Comparing capsid assembly of primate lentiviruses and hepatitis B virus using cell-free systems

Many viruses that assemble their capsids in the eukaryotic cytoplasm require a threshold concentration of capsid protein to achieve capsid assembly. Strategies for achieving this include maintaining high levels of capsid protein synthesis and targeting to specific sites to raise the effective concentration of capsid polypeptides. To understand how different viruses achieve the threshold capsid protein concentration required for assembly, we used cell-free systems to compare capsid assembly of hepatitis B virus (HBV) and three primate lentiviruses. Capsid formation of these diverse viruses in a common eukaryotic extract was dependent on capsid protein concentration. HBV capsid assembly was also dependent on the presence of intact membrane surfaces. Surprisingly, not all of the primate lentiviral capsid proteins examined required myristoylation and intact membranes for assembly, even though all contain a myristoylation signal. These findings reveal significant diversity in how different capsid proteins assemble in the same cellular extract.     

Stress and psoriasis -- a psychoneuroimmunological study

Psoriasis is a polygenetic hereditary multifactorial disease which may be influenced by a number of environmental factors. To date only a few studies experimentally investigated the influence of stress on psoriasis. One problem of these studies is that it remains unclear whether the experimental findings are relevant for the entire group of patients, or whether there are subgroups who are particularly susceptible to stress. Therefore our main objective is to examine whether experimental stressors can identify subgroups of patients who are particularly susceptible to stress and if these differ in immunological parameters. METHOD: The Trier Social Stress Test (TSST) was used as stressor. The severity was recorded both objectively using the PASI (Psoriasis Area and Severity Index) as well as subjectively by the patient. Somatic parameters for which stress reactivity is known but no direct relationship to psoriasis is assumed were selected and exploratively examined within the present study (salivary cortisol). The second set of parameters for which the stress reactivity was unclear included variables which are linked to the pathophysiology and/or the severity of psoriasis. In addition to salivary cortisol, eosinophils, ICAM-3, and sIL-2R were determined in serum. 38 psoriasis patients and 38 control subjects were examined (21 male and 17 female participants within each group). RESULTS: The PASI correlated very inconsistently with the subjective severity parameters. The relationships between severity and blood parameters tested showed a systematic relationship for eosinophils only. The TSST is suitable for eliciting stress in psoriasis patients. In one subgroup, there was an increase in skin affliction, while skin affliction in the second group remained constant or decreased. A classification into stress-reactive or non-reactive patients cannot, however, be supported by the immunological parameters tested.     

Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity

Previously, we reported an ability of NE to promote processes of plasticity in neuroblastoma cells, as observed by morphological changes such as an elongated granule-rich cell body and neuritegenesis, in addition to a progressive decrease in the pluripotent marker Oct4 and an increase in the growth cone marker GAP-43. This was accompanied by the induction of three plasticity genes forming a functional cluster, the cell adhesion molecule L1 (CAM-L1), laminin, and CREB, all involved in neuronal plasticity and neurite outgrowth. In the present study, we hypothesized that the regulation of CAM-L1, laminin, and CREB/pCREB by NE could mediate processes of plasticity in the mode of action of antidepressants, as well as in the long-term effects of stress, in rats, given the association of both with NE alterations and neuronal plasticity. In the first experiment, rats were chronically administered with antidepressants (21 days). In the second experiment, rats were exposed to chronic stress and examined 4 months later, a model shown to exhibit behavioral indices of stress. We found brain region-specific alterations in mRNA and protein levels of CAM-L1, laminin, and pCREB in rats chronically treated with the noradrenergic antidepressant desipramine and, to a lesser extent, in those treated with fluoxetine. Stressed rats presented a decrease in CAM-L1, laminin, and pCREB, specifically in brain areas implicated in stress. Our findings suggest that noradrenergic-regulated plasticity genes such as CAM-L1, laminin, and CREB play an important role both in stress and in the treatment of depression.     

Tau gene transfer, but not alpha-synuclein, induces both progressive dopamine neuron degeneration and rotational behavior in the rat

Using a viral vector for mutant (P301L) tau, we studied the effects of gene transfer to the rat substantia nigra in terms of structural and functional properties of dopaminergic neurons. The mutant tau vector caused progressive loss of pars compacta dopaminergic neurons over time, reduced striatal dopamine content, and amphetamine-stimulated rotational behavior consistent with a specific lesion effect. In addition, structural studies demonstrated neurofibrillary tangles and neuritic pathology. Wild-type tau had similar effects on neuronal loss and rotational behavior. In contrast, mutant alpha-synuclein vectors did not induce rotational behavior, although alpha-synuclein filaments formed in nigrostriatal axons. Dopamine neuron function is affected by tau gene transfer and appears to be more susceptible to tau- rather than alpha-synuclein-related damage in this model. Both tau and alpha-synuclein are important for substantia nigra neurodegeneration models in rats, further indicating their potential as therapeutic targets for human diseases involving loss of dopamine neurons.     

