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1.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526521

RESUMO

Vertebral osteomyelitis is an infection of the vertebrae that can lead to spinal degeneration, most commonly caused by Staphylococcus aureus Here, we report an unusual case of pyogenic osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a 61-year-old postmenopausal woman. The patient presented with a 2-week history of worsening lower back pain and fever and a recent episode of cystitis following re-engagement of sexual activity. Imaging revealed a deterioration of vertebrae discs and spinal canal stenosis at the L3-L4 levels with a formation of abscess in the right psoas muscle. Needle aspiration of the abscess identified G. vaginalis and S. parasanguinis and the patient was successfully treated with a 6-week course of ceftriaxone and metronidazole. This case describes an unusual coinfection of two pathogens that normally reside in the urogenital tract and oral cavity, respectively, and highlights the risk posed when these organisms breach the body's normal barriers.


Assuntos
Discite/microbiologia , Gardnerella vaginalis/isolamento & purificação , Vértebras Lombares , Osteomielite/microbiologia , Abscesso do Psoas/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus/isolamento & purificação , Antibacterianos/uso terapêutico , Técnicas de Cultura , Discite/diagnóstico por imagem , Discite/tratamento farmacológico , Discite/fisiopatologia , Feminino , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Osteomielite/fisiopatologia , Pós-Menopausa , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/tratamento farmacológico , Estenose Espinal/fisiopatologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico
2.
Cureus ; 12(9): e10646, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33133816

RESUMO

Brainstem infarction typically presents with vague symptoms, including headache, nausea, vomiting, and vertigo. Rarely do patients present with complete unilateral facial paralysis, mimicking Bell's palsy. Here we report the case of a 40-year-old woman who presented to the emergency department with intractable nausea, vomiting, and vertigo upon waking along with left-sided upper and lower extremity numbness and right-sided facial paralysis. Her atypical presentation of unilateral facial nerve paralysis in the context of nausea, vomiting, and vertigo prompted neurological studies, which were significant for a small punctate infarct in the pons involving the right facial colliculus. ​History, physical examination, and clinical suspicion are important to prevent anchoring bias. Physicians rely on history and physical examination to help distinguish true Bell's palsy from other causes of facial nerve paralysis. Stroke and other clinically emergent etiologies should be considered high on the differential diagnosis when patients have neurological signs and symptoms in addition to facial nerve palsy.

3.
Cureus ; 12(8): e9800, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32953312

RESUMO

Acute changes in electrolyte levels can result in severe physiologic complications. Rapid treatment of abnormally elevated potassium levels is essential due to the increased risk of potentially fatal cardiac arrhythmias. However, there are a number of circumstances that can lead to falsely elevated serum potassium levels, including fist clenching during phlebotomy and hemolysis of hematocytes during laboratory processing. Here we present a case of an elderly woman with chronic lymphocytic leukemia who presented with lower left quadrant pain and hematochezia. Laboratory tests revealed an elevated serum potassium level (7.5 mmol/L) on initial testing, in the absence of hyperkalemia symptoms, EKG changes, and hemolysis of the blood specimen. Abdominal CT revealed inflammatory changes consistent with diverticulitis. She was treated with intravenous calcium, insulin, glucose, and bicarbonate for her hyperkalemia and admitted for treatment for diverticulitis. A subsequent serum potassium level (3.9 mmol/L) and discussion with the hospitalist suggested a diagnosis of leukolysis-induced pseudohyperkalemia, and further treatment of hyperkalemia was halted. This case serves to remind current and future physicians about the importance of maintaining clinical suspicion and clarifying unexpected laboratory readings when the clinical picture and results do not completely align.

4.
JBJS Case Connect ; 10(3): e1900643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32910597

RESUMO

CASE: Infantile Blount disease results from deceleration of growth by the proximal posteromedial tibial physis causing tibia vara. In advanced disease stages, surgical treatment is indicated. Owing to the young age and advanced Langenskiöld stage in this patient, a novel technique was performed combining lateral proximal physeal tethering with medial hemiplateau elevation osteotomy to correct the articular surface and unload the medial proximal tibial physis. CONCLUSION: Together, these procedures allow for correction of alignment while preserving growth potential. This technique was successful in correcting tibia vara due to infantile Blount disease while allowing continued growth in a 5-year-old patient.

