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Protection against virulent Mycobacterium avium infection following DNA vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting CD4(+) T cells 下载免费PDF全文
Mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of M. avium varies from that of Mycobacterium tuberculosis, with the immunodominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this M. avium 35-kDa antigen (DNA-35) induces protective immunity against virulent M. avium infection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-gamma) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4(+) T-cell response, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and an increase in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vaccination with Mycobacterium bovis BCG and significantly greater than that for previous treated infection with M. avium. These results illustrate the importance of the 35-kDa protein in the protective response to M. avium infection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronic M. avium infection. 相似文献
23.
The individual leaves of a multileaf collimator (MLC) have a tongue-and-groove or stepped-edge design to minimize leakage radiation between adjacent leaves. This design element has a drawback in that it creates areas of underdosages in intensity-modulated photon beams unless a leaf trajectory is specifically designed such that for any two adjacent leaf pairs, the direct exposure under the tongue-and-groove is equal to the lower of the direct exposures of the leaf pairs. In this work, we present a systematic study of the optimization of a leaf sequencing algorithm for segmental multileaf collimator beam delivery that completely eliminates areas of underdosages due to tongue-and-groove or stepped-edge design of the MLC. Simultaneous elimination of tongue-and-groove effect and leaf interdigitation is also studied. This is an extension of our previous work (Kamath et al 2003a Phys. Med. Biol. 48 307) in which we described a leaf sequencing algorithm that is optimal for monitor unit (MU) efficiency under most common leaf movement constraints that include minimum leaf separation. Compared to our previously published algorithm (without constraints), the new algorithms increase the number of sub-fields by approximately 21% and 25%, respectively, but are optimal in MU efficiency for unidirectional schedules. 相似文献
24.
Although CD4(+) T cells are essential for protective immunity against Mycobacterium tuberculosis infection, recent reports indicate that CD8(+) T cells may also play a critical role in the control of this infection. However, the epitope specificity and the mechanisms of activation of mycobacteria-reactive CD8(+) T cells are poorly characterized. In order to study the CD8(+) T cell responses to the model mycobacterial antigen, MPT64, we used recombinant vaccinia virus expressing MPT64 (VVWR-64) and a panel of MPT64-derived peptides to establish that the peptide MPT64(190-198) contains an H-2D(b)-restricted CD8(+) T cell epitope. A cytotoxic T lymphocyte response to this peptide could be demonstrated in M. bovis bacillus Calmette Guerin (BCG)-infected mice following repeated in vitro stimulation. When bone marrow-derived dendritic cells (DC) were infected with BCG, the expression of MHC class I molecules by DC was up-regulated in parallel with MHC class II and B7-2, whereas CD1d expression level was not modified. Moreover, BCG-infected DC activated MPT64(190-198)-specific CD8(+) T cells to secrete IFN-gamma, although with a lower efficacy than VVWR-64-infected DC. The production of IFN-gamma by MPT64(190-198)-specific CD8(+) T cells was inhibited by antibodies to MHC class I, but not to CD1d. These data suggest that mycobacteria-specific CD8(+) T cells are primed during infection. Therefore, anti-mycobacterial vaccine strategies targeting the activation of specific CD8(+) T cells by DC may have improved protective efficacy. 相似文献
25.
Alexander J. Acua Daniel Grits Linsen T. Samuel Ahmed K. Emara Atul F. Kamath 《Clinical orthopaedics and related research》2021,479(3):589
BackgroundGiven the morbidity, mortality, and financial burden associated with venous thromboembolism (VTE) after TKA, orthopaedic providers continually seek to identify risk factors associated with this devastating complication. The association between perioperative transfusion status and VTE risk has not been thoroughly explored, with previous studies evaluating this relationship being limited in both generalizability and power.Questions/purposesTherefore, we sought to determine whether perioperative transfusions were associated with an increased risk of (1) pulmonary embolism (PE) or (2) deep vein thrombosis (DVT) after primary TKA in a large, multi-institutional sample.MethodsThe American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was implemented for our analysis. The definitions of complications, such as DVT and PE, and risk adjustment validation is monitored by the central ACS NSQIP office to ensure participating hospitals are adhering to the same guidelines to log patients. Additionally, both preoperative and intraoperative/72 hour postoperative transfusion status is included for all patients. Therefore, ACS NSQIP was determined to be the most appropriate database for our analysis. All patients who underwent primary TKA between 2011 and 2018 were identified using Current Procedural Terminology code 27447. Primary TKAs designated as “non-elective” were excluded, thereby providing a cohort composed solely of patients undergoing unilateral primary elective TKA for further analysis. The final analysis included 333,463 patients undergoing TKA (mean age 67 ± 9 years, 62% female). Preoperative transfusions were received by < 0.01% (48 of 333,463) of the patients, while 4% (14,590 of 333,463) received a transfusion within the interim between the start of surgery up to 72 hours postoperatively. All