Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Support of human cord blood progenitor cells on human stromal cell lines transformed by SV40 large T antigen under the influence of an inducible (metallothionein) promoter

We describe the development of a human bone marrow (BM) culture system which allows study of the interaction of stromal cell lines (SCL) and highly purified hematopoietic progenitor cells. Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be controlled by altering the zinc (Zn) concentration were characterized, demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF production. Suppression of SCL proliferation on removal of Zn made it possible to use these lines in coculture with purified CD34+ progenitor cells from umbilical cord blood. The ability to control proliferation of SCL has allowed us to maintain the survival and expansion of colony- forming cells in culture for up to 2 months. These lines have enabled us to test for stromal cell characteristics at a clonal level and provided us with a tool to analyze the events leading to lineage commitment and hematopoietic differentiation, as demonstrated by suppression of hematopoiesis by an antibody directed against the c-kit molecule.     

Canadian cost data associated with treating overactive bladder is lacking

IntroductionCost-effectiveness analysis forms an integral part of the approval process for new medical treatments in Canada, including drug and non-drug technologies. This study’s primary objective was to identify peer-reviewed studies that report Canadian-specific cost data for treating overactive bladder (OAB) based on the Canadian Urological Association (CUA) guideline. A secondary objective was to identify studies that report cost data from other healthcare jurisdictions that could be generalizable to the Canadian context.MethodsWe conducted a systematic review of the published peer-reviewed literature. We included studies from Organization for Economic Cooperation and Development countries, excluding the U.S., published in English since January 2009.ResultsFrom 165 abstracts identified in our initial search, 18 studies were ultimately included for analysis. This included one Canadian-based study reporting costs in Canadian dollars, all related to second-line treatments. The other studies were primarily from Europe, reporting costs in Euros or British pounds. There were no studies reporting costs for first-line treatments. Gaps in costs for select second-line and third-line treatments recommended by the CUA were also identified.ConclusionsCanadian-specific cost data for OAB treatments published in the peer-reviewed literature is limited to a single study reporting costs for only a few second-line treatments sourced from a single province over 10 years ago. Cost data from other healthcare jurisdictions are available, but the generalizability of costs associated with third-line treatments is questionable.     

High-resolution array CGH clarifies events occurring on 8p in carcinogenesis

Background  

Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes.     

既往疾病史和胆道癌关系的全人群病例对照研究

目的　研究分析既往疾病史和胆道癌 (包括胆囊癌、肝外胆管癌和壶腹部癌 )的关系。方法　自 1997年 6月～ 2 0 0 1年 5月 ,在上海市区开展了一项大规模的基于全人群的胆道癌的病例对照研究 ,共收集、调查了 6 6 4例胆道癌新病例和 894例人群对照。结果　研究发现既往有胆囊炎疾病史者患胆囊癌、肝外胆管癌的危险性升高 ,调整的比数比分别为 2 .2 (95 %CI =1.3～ 3.6 )和 1.9(95 %CI=1.0～ 3.3)。糖尿病患者患胆囊癌的危险性增加 ,调整的比数比为 1.5 (95 %CI=0 .9～ 2 .5 ) ,在非胆结石者中调整的比数比为 2 .0 (95 %CI=0 .9～ 4 .5 ) ;此外 ,研究还发现肝硬化者患肝外胆管癌的危险性明显增加 ,调整的比数比为 3.0 (95 %CI=1.0～ 9.1) ,在非胆结石者中调整的比数比为 4 .9(95 %CI=1.2～ 19.8)。结论　该项研究为论证胆囊炎症增加患胆道癌的危险性提供了依据 ,研究还提示糖尿病和肝硬化分别提高患胆囊癌和肝外胆管癌的危险性。     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.     

Computer graphics for digitally formatted images

The increasing use of digitally formatted imaging systems requires high-quality interactive gray-scale computer raster graphics systems for the management, display, and analog film recording of digital image and alphanumeric information. These systems are a combination of computer hardware and software and implement a set of graphics protocols. This paper describes a set of interactive graphics protocols that has been developed for clinical use.