Discovery of a Unique Set of Dog-Seroreactive Coccidioides Proteins Using Nucleic Acid Programmable Protein Array.

Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics.

Medullary carcinoma of the breast: MRI findings.

OBJECTIVE: The objective of our study was to describe the MRI findings of medullary carcinoma of the breast and to correlate those findings with the histopathologic findings. MATERIALS AND METHODS: From January 2005 to June 2010, MR images of 15 patients (age range, 32-73 years; mean age, 50 years) with pathologically confirmed medullary carcinoma of the breast were retrospectively evaluated according to BI-RADS. MR images were reviewed for the following: enhancement type (mass vs nonmass), size, shape, margins, contrast enhancement, signal intensity, and time-intensity curve pattern on a dynamic study. These MR features were correlated with the histopathologic features. RESULTS: All 15 tumors were seen as a mass on MRI. The median size of the masses was 2.7 cm (range, 1.5-6.3 cm) and the most common features were an oval or lobular shape (13/15, 86.7%) and a circumscribed margin (13/15, 86.7%). Rim enhancement with enhancing internal septations was seen in seven masses (46.7%), and rim enhancement was seen in six masses (40%). A hypointense rim on T2-weighted images was seen in nine tumors (9/15, 60%). Last, the kinetics curve showed a rapid initial increase in enhancement and a washout or plateau pattern on delayed phase imaging in all 15 tumors. CONCLUSION: On MRI, medullary carcinomas of the breast appeared as masses with an oval or lobular shape and circumscribed margins. Rim enhancement with or without enhancing internal septations was frequently seen on contrast enhancement.

Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi.

Tudor domains are protein modules that mediate protein-protein interactions, potentially by binding to methylated ligands. A group of germline specific single and multiTudor domain containing proteins (TDRDs) represented by drosophila Tudor and its mammalian orthologs Tdrd1, Tdrd4/RNF17, and Tdrd6 play evolutionarily conserved roles in germinal granule/nuage formation and germ cell specification and differentiation. However, their physiological ligands, and the biochemical and structural basis for ligand recognition, are largely unclear. Here, by immunoprecipitation of endogenous murine Piwi proteins (Miwi and Mili) and proteomic analysis of complexes related to the piRNA pathway, we show that the TDRD group of Tudor proteins are physiological binding partners of Piwi family proteins. In addition, mass spectrometry indicates that arginine residues in RG repeats at the N-termini of Miwi and Mili are methylated in vivo. Notably, we found that Tdrkh/Tdrd2, a novel single Tudor domain containing protein identified in the Miwi complex, is expressed in the cytoplasm of male germ cells and directly associates with Miwi. Mutagenesis studies mapped the Miwi-Tdrkh interaction to the very N-terminal RG/RA repeats of Miwi and showed that the Tdrkh Tudor domain is critical for binding. Furthermore, we have solved the crystal structure of the Tdrkh Tudor domain, which revealed an aromatic binding pocket and negatively charged binding surface appropriate for accommodating methylated arginine. Our findings identify a methylation-directed protein interaction mechanism in germ cells mediated by germline Tudor domains and methylated Piwi family proteins, and suggest a complex mode of regulating the organization and function of Piwi proteins in piRNA silencing pathways.

Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation.

Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging.

Sonographic findings of invasive cribriform carcinoma of the breast.

The purpose of this series was to evaluate the sonographic features of invasive cribriform carcinoma of the breast. Between 2004 and 2010, 3 patients had confirmed invasive cribriform carcinoma of the breast in our institution, and all of them underwent sonography. Sonograms showed masses with an oval (n = 2) or irregular (n = 1) shape, partially microlobulated (n = 2) or well-circumscribed (n = 1) margins, and a hypoechoic (n = 2) or an isoechoic (n = 1) internal echo texture. Sonographic assessments were classified as Breast Imaging Reporting and Data System category 4 in all 3 cases. Although invasive cribriform carcinoma is a rare breast malignancy, awareness of its sonographic features will be helpful for the diagnosis.

Methanogens and Methanotrophs Show Nutrient-Dependent Community Assemblage Patterns Across Tropical Peatlands of the Pastaza-Marañón Basin, Peruvian Amazonia.

