Increased numbers of spontaneous SCLC metastasis in absence of NK cells after subcutaneous inoculation of different SCLC cell lines into pfp/rag2 double knock out mice

Spontaneous metastases in small cell lung cancer (SCLC) occur regularly in patients but seldom if any in conventional xenograft mouse models. To overcome this problem, SCLC cells were grafted subcutaneously onto pore forming protein and recombination activating gene 2 double knock out (pfp/rag2) mice and in severe combined immunodeficient (scid) mice. Primary tumours grew well in both mouse strains, while metastases occurred frequently in the pfp/rag2 mice and infrequently in scid mice. Hence NK cells, which are inactive in pfp/rag2 mice, play an important role in SCLC metastasis formation in xenograft models. This observation is in agreement with clinical studies, where a high NK cell number in the blood is correlated with a better prognosis of the patient.

In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8

Background: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. Methods: A method is described to massively expand bone marrow–derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. Results: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). Conclusion: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

Case and partnership reproduction numbers for a curable sexually transmitted infection

Sexually transmitted infections (STIs) are, by definition, transmitted between sexual partners. For curable STIs an infected index case can potentially re-infect the same partner multiple times. Thus, R0, the average number of secondary infections one typical infected individual will produce during his or her infectious period is not necessarily the same as the average number of secondary cases (infected persons). Here we introduce the new concept of the case reproduction number (Rc). In addition, we define the partnership reproduction number (Rp) as the average number of secondary partnerships consisting of two infected individuals one typical infected individual will produce over his or her infectious lifetime. Rp takes into account clearance and re-infection within partnerships, which results in a prolongation of the duration of the infectious period. The two new reproduction numbers were derived for a deterministic pair model with serial monogamous partnerships using infection parameters for Chlamydia trachomatis, an example of a curable STI. We showed that re-infection within partnerships means that curable STIs can be sustained endemically even when the average number of secondary cases a person produces during his or her infectious period is below one.

Soziale Schichtung und Delinquenz. Eine empirische Anwendung eines Rational Choice-Ansatzes mit Hilfe von Querschnittsdaten des ALLBUS 1990 und 2000

Der oft postulierte Zusammenhang zwischen sozialer Schichtung und Kriminalität ist weder theoretisch abgesichert noch empirisch eindeutig belegt. Ausgehend von der ökonomischen Theorie Gary S. Beckers wird ein erweitertes Modell kriminellen Handelns entwickelt, welches den Einfluss der Schichtzugehörigkeit auf die subjektive Wahrnehmung von Kosten, Nutzen und Entdeckungs-bzw. Erfolgswahrscheinlichkeit krimineller Handlungsalternativen einbezieht. Ferner werden die ebenfalls über die Klassenlage determinierten Anreize (Gelegenheitsstrukturen) und die Internalisierung von Normen („framing“) in das ökonomische Modell integriert. Das Modell wird anhand von Daten aus dem ALLBUS 1990 und 2000 für die Delikte Ladendiebstahl und Steuerbetrug überprüft. Entsprechend den theoretischen Erwartungen kann kein genereller negativer Zusammenhang zwischen Schichtzugehörigkeit und kriminellem Handeln festgestellt werden, wohl aber ein Zusammenhang zwischen Klassenlage und Delikttyp. Sozialstrukturell divergierende Erwartungen hinsichtlich Erfolg einer kriminellen Handlung und Gelegenheitsstrukturen sind bedeutsamer für die Wahl illegaler Handlungsalternativen als Abschreckung durch Strafe oder erwarteter Nutzen aus der Tat. Internalisierte Normvorstellungen machen kriminelle Handlungsalternativen unwahrscheinlich.