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91.
Invasive pulmonary aspergillosis 总被引:2,自引:0,他引:2
Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients. The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy. The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options. Research efforts are being made constantly to improve different diagnostic techniques. Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles. 相似文献
92.
Hanna J Mussaffi H Steuer G Hanna S Deeb M Blau H Arnon TI Weizman N Mandelboim O 《Blood》2005,106(10):3465-3473
Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated natural killer (NK) subsets. Recent studies have shown that aberrant chemokine receptor expression on certain immune cells underlies the pathogenesis of clinical conditions in which recruitment of such cells is altered. Progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granulomatous lesions in the respiratory tract and the skin, has been described in a number of patients with transporter associated with antigen processing 2 (TAP-2) deficiency in the later stages of disease. Therefore, the goal of the present study was to elucidate whether the dysregulation of chemoattracting receptor expression on NK cells could explain abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic comparison, followed by verification with flow cytometry, revealed that chronically activated NK cells derived from 3 newly identified patients with TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR2 pathway in aberrant NK-cell retention at chronic inflammatory sites. 相似文献
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Ruikang Liu Jeffrey L. Americo Catherine A. Cotter Patricia L. Earl Noam Erez Chen Peng Bernard Moss 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(12)
Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases, including COVID-19, are in progress. Here, we characterize rMVAs expressing the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Modifications of full-length S individually or in combination included two proline substitutions, mutations of the furin recognition site, and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) is flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and, upon passive transfer, protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNγ+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 3 wk or 7 wk later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals.Recombinant DNA methods have revolutionized the engineering of vaccines against microbial pathogens, thereby creating opportunities to control the current COVID-19 pandemic (1). The main categories of recombinant vaccines are protein, nucleic acid (DNA and RNA), virus vectors (replicating and nonreplicating), and genetically modified live viruses. Each approach has advantages and drawbacks with regard to manufacture, stability, cold-chain requirements, mode of inoculation, and immune stimulation. Recombinant proteins have been successfully deployed as vaccines against a variety of diseases (2–5). DNA vaccines have been licensed for veterinary purposes (6, 7), although none are in regular human use. Recently developed messenger RNA (mRNA) vaccines are in use for COVID-19 and are in preclinical development for other infectious diseases (8). At least 12 virus vector vaccines based on adenovirus, fowlpox virus, vaccinia virus (VACV), and yellow fever virus have veterinary applications, but, so far, only two have been marketed for humans (9), although numerous clinical trials, particularly with attenuated adenovirus and VACV, are listed online in ClinicalTrials.gov.A variety of recombinant approaches utilizing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; abbreviated CoV-2) as immunogen are being explored to quell the COVID-19 pandemic (10). Vaccines based on mRNA and adenovirus vectors have demonstrated promising results in clinical trials and have received emergency regulatory approval (11–14). Other candidate CoV-2 vaccines, including ones based on vesicular stomatitis virus (15), an alphavirus-derived replicon RNA (16), an inactivated recombinant Newcastle Disease virus (17), and modified VACV Ankara (MVA) (18, 19) are at early stages of evaluation.Experiments with virus vectors for vaccination were carried out initially with VACV (20, 21), providing a precedent for a multitude of other virus vectors (9). The majority of current VACV vaccine studies employ the MVA strain, which was attenuated by more than 500 passages in chicken embryo fibroblasts during which numerous genes were deleted or mutated, resulting in an inability to replicate in human and most other mammalian cells (22). Despite the inability to complete a productive infection, MVA is capable of highly expressing recombinant genes and inducing immune responses (23, 24). MVA is a licensed smallpox vaccine, and numerous clinical studies of recombinant MVA (rMVA) vectors are in progress or have been completed. Protection has been obtained with MVA-based SARS-CoV-1 and Middle East respiratory syndrome CoV (MERS-CoV) in animals (25–28), and an MVA-based MERS-CoV vaccine was shown to be safe and immunogenic in a phase 1 clinical trial (29). Currently, two clinical trials for MVA-based CoV-2 vaccines are in the recruiting phase (ClinicalTrials.gov). Here, we show that one or two immunizations with rMVAs expressing the CoV-2 S proteins elicit strong neutralizing antibody responses, induce CD8+ T cells, and protect susceptible transgenic mice against a lethal intranasal challenge with CoV-2 virus, supporting clinical testing of related rMVA vaccines. 相似文献
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Sandeep P. Dave B.S. Adrian J. Greenstein M.D. David B. Sachar M.D. Noam Harpaz M.D. Ph.D. Louis Aledort M.D. 《The American journal of gastroenterology》2002,97(1):187-189
A 53-yr-old man with a 33-yr history of Crohn's ileocolitis, complicated by arthritis and cologastric fistulization, was diagnosed with GI amyloidosis at the time of proctocolectomy. He had marked proteinuria (4.2 g/24 h) and moderate renal insufficiency (BUN of 35 mg/dl and serum creatinine of 2.5 mg/dl). During the operation, he had severe bleeding that required 11 U of blood. Postoperatively, desmopressin was administered, which resulted in a prompt cessation of bleeding. This case demonstrates the efficacy of desmopressin in reversing the bleeding diathesis in surgical patients with amyloidosis complicated by renal insufficiency. 相似文献
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BACKGROUND: Endoscopic marking of intestinal lesions is essential when difficulty is anticipated with subsequent localization during surgical resection or postpolypectomy surveillance. The most commonly used indelible marker has been India ink, which must be diluted and sterilized, a cumbersome process. SPOT, a prepackaged, sterile Food and Drug Administration-approved formulation of pure carbon particles in suspension, eliminates the need for preinjection preparation. METHODS: Ten patients with colonic polyps deemed endoscopically unresectable or malignant-appearing had the area surrounding the lesions injected with SPOT and subsequently underwent surgical resection. An additional 103 patients underwent colonoscopic injection with SPOT and were followed endoscopically or underwent surgery at another hospital. RESULTS: The SPOT injection sites were visible to the surgeons in all 10 cases. On histopathologic evaluation, none of the resection specimens exhibited necrosis or abscess formation. In total, there were 118 SPOT injections in 113 patients; none had fever, abdominal pain, or any other signs or symptoms of inflammation develop. In the nonoperated group, 42 patients subsequently underwent colonoscopies at our institution, and in all cases stains were readily identifiable at the injection sites. CONCLUSIONS: SPOT is a safe and effective marker for use at colonoscopy when surgical resection is anticipated. It is also useful for endoscopic follow-up of patients who have not undergone surgery. 相似文献