IFNγ在动脉粥样硬化形成中的作用

干扰素γ（IFNγ）又称免疫干扰素，其抗病毒活性较低，免疫调节和抗细胞增殖作用较强，是一种强的巨噬细胞、NK细胞、血管内皮细胞活化剂。IFNγ增强抗原提呈，活化T淋巴细胞，与多种致炎因子相互作用，促进粥样病变处炎症反应，加重病变进展。作为脂质代谢相关酶的调节因子，IFNγ诱导泡沫细胞形成，并活化内皮细胞促进动脉粥样硬化。但也有研究显示，它可影响一些脂质受体抑制泡沫细胞形成，并减少平滑肌细胞增殖而对动脉粥样硬化形成起保护作用。     

Interferon gamma is not required for recurrent herpetic stromal keratitis

The role that interferon-γ (IFNγ) plays during herpetic stromal keratitis (HSK) has not been definitively determined. In primary HSK most reports suggest that IFNγ may help control viral replication and contribute to corneal pathology. However, its role in recurrent HSK has not been directly addressed. The present study addresses its role in recurrent HSK by comparing HSK in latently infected normal and IFNγ gene knockout (GKO) on the C57BL/6 background. We initially evaluated HSK following primary infection and observed that GKO mice had higher tear film virus titers, but virtually identical ocular disease as normal mice. In contrast, following reactivation of latent virus, GKO mice had a greater incidence and severity of opacity, neovascularization, and blepharitis. Interestingly, the incidence of reactivation after UV-B exposure was equivalent in GKO and normal mice, but virus shedding was increased in the GKO groups. We also observed diminished delayed-type hypersensitivity responses in GKO mice, as expected. These data indicate that IFNγ is important for the control of virus replication in both primary and recurrent ocular HSV infection in C57BL/6 mice. The enhanced recurrent disease seen in GKO mice may be the result of increased viral titers and persistence in these mice which act to prolong the stimulation of an inflammatory response.     

Content of Autoantibodies to Bradykinin and β-Amyloid1-42 as a Criterion for Biochemical Differences between Alzheimer's Dementias

We measured serum content of autoantibodies to -amyloid protein A_1-42, its neurotoxic fragment A_25-35, vasopressin, bradykinin, thrombin, antithrombin III, ₂-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A_1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.     

Deficient IFN-γ Expression in Umbilical Cord Blood (UCB) T Cells Can Be Rescued by IFN-γ-Mediated Increase in NFATc2 Expression

Regulation of nuclear factor of activated T cells-c2 (NFATc2) gene expression is not clearly defined. We previously reported reduced NFATc2 protein expression in cord blood T lymphocytes. Here we show that NFATc2 expression in T cells is dependent in part on the presence of IFN-gamma during primary stimulation, as blocking of IFN-gamma blunted NFATc2 protein and mRNA upregulation. Conversely, addition of exogenous IFN-gamma during stimulation resulted in increased expression of NFATc2 in cord blood T lymphocytes. This correlated with rescue of deficient IFN-gamma expression by cord blood T cells. Rescue of IFN-gamma expression in cord blood T cells was dependent on the presence of antigen-presenting cells, as addition of IFN-gamma during stimulation of purified cord blood T cells did not result in an increase of IFN-gamma expression, and depletion of monocytes ablated the rescue of IFN-gamma expression. Our results point to impaired function in the antigen-presenting cell population of cord blood, playing a role in the hyporesponsiveness of T cells.     

Effects of picrotoxin on potassium accumulation and dorsal root potentials in the frog spinal cord.

