Comparison of individual and combination DNA vaccines for B. anthracis,Ebola virus,Marburg virus and Venezuelan equine encephalitis virus

Multiagent DNA vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. Few animal studies have compared the feasibility of combining unrelated gene vaccines. Here, we demonstrate that DNA vaccines to four dissimilar pathogens that are known biowarfare agents, Bacillus anthracis, Ebola (EBOV), Marburg (MARV), and Venezuelan equine encephalitis virus (VEEV), can elicit protective immunity in relevant animal models. In addition, a combination of all four vaccines is shown to be equally as effective as the individual vaccines for eliciting immune responses in a single animal species. These results demonstrate for the first time the potential of combined DNA vaccines for these agents and point to a possible method of rapid development of multiagent vaccines for disparate pathogens such as those that might be encountered in a biological attack.     

Misplacement of a femoral venous catheter into the ascending lumbar vein: repositioning using ultrasonographic guidance

A 5-week-old infant with congenital chylothorax required long-term intravenous access for parenteral nutrition. Cannulation of the inferior vena cava via the left femoral vein was attempted, but the catheter was misplaced into the left ascending lumbar vein. Catheter removal is advised when such malposition is identified. We were able successfully to redirect the catheter into the inferior vena cava using ultrasonographic guidance. This procedure has not been described previously in children. We propose that repositioning of incorrectly placed vascular catheters can be achieved using ultrasound guidance at the bedside.     

Application of radar to detect pedestrian workers near mining equipment

Between 1990 and 1996, 133 accidents occurred and 23 mine workers were killed when haulage trucks used in surface mines collided with another smaller vehicle, a mine structure, or a pedestrian worker. These accidents were caused by a lack of visibility from the cab of the truck. Similar accidents are common with other types of equipment, such as front-end loaders and shovels. There are several methods for improving the operator's awareness of objects or people around the equipment including improved mirror designs, video cameras, and sensor technologies. Researchers at the National Institute for Occupational Safety and Health (NIOSH) are evaluating collision warning systems that are based on radar technology. These systems are mounted on the mining equipment to monitor one or more of the blind areas. An alarm is provided to the operator if an object or person enters the radar's detection area. Tests consisted of mounting the systems on a 50-ton-capacity truck typically used in quarries and a 240-ton-capacity truck used at a surface mine. This article summarizes the test procedure and results of evaluations of several off-the-shelf and prototype radar systems. False alarm rates and reliable detection zones for pedestrians were recorded for various mounting configurations on the rear of the trucks. Mounting radar systems on large equipment presents several challenges; however, the technology does show promise for this application.     

Electrically induced recovery of gait components for older patients with chronic stroke

OBJECTIVE: To compare the gains for chronic stroke patients in volitional gait pattern attained from treatment with functional neuromuscular stimulation (FNS) and intramuscular electrodes (IM) with gains attained using conventional therapy, including treatment with FNS using surface electrodes (surface-stim). DESIGN: This single-subject research design consisted of a series of two subjects. Three months of conventional therapy and surface-stim were followed by treatment using the FNS-IM system. Two stroke patients had cerebrovascular accident 1 or 4 yr before the study and ambulated with a cane. Interventions consisted of 3 months of conventional exercise and gait training including surface-stim, followed by 7-14 months of treatment with the FNS-IM system. Treatments occurred up to 3 times/wk for 1-hr sessions and a home program. Outcome measures consisted of six kinematic gait components, as measured by a six-camera video-based data-acquisition system. Coordination of isolated joint movement was measured according to the Fugl-Meyer scale. RESULTS: Both subjects improved during conventional therapy to some degree. During FNS-IM treatment, gains were made beyond those attained during conventional therapy. Statistically significant differences were found between conventional and FNS-IM therapy. CONCLUSIONS: For these two subjects, gains in volitional control of gait were made during conventional treatment (including surface-stim); for these two subjects during FNS-IM treatment, additional gains were made in volitional gait pattern, beyond those attained during conventional therapy.     

Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis

Human p55, the major palmitoylated protein associated with the cytoplasmic face of the erythrocyte membrane, is believed to modulate interactions between protein 4.1 and glycophorin C. It is the prototype of a newly described family of signaling molecules that includes hD1g, the human homologue of the Drosophila discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized by transformation to a fulminating acute leukemia, heralded by evolution of the Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The deletion of constitutive exon 5 not only marks the first abnormality of the p55 cDNA in human disease but also the first abnormality of a PDZ domain in human disease and may represent another genetic abnormality associated with CML in blast crisis.     

The spectrum of HIV-1 related cancers in South Africa

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.     

Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains

Amyloid precursor protein (APP) is a ubiquitously expressed membrane spanning glycoprotein which is endoproteolytically processed to Aβ, a 39–43 amino acid peptide that is the main component of senile plaques in Alzheimer Disease (AD). APP is a member of a highly conserved gene family, including Amyloid Precursor-Like Proteins (APLPs) APLP1 and APLP2. We now characterize APLP1 and APLP2 mRNA and protein expression in AD and aged control brains. Using in situ hybridization in hippocampal tissue from control and AD brain, we show that APLP1 and APLP2 mRNA are expressed primarily in the granule cells of the dentate gyrus, in areas CA1–CA3, and subiculum. Immunohistochemistry reveals staining for both APLP1 and APLP2 in neurons and blood vessels in AD and control cases. In addition, in AD brain, large dystrophic neurites in a subset of senile plaques are conspicuously labeled with APLP1 and APLP2 antibodies. The aged control brains have significantly fewer immunoreactive plaques and dystrophic neurites. The regional, cellular, and subcellular distribution of APLP1 and APLP2 overlap with each other and with APP. These observations support the hypothesis that the members of this family of proteins may perform similar functions.     

Second occurrence of spinal epidural metastases

We reviewed records of 79 men with spinal epidural metastases diagnosed from July 1984 to July 1989, imaged by myelography or MRI, and treated with radiation therapy. Thirteen men (16%) had second epidural metastases. The mean time between lesions that developed within two vertebral bodies of a prior lesion was 2.8 months, compared with 15.2 months for lesions that were three or more vertebral bodies from a prior lesion. Some secondary spinal metastases occurring soon after the initial metastasis may represent regrowth of tumor at the border of the radiation port, suggesting that larger radiation ports be constructed for patients with lengthy expected survival times.     

Hepatitis B immunisation rates among infants in ethnic groups with high prevalences of hepatitis B surface antigen carriers

Abstract: To determine hepatitis B immunisation rates in infants from ethnic groups with hepatitis B surface antigen chronic carrier prevalence over 5 per cent, a questionnaire was sent to all Maternal and Child Health Centres in Victoria, requesting information on the hepatitis B and diphtheria–tetanus–pertussis (DTP) or combined diphtheria–tetanus (CDT) immunisation status for all infants born between 1 July 1992 and 30 June 1993 and at risk of hepatitis B infection because of maternal ethnicity. We received data on 3611 of 5744 infants (62.9 per cent) in targeted ethnic groups. Of these, 12.8 per cent had not received hepatitis B vaccine, and 81.6 per cent, 76.8 per cent and 64.0 per cent had received at least one, two and three doses respectively, while 84 per cent had received at least three doses of DTP vaccine and/or CDT vaccine. Coverage with DTP or CDT was higher than for hepatitis B vaccine ( P < 0.001), and coverage was better in areas with a higher percentage of infants in high–prevalence ethnic groups ( P < 0.001). Changes in the program in Victoria in terms of timing of the first dose of vaccine plus greater attention to follow–up may lead to improved hepatitis B immunisation rates among infants in targeted ethnic groups. Adoption of universal infant hepatitis B immunisation, by increasing familiarity with hepatitis B vaccine, is likely to be the best way to increase immunisation coverage for these infants.     

VIP and -ala-peptide T-amide release chemokines which prevent HIV-1 GP120-induced neuronal death

Vasoactive intestinal peptide (VIP) and DAPTA ( -ala₁-peptide T-amide, a gp120-derived octapeptide homologous to VIP) prevent neuronal cell death produced by five variants of HIV-1 (human immunodeficiency virus) envelope protein (gp120). VIP or DAPTA treatment of astrocyte cultures resulted in the release of macrophage inflammatory protein-1α (MIP-1α) and RANTES, beta chemokines known to block gp120 interactions with microglial chemokine receptors. In rat cerebral cortical cultures, gp120-induced neuronal killing was partially or completely prevented by chemokines that stimulate the CXCR4, CCR3 or CCR5 chemokine receptors. Chemokines exhibited marked differences in potency and efficacy in preventing toxicity associated with five gp120 variants (LAV/BRU, CM243, RF, SF2, and MN). RANTES had the broadest and most potent inhibition (IC₅₀<3 pM for RF isolate). An octapeptide derived from RANTES also exhibited neuroprotection from gp120 (RF isolate) toxicity (IC₅₀=0.3 μM). Treatment with chemokines alone had no detectable effect on neuronal cell number. However, antiserum to MIP-1α produced neuronal cell death that was prevented by co-treatment with MIP-1α, suggesting that this endogenous chemokine exerts a tonic regulation important to neuronal survival. The neuroprotective action of VIP on gp120 was attenuated by co-treatment with anti-MIP-1α. These studies suggest that the neuroprotective action of VIP is linked in part to its release of MIP-1α. Furthermore, neuroprotection produced by chemokines is dependent on both the type of chemokine and the variant structure of gp120 and may be relevant to drug strategies for the treatment of AIDS dementia.