Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

Inhibitory effect of moricizine on reperfusion induced tachyarrhythmias in rats--a comparison study with disopyramide and mexiletine.

Acute ligation of proximal left coronary artery was performed on forty male Sprague-Dawley rats. Five min later, occlusion was released in order to evaluate the effectiveness of the 3 antiarrhythmic drugs in eliminating reperfusion ventricular arrhythmias. The drugs evaluated were moricizine (5 mg/kg), disopyramide (DSP) (5 mg/kg) and mexiletine (MXT) (5 mg/kg), which were administered intravenously 5 min before ligation of the coronary artery. Compared to control rats that underwent identical experimental procedures, all 3 drugs significantly lowered the mortality rate from 90% of the control group to 20, 20 and 0% for moricizine, DSP and MXT groups. The incidence of ventricular fibrillation (Vf) was also decreased significantly by these drugs. The duration of ventricular tachycardia (VT) and Vf of surviving rats in drug groups were 111.7 +/- 35.0 sec, 71.6 +/- 29.4 sec and 32.9 +/- 14.6 sec for moricizine, DSP and MXT, respectively. Many of the drug treated rats could be restored to the normal sinus rhythm and survived. All 3 drugs slowed the heart rate significantly, but as for the blood pressure only MXT showed significant suppressing effect. In conclusion, moricizine has the same significant preventive effect on reperfusion induced ventricular tachyarrhythmias as DSP and MXT.     

Dual energy emission computed tomography with 99mTc pyrophosphate and 201T1 in evaluating coronary reperfusion therapy in patients with acute myocardial infarction

To evaluate the clinical significance of scintigraphic overlap of thallium-201 (201T1) and technetium-99m pyrophosphate (99mTc), we observed 28 patients with acute myocardial infarction (AMI) in whom coronary reperfusion was attempted. All patients underwent dual energy emission computed tomography (D-ECT) on the third post AMI day which facilitated comparing 99mTc and 201T1 images from identical slices simultaneously. The scintigraphic results of the 28 patients were as follows: (table, see text) In conclusion, (1) significant 201T1 and 99mTc overlap on D-ECT suggest very early and successful reperfusion, and (2) none of the patients with unsuccessful reperfusion exhibits overlap.     

Influence of fibroblasts on the invasion and migration of highly or weakly metastatic b16 melanoma cells

We have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16-BL6 and weakly metastatic B16-FI cells in vitro. Co-culture of B16-BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor-cell invasion into Matrigel basement membrane than co-culture of B16-FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co-culture of fibroblasts with B16-BL6 cells without cellular contact, i.e., CM (B16-BL6/fibroblast), rather than from co-culture with B16-FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16-BL6), CM (B16-FI) or CM (fibroblast). Antibodies against TGF-β1 or FN almost completely abolished the chemotactic migration of B16-BL6 cells to the CM (B16-BL6/fibroblast) or CM (TGF-β1 -treated fibroblast) when these antibodies were c-incubated with fibroblasts and either B16-BL6 or TGF-β1. In contrast, the anti-EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF-β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF-β1 in the CM (B16-BL6) was slightly higher than in the CM (B16-FI), and the amount of FN in the CM (B16-BL6/fibroblast) was twice as high as in the CM (B16-FI /fibroblast). These results suggest that TGF-β1 released from B16-BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16-BL6 and B16-FI cells may in part be due to the amounts of TGF-β1 from tumor cells and of FN from TGF-β1 -stimulated fibroblasts.     

Cytomegalie der Kopfspeicheldrüsen bei SIDS

Zusammenfassung Es erfolgte eine retrospektive mikromorphologische Analyse der Glandula parotis und/oder der Glandula submandibularis von 180 plötzlichen Kindstodesfällen in Berlin und 75 Fällen in Hamburg. Erfaßt wurden Fälle der letzten 10 Jahre mit einem Alter zwischen 2 Wochen und einem Lebensjahr. — Typische CMV-Einschlußkörper wurden im Berliner Material in 18 Fällen (10%; Mädchen mehr als Jungen) und im Hamburger Material in 6 Fällen (7%; Jungen mehr als Mädchen) diagnostiziert. Während die meisten SIDS-Fälle sich im zweiten und dritten Lebensmonat ereigneten, war bei den CMV-Infektionen kein Altersgipfel festzustellen. Virusmaterial war mit immunhistochemischen Unterschungen sowie in-situ-Hybridisierung auch in histologisch unauffälligen Zellen nachzuweisen. — Unter Berücksichtigung der bekannten klinischen und epidemiologischen Daten zur Cytomegalie stellt die Diagnose einer lokalisierten Infektion der Kopf-speicheldrüsen keine befriedigende Erklärung für den plötzlichen Tod der Säuglinge dar; diese Befunde sind jedoch besonders beachtenswert als Hinweis auf eine Schwäche des Immunsystems.     

Relationship between the thromboxane A2 receptor gene and susceptibility to cerebral infarction.

The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p = 0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.     

Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.