Blood test results showed: lactate 5 E4 mmol/L, white blood cells 48 E3 ~10./L (neutrophils 46 E9 ~10./L), INR 1 E77, APTTR 1 E65, platelets 357 ~10./L, Clauss fibrinogen 10 E72 g/L, serum urea 10 E9 ...mmol/L, and creatinine 117 Êmol/L. CT of the head and neck showed thrombosis of the left sigmoid sinus and internal jugular vein to the level of second cervical vertebral body (figure A), and otitis media with mastoiditis, with inflammatory tissue completely occupying the middle ear and extending into the left external auditory canal, but without bone destruction (figure B).
Human monoclonal antibodies (HuMAbs) demonstrate great potential for passive immunotherapy against HIV-1. The gp41 transmembrane envelope glycoprotein of HIV has an important role in the ...pathogenicity of AIDS and importantly displays considerably less hypervariability than the gp120 surface envelope HIV glycoprotein, which makes it particularly a better candidate for the development of passive and active immunotherapies. The general aim of this study was to develop HuMAbs to HIV surface glycoproteins and particularly gp41. Peripheral blood mononuclear cells (PBMCs) were isolated from an HIV-seropositive long-term nondisease progressing patient. B-cells from this individual were then immortalized by Epstein-Barr virus (EBV) transformation, and antibody production was stabilized by fusion of transformed cells with a heteromyeloma. Subsets of the human heterohybridomas so generated were analyzed by ELISA. The hybridoma with the highest binding by immunoassay against gp160 was further analyzed. This hybridoma, designated as clone 37 (C37), was determined to be an IgM Kappa antibody and overlapping peptides of HIV envelope proteins (derived from the MN tissue culture line adapted HIV isolate) were used to map the specific binding domain of this HuMAb. Overlapping peptides designated 2026 (SWSNKSLDDIWNN, AA614-626), and 2027 (DDIWNNMTWMQWEREIDNYT, AA621-640) within the HIV-1 gp41 transmembrane glycoprotein were demonstrated to bind to C37 indicating that the specific binding domain for the antibody was DDIWNN. High affinity binding of C37 by ELISA to recombinant gp41 was demonstrated as well. Few IgM HuMAbs against HIV have been generated and characterized. Theoretically, because of the pentameric binding nature of IgM antibodies as well as their very efficient ability to activate complement, such reagents could have potential as anti-HIV agents.
The development of an efficacious vaccine against the human immunodeficiency virus (HIV) is of great urgency, because it is accepted that vaccination is the only means capable of controlling the AIDS ...pandemic. The foundation of HIV vaccine development is the analysis of immune responses during natural infection and the utilization of this knowledge for the development of protective immunization strategies. Initial vaccine development and experimentation are usually in animal models, including murine, feline, and nonhuman primates. Experimental vaccine candidates are closely studied for both efficacy and safety before proceeding to human clinical trials. There are a number of different therapeutic and prophylactic vaccine strategies currently being studied in human clinical trials. Vaccine strategies that are being tested, or have previously been tested, in humans include subunit, DNA plasmid, and viral vector, and combinations of these various strategies. Some of the results of these trials are promising, and additional research has focused on the development of appropriate chemical and genetic adjuvants as well as methods of vaccine delivery to improve the host immune response. This review summarizes the vaccine strategies that have been tested in both animal models and human clinical trials.
To assess HIV-1 DNA vaccination and co-immunization with interleukin (IL)-12 and IL-10 as immunotherapy in the HIV-1 infected chimpanzee model system.
Four chimpanzees that were infected with ...HIV-1-IIIB for longer than 4 years and remained symptom free were immunized with HIV-1 plasmid vaccines. Two chimpanzees were immunized with DNA plasmids that encoded env/rev, gag/pol along with a plasmid that encoded both chains of human IL-12. A third animal was immunized with HIV-1 DNA vaccine constructs and co-immunized with an IL-10 expressing plasmid. Finally a control animal received the HIV-1 DNA vaccine constructs alone.