5.
Am J Forensic Med Pathol ; 41(4): 315-320, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32804687

RESUMO

Crossbow fatalities are a rare occurrence, but crossbow use is on the rise. The manner of death in crossbow fatalities is overwhelmingly opined accident or suicide, not homicide. Despite their increasing use and reports of at least 14 crossbow-related homicides in the media for the last 5 years, crossbow homicides are rarely reported in the medical literature; only 10 articles that discussed 20 crossbow homicides were identified in the PubMed database. Here, we describe a case of a 20-year-old man who was found dead in his driveway after being shot in the abdomen with a crossbow by another person. The crossbow bolt had a mechanical 2-blade broadhead that transected the descending aorta and lodged in his vertebra. When completing a medicolegal death investigation and postmortem examination on suspected crossbow-related deaths, knowledge of crossbow components, its utility as a weapon, wound patterns, and how it can cause death are important. This case serves to build on the limited medical literature of crossbow homicides, educate forensic pathologists about the features of crossbow deaths, and highlight manner of death considerations.

6.
Am J Forensic Med Pathol ; 41(3): 220-222, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32568885

RESUMO

The majority of hanging deaths are relatively straightforward when opining the manner of death, typically determined to be suicide. However, there are rare hanging deaths that require the forensic pathologist to seek additional information. Forensic pathologists commonly consider an accidental manner of death when the hanging death scene includes evidence of solitary sexual activity consistent with autoerotic asphyxia. Here, the authors present a case of an initially apparent suicidal hanging where important death scene details photographed by the medical examiner investigator and history provided by family members during subsequent conversations ultimately helped the forensic pathologist conclude an opinion that the hanging was accidental, likely due to autoerotic activity. The decedent, who hanged himself in the closet of his bedroom, was wearing shorts that were initially believed to be inadvertently torn; however, further investigation revealed his shorts were intentionally modified to expose his genitalia. Additional evidence documented from the death scene photographs and conversations with his mother revealed items and activities consistent with autoerotic behavior. Before opining a manner of death in hanging deaths, forensic pathologists are encouraged to consider details beyond that obtained from the initial death scene investigation and postmortem examination. A thorough medicolegal death investigation should not be viewed as introducing cognitive bias, but rather as necessary information needed to determine the most accurate cause and manner of death.

7.
Adv Physiol Educ ; 44(2): 239-246, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412383

RESUMO

Few discussions regarding instructional methods incite as much passion as the debate over dissection versus prosection. Despite numerous analyses, few studies have isolated the impact of dissection versus prosection from the numerous variables that are involved in anatomy education. This study used a retrospective design to assess the effect of peer teaching with dissection or prosection on anatomical knowledge retention of the peer teachers. Exam scores were analyzed from three cohorts of students (N = 184) who were enrolled in a Musculoskeletal System course in an allopathic medical school between academic years 2014-2017. Students in the first 2 yr learned anatomy of an assigned region through traditional dissection, whereas students in the third year learned anatomy of the same regions on prosected specimens. The effect of these instructional methods on anatomical knowledge retention was measured by student performance on a teaching-readiness quiz, written exam, and practical examination. One advantage of this study is the stability of variables between cohorts. Student groups peer taught the same objectives; course sequencing and content remained consistent between years; students spent the same amount of time learning their material, regardless of learning modality (dissection or prosection); and students were tested in the same manner. Comparisons of student performance data suggest that anatomy knowledge was equivalent, regardless of the instructional method (dissection or prosected cadavers) but is strongly associated with prior anatomy experience. Findings from this study support previous studies that conclude that there are no disparities in the effectiveness of learning anatomy via dissection or prosection.

8.
Cureus ; 12(1): e6800, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32140358

RESUMO

Medical laboratory tests are becoming more reliable with increased specificity and sensitivity, leading to their use as definitive diagnostic tests for many medical conditions. Enzyme-linked immunosorbent assay (ELISA) tests are convenient, sensitive, and standardly used for rapid detection and quantification of antigens or patient antibodies against specific antigens. However, based upon the specificity and sensitivity of an ELISA test, the results may not be definitive for a specific disease but merely suggestive, due to potential cross-reactivity of antigens and antibodies. Here, we present a case of a 15-year-old male who presented with fever, nausea, and right upper quadrant pain. Computed tomography scan showed an 18-cm liver mass with cystic features. Biopsy results confirmed a diagnosis of undifferentiated embryonal sarcoma of the liver; however, the clinical picture was complicated by positive ELISA results for Echinococcus, Entamoeba histolytica, and histoplasmosis. Due to the absence of travel and positive ELISA result for three different infectious agents, we hypothesize that tumor molecular mimicry might have led to false-positive ELISA results in the absence of infection in this case, demonstrating a limitation of ELISA serology. Critical appraisal of all possible evidence to ensure alignment when assigning the final diagnosis is essential for optimal patient outcomes.

