RESUMO
Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.
Assuntos
Adenomioepitelioma , Neoplasias da Mama , Humanos , Feminino , Adenomioepitelioma/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Mamografia , BiópsiaRESUMO
Infertility is a common diagnosis that prompts many couples and individuals to seek assisted reproductive technology (ART) for assistance with conception. These technologies have become increasingly used in the United States in the past several decades, with 326 468 ART cycles performed in 2020, resulting in 75 023 live births. This ubiquity of ART also increases the likelihood that radiologists will encounter both normal and abnormal imaging findings associated with these treatments. Thus, radiologists of all subspecialties should be familiar with the multimodality appearance of the ovaries and pelvis in patients undergoing ART treatments. Furthermore, it is imperative that radiologists understand the appearance expected during different stages of the ART process. During stimulated ovulatory cycles, it is normal and expected for the ovaries to appear enlarged and to contain numerous cystic follicles, often with a small to moderate volume of pelvic free fluid. After oocyte retrieval, hemorrhagic ovarian follicles and a small to moderate volume of blood products in the cul-de-sac can be expected to be seen. Multiple nonemergency and emergency complications are related to ART, many of which can be seen at imaging. The most encountered emergency complications of ART include ovarian hyperstimulation syndrome, ectopic pregnancy, heterotopic pregnancy, multiple gestations, ovarian torsion, and procedural complications related to oocyte retrieval. These complications have important clinical implications, thus necessitating accurate and timely detection by the radiologist and the clinical team. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.
Assuntos
Síndrome de Hiperestimulação Ovariana , Gravidez Ectópica , Feminino , Humanos , Gravidez , Imagem Multimodal , Síndrome de Hiperestimulação Ovariana/diagnóstico , Síndrome de Hiperestimulação Ovariana/etiologia , Gravidez Múltipla , Técnicas de Reprodução Assistida/efeitos adversosRESUMO
Early detection of breast cancer through screening mammography saves lives. However, the sensitivity of mammography for breast cancer detection is reduced in women with dense breast tissue. Imaging modalities for supplemental breast cancer screening include MRI, whole breast US, contrast-enhanced mammography, and molecular breast imaging (MBI). Molecular breast imaging with 99mTc-sestamibi is a functional imaging test to identify metabolically active areas in the breast with positioning analogous to mammography. Since 2011, there have been six large, published studies of screening MBI as a supplement to mammography involving over 6000 women from four different institutions. A multicenter, prospective clinical trial of 3000 women comparing breast cancer detection using screening digital breast tomosynthesis alone or in combination with MBI recently completed enrollment. This review focuses on the current evidence of MBI use for supplemental breast cancer screening, the strengths and limitations of MBI, and recent technological advances.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Mamografia/métodos , Densidade da Mama , Estudos Prospectivos , Detecção Precoce de Câncer/métodos , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE: To evaluate the feasibility and safety of percutaneous image-guided cryoablation of abdominal wall endometriosis (AWE). MATERIALS AND METHODS: A retrospective review of percutaneous cryoablation (CT or MR) of AWE was performed from January 2018 to December 2020. Eighteen patients were identified from an internal percutaneous ablation database. Technical success, complications, and outcomes were analyzed according to standard nomenclature. RESULTS: Patients comprised 18 females (mean age 36.9 years) who underwent 18 cryoablation procedures to treat 23 AWE deposits. Three of the 18 cases were performed under MR guidance, while the remaining 15 employed CT guidance. Technical success was achieved in all 18 cases (100%). Fifteen of 18 patients (83%) had biopsy proven AWE deposits prior to treatment. Hydrodisplacement was used to displace adjacent bowel, bladder, or neurovascular structures in 13/18 cases (72%). The mean number of probes used per case was 3. Sixteen of 23 (70%) of AWE deposits had imaging follow-up (median 85 days). Of the 16 lesions with imaging follow-up, 15 (94%) demonstrated no residual enhancement or T1 hyperintensity at the treatment site and 1 lesion (6%) demonstrated residual/progressive disease. At clinical follow-up, 13 of 14 (93%) patients reported improvement in AWE-related symptoms. Eleven patients had clinically documented pain scores before and after ablation and all demonstrated substantial symptomatic improvement. No society of interventional radiology (SIR) major complications were observed. CONCLUSIONS: Percutaneous cryoablation of AWE is feasible with a favorable safety profile. Further longitudinal studies are needed to document durable response over time.
