Modification of radiation hazards to the adult and its fetus from nuclear medicine procedures

The effects of perchlorate on the quantitative distribution patterns of / sup 99m/Tc intravenously administered as pertechnetate in the human adult and its fetus were studied in a variety of situations and are summarized. Perchlorate, when administered shortly before /sup 99m/Tc, suppresses concentration in the adult thyroid gland, stomach, and urine; but tends to increase intestinal localization; and prolongs disappearance from the blood. It also inhibits concentration in the placenta and fetus. The greatest reductions in fetal concentrations occur in the femur, spleen, stomach, and thyroid. The estimated radiation absorbed doses to the human fetus are about 80 mrad/mCi for /sup 99m/Tc- pertechnetate alone, and around 30 mrad/mCi if pretreatment with perchlorate is used. Previously localized /sup 99m/Tc may be released by perchlorate from the thyroid gland and stomach, but not from the placenta and fetus. (auth

The effect on melanoma risk of genes previously associated with telomere length.

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/dju26

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Comparative biokinetics of radiogallium and radioindium in mice

The biokinetics of radiogallium and radioindium in normal mice are compared using the compartmental modelling analysis. The rate constants obtained provide useful information in understanding the physiological and biochemical kinetics of radionuclides in the intact object. A comparison of the compartmental models for gallium and indium reveals the similarities and differences between the biokinetics of the two radionuclides. Furthermore, the results provide valuable information and guidance for human studies and clinical use

Response of the mouse fetus to radiation from Na/sup 99m/TcOsub4sub 4

The element technetium has recently assumed ecological importance as a source of low-level radiation, with the use of /sup 99m/Tc in nuclear medicine and production of /sup 99m/Tc during generation of electricity by nuclear reaction. When technetium is introduced as pertechnetate into the blood stream of pregnant females, it is transported across the placental barrier to the fetus, where a portion appears to be incorporated into biomolecules. When combined as biomolecules, radionuclides that decay by electron capture or isomeric transition show a lethality greater than that predicted in cell cultures and radiation therapy. The decay of /sup 99m/Tc by isomeric transition, together with the other considerations, places a high priority on the investigation of its radiation effects due to clinical doses of up to 25 mCi. Female mice were given daily i.v. injections of 0, 5, 50, and 500 $mu$ Ci of /sup 99m/Tc as pertechnetate in isotonic saline throughout gestation, gestation and lactation, or lactation. At two months of age, the progeny were mated with randomly selected litter mates to produce a second generation; the process was repeated with their progeny for production of the third generation.Preliminary results reinforce the existing concern about use of /sup 99m/Tc-pertechnetate in pregnant or potentially pregnant subjects. (auth

Conjugate whole-body scanning system for quantitative measurement of organ distribution in vivo

The determination of accurate, quantitative, biokinetic distribution of an internally dispersed radionuclide in humans is important in making realistic radiation absorbed dose estimates, studying biochemical transformations in health and disease, and developing clinical procedures indicative of abnormal functions. In order to collect these data, a whole-body imaging system is required which provides both adequate spatial resolution and some means of absolute quantitation. Based on these considerations, a new whole-body scanning system has been designed and constructed that employs the conjugate counting technique. The conjugate whole-body scanning system provides an efficient and accurate means of collecting absolute quantitative organ distribution data of radioactivity in vivo