Single lead acetate insult, testosterone therapy, and erythropoiesis in mice

Lead acetate (PbAc) was tested for its effects on the production and release of erythrocytes-that is, erythropoiesis-in ICR mice. Dose-survival data indicate that a dosage of 20 mg PbAc/100 g body weight represents the maximum tolerable treatment level. No differences in survival at the various levels of the salt were observed with regard to sex or age. For erythropoietic effects of PbAc, mice were injected on day O, and radioiron (59Fe) incorporation percentages were determined at daily intervals through day 8 for both erythrocytes and splenic tissue. Control mice received isotonic saline as the injectate. On day 3, the percentages obtained from PbAc-treated mice showed a decline, reaching their minimum value by day 4. Recovery from erythropoietic suppression appeared to be complete by day 6 or 7; no positive overshoots in 59Fe percentages were found following recovery. These trends were typical for both peripheral red blood cells and spleen. Testosterone was administered to mice receiving saline or PbAc on two consecutive days (days -1 and O). Radioiron uptake percentages for females receiving testosterone and saline showed an abrupt increase on day 4. No accelerative effect due to testosterone was found in recipient males. For females treated with testosterone and PbAc, the radioiron percentages for erythrocytes and spleen paralleled those for females receiving saline only. Male mice treated with both androgen and PbAc demonstrated 59Fe percentages typical of males treated with PbAc alone.     

YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells

Extracellular Yersinia disarm the immune system of their host by injecting effector Yop proteins into the cytosol of target cells. Five effectors have been described: YopE, YopH, YpkA/YopO, YopP and YopM. Delivery of these effectors by Yersinia adhering at the cell surface requires other Yops (translocators) including YopB. Effector and translocator Yops are secreted by the type III Ysc secretion apparatus, and some Yops also need a specific cytosolic chaperone, called Syc. In this paper, we describe a new Yop, which we have called YopT (35.5kDa). Its secretion required an intact Ysc apparatus and SycT (15.0kDa, pl4.4), a new chaperone resembling SycE. Infection of macrophages with a Yersinia, producing a hybrid YopT-adenylate cyclase, led to the accumulation of intracellular cAMP, indicating that YopT is delivered into the cytosol of eukaryotic cells. Infection of HeLa cells with a mutant strain devoid of the five known Yop effectors (deltaHOPEM strain) but producing YopT resulted in the alteration of the cell cytoskeleton and the disruption of the actin filament structure. This cytotoxic effect was caused by YopT and dependent on YopB. YopT is thus a new effector Yop and a new bacterial toxin affecting the cytoskeleton of eukaryotic cells.     

Overt behavior problems and serotonergic function in middle childhood among male and female offspring of alcoholic fathers

A large body of literature indicates that the serotonergic system is involved in behavioral regulation, as evidenced by the inverse relationship between impulsive aggression and serotonergic function found in adult alcoholics and nonalcoholics. However, studies of this relationship among child and adolescent offspring of alcoholics (COAs) have not previously been done. This study examines the potentially parallel relationship between behavioral dysregulation and low serotonergic function in young COAs. The relationship is of potential interest as a phenotypic marker of biological vulnerability to aggressiveness, which itself has been hypothesized to be a risk factor for later antisocial alcoholism. The present work is part of an ongoing prospective study of the development of risk for alcohol abuse/dependence and other problematic outcomes in a sample of families subtyped by the fathers' alcoholism classification. We examined the relationship between overt behavior problems in middle childhood (mean age = 10.5 +/- 1.7 years) and whole blood serotonin (5-HT) in a subsample of the offspring (N = 32 boys and 12 girls). Using a Child Behavior Checklist (CBCL) index of behavioral undercontrol, we obtained results indicating that high total behavior problem (TBP) children had lower levels of whole blood 5-HT than did low-TBP children (p < 0.01). These results support the hypothesis that there is an inverse relationship between whole blood serotonin levels and behavior problems in young male and female COAs. A father's alcoholism status was not significantly related to his child's 5-HT level, i.e., the child's phenotypic expression of behavioral dysregulation was more reliably connected to serotonergic function than was paternal alcoholism.