Assuntos
Parede Abdominal , Ablação por Cateter , Criocirurgia , Endometriose , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/cirurgia , Adulto , Criocirurgia/métodos , Endometriose/diagnóstico por imagem , Endometriose/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
STUDY OBJECTIVE: To compare the rate of postoperative urinary retention (POUR) after total laparoscopic hysterectomy (TLH) using the autofill vs the backfill void trial. Secondary objectives were to compare the time to discharge from the recovery room, rate of postoperative urinary tract infection (UTI), perceived bladder condition, the effect of bladder function on life, and patient satisfaction. DESIGN: Randomized controlled trial. SETTING: Single academic medical center. PATIENTS: Women who underwent TLH by conventional laparoscopy or robotic-assisted laparoscopy for benign non-urogynecologic indications. INTERVENTIONS: After TLH, participants were randomized to have an autofill void trial (group A) or a backfill void trial once they were able to ambulate (group B). Failure rate, time to discharge, and UTI rate were assessed. Participants completed the patient perception of bladder condition and the incontinence impact questionnaire-short form questionnaires. Patient satisfaction was assessed. Multiple regression analysis was performed to determine the predictors of POUR. MEASUREMENTS AND MAIN RESULTS: Eighty-two participants completed the study after randomization, 42 in group A and 40 in group B. There were no statistically significant differences in demographic or perioperative outcomes. Seven participants had POUR in group A (16.7%) and 11 in group B (27.5%) (pâ¯=â¯.36), respectively. The median time to discharge was 176 minutes for group A (160.5, 255.5) and 218 minutes for group B (180, 265) (pâ¯=â¯.01), respectively. There were no statistically significant differences in rate of postoperative UTI (pâ¯>.99), patient perception of bladder condition scores (pâ¯=â¯.24), incontinence impact questionnaire-short form scores (pâ¯=â¯.23), and patient satisfaction scores (pâ¯=â¯.26). A stepwise logistic regression analysis did not demonstrate any predictors of POUR. CONCLUSION: Backfill void trial once the participant was able to ambulate was not superior to the autofill void trial with respect to the rate of POUR. The autofill void trial resulted in faster same-day discharge.
Assuntos
Laparoscopia , Retenção Urinária , Feminino , Humanos , Histerectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Retenção Urinária/etiologia , MicçãoRESUMO
Alveolar macrophages (AMs) and epithelial cells (ECs) are the lone resident lung cells positioned to respond to pathogens at early stages of infection. Extracellular vesicles (EVs) are important vectors of paracrine signaling implicated in a range of (patho)physiologic contexts. Here we demonstrate that AMs, but not ECs, constitutively secrete paracrine activity localized to EVs which inhibits influenza infection of ECs in vitro and in vivo. AMs exposed to cigarette smoke extract lost the inhibitory activity of their secreted EVs. Influenza strains varied in their susceptibility to inhibition by AM-EVs. Only those exhibiting early endosomal escape and high pH of fusion were inhibited via a reduction in endosomal pH. By contrast, strains exhibiting later endosomal escape and lower fusion pH proved resistant to inhibition. These results extend our understanding of how resident AMs participate in host defense and have broader implications in the defense and treatment of pathogens internalized within endosomes.
