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Methamphetamine is a highly addictive psychostimulant with tens of millions of abusers around the world. There is no effective or approved medication for treating an addiction to it. Monoclonal antibodies with a high affinity for methamphetamine have the potential to sequester the drug in the vascular compartment and reduce entry into the brain, thereby acting as peripheral pharmacokinetic antagonists without inducing adverse effects on neurons. However, to maintain the antibodies at an effective level, repeated administration is required, which would be expensive and problematic for patient compliance. In this study, we intended to investigate whether using a recombinant adeno-associated virus-mediated gene transfer technique can be an effective approach to achieve long-term expression of anti-methamphetamine monoclonal antibodies in mouse models. We generated a recombinant adeno-associated virus vector encoding the heavy and light chains of an anti-methamphetamine monoclonal antibody, which was constructed in a single open reading frame and linked with a 2A self-processing sequence. In the context of virus-mediated gene transfer, the expression of full-length and functional monoclonal antibodies was successfully demonstrated in vitroand in vivo. Further investigations are ongoing concerning dose optimization, longterm expression, and protection from methamphetamine challenge in mouse models.

Abstract: When the envelope of the conducting strips for the input transducer of magnetostatic surface wave (MSSW) device is designed according to the wavelet-function envelope, the impulse-response function of the input transducer for MSSW device is equal to the wavelet function, so that single-scale wavelet-transform processor of MSSW type is fabricated. First, according to the envelope function of the wavelet, the length function of the conducting strips is defined, then, the lengths of the conducting strips can be calculated from the length function of the conducting strips, finally, the input transducer can be designed according to the lengths and widths for the conducting strips. The compensation method of the insertion loss for single-scale wavelet transform processor of MSSW type is also given in the paper. When the output end of single-scale wavelet transform processor of MSSW type is connected to the amplifier, its insertion loss can be compensated.

It is generally thought that parvovirus B19 is stable genetically. Consistently, genetic drift has not been found in patients with persistent B19 infection. In this report, longitudinal genetic changes in NS1and VP1gene of B19 isolates from three AIDS patients with persistent B19 infection were studied. One of the three patients was not treated with highly active anti‐retroviral therapy (HAART). B19 viral DNA from these patients was amplified by polymerase chain reaction (PCR) and then sequenced directly. A single genetic change was found in the B19 isolate obtained from the patient not treated with HAART on Day 10 after intravenous immunoglobulin (IVIG) treatment. The nucleotide sequences of B19 isolated from this patient, then remained unchanged over a period of 11 months. Analysis of NS1 clones derived from his longitudinal viral isolates showed the existence of quasi‐species but genetic drift was not found. One of the other two patients treated with HAART experienced treatment failure; he was later treated with mega‐HAART. In contrast to the genetic stability of B19 isolates from the patient not treated with HAART, multiple genetic changes were discovered in the viral isolates from the two other patients after HAART and mega‐HAART, respectively. Through analysis of B19 clones, the frequency of clones containing these mutations confirmed the genetic drift. Nucleotide substitutions seen in VP2gene of isolates with genetic drift from both patients were all non‐conserved, suggesting that they are positively selected. J. Med. Virol. 78:1374–1384, 2006. © 2006 Wiley‐Liss, Inc.

To understand the clinical significance and mechanisms of cutaneous denervation in systemic lupus erythematosus (SLE), we assessed intraepidermal nerve fibre (IENF) density of the distal leg in 45 SLE patients (4 males and 41 females, aged 38.4 ± 13.6 years) and analysed its correlations with pathology, lupus activity, sensory thresholds and electrophysiological parameters. Compared with age- and gender-matched control subjects, SLE patients had lower IENF densities (3.08 ± 2.17 versus 11.27 ± 3.96 fibres/mm, P < 0.0001); IENF densities were reduced in 38 patients (82.2%). Pathologically, 11 patients (24.4%) were found to have definite cutaneous vasculitis; the severity and extent of cutaneous vasculitis were correlated with IENF densities. Patients with active lupus had even lower IENF densities than those with quiescent lupus (1.86 ± 1.37 versus 4.15 ± 2.20 fibres/mm, P = 0.0002). By linear regression analysis, IENF densities were negatively correlated with the SLE disease activity index (r = 0.527, P = 0.0002) and cumulative episodes of lupus flare-up within 2 years before the skin biopsy (r = 0.616, P = 0.0014). Clinically, skin denervation was present not only in the patients with sensory neuropathy but also in the patients with neuropsychiatric syndrome involving the CNS. SLE patients had significantly elevated warm threshold temperatures (P = 0.003) and reduced cold threshold temperatures (P = 0.048); elevated warm threshold temperatures were associated with the reduced IENF densities (P = 0.032). In conclusion, cutaneous vasculitis and lupus activities underlie skin denervation with associated elevation of thermal thresholds as a major manifestation of sensory nerve injury in SLE.

Anaemia caused by persistent parvovirus B19 infection can be remitted by intravenous immunoglobulin (IVIG) treatment. However, maintenance IVIG therapy is required in some AIDS patients as well as patients with combined immuno-deficiency because of relapse of anaemia. We used a simple semi-quantitative polymerase chain reaction (PCR) method to trace plasma B19 viral load after administration of IVIG. We noted that the rebound of B19 viral load occurred 6 weeks prior to detection of anaemia. This method may be helpful in determining the interval of maintenance IVIG therapy.