Tropical peatlands are globally important carbon reservoirs that play a crucial role in fluxes of atmospheric greenhouse gases. Amazon peatlands are expected to be large source of atmospheric methane (CH4) emissions, however little is understood about the rates of CH4 flux or the microorganisms that mediate it in these environments. Here we studied a mineral nutrient gradient across peatlands in the Pastaza-Marañón Basin, the largest tropical peatland in South America, to describe CH4 fluxes and environmental factors that regulate species assemblages of methanogenic and methanotrophic microorganisms. Peatlands were grouped as minerotrophic, mixed and ombrotrophic categories by their general water source leading to different mineral nutrient content (rich, mixed and poor) quantified by trace elements abundance. Microbial communities clustered dependent on nutrient content (ANOSIM p < 0.001). Higher CH4 flux was associated with minerotrophic communities compared to the other categories. The most dominant methanogens and methanotrophs were represented by Methanobacteriaceae, and Methylocystaceae, respectively. Weighted network analysis demonstrated tight clustering of most methanogen families with minerotrophic-associated microbial families. Populations of Methylocystaceae were present across all peatlands. Null model testing for species assemblage patterns and species rank distributions confirmed non-random aggregations of Methylococcacae methanotroph and methanogen families (p < 0.05). We conclude that in studied amazon peatlands increasing mineral nutrient content provides favorable habitats for Methanobacteriaceae, while Methylocystaceae populations seem to broadly distribute independent of nutrient content.

Inhaled corticosteroid-related tooth problems in asthmatics.

BACKGROUND: The recent Global Initiative for Asthma guideline states that inhaled corticosteroids (ICSs) may induce osteoporosis as a systemic adverse effect. New ICSs, such as fluticasone propionate, have a high topical potency and may therefore induce tooth problems as a result of direct exposure without hepatic metabolism more frequently than older ICSs. OBJECTIVE: We evaluated asthma patients who underwent long-term treatment with a new ICS to determine if they had tooth problems that were related to osteoporosis of the mandible. METHODS: When the conventional bone mineral density (BMD) of asthmatics that received the ICS treatment for at least one year was measured using dual-energy X-ray absorptiometry, the BMD of the mandible was also measured. The T-score of the mandible BMD was then determined based on the mean BMD +/- the standard deviation of normal young adults. RESULT: Asthma patients with tooth loss (n = 36) and with caries or other tooth problems (n = 28) were found to have a significantly higher prevalence of osteoporosis in the mandible than those without tooth problems (n = 17; 22.2%, 7.1%, 0%, respectively; chi(2) = 6.34, p < 0.05). In addition, the presence of mandibular osteoporosis (odds ratio: 6.14, p = 0.02) and a T-score of < -1.0 for the femoral neck (odds ratio: 3.25, p = 0.01) were found to be significant risk factors for tooth loss in the asthma patients. Finally, the T-score of the mandible was found to be correlated with age (r = -0.316, p < 0.01), and with the T-scores of the lumbar spine (r = 0.413, p < 0.001) and femoral neck (r = 0.446, p < 0.001). CONCLUSION: Tooth loss in asthma patients undergoing long-term treatment with a topically potent ICS was found to be related to a decrease in BMD, especially in the mandible. Therefore, patients using these types of ICS should have their mandibular BMD checked regularly, especially if they have any risk factors for osteoporosis. In addition, it would be wise for such patients to reduce their ICS dose.

Efficacy of MRI versus arthroscopy for evaluation of sinus tarsi syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) has been used to diagnose sinus tarsi syndrome (STS) because of its non-invasiveness and accuracy. The purpose of the present study was to evaluate the diagnostic efficiency of MRI compared with subtalar arthroscopy for STS. MATERIALS AND METHODS: Twenty-eight patients (30 feet) who had undergone both MRI and subtalar arthroscopy for STS were evaluated. MRI results were compared with arthroscopic findings, which were considered the standard. Sensitivity, specificity, and positive and negative predictive values were calculated, and correlations between MRI and arthroscopic findings were investigated. RESULTS: MRI was found to detect interosseous talocalcaneal ligament (ITCL) tears, cervical ligament (CL) tears, sinus tarsi fat alterations, and synovial thickening, with sensitivities, specificities, positive and negative predictive accuracies of: 44%, 60%, 85%, 18% (ITCL tears); 73%, 89%, 80%, 86% (CL tears); 71%, 92%, 93%, 71% (sinus tarsi fat alterations); and 86%, 87%, 67%, 95% (synovial thickening). Correlations between MRI and arthroscopic findings showed full agreement in 10%, partial agreement in 50%, and no agreement in 40%. CONCLUSION: MRI is useful for detecting CL tears, sinus tarsi fat alterations, and synovial thickening, but is inadequate for correctly detecting ITCL tears.