Assuntos
Endossomos , Vesículas Extracelulares/imunologia , Vírus da Influenza A/imunologia , Macrófagos Alveolares/imunologia , Comunicação Parácrina/imunologia , Internalização do Vírus , Células A549 , Animais , Cães , Endossomos/imunologia , Endossomos/patologia , Endossomos/virologia , Células HEK293 , Humanos , Macrófagos Alveolares/patologia , Células Madin Darby de Rim Canino , Camundongos , Ratos , Ratos Wistar , Células THP-1RESUMO
Nitrate (NO3 ¯ ) is an effective non-protein nitrogen source for gut microbes and reduces enteric methane (CH4 ) production in ruminants. Nitrate is reduced to ammonia by rumen bacteria with nitrite (NO2 ¯ ) produced as an intermediate. The absorption of NO2 ¯ can cause methaemoglobinaemia in ruminants. Metabolism of NO3 ¯ and NO2 ¯ in blood and animal tissues forms nitric oxide (NO) which has profound physiological effects in ruminants and has been shown to increase glucose uptake and insulin secretion in rodents and humans. We hypothesized that absorption of small quantities of NO2 ¯ resulting from a low-risk dose of dietary NO3 ¯ will increase insulin sensitivity (SI ) and glucose uptake in sheep. We evaluated the effect of feeding sheep with a diet supplemented with 18 g NO3 ¯ /kg DM or urea (Ur) isonitrogenously to NO3 ¯ , on insulin and glucose dynamics. A glucose tolerance test using an intravenous bolus of 1 ml/kg LW of 24% (w/v) glucose was conducted in twenty sheep, with 10 sheep receiving 1.8% supplementary NO3 ¯ and 10 receiving supplementary urea isonitrogenously to NO3 ¯ . The MINMOD model used plasma glucose and insulin concentrations to estimate basal plasma insulin (Ib ) and basal glucose concentration (Gb ), insulin sensitivity (SI ), glucose effectiveness (SG ), acute insulin response (AIRg) and disposition index (DI). Nitrate supplementation had no effect on Ib (p > .05). The decrease in blood glucose occurred at the same rate in both dietary treatments (SG ; p = .60), and there was no effect of NO3 ¯ on either Gb , SI , AIRg or DI. This experiment found that the insulin dynamics assessed using the MINMOD model were not affected by NO3 ¯ administered to fasted sheep at a low dose of 1.8% NO3 ¯ in the diet.
Assuntos
Ração Animal/análise , Glicemia/efeitos dos fármacos , Dieta/veterinária , Resistência à Insulina/fisiologia , Nitratos/farmacologia , Ovinos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Suplementos Nutricionais , Metemoglobinemia/veterinária , Nitratos/administração & dosagem , Nitritos/sangue , Ovinos/sangue , Ureia/administração & dosagem , Ureia/farmacologiaRESUMO
STUDY QUESTION: Is there perfusion to the fallopian tubes in ex-vivo and in-vivo uteri at the time of total laparoscopic hysterectomy (TLH), as observed using laser angiography with indocyanine green (ICG)? SUMMARY ANSWER: The fallopian tubes may have perfusion from the utero-ovarian vasculature alone. WHAT IS KNOWN ALREADY: The fallopian tubes are perfused by the uterine and utero-ovarian vessels. Perfusion can be measured using laser angiography with ICG. STUDY DESIGN, SIZE, DURATION: This prospective pilot cohort study included 15 women, ages 32-59 years old, who underwent TLH with bilateral salpingectomy for benign indications. PARTICIPANTS/MATERIALS, SETTING, METHODS: In five participants, TLH was performed and the utero-ovarian artery was cannulated ex vivo and injected with ICG. The other 10 participants underwent the in-vivo protocol. The mesosalpinx and uterine vessels were transected in the partial protocol. Colpotomy was also performed in the complete protocol. All fallopian tubes were imaged using laser angiography with ICG. The relative fluorescence and the fluorescence intensity ratio (length of fluorescent fallopian tube/total length of fallopian tube) of the fallopian tubes were measured in the ex-vivo and in-vivo protocols, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Ex vivo, the fimbria of the ipsilateral fallopian tube had 47% median relative fluorescence as compared to the contralateral fallopian tube, which had 2.4% median relative