CT Imaging Manifestations of Tuberculous Aortic Aneurysm.

Background: Tuberculous aortic aneurysm (TBAA) is a rare complication of TB and is associated with high mortality. Early diagnosis is critical; however, it is challenging due to nonspecific symptoms. This study summarized the computed tomography (CT) features of TBAA with the aim of assisting with timely clinical diagnosis. Methods: Seventeen patients with TBAA between 2015 and 2020 were included in this study. The clinical manifestations, past medical history, laboratory and imaging examinations, treatments, and other data were collected and analyzed. CT angiography was performed in all patients. Results: All tuberculous aneurysms were pseudoaneurysms, which were located in the thoracic aorta (8/17, 47%), abdominal aorta (7/17, 41%), junction of the thoracic and abdominal aorta (1/17, 6%) or abdominal aorta and iliac artery (1/17, 6%) region. The shapes of all aneurysms were saccular, and nine of them were lobulated. The aneurysm diameter ranged from 3 to 12 cm. Of the 17 patients, 12 (71%) had calcification; 14 (82%) had intraluminal thrombus; 12 (71%) showed enlarged lymph nodes, which were closely related to the aneurysm; and 9 (53%) had tuberculous spondylitis including TB of the thoracic lumbar and lumbosacral spine. Psoas abscess was detected in 4 (23%) patients and iliopsoas abscess was detected in 1 (6%) patient. Conclusions: TBAA typically shows mycotic shapes on CT scans. Another feature is that the surrounding tissues and adjacent organs of tubercular aneurysms are usually infected with TB, and most of them are accompanied by other sites of TB.

Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation.

The aggregation of amyloid ß-peptide (Aß) is thought to play a pivotal role in the disease progression of Alzheimer's disease (AD). Amyloid ß directed immunotherapy has been considered an alternative AD treatment. In this study, we constructed a DNA vaccine, p(Aß3-10)10-mIL-4, encoding ten tandem repeats of Aß3-10 fused with mouse IL-4. Eight-month-old APP/PS1 transgenic mice were injected intramuscularly with p(Aß3-10)10-mIL-4 followed by in vivo electroporation. Immunization with the vaccine induced high-titer anti-Aß antibodies and attenuated the behavior impairment. Immunoglobulin isotyping revealed a predominantly IgG1 response and ex vivo cultured splenocytes exhibited a low IFN-γ and high IL-4 response, indicating a Th2 anti-inflammatory response. Immunohistochemical analysis revealed that p(Aß3-10)10-mIL-4 immunization decreased Aß deposition, and the microglial attraction significantly decreased accompanied by the clearance of Aß. There was no microhemorrhage in the brain of the immunized mice. These results suggest that the immunization potentially reduced the inflammation in brain of transgenic mice and therefore improved their cognitive ability. This novel DNA vaccine p(Aß3-10)10-mIL-4 may be an effective immunization method as therapy for AD.

In vivo electroporation of a new gene vaccine encoding ten repeats of Aß3-10 prevents brain Aß deposition and delays cognitive impairment in young Tg-APPswe/PSEN1dE9 mice.

Active immunization holds great promise for the treatment of Alzheimer's disease but the infiltration of T-lymphocytes and associated meningoencephalitis observed in clinical trials needs to be overcome. To avoid this toxicity, previous studies have used synthetic truncated derivatives of Aß to promote humoral immunity. In this study, we developed a novel vaccine [p(Aß3-10)10-MT] that expresses ten repeats of Aß3-10 with melatonin (MT) as an adjuvant, and administered it intramuscularly in three-month-old Tg-APPswe/PSEN1dE9 (Tg) mice by in vivo electroporation. The p(Aß3-10)10-MT vaccine induced high titers of anti-Aß antibodies, which in turn reduced Aß deposits in the mouse brains and decreased cognitive impairment. Immunoglobulin isotyping revealed a predominantly IgG1 response, indicating a Th2 anti-inflammatory response. Ex vivo cultured splenocytes exhibited a low IFN-γ and high IL-4 response. Immunohistochemical analysis revealed that glial cell activation was also attenuated. These results indicate that p(Aß3-10)10-MT may potentially be an effective vaccine to reduce accumulated Aß and attenuate cognitive deficits.

DNA vaccines targeting amyloid-ß oligomer ameliorate cognitive deficits of aged APP/PS1/tau triple-transgenic mouse models of Alzheimer's disease.

The amyloid-ß (Aß) oligomer, rather than the Aß monomer, is considered to be the primary initiator of Alzheimer's disease. It was hypothesized that p(Aß3-10)10-MT, the recombinant Aß3-10 gene vaccine of the Aß oligomer has the potential to treat Alzheimer's disease. In this study, we intramuscularly injected the p(Aß3-10)10-MT vaccine into the left hindlimb of APP/PS1/tau triple-transgenic mice, which are a model for Alzheimer's disease. Our results showed that the p(Aß3-10)10-MT vaccine effectively reduced Aß oligomer levels and plaque deposition in the cerebral cortex and hippocampus, decreased the levels tau protein variants, reduced synaptic loss, protected synaptic function, reduced neuron loss, and ameliorated memory impairment without causing any cerebral hemorrhaging. Therefore, this novel DNA vaccine, which is safe and highly effective in mouse models of Alzheimer's disease, holds a lot of promise for the treatment of Alzheimer's disease in humans.

