Engineering kidneys from simple cell suspensions: an exercise in self-organization

Increasing numbers of people approaching and living with end-stage renal disease and failure of the supply of transplantable kidneys to keep pace has created an urgent need for alternative sources of new organs. One possibility is tissue engineering of new organs from stem cells. Adult kidneys are arguably too large and anatomically complex for direct construction, but engineering immature kidneys, transplanting them, and allowing them to mature within the host may be more feasible. In this review, we describe a technique that begins with a suspension of renogenic stem cells and promotes these cells’ self-organization into organ rudiments very similar to foetal kidneys, with a collecting duct tree, nephrons, corticomedullary zonation and extended loops of Henle. The engineered rudiments vascularize when transplanted to appropriate vessel-rich sites in bird eggs or adult animals, and show preliminary evidence for physiological function. We hope that this approach might one day be the basis of a clinically useful technique for renal replacement therapy.     

A longitudinal analysis of the effects of a DRD4 polymorphism on marijuana use

The current study used a variable- and person-centered approach to examine whether a DRD4 polymorphism explained within-individual differences in frequency of marijuana use from adolescence into emerging adulthood. Data were analyzed from 1897 respondents from the genetic subsample of the National Longitudinal Study of Adolescent Health (Add Health) at waves I (ages 13–17), II (ages 14–18), and III (ages 21–25). Latent class growth model results revealed that marijuana use was characterized by four trajectories (non-users/experimenters, increasers, desisters, and chronic users), and that the DRD4 polymorphism differentiated increasers from non-users/experimenters. Overall, the results suggested that the DRD4 polymorphism may be relevant to differences in the developmental trajectories of marijuana use.     

Involved field radiation for Hodgkin's lymphoma: The actual dose to breasts in close proximity

To decrease the risk of late toxicities in Hodgkin's lymphoma (HL) patients treated with radiation therapy (RT) (HL), involved field radiation therapy (IFRT) has largely replaced the extended fields. To determine the out-of-field dose delivered from a typical IFRT to surrounding critical structures, we measured the dose at various points in an anthropomorphic phantom. The phantom is divided into 1-inch-thick slices with the ability to insert TLDs at 3-cm intervals grid spacing. Two treatment fields were designed, and a total of 45 TLDs were placed (equally spaced) at the margin of the each of the 2 radiation fields. After performing a computed tomography simulation, 2 treatment plans targeting the mediastinum, a typical treatment field in patients with early stage HL, were generated. A total dose of 3060 cGy was delivered to the gross tumor volume for each field consecutively. The highest measured dose detected at 1 cm from the field edge in the planning target volume was 496 cGy, equivalent to 16% of the isocentric dose. The dose dropped significantly with increasing distance from the field edge. It ranged from 1.1–3.9% of the isocentric dose at a distance of 3.2–4 cm to <1.6% at a distance of >6 cm. Although the computer treatment planning system (CTPS) frequently underestimated the dose delivered, the difference in dose between measured and generated by CTPS was <2.5% in 90 positions measured. The collateral dose of radiation to breasts from IFRT is minimal. The out-of-field dose, although mildly underestimated by CTPS, becomes insignificant at >3 cm from the field edge of the radiation field.     

Thyrogen® Scans for Detecting Recurrent Thyroid Cancer

Although the thyroid gland is a relatively small organ in the body, it plays a major role in health. Patients who are diagnosed with well-differentiated thyroid cancer can be effectively treated and have excellent rates of survival. After initial surgery and treatment with radioactive iodine ablation, these patients will require lifelong monitoring for recurrence of disease. The use of Thyrogen^® stimulated positron emission tomography/computed tomography scans plays an important role in long-term monitoring. The radiology nurse's role as patient advocate is essential in helping patients have a successful journey through a Thyrogen^® study.     

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405^EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.