9.
BMJ Case Rep ; 13(2)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32102891

RESUMO

A Morel-Lavallée lesion (MLL) is a rare injury caused by blunt force trauma causing separation of subcutaneous tissue from the deep fascia. It is frequently seen in orthopaedic cases involving fractures of the hip or pelvis but is rare in the lower leg. The rarity of this condition often leads to misdiagnosis. A 66-year-old man presented to the emergency department after a 300-pound safe sheered across his left anterolateral leg causing skin avulsion, tenderness, swelling, ecchymosis, and erythema. The patient was treated for suspected cellulitis with oral antibiotics, but the lesion evolved into a necrotic eschar necessitating surgical intervention. In hindsight, MLL is a more appropriate diagnosis based on injury mechanism, disease progression and intraoperative findings. A history of shearing trauma with diffuse ecchymosis and erythema should prompt consideration of MLL. Due to rampant misdiagnosis, this case aims to increase awareness, as early diagnosis of MLL will improve patient outcomes.


Assuntos
Desenluvamentos Cutâneos/classificação , Desenluvamentos Cutâneos/diagnóstico , Erros de Diagnóstico , Traumatismos da Perna/classificação , Traumatismos da Perna/diagnóstico , Tela Subcutânea/patologia , Idoso , Equimose/complicações , Edema/complicações , Eritema/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Necrose , Ultrassonografia Doppler , Raios X
10.
J Forensic Sci ; 65(3): 1009-1011, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31895974

RESUMO

The majority of opioid-related deaths are accidental. However, the number of opioid-related suicidal deaths is likely under recognized. Presented here is a case of suicide by heroin overdose. The manner of death would have likely been deemed accidental if not for critical information shared by the decedent's family during follow-up telephone interviews between the forensic pathologist and the decedent's family, which included text messages that were sent by the decedent just before his death that were not known at the time of the initial medicolegal death scene investigation. This case highlights that when a forensic pathologist establishes an engaged relationship with the decedent's family, the information elucidated can prove to be invaluable in reaching an informed opinion about the manner of death. For overdose cases, identifying an accurate manner of death allows the design of public health efforts that adequately address the health risks in the community. For aid in the determination of the manner of death for overdose cases, we propose a five-step checklist that may assist forensic pathologists and medicolegal death investigators when approaching similar cases.

11.
J Vasc Surg ; 71(4): 1276-1285, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31519512

RESUMO

OBJECTIVE: To evaluate the safety and effectiveness of infrainguinal artery revascularization via atherectomy supplemented with other endovascular techniques in an office endovascular center (OEC) setting. METHODS: A retrospective study was conducted examining 352 lower extremity atherectomy revascularization procedures between 2011 and 2016 at an OEC by five board-certified vascular surgeons. Patients received laser atherectomy or orbital atherectomy followed by angioplasty or angioplasty and stent placement as needed. Reintervention was indicated based on evidence of clinical symptoms and imaging studies. Demographics, vessel-specific data, treatment information, and outcome of procedures were recorded. Data analysis was carried out using Kaplan-Meier survival curves. RESULTS: Lower extremity atherectomy was carried out in 282 patients in 352 limbs with average age of 69 ± 11 years. Technical success of <30% residual stenosis by angiogram was achieved in 571/594 vessels treated. Within 30 days of procedure, 23/352 limbs required major amputation resulting from pre-existing disease, ranging from 3 Rutherford class 4, 17 Rutherford class 5, to 3 Rutherford class 6 limbs. No 30-day mortality was noted. The primary patency of the 571 treated vessels at 12 months was 90%, and 84% at 29 months. The patency of treated vessels that reached >50% stenosis on follow-up and required reintervention (51/571 vessels) or did not require reintervention (79/571) was 72% and 87% at 23 months' follow-up, respectively, with no difference in risk of occlusion identified (P = .181). There was a significantly increased risk of occlusion for vessels treated with laser atherectomy as compared with orbital atherectomy (odds ratio, 2.552; 95% confidence interval, 1.375-4.735; P = .003). No significant difference in risk of occlusion was found between treatment with atherectomy and angioplasty (466/571 vessels) compared with atherectomy, angioplasty, and stenting (102/571) with secondary patency of 90% and 85% at 6 months' follow-up, respectively. There was no difference in patency between claudicants and patients with critical limb ischemia. CONCLUSIONS: Atherectomy in conjunction with angioplasty and/or stenting has satisfactory patency with minimal complications when the procedure is carried out in an OEC. Asymptomatic >50% restenosis of treated vessels does not warrant reintervention unless the patient presents with clinical symptoms. Various atherectomy devices may result in different outcomes.