fluorescence. In vivo, the post-ICG fluorescence intensity ratios were 0.61 ± 0.40 for the partial protocol, and 0.78 ± 0.30 for the complete protocol, with mean differences of 0.37 (95% CI: 0.23-0.50, P < .0001) and 0.22 (95% CI: 0.12-0.31, P < 0.0001), respectively, between the pre-procedure and the post-ICG fluorescence intensity ratios. Greater than 0.75 fluorescence intensity ratios (i.e. >75% tubal length fluorescence) was seen in 60% of fallopian tubes. LIMITATIONS, REASONS FOR CAUTION: This is a pilot study with a small sample size and pathologic uteri, which would not be appropriate for uterine transplantation. No conclusions can be made regarding the functionality of the fallopian tubes. WIDER IMPLICATIONS OF THE FINDINGS: The fallopian tubes may have perfusion with the utero-ovarian vasculature alone, potentially allowing for future animal studies regarding tubal viability in recipients of uterine-tubal transplants. If successful, human uterine-tubal transplantation may allow for spontaneous conception rather than IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. S.F., P.F.P., K.A.S. and R.F. have no conflicts of interest to report. M.L.S. is an educational consultant for Medtronic (Dublin, Republic of Ireland) and Applied Medical (Rancho Santa Margarita, CA, USA), as well as a stockholder for SynDaver Labs (Tampa, FL, USA). S.E.Z. is an educational consultant for Applied Medical (Rancho Santa Margarita, CA, USA) and is on the advisory board for AbbVie Inc. (Chicago, IL, USA). TRIAL REGISTRATION NUMBER: Not applicable.
Assuntos
Tubas Uterinas/diagnóstico por imagem , Útero/cirurgia , Adulto , Angiografia , Feminino , Humanos , Histerectomia , Laparoscopia , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Útero/diagnóstico por imagemRESUMO
OBJECTIVE: To develop a realistic simulation model for performance of laparoscopic colpotomy and evaluate its construct and face validity. METHODS: A simulation model was developed and constructed using polyvinyl chloride piping, a uterine manipulator, and synthetic vaginal tissue paired with a commercially available laparoscopic trainer. An observational study was conducted to validate the simulation model for use as a teaching tool. Construct validity was measured through performance evaluation of novice and expert surgeons using a standard and modified Global Operative Assessment of Laparoscopic Skills scale with possible score ranges of 5-25 and 5-40, respectively. Expert surgeons included attending surgeons across various gynecologic subspecialties who teach total laparoscopic hysterectomy to trainees and perform more than 50 total laparoscopic hysterectomies annually. Novice surgeons included residents who perform total laparoscopic hysterectomy as part of their training. Standards were set using a modified contrasting groups approach. Interrater reliability was calculated using Kendall's τ correlation coefficient. Participants were surveyed regarding the realism of the model and its utility as a teaching tool to assess face validity. RESULTS: Five expert and 15 novice surgeons volunteered to participate. Expert surgeons scored higher than novice surgeons on the Global Operative Assessment of Laparoscopic Skills scale (22.8±1.52 vs 13.53±2.69, respectively) with a mean difference of 9.27 (95% CI 7.12-11.4, P<.01) and on a modified Global Operative Assessment of Laparoscopic Skills scale (36.9±2.19 vs 22.6±3.95, respectively) with a mean difference of 14.30 (95% CI 11.2-17.4, P<.01). Suggested passing range was set at 30.5-32.5 out of 40 total points. Kendall's τ interrater reliability was 0.86 (95% CI 0.798-0.923) and 0.87 (95% CI 0.818-0.922), respectively. All participants agreed that the training model was useful for teaching and learning laparoscopic colpotomy and for assessing the learner's ability to perform colpotomy before live surgery. CONCLUSION: This validated simulation system offers novice surgeons an opportunity to practice the skill set necessary to perform laparoscopic colpotomy efficiently and may be used as an educational tool.
