Stimulus generalization of fear responses: effects of auditory cortex lesions in a computational model and in rats

The conditioning of fear responses to a simple acoustic stimulus (pure tone) paired with footshock can be mediated by the transmission of auditory information to the lateral nucleus of the amygdala from either the auditory thalamus or the auditory cortex. We examined the processing capacity of the thalamo-amygdala pathway by making lesions of the auditory cortex and testing the extent to which conditioned fear responses generalized to tones other than the one paired with footshock. Two studies were performed, one in an anatomically constrained computational model of the fear conditioning network and the other in rats. Stimulus generalization was unaffected in both. These findings support the validity of the model as an approach to studying the neural basis of conditioned fear learning, and in addition suggest that the thalamo-amygdala pathway, possibly by the use of population coding, is capable of performing at least crude stimulus discriminations.      

Visual acuity in an Australian Aboriginal population

Background: Australia is a developed country, However; Aboriginal Australians have rates of blindness comparable to Third World countries. There have been well-funded eye health programs for 15 years in Central Australia. This paper examines if there has been an improvement in visual disability of one traditional group of Aboriginal Australians. Methods: Results from an eye health survey of the Anangu Pitjantjatjara of South Australia in 1990 are presented. These data are compared with results for ‘blindness’ and ‘poor vision’ from a national survey undertaken in 1976. The two surveys were comparable in design, both were cross-sectional population-based prevalence surveys. Prevalence rates were adjusted for the size of the source population. Results: Young rural Aboriginal Australians have good visual acuity. Low vision and blindness (WHO definitions) occur in 19.6% and 10.4% of 60+ year olds, respectively. Women were more likely than men to be blind or have low vision (OR= 1.93; 1.06-3.58). There was a decline in ‘poor vision’ between surveys (OR=2.86; 1.86-4.75) but not in ‘blindness’. Conclusion: Although there has been a reduction in the prevalence of visual disability in rural Aboriginal Australians, improvements in the provision of eye care for the elderly need to occur.     

Renal failure in giant cell vasculitis

A 59-year-old white woman with temporal arteritis developed progressive renal failure. Renal biopsy results showed focal and segmental necrotizing glomerulonephritis; furthermore, giant cells were present in the destructed vessel walls. Immunosuppressive therapy did not prevent terminal renal failure. This case shows that renal involvement may be a feature of temporal arteritis.     

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction

Summary— Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H₂O₂. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0***) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24–96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 ± 0.80 (T0***) to 4.57 ± 1.24 (peak), and decreased to 2.96 ± 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.7 ± 7.5 hours. The iron increased significantly from 0.67 ± 0.34 (T0) to 1.15 ± 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 ± 0.28 UI/L at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.4 ± 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.     

T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: heterogeneity of antigenic sites on the alpha-subunit.

The alpha-subunit of the nicotinic acetylcholine receptor is the major target of the autoimmune response in myasthenia gravis. We investigated the proliferative response of T cells from patients with myasthenia gravis and healthy volunteers to recombinant polypeptides of the human acetylcholine receptor including the full-length alpha-subunit (alpha 1-437). T cells from 20 (71%) of 28 patients and 7 (37%) of 19 healthy volunteers responded in primary cultures. Subsequently, specific T-cell lines were established: CD4+, CD8-, UCHL1+, and major histocompatibility complex (MHC) class II-restricted. Using a set of fragments of the alpha-subunit, major antigenic sites could be localized on the extracellular, N-terminal part of the molecule as well as close to the C-terminus. The T-cell response was heterogeneous, both among different individuals and among T-cell lines from a single donor. These T cells did not cross-react with Torpedo acetylcholine receptor, which was previously used as a substitute for human muscle acetylcholine receptor, suggesting that the T cells had a bias for unique human sequences. A single antigenic fragment could be presented in the context of different MHC class II molecules, and different fragments could be presented in the context of the same MHC molecule. This supports earlier observations of considerable heterogeneity in dealing with acetylcholine receptor as an autoantigen on the level of both T cells and antigen-presenting cells. The data also demonstrate that acetylcholine receptor-specific T cells are present in the normal immune repertoire, and emphasize the role of immune regulation for maintaining a state of tolerance.