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Biomedical subjects

S Dorman

Publications and source records attributed to S Dorman.

6 recordsLinked to original sources

Optimization of ENU mutagenesis of Caenorhabditis elegans.

Chemical mutagenesis of Caenorhabditis elegans has relied primarily on EMS to produce missense mutations. The drawback of EMS mutagenesis is that the molecular lesions are primarily G/C --> A/T transitions. ENU has been shown to produce a different spectrum of mutations, but its greater toxicity to C. elegans makes it a difficult mutagen to use. We describe here methods for minimizing ENU toxicity in C. elegans. Methods include preparing ENU stocks in absolute ethanol and storing stock solutions for not more than 2 weeks at -20 degrees C. To maintain reasonable brood sizes of mutagenized animals, mutagenic solutions should not exceed 1.0mM ENU. We provide data which suggest ENU is degraded or altered to more toxic products in aqueous solution, but less so in solvents such as absolute ethanol.

Animals↗

Loss of insulin-like growth factor II receptor expression promotes growth in cancer by increasing intracellular signaling from both IGF-I and insulin receptors.

The insulin-like growth factor-II receptor (IGF-IIR) is frequently mutated or deleted in some malignant human tumors, suggesting that the IGF-IIR is a tumor suppressor. However, the exact mechanism by which IGF-IIR suppresses growth in tumors has not been definitively established. We demonstrate that IGF-IIR-deficient murine L cells (D9) have higher growth rates than IGF-IIR-positive L cells (Cc2) in response to IGF-II. IGF-II levels are higher in growth-conditioned medium from D9 versus Cc2 cells. Receptor neutralization studies and measurements of insulin receptor substrate 1 phosphorylation confirm that the enhanced growth of D9 cells is due to increased stimulation of the IGF-I and insulin receptors by IGF-II. In contrast, the levels of secreted latent and active transforming growth factor beta (TGF-beta) are similar for both D9 and Cc2 cells, indicating that the slower growth of Cc2 cells is not due to activation of latent TGF-beta by IGF-IIR and growth inhibition. The results directly demonstrate that down regulation of the IGF-IIR promotes the growth of transformed D9 cells by sustaining IGF-II, which binds to and activates IGF-IR and insulin receptor to increase intracellular growth signals.

Animals↗

Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction.

We report two cases of hyperkalaemia related to the use of the salt substitute 'Lo Salt' in hypertensive patients on treatment with ACE inhibitors. In each case serum potassium returned to the normal range after cessation of the salt substitute. Without vigilance the contribution of the salt substitute to hyperkalaemia would have been overlooked and an ACE inhibitor erroneously withdrawn.

Aged↗

Incipient germ cell tumor in a cryptorchid testis.

A 13-year-old male who had bilateral cryptorchid testes since birth underwent testicular biopsies and subsequent left orchiectomy following a diagnosis of malignant germ cell tumor. No tumor mass was noted although the malignant cells were seen within the seminiferous tubules and the interstitium. Five recorded cases of in-situ or incipient germ cell neoplasms of the testes are reviewed; three were infertile, another had a cryptorchid testis, and the fifth was both infertile and cryptorchid. Two of these patients have developed frank carcinoma, which would suggest that the process represents an early phase of invasive germ cell neoplasia.

Adolescent↗

Contracting for intensive care services.

Purchasers will increasingly expect clinical services in the NHS internal market to provide objective measures of their benefits and cost effectiveness in order to maintain or develop current funding levels. There is limited scientific evidence to demonstrate the clinical effectiveness of intensive care services in terms of mortality/morbidity. Intensive care is a high-cost service and studies of cost-effectiveness need to take account of case-mix variations, differences in admission and discharge policies, and other differences between units. Decisions over development or rationalisation of intensive care services should be based on proper outcome studies of well defined patient groups. The purchasing function itself requires development in order to support effective contracting.

Contract Services↗