Assuntos
Colpotomia/educação , Ginecologia/educação , Laparoscopia/educação , Treinamento por Simulação/métodos , Cirurgiões/educação , Adulto , Competência Clínica , Avaliação Educacional , Feminino , Humanos , Histerectomia/educação , Internato e Residência/métodos , Masculino , Reprodutibilidade dos TestesRESUMO
Surgical adhesions can lead to significant consequences including abdominopelvic pain, bowel obstruction, subfertility, and subsequent surgery. Although laparoscopic surgery is associated with a decreased risk of adhesion formation, methods to further decrease adhesions are warranted. We systematically reviewed literature addressing the management, prevention, and sequelae of adhesions in women undergoing laparoscopic gynecologic surgery. We searched PubMed, EMBASE, EBSCOhost, and Cochrane Central Register of Controlled Trials and found 6566 records. The primary outcome was adhesion formation. The secondary outcomes were abdominopelvic pain, quality of life, subfertility, pregnancy, bowel obstruction, urinary symptoms, and subsequent surgery. After applying inclusion and exclusion criteria, 52 studies remained for qualitative synthesis. Risk of bias assessments were applied independently by 2 authors. There was evidence that Hyalobarrier Gel (Anika Therapeutics, Bedford, MA), HyaRegen NCH Gel (Bilar Medikal, Istanbul, Turkey), Oxiplex/AP Gel (Fziomed, Inc., San Luis Obispo, CA), SprayGel (Confluent Surgical Inc., Waltham, MA), and Beriplast (CSL Behring, LLCm King of Prussia, PA) all decrease the incidence of adhesions. Adept (Baxter, Deerfield, IL) significantly decreased de novo adhesion scores of the posterior uterus. Using an integrated treatment approach to pelvic pain significantly improved pain and quality of life compared with standard laparoscopic treatment. Lastly, Hyalobarrier Gel Endo (Anika Therapeutics, Bedford, MA) placement led to a higher pregnancy rate than no barrier usage. Our findings underscore the need for high-quality trials to evaluate the efficacy of surgical techniques, adhesion barriers, and other treatment modalities on the management and prevention of adhesions and their clinical sequelae. This review was registered on PROSPERO (ID = CRD42017068053).
Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Laparoscopia/efeitos adversos , Aderências Teciduais/prevenção & controle , Dor Abdominal/etiologia , Dor Abdominal/prevenção & controle , Ensaios Clínicos como Assunto , Endometriose/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Infertilidade Feminina/cirurgia , Obstrução Intestinal/cirurgia , Laparoscopia/métodos , Dor Pélvica/etiologia , Dor Pélvica/prevenção & controle , Qualidade de Vida , Reoperação/estatística & dados numéricos , Aderências Teciduais/cirurgiaRESUMO
STUDY OBJECTIVE: To reduce operative costs involved in the purchase, packing, and transport of unnecessary supplies by improving the accuracy of surgeon preference cards. STUDY DESIGN: Quality improvement study (Canadian Task Force classification II-3). SETTING: Gynecologic surgery suite of an academic medical center. PARTICIPANTS: Twenty-one specialized and generalist gynecologic surgeons. INTERVENTIONS: The preference cards of up to the 5 most frequently performed procedures per surgeon were selected. A total of 81 cards were distributed to 21 surgeons for review. Changes to the cards were communicated to the operating room charge nurse and finalized. MEASUREMENTS AND MAIN RESULTS: Fourteen surgeons returned a total of 48 reviewed cards, 39 of which had changes. A total of 109 disposable supplies were removed from these cards, at a total cost savings of $767.67. The cost per card was reduced by $16 on average for disposables alone. Three reusable instrument trays were also eliminated from the cards, resulting in savings of approximately $925 in processing costs over a 3-month period. Twenty-two items were requested by surgeons to be available on request but were not routinely placed in the room at the start of each case, at a total cost of $6,293.54. The rate of return of unused instruments to storage decreased after our intervention, from 10.1 to 9.6 instruments per case. CONCLUSIONS: Surgeon preference cards serve as the basis for economic decision making regarding the purchase, storing, packing, and transport of operative instruments and supplies. A one-time surgeon review of cards resulted in a decrease in the number of disposable and reusable instruments that must be stocked, transported, counted in the operating room, or returned, potentially translating into cost savings. Surgeon involvement in preference card management may reduce waste and provide ongoing cost savings.
