-adenosine receptors, led to the A1 selective antagonist 4b. A direct correlation between yeast functional activity and binding data was established. Practical compounds with polar residues at C-4 of the pyrrolopyrimidine system required H-bond donor functionality for high potency.

Binding, Competitive↗
PubMed1999

Impacts of structural photomodification on the toxicity of environmental contaminants: anthracene photooxidation products.

The toxicity of polycyclic aromatic hydrocarbons (PHAs) is known to be enhanced by light via photosensitization reactions (production of active oxygen) and photomodification of the chemicals (e.g., oxidation) to more toxic compounds. Anthracene (ANT) toxicity in particular has been found to increase dramatically following photomodification. The objective of this study was to identify the photooxidation products of ANT and assess the toxicity of selected photoproducts. High performance liquid chromatography (HPLC) analysis of anthracene photooxidation revealed a complex array of oxidation products; prevalent among these were anthraquinone (ATQ) and hydroxy-anthraquinones (hATQs). Eleven of these compounds were tested for toxicity using growth inhibition of the duckweed Lemna gibba L. G-3. All but one of the compounds tested were found to be toxic, and when UV radiation was present in the light source toxicity was generally enhanced. The chemicals were also irradiated under SSR prior to toxicity testing. In about half the cases, the ATQ compounds were rapidly photooxidized and the resultant photoproducts were more toxic than the parent compounds. Interestingly, 2-hydroxyanthraquinone, which was not subject to photooxidation, was the most toxic of the compounds tested. As a light stable compound it presents the risk of a persistent environmental hazard.

Anthracenes↗
PubMed1996

Changes in insulin-like growth factor-I receptor expression and binding protein secretion associated with tamoxifen resistance and estrogen independence in human breast cancer cells in vitro.

Conditioned medium from a series of human breast cancer cell lines representing the phenotypes of estrogen dependence ZR-75-1, MCF-7), tamoxifen resistance (Z(+)-75-9a1, LY2) and estrogen independence (ZR-PR-Lt) contained four detectable insulin-like growth factor binding proteins (IGFBPs) of MW 24, 34, 44 and 70 kDa. in the tamoxifen resistant lines secretion of the 24 kDA IGFBP was depressed in comparison to the parent lines whilst secretion of the 44 kDa IGFBP was unaffected. Secretion of this species by ZR-PR-LT cells was reduced. Following incubation in medium containing 1% serum both tamoxifen resistant cell lines secreted higher levels of the 44 kDa IGFBP than the respective parent lines. These changes in IGFBP secretion associated with the development of tamoxifen resistance and estrogen independence were accompanied by changes in the expression of receptors for IGF-1.

Breast Neoplasms↗
PubMed1996

Expression of receptors for epidermal growth factor and insulin-like growth factor I by ZR-75-1 human breast cancer cell variants is inversely related: the effect of steroid hormones on insulin-like growth factor I receptor expression.

We have investigated the expression of insulin-like growth factor I receptors (IGFR) by the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. ZR-75-1 cells expressed 6633+/-953 receptors per cell,(K(d) 0.24+/-0.06 nM). IGFR expression was reduced in ZR-75-9a1 cells (1180+/-614 receptors per cell, K(d) 0.13+/-0.05) and increased in the ZR-PR-LT cell line (18 430+/-3210 receptors per cell, K(d) 0.24+/-17). A comparison of these data with previously published findings for epidermal growth factor receptor (EGFR) expression by these cell lines revealed that IGFR and EGFR expression are inversely related in the variant lines whereas ZR-75-1 cells express similar numbers of both receptors. Since the changes in IGFR expression observed are associated with changes in steroid hormone receptor status, we also investigated the effects of oestradiol, the synthetic progestin ORG 2058 and dexamethasone on IGFR expression. Oestradiol increased IGFR expression only in the ZR-75-1 cell line. Low concentrations of ORG 2058 increased IGFR levels in the two cell lines positive for progesterone receptor (ZR-75-1 and ZR-PR-LT). High concentrations of ORG 2058 increased IGFR expression in all cell lines, as did dexamethasone. These data suggest that EGFR and IGFR expression may be linked in breast cancer, and that EGFR/IGFR ratios in breast cancer may be a more sensitive prognostic indicator than EGFR expression alone. Regardless of basal IGFR expression by the cell studied, ORG 2058 increased IGFR expression, possibly via both the progesterone and glucocorticoid receptors.

Breast Neoplasms↗
PubMed1994

Immunoreactive endothelin distribution in ocular tissues.

PURPOSE: To study the distribution of the endothelins in the eye using ocular tissues of human, rat, and porcine origin. METHODS: Extracts of ocular tissues were examined for immunoreactivity to endothelin 1 and 3 and pro-endothelin 1 using radioimmunoassay. Characterization of immunoreactivity was verified using high-performance liquid chromatography. RESULTS: Immunoreactivity to endothelin 1 and endothelin 3 was found in all ocular tissues except the cornea, which contained no immunoreactivity to endothelin 3. Highest levels were found in the choroid, although species-related differences were present. Immunoreactivity to endothelin 3 was generally twofold to threefold higher than immunoreactivity to endothelin 1. The majority of endothelin-like-immunoreactivity in the retina was blood vessel-associated. High-pressure liquid chromatography (HPLC) confirmed that immunoreactive endothelin 1 and endothelin 3 in the tissue extracts eluted in identical positions to their respective standard synthetic peptides. CONCLUSIONS: The endothelins are abundantly distributed in the eye. Endothelin 1 is present in its mature, 21 amino acid form, and only minimal amounts of the precursor pro-endothelin is found in ocular tissues. The wide distribution patterns point to complex roles for these peptides in blood vessel physiology and in such other functions as regulation of aqueous outflow, and in neurotransmission or modulation.

Aged↗
PubMedDate not supplied

Treatment of portwine stains using the pulsed dye laser.

Five years of clinical experience of the treatment of portwine stains using the flashlamp-pumped dye laser is presented. The dye laser, when turned to a wavelength of 577 nanometres with a short pulsewidth of the order of 340 microseconds, may be used to target selectively the dilated vasculature constituting the lesion. Patients with ages ranging from 5-45 years were treated under general anaesthetic using a computer controlled scanning system developed by the authors. Several repeat treatments were found to be necessary. Results are presented ranging from total eradication of the lesion to marginal lightening only. No scarring of the treated sites was evident.

Adolescent↗