There was no evidence of systemic toxicity associated with the administration of the DNA vaccines or the cytokine-expressing plasmids. We observed that the IL-12/HIV-1 DNA vaccinated animals had enhanced proliferative responses to multiple HIV-1 antigens at multiple time points. The animal that was co-immunized with HIV-1 and IL-10 did not have any changes in the proliferative responses. Finally, the control chimpanzee demonstrated moderate increases in the proliferative responses to HIV-1 antigens. The animal that received HIV-1 vaccines alone and the animals co-immunized with IL-12 all had declines in viral load over the course of the study, however, the decrease in viral loads were transient in all animals.
Immunization of HIV-1 infected chimpanzees with DNA based vaccines containing the env, gag and pol genes can transiently boost the env specific proliferative responses. Co-administration of IL-12 expressing plasmids further leads to transient boosting of the proliferative response to the core protein, p24 as well. However, at these doses the impact on viral load is minimal.
With the global rise in human immunodeficiency virus-1 (HIV-1) infection in women of childbearing age, there has also been an alarming rise in the number of mother-to-child transmissions of HIV-1. ...Although drug therapies such as zidovudine as well as nevirapine have been demonstrated to significantly decrease the incidence of vertical transmission of HIV-1, these therapeutic regimens are still not widely available in some developing countries where maternal-to-child transmission of HIV-1 continues to occur at an alarming rate. Therefore, the continued studies of mechanisms and correlates of vertical transmission of HIV-1 are warranted. The current status of immunological and virological correlates of vertical transmission are summarized in this review. In addition, information concerning recent therapeutic agents for the prevention of HIV-1 vertical transmission is presented.
Non-invasive reporter systems are powerful tools to query physiological and transcriptional responses in organisms. For example, fluorescent and bioluminescent reporters have revolutionized cellular ...and organismal assays and have been used to study plant responses to abiotic and biotic stressors. Integrated, cooled charge-coupled device (CCD) camera systems have been developed to image bioluminescent and fluorescent signals in a variety of organisms; however, these integrated long-term imaging systems are expensive.
We have developed self-assembled systems for both growing and monitoring plant fluorescence and bioluminescence for long-term experiments under controlled environmental conditions. This system combines environmental growth chambers with high-sensitivity CCD cameras, multi-wavelength LEDs, open-source software, and several options for coordinating lights with imaging. This easy-to-assemble system can be used for short and long-term imaging of bioluminescent reporters, acute light-response, circadian rhythms, delayed fluorescence, and fluorescent-protein-based assays in vivo.
We have developed two self-assembled imaging systems that will be useful to researchers interested in continuously monitoring in vivo reporter systems in various plant species.
Observational.
To assess the effects of spinal decompression procedures performed during a clinical exam on low back pain (LBP) symptoms.
Not all patients report an immediate or complete improvement ...in symptoms when the direction of lumbar motion or alignment is corrected according to principles of the movement system impairment (MSI) model. Axial compression of the spine may be responsible for the remaining symptoms.
Seventy subjects (mean ± SD age, 41.9 ± 11.5 years; 38 females, 32 males) with chronic LBP were evaluated using a standardized MSI exam. Seven tests assessing the effects of spinal decompression on LBP were added to the exam if the subjects' symptoms were not alleviated with typical standardized corrections of movement and alignment. For each test of decompression, subjects reported their symptoms compared to a reference movement or position.
When decompression was performed during lateral bending to the right and left, 21 of 21 (100%) and 16 of 20 (80%) subjects, respectively, reported an improvement. When traction was applied to subjects in right and left sidelying, 6 of 11 (55%) and 7 of 9 (78%), respectively, reported an improvement. When patients performed a push-up in sitting, 36 of 51 (71%) reported an improvement. In subjects who had symptoms in unsupported sitting, 41 of 57 (72%) reported an improvement in supported sitting. In subjects who reported symptoms in standing, 33 of 47 (70%) reported an improvement in hook-lying.
Patients with chronic LBP consistently reported an improvement in symptoms with tests proposed to decrease the axial load on the spine. These tests are a quick and effective way to assess the contribution of axial decompression to LBP symptoms and potentially could be used as part of the plan of care.
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