Assuntos
Comportamento do Consumidor , Equipamentos Descartáveis/economia , Papel do Médico , Melhoria de Qualidade , Cirurgiões , Instrumentos Cirúrgicos/economia , Adulto , Comportamento do Consumidor/economia , Comportamento do Consumidor/estatística & dados numéricos , Redução de Custos , Equipamentos Descartáveis/estatística & dados numéricos , Equipamentos Descartáveis/provisão & distribuição , Feminino , Humanos , Masculino , Sistemas de Registro de Ordens Médicas/economia , Sistemas de Registro de Ordens Médicas/estatística & dados numéricos , Pessoa de Meia-Idade , Salas Cirúrgicas/economia , Melhoria de Qualidade/economia , Alocação de Recursos/economia , Alocação de Recursos/estatística & dados numéricos , Estudos Retrospectivos , Cirurgiões/economia , Cirurgiões/normas , Cirurgiões/estatística & dados numéricos , Instrumentos Cirúrgicos/estatística & dados numéricos , Instrumentos Cirúrgicos/provisão & distribuição , Recursos HumanosRESUMO
Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+) cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-ß adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/-) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1(-/-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice.
Assuntos
Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Nematospiroides dubius/imunologia , Infecções por Strongylida/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Linfócitos T CD4-Positivos/imunologia , Granuloma/genética , Granuloma/imunologia , Interleucina-17/biossíntese , Interleucina-4/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Receptores Tipo I de Interleucina-1/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Infecções por Strongylida/parasitologia , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor 5 Toll-Like/genética , Receptor Toll-Like 9/genéticaRESUMO
The nematode Heligmosomoides polygyrus is an excellent model for intestinal helminth parasitism. Infection in mice persists for varying lengths of time in different inbred strains, with CBA and C57BL/6 mice being fully susceptible, BALB/c partially so and SJL able to expel worms within 2-3 weeks of infection. We find that resistance correlates not only with the adaptive Th2 response, including IL-10 but with activation of innate lymphoid cell and macrophage populations. In addition, the titer and specificity range of the serum antibody response is maximal in resistant mice. In susceptible strains, Th2 responses were found to be counterbalanced by IFN-γ-producing CD4(+) and CD8(+) cells, but these are not solely responsible for susceptibility as mice deficient in either CD8(+) T cells or IFN-γ remain unable to expel the parasites. Foxp3(+) Treg numbers were comparable in all strains, but in the most resistant SJL strain, this population does not upregulate CD103 in infection, and in the lamina propria the frequency of Foxp3(+)CD103(+) T cells is significantly lower than in susceptible mice. The more resistant SJL and BALB/c mice develop macrophage-rich IL-4Rα-dependent Type 2 granulomas around intestinal sites of larval invasion, and expression of alternative activation markers Arginase-1, Ch3L3 (Ym1) and RELM-α within the intestine and the peritoneal lavage was also strongly correlated with helminth elimination in these strains. Clodronate depletion of phagocytic cells compromises resistance of BALB/c mice and slows expulsion in the SJL strain. Thus, Type 2 immunity involves IL-4Rα-dependent innate cells including but not limited to a phagocyte population, the latter likely involving the action of specific antibodies.