Active immunotherapy facilitates Aß plaque removal following through microglial activation without obvious T cells infiltrating the CNS.

Immunization of AD mouse models with Aß reduced Aß deposits and improved memory and learning deficits, but some clinical trials of immunization with Aß were halted due to brain inflammation which was presumably induced by a T cell-mediated autoimmune response. We have developed a "possibly safer" vaccine. Our results demonstrate that pcDNA3.1 vector encoding ten repeats of Aß3-10 fragments elicited high titers of antibodies which reacted well with not only monomeric but also oligomeric and fibrillar forms of Aß42 peptide. Induced antibodies strongly reacted with amyloid plaques in the brain, demonstrating functional activity of the antibodies. Immunohistochemical and immunofluorescence showed there was significantly less plaque deposition accomplied with less microglia activation as detected both in the frontal cortex and hippocampus. These data suggested that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. No obvious inflammation T cell and Prussian blue positive cell was found indicated that inflammation T cell infiltration and microhemmorage can be avoided or at least reduced to the minimum level.

Nasal mucosal inhalation of amyloid-beta peptide 3-10 defective adenovirus attenuates cytotoxicity induced by beta-amyloid (1-42).

Three-month-old Alzheimer's disease model transgenic mice were immunized with Aß1-42 Plp-Adenovirus [Ad]-X-CMV-(Aß3-10)10-CpG [AdCpG-(Aß3-10)10] or AdCpG virus fluid via nasal mucosal inhalation, respectively. ELISA analysis of serum showed Aß42 antibody titers were significantly increased in mice immunized with Aß1-42 and AdCpG-(Aß3-10)10. Concanavalin A and AdCpG-(Aß3-10)10 stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG(Aß3-10)10 and Aß42 groups compared with the control group. In the AdCpG(Aß3-10)10 group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-γ were decreased. In the Aß42 group, levels of IL-4, IL-10, IL-2 and interferon-γ were all increased. Experimental findings indicate that AdCpG-(Aß3-10)10 vaccine can produce strong T helper 2 (Th2) humoral immune responses in addition to the production of Aß42 antibody. The cellular immunologic response was weak and avoided Aß1-42-mediated cytotoxicity.

Reduction of cerebral Aß burden and improvement in cognitive function in Tg-APPswe/PSEN1dE9 mice following vaccination with a multivalent Aß3-10 DNA vaccine.

To develop a safe and efficient Aß vaccine for Alzheimer's disease, we constructed a plasmid DNA vaccine encoding ten repeats of Aß3-10 and three copies of C3d-p28 as a molecular adjuvant and administered it intramuscularly in 12-month-old female Tg-APPswe/PSEN1dE9 mice. Therapeutic immunization with p(Aß3-10)10-C3d-p28.3 stimulated a Th2 immune response that elicited therapeutic levels of anti-Aß antibodies and improved cognitive function. In addition, the vaccine reduced the cerebral Aß burden and astrocytosis without increasing the incidence of microhemorrhage. Our results indicate that the p(Aß3-10)10-C3d-p28.3 vaccine is a promising immunotherapeutic option for Aß vaccination in Alzheimer's disease.

A new DNA vaccine fused with the C3d-p28 induces a Th2 immune response against amyloid-beta.

To enhance anti-amyloid-beta (Aß) antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p(Aß3-10)10-C3d-p28.3 encoding ten repeats of Aß3-10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant cularly to female C57BL/6J mice at 8-10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aß antibody, isotypes, and cytokines in splenic T cells. A 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cells. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aß antibodies to Aß plaques. The p(Aß3-10)10-C3d-p28.3 vaccine induced high titers of anti-amyloid-ß antibodies, which bound to Aß plaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer's disease. Moreover, the vaccine elicited a predo-minantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, dicating that the vaccine could shift the cellular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p(Aß3-10)10-C3d-p28.3 vaccine is a promising immunothe-peutic option for Aß vaccination in Alzheimer's disease.

Immunization with a new DNA vaccine for Alzheimer's disease elicited Th2 immune response in BALB/c mice by in vivo electroporation.