missing values were imputed through multiple imputation by chained equation to avoid variable availability-based selection and the subsequent listwise deletion-associated bias in the estimate of parameters. A multivariable logistic regression analysis was conducted using variables identified in a univariate model to calculate adjusted odds ratios and 95% confidence intervals for risk factors associated with symptomatic DVT and/or PE. For variables that maintained significance in the multivariable model, an additional model without confounders was used to generate fully adjusted ORs and 95% CIs. A propensity score matched comparison between recipients versus nonrecipients (1:1) of transfusion (preoperative and intraoperative/72 hours postoperative) was then conducted to evaluate the independent association between DVT/PE development and patients’ transfusion status. Significance was determined at a p value < 0.05.ResultsAdjusted multivariable regression analysis accounting for patient age, sex, race, BMI, American Society of Anesthesiologists (ASA) class and baseline comorbidities demonstrated the absence of an association between preoperative (OR 1.75 [95% CI 0.24 to 12.7]; p = 0.58) or intraoperative/72 hours postoperative (OR 1.12 [95% CI 0.93 to 1.35]; p = 0.23) transfusions and higher odds of developing PE. Similar findings were demonstrated after propensity score matching. Although multivariable regression demonstrated the absence of an association between preoperative transfusion and the odds of developing DVT within the 30-day postoperative period (OR 1.85 [95% CI 0.43 to 8.05]; p = 0.41), intraoperative/postoperative transfusion was associated with higher odds of DVT development (OR 3.68 [95% CI 1.14 to 1.53]; p < 0.001) relative to transfusion naïve patients. However, this significance was lost after propensity score matching.ConclusionAfter controlling for various potential confounding variables such as ASA Class, age, anesthesia type, and BMI, the receipt of an intra- or postoperative transfusion was found to be associated with an increased risk of DVT. Our findings should encourage orthopaedic providers to strictly adhere to blood management protocols, further tighten transfusion eligibility, and adjust surgical approach and implant type to reduce the incidence of transfusion among patients with other DVT risk factors. Additionally, our findings should encourage a multidisciplinary approach to VTE prophylaxis and prevention, as well as to blood transfusion guideline adherence, among all providers of the care team.Level of EvidenceLevel III, therapeutic study. 相似文献
26.
Yuki Bekki Josep Marti Takeo Toshima Sara Lewis Amita Kamath Pamela Argiriadi William Simpson Lucas Facciuto Rahul S. Patel Ganesh Gunasekaran Edward Kim Thomas D. Schiano Marcelo E. Facciuto 《Surgery》2021,169(5):1044-1051
BackgroundPortal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data.MethodsWe retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease.ResultsSeventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90.ConclusionBoth preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery. 相似文献
27.
Lavanya Yohanathan Cristina C. Campioli Omar Y. Mousa Kymberly Watt Daniel Z. P. Friedman Vijay Shah Resham Ramkissoon Alexander S. Hines Patrick S. Kamath Raymund R. Razonable Andrew D. Badley Erin S. DeMartino Michael J. Joyner Rondell Graham Paschalis Vergidis Doug A. Simonetto William Sanchez Timucin Taner Julie K. Heimbach Elena Beam Michael D. Leise 《American journal of transplantation》2021,21(8):2890-2894
Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies. 相似文献
28.
STUDY DESIGN: Seventy-five surgically excised prolapsed intervertebral discs were histopathologically evaluated. Fifteen prospective normal cadaveric discs were used as control specimens. OBJECTIVE: To compare the morphologic features between the prolapsed and normal discs. SUMMARY OF BACKGROUND DATA: The histologic criteria were edge neovascularization of the fibrocartilage, chondrocyte cloning, fibrillation with fraying, and granular change. METHODS: Sections stained with hematoxylin and eosin, Van Gieson's, and toluidine blue were studied. The presence or absence of edge neovascularization was noted. The other criteria were graded based on a semiquantitative scoring system. RESULTS: Edge neovascularization was observed in 56% of the discs in the test group and in none of the control specimens. Fibrillation with fraying was the most significant finding in the test group (P < 0.001). Although the mean grades were higher in the test group, they did not predict the presence of edge neovascularization. CONCLUSIONS: Edge neovascularization was the most significant finding to confirm disc prolapse. Fibrillation with fraying, was observed more frequently in prolapsed intervertebral discs and the grades of fibrillation with fraying, chondrocyte cloning, and granular change were significantly higher in the test group. Pathologists can usually agree on the presence or absence of a particular histologic characteristic but are rarely consistent when they estimate the degree. Simple, reproducible agreed-on criteria are needed before semiquantitative evaluations become reliable. 相似文献
29.
B D Shenoy N Udupa R Kamath P U Devi 《Indian journal of physiology and pharmacology》1999,43(2):259-262
Anti-tumor efficacy of Centchroman formulated as niosomes and gel implant was evaluated in Swiss albino mice bearing Ehrlich ascites carcinoma at 10 mg/kg body weight dose given subcutaneously. Median day of death, percentage increase in host life span and changes in body weight were studied. Centchroman significantly (P < 0.05) increased the median day of death both in free and formulated systems. Also, injectable formulations exhibited a significant (P < 0.05) increase in host life span compared to free drug, hence, enhanced anti-tumor efficacy against Ehrlich ascites carcinoma. 相似文献
30.