Differential effects of interleukin-4 in peptide induced autoimmunity

BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease.     

Immunoradiometric assay for cytomegalovirus-specific IgG antibodies: assay development and evaluation in blood transfusion practice

An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specificity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT), in that 53% of these sera were positive by RIST and 48% positive by CFT. There were 1303 concordant results, 88 sera positive only by RIST and 19 sera were only positive by CFT. These discrepant results remained after an attempt to exclude false positive reactivity; their significance is discussed. Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate.     

Investigation and comparison of some models for removing ocular artefacts from EEG signals

An investigation of ocular artefacts (OAs) in the human electroencephalogram (EEG) to quantify the effectiveness of OA removal, and to find the most effective model for removing OAs online is described. It was found unnecessary to use the vertical and horizontal EOGs of both eyes, although more than one EOG signal is required for adequate OA removal. The model using the vertical right EOG and the two horizontal EOGs was the best overall, but in most cases the use of only the vertical and horizontal right EOGs was sufficient. OAs were not completely removed by any of the models investigated, suggesting that more complex models are necessary.     

Characterization of a monoclonal antibody panel shows that the myotonic dystrophy protein kinase, DMPK, is expressed almost exclusively in muscle and heart

Myotonic dystrophy (DM) is a multisystemic disorder caused by an inherited CTG repeat expansion which affects three genes encoding the DM protein kinase (DMPK), a homeobox protein Six5 and a protein containing WD repeats. Using a panel of 16 monoclonal antibodies against several different DMPK epitopes we detected DMPK, as a single protein of approximately 80 kDa, only in skeletal muscle, cardiac muscle and, to a lesser extent, smooth muscle. Many earlier reports of DMPK with different sizes and tissue distributions appear to be due to antibody cross-reactions with more abundant proteins. One such antibody, MANDM1, was used to isolate two related protein kinases, MRCK alpha and beta, from a human brain cDNA library and the shared epitope was located at the catalytic site of DMPK using a phage-displayed random peptide library. The peptide library also identified an epitope shared between DMPK and a 55 kDa muscle-specific protein. The results suggest that effects of the repeat expansion on the DMPK gene may be responsible for muscle and heart features of DM, whereas clinical changes in other tissues may be due to effects on the other two genes.     

Beare-Stevenson cutis gyrata syndrome.

Beare-Stevenson cutis gyrata syndrome consists of skin furrows of corrugated appearance, acanthosis nigricans, craniofacial anomalies, particularly craniosynostosis and ear defects, anogenital anomalies, skin tags, and prominent umbilical stump. Four cases of this striking syndrome are reported. Together with two previously reported cases, the syndrome is delineated from the six known cases. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. Craniosynostosis is present in four cases, with cloverleaf skull in three of these. Intrauterine growth has been normal in all cases. Performance and life expectation appear to be related to the presence or absence of cloverleaf skull. All cases observed to date have been sporadic. Increased paternal age suggests the possibility of an autosomal dominant mutation.     

Actions of microiontophoretically applied oxytocin, and immunohistochemical localization of oxytocin, vasopressin and neurophysin in the rat caudal medulla

Oxytocin-, vasopressin- and neurophysin-containing axons were visualized within the rat caudal medulla using the immunoperoxidase technique. The highest densities of axons and terminals were found in the nucleus tractus solitarius, nucleus dorsalis vagus, nucleus commissuralis, nucleus reticularis lateralis and within the marginal layer of the nucleus trigeminalis. In these areas, oxytocin fibres predominated markedly over vasopressin fibres. In a series of electrophysiological experiments, neurones in these and surrounding areas were predominantly depressed following the iontophoretic application of oxytocin. This depression was seen on both spontaneous and glutamate-evoked neuronal firing.