Assuntos
Imunidade Adaptativa , Resistência à Doença/genética , Resistência à Doença/imunologia , Helmintíase/genética , Helmintíase/imunologia , Helmintos/imunologia , Imunidade Inata , Enteropatias/genética , Enteropatias/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos Anti-Helmínticos/imunologia , Ácido Clodrônico/farmacologia , Feminino , Granuloma , Helmintíase/tratamento farmacológico , Helmintíase/metabolismo , Helmintíase/patologia , Helmintíase Animal , Imunidade Celular , Imunidade Inata/efeitos dos fármacos , Interferon gama/metabolismo , Enteropatias/tratamento farmacológico , Enteropatias/metabolismo , Enteropatias/patologia , Enteropatias Parasitárias , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Camundongos , Receptores de Interleucina-4/metabolismo , Transdução de SinaisRESUMO
IL-6 plays a pivotal role in favoring T-cell commitment toward a Th17 cell rather than Treg-cell phenotype, as established through in vitro model systems. We predicted that in the absence of IL-6, mice infected with the gastrointestinal helminth Heligmosomoides polygyrus would show reduced Th17-cell responses, but also enhanced Treg-cell activity and consequently greater susceptibility. Surprisingly, worm expulsion was markedly potentiated in IL-6-deficient mice, with significantly stronger adaptive Th2 responses in both IL-6(-/-) mice and BALB/c recipients of neutralizing anti-IL-6 monoclonal Ab. Although IL-6-deficient mice showed lower steady-state Th17-cell levels, IL-6-independent Th17-cell responses occurred during in vivo infection. We excluded the Th17 response as a factor in protection, as Ab neutralization did not modify immunity to H. polygyrus infection in BALB/c mice. Resistance did correlate with significant changes to the associated Treg-cell phenotype however, as IL-6-deficient mice displayed reduced expression of Foxp3, Helios, and GATA-3, and enhanced production of cytokines within the Treg-cell population. Administration of an anti-IL-2:IL-2 complex boosted Treg-cell proportions in vivo, reduced adaptive Th2 responses to WT levels, and fully restored susceptibility to H. polygyrus in IL-6-deficient mice. Thus, in vivo, IL-6 limits the Th2 response, modifies the Treg-cell phenotype, and promotes host susceptibility following helminth infection.
Assuntos
Interleucina-6/metabolismo , Nematospiroides dubius/imunologia , Infecções por Strongylida/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Células Th2/imunologia , Animais , Anticorpos Bloqueadores/administração & dosagem , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Suscetibilidade a Doenças , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica/genética , Interleucina-6/genética , Interleucina-6/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Carga Parasitária , Fenótipo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
As part of an undergraduate microbiology course, a yellow-orange-pigmented, Gram-staining negative, rod-shaped, non-motile bacterial strain was isolated from a glass tank housing several red-spotted newts (Notophthalmus viridescens). The sequence of the 16S rRNA gene of this strain, designated KM(T), was 97.4-98.0â% similar to those of the type strains of Chryseobacterium luteum, C. shigense and C. vrystaatense, while the similarity levels for protein-coding genes were less than 94.7â% for rpoB, less than 92.1â% for groEL and less than 87.1â% for gyrB. These values are lower than for many other established distinct species. Polyphasic characterization and comparison to these relatives revealed that strain KM(T) was similar to other Chryseobacterium strains in that it contained MK-6 as its major respiratory quinone and phosphatidylethanolamine as the most abundant polar lipid, produced flexirubin-type pigments, oxidase and catalase and primarily contained the fatty acids iso-C15â:â0, iso-C17â:â1ω9c, iso-C17â:â0 3-OH and summed feature 3 (comprising C16â:â1ω6c and/or C16â:â1ω7c). Based on the results of this study, strain KM(T) represents a novel species, for which the name Chryseobacterium angstadtii sp. nov. is proposed. The type strain is KM(T) (â=âATCC BAA-2160(T)â=âNRRL B-59516(T)â=âKCTC 23297(T)).