The effects of picrotoxin on the changes of extracellular potassium concentration (Δ[K⁺]_e), field potentials and dorsal root potentials evoked by afferent stimulation, were studied in the isolated spinal cord of the frog. Δ[K⁺]_e was measured with potassium selective micro-electrodes. In a normal Ringer's solution the Δ[K⁺]_e evoked by a single pulse applied to a dorsal root did not exceed 0.05 mM. In solutions containing picrotoxin (10^?7?10^?5m) the Δ[K⁺]_e increased to 0.06–0.1 mm. At higher concentrations (10^?4?10^?3m) of picrotoxin the Δ[K⁺]_e reached 3–6 mm and spontaneous elevations of [K⁺]_e were observed synchronously with the dorsal root potentials. The latter were depressed by 20–40% and considerably prolonged. The time constant of their ascending phase increased from 9 to 10 ms to 30–40 ms. The second component of the negative field potential, recorded from the intermediate region, increased and its time course corresponded to that of the evoked dorsal root potentials. Impulse activity of motoneurones and interneurones evoked by afferent stimulation was greatly enhanced. Picrotoxin (10^?4?5.10^?4m) was found to have no effect on the ‘asynaptic’ component of evoked dorsal root potentials, which is resistant to 20 mm MgSO₄ and to the absence of Ca²⁺. It is therefore unlikely that the depressant effect of picrotoxin on the evoked dorsal root potentials is produced by its direct action on the potassium conductance of primary afferents.The findings are consistent with a dual mechanism of dorsal root potentials. The fast component of evoked dorsal root potentials which is depressed by picrotoxin is apparently produced by activation of axo-axonic synapses at the primary afferents, while the slow component is due to transient accumulation of extracellular K⁺. The potassium component of the evoked dorsal root potentials becomes dominant in solutions with high concentrations of picrotoxin (10^?4?10^?3m) when impulse transmission is greatly enhanced.     

Veränderungen von Spontanaktivität und Reizantwort retinaler und geniculärer Neurone der Katze bei fraktionierter Injektion von Pentobarbital-Na (Nembutal)

Zusammenfassung 1. Die Veränderungen der spontanen und Reaktionsaktivität von Neuronen des Tractus opticus und der Radiatio optica wurden bei fraktionierter Injektion von Pentobarbital-Na (Nembutal) untersucht. Dabei wurden in 5 min-Abständen jeweils 5 mg Nembutal injiziert und die mittlere Entladungsrate, das Intervall- und Poststimulushistogramm aufgenommen.2. Die Spontanaktivität der meisten retinalen Neurone zeigte bei Nembutaldosen zwischen 5 und 30 mg eine Zunahme der mittleren Entladungsrate, bei Experimenten mit geringer Spontantätigkeit bereits in der Kontrolle wurde von Anfang an eine Aktivitätsminderung beobachtet. Über 30 mg fällt die mittlere Entladungsrate bei allen Neuronen ab. Nach jeder Einzelinjektion kommt es zu einem mehrphasischen Verlauf der Entladungstätigkeit mit initialer Zunahme, sekundärer überschießender Verminderung und langsamer Erholung in einen steady state. Bei post-geniculären Neuronen fehlt die initiale Aktivitätssteigerung.3. Retinale Ganglienzellen zeigen bei niedrigen und mittleren Barbituratdosen charakteristische Veränderungen des Entladungsmusters mit gruppierten Entladungen und multimodalen Intervallverteilungen. Dabei sind die kürzesten Intervalle bei allen Neuronen mit 4–5 msec außerordentlich konstant und dosisunabhängig. Die längeren Intervalle (15–35 msec und Vielfache) sind variabler und dosisabhängig. Die beobachteten Vorzugsintervalle werden durch die supra- und subnormale Phase der Neurone nach dem Aktionspotential erklärt (delayed depolarization und polarizing afterpotential).4. Die Reaktion auf Lichtpunktreize im rezeptiven Feldzentrum zeigt eine stärkere Verminderung der späten tonischen als der initialen phasischen Reizantwort. Bei on-Zentrum-Neuronen tritt mit abnehmender steady-state-Aktivität eine off-Erregung in Erscheinung, die vor der Narkose zwar bereits vorhanden, aber nicht erkennbar war. Off-Zentrum-Neurone zeigen nur eine leichte Verminderung der off-Aktivierung. Die Reaktionen geniculärer Neurone wurden stärker vermindert als die von retinalen Neuronen.5. Die Bedeutung peripherer und allgemeiner neuronaler Faktoren für die Interpretation von Narkoseeffekten wird hervorgehoben.Die Arbeit wurde mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt (Cr 30).     

Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1β

Journal of Clinical Immunology - The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1β (IL-1β) production by human peripheral blood...