Biomedical subjects
G Wallis
Publications and source records attributed to G Wallis.
Phenyl-N-tert-butylnitrone demonstrates broad-spectrum inhibition of apoptosis-associated gene expression in endotoxin-treated rats.
Systemic exposure to gram-negative bacterial substances such as lipopolysaccharide (LPS, or endotoxin) induces an uncontrolled, massive inflammatory reaction which culminates in multiple system organ failure and death. Septic shock often does not respond to corticosteroids; however, certain low-molecular-weight antioxidant compounds have been discovered to possess potent anti-inflammatory action, and some of these novel compounds can rescue animals from experimentally induced septic shock. Phenyl-N-tert-butylnitrone (PBN) is the archetype of the nitrone class of antioxidants which we have previously shown to suppress LPS-induced cytokine biosynthesis in vivo. Using a multiprobe ribonuclease protection assay, we now demonstrate the ability of PBN to suppress proapoptotic gene expression in the LPS-induced model of endotoxic shock. The broad-spectrum gene-suppressive affects of PBN are discussed in the context of inflammatory signal transduction and models are proposed to explain why certain antioxidants may also possess anti-inflammatory and antiapoptotic properties.
Learning to recognize objects.
Evidence from neurophysiological and psychological studies is coming together to shed light on how we represent and recognize objects. This review describes evidence supporting two major hypotheses: the first is that objects are represented in a mosaic-like form in which objects are encoded by combinations of complex, reusable features, rather than two-dimensional templates, or three-dimensional models. The second hypothesis is that transform-invariant representations of objects are learnt through experience, and that this learning is affected by the temporal sequence in which different views of the objects are seen, as well as by their physical appearance.
Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint maps to an 11-cM region on chromosome 4q35.
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Evidence for genetic anticipation in nodal osteoarthritis.
OBJECTIVE: Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA). METHODS: Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed. RESULTS: The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p < 0.001) as was larger joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p < 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents. CONCLUSIONS: These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.
Spin trapping and electron paramagnetic resonance spectroscopy.
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Spatio-temporal influences at the neural level of object recognition.
In late 1988, Miyashita published work reporting recordings of single cells in the inferotemporal cortex of the macaque monkey (Miyashita 1988 Nature 335 817-20). He described the responses of neurons to a sequence of random fractal pattern images, and how many of the neurons tested were seen to respond strongly to a subset of the images on the basis of sequence presentation order, i.e. appearance in time, rather than their spatial similarity. In this work, I describe a local Hebb-like learning rule which in conjunction with a simple feedforward neural architecture is capable of replicating the type of temporal-order association apparent in the cells from which he made recordings. The paper also advances reasons for requiring such learning by describing its possible role in establishing transformation invariant representations of objects.
Spin trapping agent phenyl N-tert-butylnitrone protects against the onset of drug-induced insulin-dependent diabetes mellitus.
Insulin-dependent diabetes mellitus is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to be involved in this destruction. Phenyl N-tert-butylnitrone (PBN) has demonstrated protective effects against several pathological conditions including ischemia-reperfusion injury and endotoxin-induced shock. We report here that PBN co-administration can prevent the onset of the STZ-induced diabetes in mice. PBN co-treatment inhibited the streptozotocin (STZ)-induced hyperglycemia, the elevation in the level of glycated hemoglobin and weight loss in the treated mice. Histological observations indicated destruction of B-cells in the STZ-treated animals and its prevention by PBN co-treatment. EPR spin trapping experiments in the pancreas indicated the in vivo formation of NO in STZ-treated animals and its attenuation by PBN treatment.
Invariant face and object recognition in the visual system.
Neurophysiological evidence is described, showing that some neurons in the macaque temporal cortical visual areas have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. A theory is then described of how such invariant representations may be produced in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory proposes that neurons in these visual areas use a modified Hebb synaptic modification rule with a short-term memory trace to capture whatever can be captured at each stage that is invariant about objects as the object changes in retinal position, size, rotation and view. Simulations are then described which explore the operation of the architecture. The simulations show that such a processing system can build invariant representations of objects.
