Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1.

Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dose-dependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite the known link between apoptosis and blood vessel regression, this was not the cause of reduced vessel density observed in the absence of endothelial MCL1. Rather, the reduction in vessel density was linked to ectopic apoptosis in regions of the angiogenic vasculature where EC proliferation and new vessel growth occurs. We have therefore identified MCL1 as an essential survival factor for ECs that is required for blood vessel production during angiogenesis.

Genetic diversity at the HUMTHO1 locus.

A World-wide population genetic study on the highly polymorphic DNA locus HUMTHO1, was performed using data collected from 48 studies. Also this study reports new allele frequency data of a Punjabi population (n = 125) from North India. This population is in Hardy-Weinberg equilibrium with 77.6% heterozygosity and power of exclusion at 0.538. Allele frequency graphs were used to demonstrate that world populations show a distinguishable ethnic trend at the HUMTHO1 locus. Heterozygosity (H) and power of exclusion (PE) estimates differ with respect to ethnicity. For example, Caucasian populations have the highest average H and PE and tribal populations the lowest. Using correspondence analysis, it is demonstrated that there is an ethnic trend for this locus. Examination of this trend indicates that some alleles at this locus may be more frequent in specific ethnic populations. This study concludes that the HUMTHO1 locus may be used as one of a number of STR loci for ethnic differentiation studies.

Parathyroid imaging with thallium-201 subtraction scintigraphy: a report of 33 cases.

Thallium-201 subtraction scintigraphy has been used in Wellington Hospital for preoperative localisation of parathyroid adenomas since 1984. The technique wa audited by comparing the scan reports with the outcome at operation in 33 patients, 30 of whom underwent a primary exploration. In our unselected patients we found the technique to have poor sensitivity (45.4%) with a high false positive rate (21%). There was no difference in the mean size of the glands correctly identified compared to those that were missed. Our experience has led us to believe that thallium-201 subtraction scintigraphy has not lived up to its early promise and is not a useful technique for routine preoperative localisation of parathyroid adenomas.

Parathyroid surgery in chronic renal failure.

In hyperparathyroidism associated with endstage renal failure, either subtotal, or total parathyroidectomy with autotransplantation have been advocated as potentially curative for those patients non-responsive to medical therapy. Seventeen such patients managed by the Wellington renal unit were reviewed as to indications for, and responses to, surgery. Itch, psychiatric symptoms, joint ache, muscular weakness, gritty eyes and thirst were the major symptoms for which surgery was recommended. Hypercalcaemia (universal in women) and deterioration in bone radiology were additional indications for operation. All showed remarkable postoperative improvement. Symptomatic hypocalcaemia was significant in 41%. This observation has led to intensified pre- and postoperative vitamin D and calcium therapy. Postoperative radiologic improvement at three months was apparent in 80% of patients. We advocate subtotal parathyroidectomy as the effective surgical treatment of choice for uraemic hyperparathyroidism.

Problems in evaluating radiation dose via terrestrial and aquatic pathways.

This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being.