Assuntos
Aterectomia/métodos , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Idoso , Amputação/estatística & dados numéricos , Angioplastia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Stents , Artérias da Tíbia , Grau de Desobstrução Vascular
12.
J Foot Ankle Surg ; 58(4): 814-820, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256901

RESUMO

Polydactyly of the foot occurs in 1.7 cases per 1000 live births, comprising 45% of congenital abnormalities of the foot. Most reported cases of polydactyly of the foot are postaxial, and 15% are preaxial; of those, tarsal type preaxial polydactyly (a true prehallux) occurs in only 3% of cases. Because of this rarity, there is minimal literature available to guide management or surgical reconstruction. Two newborns presented with similar tarsal type preaxial polydactylies in the context of multiple congenital anomalies at a single institution. Patient 1 presented at birth with an accessory digit arising medially from the right foot at the medial malleolus. Two weeks later, genetically unrelated, patient 2 presented at birth with an accessory digit arising medially from the right foot at the talus. Both patients underwent resection of the extra digit and reconstruction including transfer of the accessory anterior tibial tendon arising from the preaxial extra digit to the remaining first ray. Two years after surgery, both patients are walking well with preserved dorsiflexion strength. Given the rarity of true prehallux cases, reported surgical treatment and outcomes are lacking. This case demonstrates the management of 2 patients to better guide future patient care. Although nonsurgical treatment with shoewear modification is an option, surgical reconstruction facilitated wearing typical shoes while preserving ambulatory ability. Both patients in this series had an accessory anterior tibial tendon. Surgical transfer of the tendon prevented loss of dorsiflexion strength and foot drop postoperatively.


Assuntos
Hallux/anormalidades , Polidactilia/cirurgia , Feminino , Hallux/diagnóstico por imagem , Hallux/cirurgia , Humanos , Lactente , Masculino , Polidactilia/diagnóstico por imagem , Radiografia
13.
BMJ Case Rep ; 12(1)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30696647

RESUMO

A 21-year-old young man with no history of diabetes or thyroid disease presented to the emergency department with simultaneous thyroid storm and diabetic ketoacidosis. Notable findings on admission were a ventricular rate of 235 beats/min, tachypnoea, tremors, polydipsia and a lack of fever. Due to the unusual constellation of symptoms, diagnosis was only possible after initial laboratory results came back. While the lack of fever is unusual in thyroid storm, diabetic ketoacidosis has previously been reported to suppress fever, and this case supports the occurrence of this phenomenon. This case was highly unusual because the patient had not previously been diagnosed with either type 1 diabetes or Graves' disease.


Assuntos
Cetoacidose Diabética/complicações , Crise Tireóidea/complicações , Adulto , Antiarrítmicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antitireóideos/uso terapêutico , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Hidrocortisona/uso terapêutico , Insulina/uso terapêutico , Masculino , Metimazol , Propranolol/uso terapêutico , Propiltiouracila/uso terapêutico , Taquicardia/complicações , Taquicardia/tratamento farmacológico , Crise Tireóidea/diagnóstico , Crise Tireóidea/tratamento farmacológico , Adulto Jovem
14.
J Invest Surg ; 30(1): 47-55, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27463073

