Biological properties of interleukin-12 and its therapeutic use in persistent hepatitis B virus and hepatitis C virus infection

Summary. Interleukin (IL)-12 is a pleiotropic cytokine produced by antigen-presenting cells in response to diverse stimuli. IL-12 is a key molecule in the regulation of host's immune responses. In particular, IL-12 influences the balance between the T-helper cells type 1 (TH₁) and type 2 (TH₂); it modulates macrophage responses through the control of interferon-gamma synthesis by TH₁ cells; and, suppresses IgE class antibody production (has a suppressive effect on allergic reactions) and promotes a shift in the IgG subclasses. IL-12 enhances resistance to several infectious diseases, is a powerful antitumor agent in vivo , and acts as a vaccine adjuvant. The biological properties of IL-12 point to the potential therapeutic use in persistent hepatitis B virus and hepatitis C virus infection.     

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

Depression Scale (DEPS) among suicide attempters

The Depression Scale (DEPS), a new screening instrument for detecting depression in primary health care, was compared with the Hamilton Depression Scale (HDS) among 50 suicide attempters. Using the HDS as a gold standard, the positive and negative predictive values of the DEPS for the diagnosis of depression were 98% and 20%, respectively. The correlation between the total HDS scores and the total DEPS scores was 0.60. The DEPS may help general practitioners to detect depression among suicide attempters, but it should not be used to exclude depression.     

The multifunctionality of FGF-2 in the adrenal medulla

 Chromaffin cells of the adrenal medulla and their tumor counterparts, the pheochromocytoma (PC12) cells, are well-established model systems in neurobiology. The development of sympathoadrenal progenitor cells to chromaffin cells can be studied with regard to developmental signals which trigger the differentiation. With regard to potential treatments of neurological disorders like Parkinson’s disease chromaffin cell grafting can be used as one therapeutical approach. The beneficial effect of chromaffin cell grafts is possibly not only related to the release of dopamine but may also be linked to the release of growth factors. One of the growth factors that is synthesized by chromaffin and PC12 cells is basic fibroblast growth factor (FGF-2). The experimental data available so far, are in agreement with different functional roles of FGF-2. This article summarizes the putative physiological functions of FGF-2 in the adrenal medulla. Three differential functional roles of FGF-2 are discussed: (1) as a differentiation factor for sympathoadrenal progenitor cells; (2) as a target-derived neurotrophic factor for preganglionic sympathetic neurons which innervate adrenal medullary cells; (3) as an auto-/paracrine factor in the adrenal medulla. Accepted: 21 August 1996     

Cytokine Production by Lymphocytes in Pregnancy

PROBLEM: In the presence of progesterone lymphocytes of pregnant women release a 34- kDa protein named the progesterone-induced blocking factor (PIBF). PIBF mediates the immunomodulatory and anti-abortive effects of progesterone and its presence is related to the outcome of pregnancy. PIBF induces production of Th2 type cytokines by activated lymphocytes. The in vivo relationship between PIBF- and cytokine production of pregnancy lymphocytes and the outcome of pregnancy was investigated. METHOD OF STUDY: Interleukin (IL)-12 and IL-10 production and PIBF expression in peripheral lymphocytes of 111 healthy pregnant women and 120 women at risk for premature pregnancy termination were detected by immunocytochemistry. RESULTS: We found increased IL-12 and low PIBF and IL-10 expression on lymphocytes of “risk” patients, and a high rate of IL-10 and PIBF positivity on lymphocytes from healthy pregnant women. The cytokine production pattern of the lymphocytes was related to the presence or absence of previous abortions as well as to the outcome of pregnancy. CONCLUSION: These data suggest the involvement of an altered cytokine production pattern in the immunologic effects of progesterone.     

Mood state and cerebral metabolism in persons with age-associated memory impairment

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4±9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.     

Evaluation of a Swedish version of the Arthritis Self-Efficacy Scale.

There is a great need today for clinically useful instruments in the rehabilitation of chronic pain patients. The Arthritis Self-efficacy Scale measures patients' perceived self-efficacy to cope with the consequences of chronic arthritis. The aim of the present study was to evaluate a Swedish version of the Arthritis Self-efficacy Scale with respect to factor structure and reliability. Twenty-five chronic pain patients and twenty-four rheumatology patients were given a Swedish version of the Arthritis Self-efficacy Scale twice within a three week interval. The three factor structure of the scale was confirmed; Cronbach's alpha for internal consistency ranged between 0.82-0.91 and test-retest correlations ranged between 0.81-0.91, showing that the instrument satisfactorily met psychometric standards.     

Antiviral triterpenes fromPrunella vulgaris

Two triterpenes 1 and 2 with antiviral activity againstHerpes simplex virus type 1in vitro were isolated fromPrunella vulgaris. Each compound caused a significant reduction in viral cytopathic effect whenvero cells were exposed to them for 72 hours after viral challenge. They were identified asbetulinic acid(1) and 2α, 3α-dihydroxyurs-12-en-28-oic acid(2) on the basis of their spectroscopic properties. The antiviral activity of them was estimated as EC₅₀=30 μg/ml(1) and 8 μg/ml(2), respectively by plaque reduction assay.     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Myoblast fusion in Drosophila melanogaster is mediated through a fusion-restricted myogenic-adhesive structure (FuRMAS).

During myogenesis in Drosophila embryos, a prominent adhesive structure is formed between precursor cells and fusion-competent myoblasts (fcms). Here, we show that Duf/Kirre and its interaction partners Rols7 (found in founder myoblasts and growing myotubes) and Sns (found in fcms) are organized in a ring-structure at the contact points of fcms with precursor cells, while cytoskeletal components like F-actin and Titin are centered in this ring in both cell types. The cytoplasmic protein Blow colocalizes with the actin plugs in fcms after cell adhesion. Furthermore, the requirement of additional as yet unidentified components was demonstrated by using mammalian C2C12 myoblasts. In this study, we propose that the fusion-restricted myogenic-adhesive structure (FuRMAS) is pivotal in linking cell adhesion as well as local F-actin assembly and dynamics to downstream events that ultimately lead to plasma membrane fusion. Moreover, we suggest that the FuRMAS may restrict the area of membrane breakdown.