Assuntos
Chryseobacterium/classificação , Filogenia , Salamandridae , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Chaperonina 60/genética , Chryseobacterium/genética , Chryseobacterium/isolamento & purificação , DNA Girase/genética , DNA Bacteriano/genética , Ácidos Graxos/química , Dados de Sequência Molecular , Fosfatidiletanolaminas/química , Polienos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Infection with gastrointestinal helminths generates a dominant type 2 response among both adaptive (Th2) and innate (macrophage, eosinophil, and innate lymphoid) immune cell types. Two additional innate cell types, CD11c(high) dendritic cells (DCs) and basophils, have been implicated in the genesis of type 2 immunity. Investigating the type 2 response to intestinal nematode parasites, including Heligmosomoides polygyrus and Nippostrongylus brasiliensis, we first confirmed the requirement for DCs in stimulating Th2 adaptive immunity against these helminths through depletion of CD11c(high) cells by administration of diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in mice depleted of basophils by antibody treatment. Th2 responses can be induced by adoptive transfer of DCs, but not basophils, exposed to soluble excretory-secretory products from these helminths. However, innate type 2 responses arose equally strongly in the presence or absence of CD11c(high) cells or basophils; thus, in CD11c.DOG mice, the alternative activation of macrophages, as measured by expression of arginase-1, RELM-α, and Ym-1 (Chi3L3) in the intestine following H. polygyrus infection or in the lung following N. brasiliensis infection, was unaltered by depletion of CD11c-expressing DCs and alveolar macrophages or by antibody-mediated basophil depletion. Similarly, goblet cell-associated RELM-ß in lung and intestinal tissues, lung eosinophilia, and expansion of innate lymphoid ("nuocyte") populations all proceeded irrespective of depletion of CD11c(high) cells or basophils. Thus, while CD11c(high) DCs initiate helminth-specific adaptive immunity, innate type 2 cells are able to mount an autonomous response to the challenge of parasite infection.
Assuntos
Antígeno CD11c/metabolismo , Células Dendríticas/imunologia , Imunidade Inata/fisiologia , Nematospiroides dubius/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Animais , Basófilos/imunologia , Antígeno CD11c/genética , Citocinas/genética , Citocinas/metabolismo , Citometria de Fluxo , Macrófagos/metabolismo , Macrófagos Alveolares/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Proteínas de Helminto/farmacologia , Fator 88 de Diferenciação Mieloide/metabolismo , Fagossomos/efeitos dos fármacos , Choque Séptico/prevenção & controle , Receptor 4 Toll-Like/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/imunologia , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Imunológicos , Fator 88 de Diferenciação Mieloide/imunologia , Fagossomos/imunologia , Fagossomos/metabolismo , Choque Séptico/genética , Choque Séptico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologiaRESUMO
Recent research in line with the "hygiene hypothesis" has implicated virus infection in the delay or prevention of autoimmunity in murine models of type 1 diabetes such as the NOD mouse. We found that intraperitoneal or intranasal infection of NOD mice with the murine gammaherpesvirus-68 (MHV-68) significantly delayed diabetes onset in an age-dependent manner. The acute phase following intraperitoneal infection was associated with significantly reduced trafficking of autoreactive BDC2.5NOD CD4(+) T cells to the pancreas but not the pancreatic lymph node (PLN); this was not as a result of MHV-68 M3 pan-chemokine binding protein expression. Autoreactive BDC2.5NOD CD4(+) T cells within the PLN of MHV-68 infected mice were significantly more naive and proliferated to a lesser extent than those cells within the PLN of uninfected mice. These changes in autoreactive CD4(+) T cell activation were associated with reduced dendritic cell endocytosis and soluble Ag presentation but were not as a result of virally induced IL-10 or changes in Ag-specific regulatory T cell populations.