RESUMO

BACKGROUND: Liver transplantation is the second most common transplant procedure in the United States. A leading cause of post-transplantation organ dysfunction is I/R injury. During I/R injury, the serine/threonine kinase Akt is activated, stimulating downstream mediators to promote cellular survival. Due to the cellular effects of Akt, therapeutic manipulation of the Akt pathway can help reduce cellular damage during hepatic I/R that occurs during liver transplantation. OBJECTIVE: A full description of therapeutic options available that target Akt to reduce hepatic I/R injury has not been addressed within the literature. The purpose of this review is to illuminate advances in the manipulation of Akt that can be used to therapeutically target I/R injury in the liver. METHODS: An in depth literature review was performed using the Scopus and PubMed databases. A total of 75 published articles were utilized for this manuscript. Terminology searched includes a combination of "hepatic ischemia/reperfusion injury", "Akt/PKB", "preconditioning" and "postconditioning." RESULTS: Four principal methods that reduce I/R injury include hepatic pre- and postconditioning, pharmacological intervention and future miRNA/gene therapy. Discussed therapies used serum alanine aminotransferase levels, liver histology and phosphorylation of downstream mediators to confirm the Akt protective effect. CONCLUSION: The activation of Akt from the reviewed therapies has resulted in predictable reduction in hepatocyte damage using the previously mentioned measurements. In a clinical setting, these therapies could potentially be used in combination to achieve better outcomes in hepatic transplant patients. Evidence supporting reduced I/R injury through Akt activation warrants further studies in human clinical trials.


Assuntos
Transplante de Fígado/efeitos adversos , Fígado/metabolismo , Disfunção Primária do Enxerto/tratamento farmacológico , Disfunção Primária do Enxerto/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Alanina Transaminase/sangue , Animais , Apoptose , Citocinas/genética , Citocinas/uso terapêutico , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Fosforilação , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/fisiopatologia , Espécies Reativas de Oxigênio/toxicidade , Transdução de Sinais/efeitos dos fármacos
15.
J Bacteriol ; 198(8): 1347-55, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26883826

RESUMO

UNLABELLED: Chlamydia trachomatis is an obligate intracellular pathogen that is the etiological agent of a variety of human diseases, including blinding trachoma and sexually transmitted infections. Chlamydiae replicate within a membrane-bound compartment, termed an inclusion, which they extensively modify by the insertion of type III secreted proteins called Inc proteins. IncA is an inclusion membrane protein that encodes two coiled-coil domains that are homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) motifs. Recent biochemical evidence suggests that a functional core, composed of SNARE-like domain 1 (SLD-1) and part of SNARE-like domain 2 (SLD-2), is required for the characteristic homotypic fusion of C. trachomatis inclusions in multiply infected cells. To verify the importance of IncA in homotypic fusion in Chlamydia, we generated an incA::bla mutant. Insertional inactivation of incA resulted in the formation of nonfusogenic inclusions, a phenotype that was completely rescued by complementation with full-length IncA. Rescue of homotypic inclusion fusion was dependent on the presence of the functional core consisting of SLD-1 and part of SLD-2. Collectively, these results confirm in vitro membrane fusion assays identifying functional domains of IncA and expand the genetic tools available for identification of chlamydia with a method for complementation of site-specific mutants. IMPORTANCE: Chlamydia trachomatis replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusions are nonfusogenic with vesicles in the endocytic pathway but, in multiply infected cells, fuse with each other to form a single large inclusion. This homotypic fusion is dependent upon the presence of a chlamydial inclusion membrane-localized protein, IncA. Specificity of membrane fusion in eukaryotic cells is regulated by SNARE (soluble N-ethylmaleimide sensitive factor attachment receptor) proteins on the cytosolic face of vesicles and target membranes. IncA contains two SNARE-like domains. Newly developed genetic tools for the complementation of targeted mutants in C. trachomatis are used to confirm the minimal requirement of SNARE-like motifs necessary to promote the homotypic fusion of inclusions.


Assuntos
Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/metabolismo , Fusão de Membrana/fisiologia , Proteínas de Membrana/metabolismo , Proteínas de Bactérias/genética , Chlamydia trachomatis/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Células HeLa , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas SNARE/metabolismo
16.
Infect Immun ; 83(12): 4710-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26416906

RESUMO

Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a membrane-bound vacuole termed the inclusion. Early in the infection cycle, the pathogen extensively modifies the inclusion membrane through incorporation of numerous type III secreted effector proteins, called inclusion membrane proteins (Incs). These proteins are characterized by a bilobed hydrophobic domain of 40 amino acids. The presence of this domain has been used to predict up to 59 putative Incs for C. trachomatis; however, localization to the inclusion membrane with specific antibodies has been demonstrated for only about half of them. Here, we employed recently developed genetic tools to verify the localization of predicted Incs that had not been previously localized to the inclusion membrane. Expression of epitope-tagged putative Incs identified 10 that were previously unverified as inclusion membrane localized and thus authentic Incs. One novel Inc and 3 previously described Incs were localized to inclusion membrane microdomains, as evidenced by colocalization with phosphorylated Src (p-Src). Several predicted Incs did not localize to the inclusion membrane but instead remained associated with the bacteria. Using Yersinia as a surrogate host, we demonstrated that many of these are not secreted via type III secretion, further suggesting they may not be true Incs. Collectively, our results highlight the utility of genetic tools for demonstrating secretion from chlamydia. Further mechanistic studies aimed at elucidating effector function will advance our understanding of how the pathogen maintains its unique intracellular niche and mediates interactions with the host.