Immunization with synthetic amyloid ß-protein (Aß) peptide has resulted in preventing and clearing Aß deposits as well as improving cognitive function in transgenic mouse models of Alzheimer's disease (AD). But similar immunization studies in humans were halted due to the risk of inducing T cell-mediated meningoencephalitis. A safe and effective vaccine for AD requires not only therapeutic levels of anti-Aß antibodies but also the prevention of an adverse T cell-mediated, proinflammatory autoimmune response. In this study, we developed a DNA vaccine, p(Aß(3-10))(10)-IL-4, encoding ten tandem repeats of Aß(3-10) fused with mouse cytokine interleukin-4 (IL-4) as a molecular adjuvant. Wild-type mice were injected intramuscularly with p(Aß(3-10))(10)-IL-4 followed by in vivo electroporation. The p(Aß(3-10))(10)-IL-4 vaccine elicited high titer anti-Aß antibodies which bound to Aß plaque in brain tissue from a ten-month-old APP/PS1 transgenic mouse. The antibody isotype was mainly IgG(1) and the IgG(1)/IgG(2a) ratio in the p(Aß(3-10))(10)-IL-4 group was approximately eight times greater than that of the Aß(42) group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aß(3-10))(10)-IL-4 exhibited a low IFN-γ response and a high IL-4 response compared with the control group. These results indicate that immunization with the p(Aß(3-10))(10)-IL-4 vaccine induced effective anti-Aß antibodies and elicited a Th2-polarized immune response that had a lower potential to cause an inflammatory T cell response. Thus, the DNA vaccine, p(Aß(3-10))(10)-IL-4, may be a safe and efficient vaccine for AD.

Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Aß3-10 reduces AD-like pathology and cognitive impairment in Tg-APPswe/PSEN1dE9 mice.

To develop a safe and efficient vaccine for AD treatment, we constructed an adenovirus vector vaccine encoding ten repeats of Aß3-10 and CpG motif as a molecular adjuvant. We demonstrated that therapeutic immunization with Ad-10×Aß3-10-CpG elicits Aß3-10 specific Th2-polarized immune response with high titers of anti-Aß antibodies in APPswe/PSEN1dE9 mice, which in turn reduced Aß deposits in brains and cognitive impairment. In addition, Ad-10×Aß3-10-CpG reduced astrocytosis without increasing the incidence of microhemorrhage. Our findings of this study raise the possibility that the adenovirus vaccine Ad-10×Aß3-10-CpG would be a safe and effective alternative for AD immunotherapy.

Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Aß3-10 induces Th2 immune response against amyloid-ß in wild-type mouse.

To develop a safe and efficient vaccine for the treatment of Alzheimer's disease, we constructed a novel adenovirus vaccine encoding ten repeats of Aß3-10 and CpG motif as an adjuvant and investigated the immune response in BALB/c mouse after intranasal inoculation with this vaccine. The Ad-10×Aß3-10-CpG induces an IgG1 predominant humoral response and production of IL-4 and IL-10 in splenocytes in vitro, indicating a Th2-polarized immune response. Stimulation of splenocytes with Aß3-10 peptide induces robust proliferation but not with full-length Aß42 peptide, demonstrating that Ad-10×Aß3-10-CpG does not induces Aß42 specific T cell immune response. The findings raise the possibility that the adenovirus vaccine Ad-10×Aß3-10-CpG could be a safe and effective alternative for immunotherapy in Alzheimer's disease.

Amyloid ß 3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice.

BACKGROUND: Amyloid ß(1-42) (Aß(42)) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models. But the phase II trial of Aß(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Aß(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice. METHODS: BALB/c mice were vaccinated intramuscularly with p(Aß(3-10))(10)-CpG plasmids. Aß(42) peptide, pcDNA3.1(+) empty vector and PBS were injected to the control groups. Expression of interesting gene in injected muscle was identified by immunohistochemistry. Anti-Aß antibody titers, isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: P(Aß(3-10))(10)-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry. The p(Aß(3-10))(10)-CpG vaccine induced high titers of anti-Aß antibodies in BALB/c mice. And isotype of the antibodies was mainly IgG1, the IgG1/IgG2a ratio for the p(Aß(3-10))(10)-CpG group was approximately 5 times greater than that for the Aß(42) peptide group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aß(3-10))(10)-CpG exhibited high interleukin-4 response and low interleukin-γ (IFN-γ) response. CONCLUSIONS: Immunization with p(Aß(3-10))(10)-CpG vaccine primarily induces a T(H)2 type of response, thus reduces the probability of inflammation. This p(Aß(3-10))(10)-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.

Improving memory and decreasing cognitive impairment in Tg-APPswe/PSEN1dE9 mice with Aß3-10 repeat fragment plasmid by reducing Aß deposition and inflammatory response.

The present study aimed to investigate the effects of Aß3-10 repeat fragment plasmid for the treatment of Tg-APPswe/PSEN1dE9 (Tg) mice. The plasmid pcDNA3.1-(Aß3-10)10-CpG was constructed and intramuscularly injected into 12-month-old Tg mice. Through the use of behavioral tests, anti-Aß antibody and Aß assays, cytokine assay, Aß deposition, and astrocytes analysis results demonstrated that Aß3-10 repeat fragment plasmid exhibited immunogenicity and reduced memory impairment in Tg mice via clearance of cerebral Aß deposition, without significant side effects. Aß3-10 repeat fragment plasmid immunization reduced Th1 cell-mediated immunity, secretion of interferon-γ, and stimulation to astrocytes. These data showed that the Aß3-10 repeat fragment plasmid improved memory and decreased cognitive impairment in Tg mice by reducing Aß deposition and inflammatory responses.