Successful immunotherapy with intraperitoneal Corynebacterium parvum in a murine ovarian cancer model is associated with the recruitment of tumor-lytic neutrophils into the peritoneal cavity

The rejection of a murine ovarian teratocarcinoma (MOT) after i.p. injection of Corynebacterium parvum was investigated. Treatment with C. parvum (1400 micrograms) 24 hr after i.p. inoculation of a lethal number of tumor cells (10(5] induced an antitumor effect that cured 75 to 95% of the mice. Morphologic analysis and an in vivo cytotoxicity assay that measured the rate of disappearance of radioactivity from the peritoneal cavity after injection of 125IUdR-labeled tumor cells indicated that the antitumor effect was initiated during the first 24 hr after C. parvum injection. During this period of time, host effector cells retrieved from the peritoneal cavity prevented tumor growth in a Winn assay and lysed radiolabeled MOT targets in a 4-hr Cr-release assay. After separation of peritoneal inflammatory cells on a Percoll gradient, neutrophil-enriched fractions demonstrated significant in vitro tumor lysis, but neutrophil-depleted populations were ineffective. Microscopic analysis of lysis at the single cell level confirmed that neutrophils were binding to and lysing MOT targets. Further characterization of these tumor cytolytic neutrophils revealed that they are nylon wool-adherent, not generated in indomethacin-pretreated mice (but effectively generated in whole body-irradiated mice), and achieve lysis within 30 min after binding to MOT targets. These results indicate that neutrophils must be considered potential antitumor effectors that can be recruited by treatment with biologic response modifiers.     

Etiological overlap between obsessive‐compulsive disorder and anorexia nervosa: a longitudinal cohort,multigenerational family and twin study

Obsessive‐compulsive disorder (OCD) often co‐occurs with anorexia nervosa (AN), a comorbid profile that complicates the clinical management of both conditions. This population‐based study aimed to examine patterns of comorbidity, longitudinal risks, shared familial risks and shared genetic factors between OCD and AN at the population level. Participants were individuals with a diagnosis of OCD (N=19,814) or AN (N=8,462) in the Swedish National Patient Register between January 1992 and December 2009; their first‐, second‐ and third‐degree relatives; and population‐matched (1:10 ratio) unaffected comparison individuals and their relatives. Female twins from the population‐based Swedish Twin Register (N=8,550) were also included. Females with OCD had a 16‐fold increased risk of having a comorbid diagnosis of AN, whereas males with OCD had a 37‐fold increased risk. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for a later diagnosis of AN (risk ratio, RR=3.6), whereas individuals first diagnosed with AN had an even greater risk for a later diagnosis of OCD (RR=9.6). These longitudinal risks were about twice as high for males than for females. First‐ and second‐degree relatives of probands with OCD had an increased risk for AN, and the magnitude of this risk tended to increase with the degree of genetic relatedness. Bivariate twin models revealed a moderate but significant degree of genetic overlap between self‐reported OCD and AN diagnoses (r_a=0.52, 95% CI: 0.26‐0.81), but most of the genetic variance was disorder‐specific. The moderately high genetic correlation supports the idea that this frequently observed comorbid pattern is at least in part due to shared genetic factors, though disorder‐specific factors are more important. These results have implications for current gene‐searching efforts and for clinical practice.     

Childhood Symptoms of ADHD Overrule Comorbidity in Relation to Psychosocial Outcome at Age 15: A Longitudinal Study

Objective

Neurodevelopmental problems (NDPs) may influence the transition from childhood to adolescence. Our aim was to study long-term psychosocial outcomes of NDPs, focusing on ADHD.

Method

Data was collected through a telephone interview with parents of twins at ages 9 or 12 years. NDP screen-positive children were clinically assessed at age 15; N = 450. Psychosocial outcome concerning peers, school, internalizing problems, antisocial behavior, alcohol misuse, drug misuse, and impaired daily functioning was examined.

Results

Even after controlling for other NDP comorbidity, screen-positivity for ADHD doubled or tripled the odds of later psychosocial problems. When controlling for parental education level, the significant effect of ADHD remained only for antisocial behavior and impaired daily functioning.

Conclusions

Signs of NDPs as well as other psychiatric diagnoses at ages 9 or 12 years are associated with a more problematic adolescence. However, despite the presence of comorbidity, early ADHD symptoms stand out as the most important risk factor for later antisocial development and impaired daily functioning.