Assuntos
Proteínas de Bactérias/genética , Chlamydia trachomatis/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/genética , Proteínas Recombinantes de Fusão/genética , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/metabolismo , Chlamydia trachomatis/ultraestrutura , Chlorocebus aethiops , Células HeLa , Humanos , Corpos de Inclusão/química , Corpos de Inclusão/metabolismo , Microdomínios da Membrana/química , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Anotação de Sequência Molecular , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Sistemas de Secreção Tipo III/genética , Sistemas de Secreção Tipo III/metabolismo , Vacúolos/química , Vacúolos/metabolismo , Células Vero , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/metabolismo
17.
J Biol Chem ; 289(48): 33469-80, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25324548

RESUMO

Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2.


Assuntos
Proteínas de Bactérias/química , Chlamydia trachomatis/química , Proteínas de Membrana/química , Multimerização Proteica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/genética , Chlamydia trachomatis/metabolismo , Dicroísmo Circular , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade
18.
J Bacteriol ; 196(7): 1325-34, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24443531

RESUMO

Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a vacuole termed the inclusion. Many of the interactions of chlamydiae with the host cell are dependent upon bacterial protein synthesis and presumably exposure of these proteins to the cytosol. Because of the dearth of genetic tools for chlamydiae, previous studies examining secreted proteins required the use of heterologous bacterial systems. Recent advances in genetic manipulation of chlamydia now allow for transformation of the bacteria with plasmids. We describe here a shuttle vector system, pBOMB4, that permits expression of recombinant proteins under constitutive or conditional promoter control. We show that the inclusion membrane protein IncD is secreted in a type III-dependent manner from Yersinia pseudotuberculosis and also secreted from C. trachomatis in infected cells where it localizes appropriately to the inclusion membrane. IncD truncated of the first 30 amino acids containing the secretion signal is no longer secreted and is retained by the bacteria. Cytosolic exposure of secreted proteins can be confirmed by using CyaA, GSK, or microinjection assays. A protein predicted to be retained within the bacteria, NrdB is indeed localized to the chlamydia. In addition, we have shown that the chlamydial effector protein, CPAF, which is secreted into the host cell cytosol by a Sec-dependent pathway, also accesses the cytosol when expressed from this system. These assays should prove useful to assess the secretion of other chlamydial proteins that are potentially exposed to the cytosol of the host cell.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/metabolismo , Proteínas de Bactérias/genética , Chlamydia trachomatis/genética , Citoplasma/genética , Citoplasma/metabolismo , Citosol/metabolismo , Regulação Bacteriana da Expressão Gênica , Humanos , Dados de Sequência Molecular , Transporte Proteico
19.
Open J Immunol ; 2(1): 25-39, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23264931

RESUMO

We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in suppressing anti-bacterial immunity.

20.
Dev Cell ; 15(4): 497-508, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18854135

RESUMO

The past decade and a half has witnessed the discovery of a large, evolutionarily conserved family of cellular genes bearing homology to the prototype baculovirus Inhibitor of Apoptosis (IAP). The logical decision in the field to also refer to these cellular proteins as IAPs fails to do justice to this versatile group of factors that play a wide range of roles in eukaryotic development and homeostasis which include, but are not limited to, the regulation of programmed cell death. Here we describe the shared functional characteristics of several well-characterized IAPs whose defining motifs place them more in the category of multifunctional modular protein interaction domains.


Assuntos
Apoptose/fisiologia , Evolução Molecular , Proteínas Inibidoras de Apoptose/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Apoptose/genética , Caspases/metabolismo , Proteínas Inibidoras de Apoptose/química , Proteínas Inibidoras de Apoptose/genética , Modelos Biológicos , Dados de Sequência Molecular , Ligação Proteica/genética , Estrutura Terciária de Proteína/genética , Homologia de Sequência de Aminoácidos
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