Recently various genetic defects in immunity mediated by interferon γ (IFN-γ) have been described, including mutations in the IFN-γ receptor 1 (IFN-γR1) and receptor 2 (IFN-γR2), signal transducer ...and activator of transcription 1 (STAT 1), and interleukin 12 receptor β 1 (IL-12Rβ1), and IL-12 p40 genes. These mutations are associated with the occurrence of severe infections with intracellular pathogens especially nontuberculous mycobacteria and vaccine-associated bacilli Calmette-Guérin (BCG). Here we report data on a previously healthy adult patient primarily presenting with severe infections with Burkholderia cocovenenans and subsequently Mycobacterium cheloneae. We found a strong inhibitory anti–IFN-γ activity in the patient’s plasma and identified a highaffinity neutralizing anti–IFN-γ autoantibody. Unfortunately, the patient died due to severe sepsis before we knew the nature of the inhibitory activity. The application of alternative therapeutic approaches such as intravenous immunoglobulin or immunoadsorption may have been beneficial in this case. Screening for neutralizing anti–IFN-γ autoantibodies should supplement testing for IFN-γ and IL-12 pathway defects in patients with recurrent infections with intracellular pathogens, especially with nontuberculous mycobacteria.
Late Cretaceous sandstones from the Subu-1 and -2 wells (Aure Scarp, Papua New Guinea) contain patchily distributed solid bitumens. The solid bitumens vary in reflectance and geochemistry, indicating ...that they formed by the biodegradation of two different families of crude oils, termed Family A and Family B. Biomarker characteristics, such as the high abundance of rearranged hopanes and steranes, indicate that the Family A solid bitumens were derived originally from a clay-rich, marine source rock low in sulphur, which had significant input of terrestrial organic matter. These correlate with oils from the Iagifu-7X, Gobe-3X, Omati-1 and Puri-1 wells that are believed to be generated from sources of Jurassic age. The Family B solid bitumens and a fluid inclusion oil from Subu-1 have a high abundance of 2α-methylhopanes, bisnorhopanes, and dibenzothiophene and originated from a marine source rock with a calcareous component. This source rock had a high proportion of prokaryotic organic matter input, a greater sulphur content, and a more reducing depositional environment than the Jurassic source rocks. The lack of correlation with other oils in Papua New Guinea suggests the presence of a second, so far unidentified, generative marine source rock in the East Papuan Basin.
The fine-grained samples in the Subu wells are thermally immature (VRE 0.5–0.6%), organically lean, and contain type III organic matter with little hydrocarbon generation potential. Most of the solid bitumens have peak oil window thermal maturities (VRE 0.8–1.0%), but some have lowered maturities that are interpreted to be due to co-extraction of indigenous, detrital, low maturity organic matter. Low molecular weight
n-alkanes, alkylcyclohexanes, methylalkylcyclohexanes, and alkylbenzenes in many of the samples are attributed to overprinting of pre-existing, variably biodegraded solid bitumens in the sandstones with pristine hydrocarbon charge with a condensate composition. This condensate charge has not undergone any major biodegradation or water-washing, implying that it is a relatively recent event. Solid bitumen from a vein in a Miocene volcanolithic sandstone from the Ouha anticline was generated from an early mature Palaeogene or late Cretaceous source rock that contained predominantly terrestrial organic matter deposited in an oxic environment. This sample proves the existence of a different oil generative source rock in the East Papuan Basin in addition to the two oil source rocks inferred from the Subu data.
Purpose: More than one third of patients with epilepsy have inadequate control of seizures with drug therapy, but mechanisms of intractability are largely unknown. Because of this large number of ...pharmacoresistant patients with epilepsy, the existing process of antiepileptic drug (AED) discovery and development must be reevaluated with a focus on preclinical models of therapy‐resistant epilepsy syndromes such as mesial temporal lobe epilepsy (TLE). However, although various rodent models of TLE are available, the pharmacoresponsiveness of most models is not well known. In the present study, we used a post–status epilepticus model of TLE to examine whether rats with spontaneous recurrent seizures (SRSs) differ in their individual responses to phenobarbital (PB).
Methods: Status epilepticus was induced in Sprague–Dawley rats by prolonged electrical stimulation of the basolateral amygdala. Once the rats had developed SRSs, seizure frequency and severity were determined by continuous EEG/video recording over a 6‐week period (i.e., a predrug control period of 2 weeks, followed by PB treatment for 2 weeks, and a postdrug control period of 2 weeks). PB was administered twice daily at maximal tolerated doses.
Results: Analysis of plasma drug concentrations showed that drug concentrations within the therapeutic range (10–40 μg/ml) were maintained in all rats throughout the period of treatment. In six (55%) of 11 rats, complete control of seizures was achieved, and another rat exhibited a >90% reduction of seizure frequency. These seven rats were considered responders. The remaining four (36%) rats showed either no response at all (n = 3) or only moderate reduction in seizure frequency and were therefore considered nonresponders. Plasma drug concentrations did not differ between these two groups of rats.
Conclusions: These data demonstrate that, similar to patients with epilepsy, rats with SRSs markedly differ in their individual responses to AED treatment. Pharmacoresistant rats selected by prolonged drug treatment from groups of rats with SRSs may provide a unique model to study mechanisms of pharmacoresistance and to identify novel AEDs for treating seizures of patients currently not controlled with existing therapies.
We present measurements of the mid-infrared (MIR) emission from SN 1987A, made using the Infrared Space Observatory (ISO) 11 years after outburst. They are the only late epoch detections of this ...source in the thermal IR regime. The position of the source, determined from an offset to an IR-emitting star, suggests that the emission is associated with SN 1987A or its extended supernova remnant (SNR). A predominantly circumstellar origin is however suggested by the size and orientation of the IR-emitting region, which is comparable with the extension of the inner ring seen with the Hubble Space Telescope (HST). The emission is most probably from collisionally-heated circumstellar grains embedded in shocked gas downstream of the blast wave. The MIR extent is consistent with the hypothesis that the blast wave was propagating into material of moderate density interior to the thick inner ring at the epoch of the ISOCAM observations.
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