Adolescent pregnancy: current trends and issues

The prevention of unintended adolescent pregnancy is an important goal of the American Academy of Pediatrics and our society. Although adolescent pregnancy and birth rates have been steadily decreasing, many adolescents still become pregnant. Since the last statement on adolescent pregnancy was issued by the Academy in 1998, efforts to prevent adolescent pregnancy have increased, and new observations, technologies, and prevention effectiveness data have emerged. The purpose of this clinical report is to review current trends and issues related to adolescent pregnancy, update practitioners on this topic, and review legal and policy implications of concern to pediatricians.     

Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine

BACKGROUND: Heptavalent pneumococcal conjugate vaccine was licensed in the United States in February 2000 and, following national guidelines, universally distributed in Massachusetts starting in July 2000 to children younger than 2 years of age and selected children 2-5 years of age. We performed statewide surveillance for all cases of invasive pneumococcal disease (IPD) in children younger than 18 years of age to determine risk features and contribution of vaccine failure to ongoing pneumococcal invasive disease. METHODS: Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children younger than 18 years for 2 years starting in October 2001. Serotyping was performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Case demographic and clinical data (including dates of prior doses of PCV7) were collected via follow-up telephone interviews with case primary care providers and/or parents. RESULTS: Between October 1, 2001 and September 30, 2003, 191 cases of IPD were identified statewide (138 in children younger than 5 years). Annual incidence rate for IPD was 17.4 per 100,000 children younger than 5 years, representing a decline of 69% when compared with annual incidence rate of 56.9 per 100,000 from Massachusetts statewide active surveillance performed 1990-1991. In 2001-2003, 30% of cases occurred in the first year of life (36.5 per 100,000), representing a 7.8-fold increased risk compared with children older than 1 year of age. Race-specific annual incidence rates in blacks and Hispanics were 2.3-fold (95% confidence interval, 1.21-4.42) and 1.9-fold (95% confidence interval, 1.06-3.37), greater than in whites. Fifty-nine cases were reported to have underlying comorbid conditions. Serotyping was available for 136 of 191 (71%) cases younger than 18 years; of isolates available for serotyping, 40 (29%) were vaccine serotype (ST), 31 (23%) vaccine-related ST and 65 (48%) nonvaccine ST. Seven of 40 cases with IPD caused by vaccine ST received at least 3 doses of PCV7 vaccine before IPD. CONCLUSIONS: Universal administration of PCV7 to children younger than 2 years of age and selective administration to children 2-5 years of age has resulted in a significant decline in IPD in Massachusetts. Children younger than 1 year of age, African American and Hispanic children and those with recognized comorbid illnesses (malignancy, human immunodeficiency virus, immune deficiency, nephrotic syndrome, etc.) continue to remain at risk for IPD. These risk features should be considered when evaluating febrile infants and children.     

Cardiac Trauma in Children

Although major penetrating or blunt cardiac trauma is rare in children, severe sequelae may result if patients are not managed in a thorough and systematic manner. Penetrating cardiac injuries are fatal in most patients, but survival is possible in patients who maintain vital signs until hospital arrival and can be transported to the OR without delay.The most common cardiac injury from blunt trauma is a cardiac contusion. Patients who have normal vital signs, examination findings, and ECG on arrival are very unlikely to have significant cardiac sequelae. Differences exist in the literature regarding the proper evaluation of blunt cardiac injury, but all patients should have an initial ECG and careful physical examination. Any significant abnormality requires admission for monitoring, frequent reexamination, and consideration of further testing such as troponins, serial ECGs, and/or an echocardiogram.     

Scheme-based benzodiazepine detoxification with oxcarbazepine -- a case report

We attempted to evaluate the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification, by observing several cases. Detoxification followed a predefined dosage scheme. All patients detoxified with oxcarbazepine completed the withdrawal successfully, without withdrawal symptoms. The administration of oxcarbazepine according to the scheme proved to be tolerable. The dosage was sufficient. Though uncontrolled case observations must be interpreted with caution, oxcarbazepine appears to be a promising drug in inpatient benzodiazepine withdrawal. It should be examined in further randomized placebo-controlled studies including long-term follow-ups.