In vivo spin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: a time-course study.
Spin trapping of nitric oxide (NO.) in vivo in liver, small intestine, kidney, and plasma of intact rats was accomplished using diethyldithiocarbamate (DETC) administered intraperitoneally. DETC combines with Fe2+ to form (DETC)2-Fe and is an excellent trapping agent for nitric oxide. DETC distribution and uptake by the organs of interest was determined and the formation of the active trapping agent (DETC)2-Fe was assayed in the various organs and plasma. The capacity of this spin trap to capture NO. in vivo was demonstrated by administering sodium nitroprusside to the animals. The trapping procedure was then used to assess the course of NO. generation during a 6 h period in animals that had been treated with endotoxin. The rate of NO. generation/gram tissue was determined during the last 15 min of each time period. The results indicate that induction of nitric oxide generation begins earliest in the small intestine, then in the liver, and still later in the kidney and plasma. Nitric oxide production was most intense in the liver and was still increasing at the end of the experiment. Control animals receiving the spin trapping agent showed only little or no evidence of nitric oxide production except for the small intestine. The results show that induction of NO. generation caused by endotoxin begins at different times in different organs.
Should we buy liaison psychiatry?
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Seven polymorphisms at the COL10A1 locus.
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Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.
The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None of the 38 pedigrees showed evidence of recombination between the OI gene and both collagen loci, suggesting that the frequency of unlinked loci in the population must be low. From these results, approximate 95% confidence limits for the proportion of families linked to the type I collagen genes can be set between .91 and 1.00. This is high enough to base prenatal diagnosis of dominantly inherited OI on linkage to these genes even in families which are too small for the linkage to be independently confirmed to high levels of significance. When phenotypic features were compared with the concordant collagen locus, all eight pedigrees with Sillence OI type IV segregated with COL1A2. On the other hand, Sillence OI type I segregated with both COL1A1 (17 pedigrees) and COL1A2 (7 pedigrees). The concordant locus was uncertain in the remaining six OI type I pedigrees. Of several other features, the presence or absence of presenile hearing loss was the best predictor of the mutant locus in OI type I families, with 13 of the 17 COL1A1 segregants and none of the 7 COL1A2 segregants showing this feature.
Emery-Dreifuss syndrome and X-linked muscular dystrophy with contractures: evidence for homogeneity.
We report on a family in which individuals have clinical features of both Emery-Dreifuss syndrome (EMD) and X-linked muscular dystrophy with contractures (XLMDC). Molecular studies on this kindred showed linkage between the disorder and probe DXS 52 (St14) located at Xq28. The gene for conventional EMD has previously been mapped to this region and our molecular findings therefore suggest that EMD and XLMDC represent the phenotypic spectrum of the same mutated gene rather than heterogeneity, as sometimes postulated.
Italian psychiatric care.
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X-linked mixed deafness with stapes fixation in a Mauritian kindred: linkage to Xq probe pDP34.
Molecular linkage analysis was undertaken on a large Mauritian kindred with X-linked mixed deafness, stapes fixation, and perilymphatic gusher (X-LDSF). DNA probe pDP34 (DXYS1) was tightly linked to the disorder, with a lod score of 6.32 at zero recombination. This observation indicates that the gene for this form of deafness maps to the Xq13-q21.1 region and has important implications for carrier screening and antenatal diagnosis.
Osteogenesis imperfecta in Southern Africa. Diagnostic categorisation and biomolecular findings.
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Duchenne muscular dystrophy in South Africa. Prevention by molecular techniques.
The availability of DNA markers closely linked to the Duchenne muscular dystrophy (DMD) gene locus has facilitated carrier detection and prenatal diagnosis of this condition. More than 50 affected South African kindreds are being studied using DNA probes within and flanking the DMD region of the X chromosome in order to ascertain the nature of the molecular defects in affected males and to investigate the feasibility of genetic management by means of these techniques. The results of this study and the implications of this new molecular technology for DMD patients in South Africa are reviewed and discussed.