FDG PET/CT for the detection and evaluation of breast diseases: usefulness and limitations.

Positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) is used to diagnose, stage, and monitor breast cancer. FDG PET has the capability to depict abnormal metabolic activity before any anatomic change occurs; however, in the absence of identifiable anatomic structures on PET images, it may be impossible to identify the location of areas of increased radionuclide uptake. In such cases, the coregistration of PET images with images from computed tomography (CT) may help improve diagnostic accuracy and lead to better clinical management of patients with breast cancer. Although FDG PET/CT may have limited diagnostic value for detecting small primary breast tumors, well-differentiated breast cancer, or regional lymph node involvement, it is superior to conventional imaging modalities for detecting distant metastases and recurrences and for monitoring the response to therapy.

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Imaging features of hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation.

OBJECTIVE: The purpose of this pictorial essay is to show the imaging features of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and radiofrequency thermal ablation on CT, MRI, and contrast-enhanced sonography and to describe the advantages and limitations of each imaging technique in evaluating the therapeutic effect on HCC. CONCLUSION: CT is the standard imaging technique for monitoring the effectiveness of TACE and radiofrequency ablation. Contrast-enhanced sonography and MRI can complement CT in evaluating the therapeutic response.

Giant Cell Tumor with Secondary Aneurysmal Bone Cyst Shows Heterogeneous Metabolic Pattern on 18F-FDG PET/CT: A Case Report.

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on 18F-FDG PET/CT.

Inferior vena cava filter insertion through the popliteal vein: enabling the percutaneous endovenous intervention of deep vein thrombosis with a single venous access approach in a single session.

PURPOSE: We aimed to evaluate the efficiency of placing an inferior vena cava (IVC) filter through the same popliteal vein access site used for percutaneous endovenous intervention in patients with extensive lower extremity deep vein thrombosis. METHODS: This retrospective study included 21 patients who underwent IVC filter insertion through the popliteal vein over a three-year period. Patient medical records were reviewed for the location of the deep vein thrombosis, result of filter removal, and total number of endovascular procedures needed for filter insertion and recanalization of the lower extremity venous system. Follow-up lower extremity computed tomography (CT) venography was also reviewed in each patient to assess the degree of filter tilt in the IVC. RESULTS: All patients had extensive lower extremity deep vein thrombosis involving the iliac vein and/or femoral vein. Seventeen patients showed deep vein thrombosis of the calf veins. In all patients, IVC filter insertion and the recanalization procedure were performed during a single procedure through the single popliteal vein access site. In the 17 patients undergoing follow-up CT, the mean tilt angle of the filter was 7.14°±4.48° in the coronal plane and 8.77°±5.49° in the sagittal plane. Filter retrieval was successful in 16 of 17 patients (94.1%) in whom filter retrieval was attempted. CONCLUSION: Transpopliteal IVC filter insertion is an efficient technique that results in low rates of significant filter tilt and enables a single session procedure using a single venous access site for filter insertion and percutaneous endovenous intervention.

Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy.

The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.

Transarterial embolization for postoperative hemorrhage after abdominal surgery.

The study goal was to evaluate the efficacy, safety, and clinical outcome of transarterial embolization for postoperative hemorrhage after abdominal surgery. Thirty-three patients were referred for angiography because of gastrointestinal or intra-abdominal bleeding after abdominal surgery. Urgent angiography and transarterial embolization was performed in all 33 patients. The clinical and angiographic features were retrospectively reviewed. Angiography revealed a discrete bleeding focus in 26 (79%) of 33 patients. Transarterial embolization was technically successful in 24 (92%) of 26 patients with a discrete bleeding focus. Rebleeding occurred in four (17%) of 24 patients. They were successfully managed with repeat embolization. There was no procedure-related complication during follow-up period. Angiography has a high detection rate of bleeding site in patients with postoperative hemorrhage after abdominal surgery. Transarterial embolization is considered to be an effective and safe means in the management of postoperative hemorrhage.

CT in blunt liver trauma.

Nonsurgical treatment has become the standard of care in hemodynamically stable patients with blunt liver trauma. The use of helical computed tomography (CT) in the diagnosis and management of blunt liver trauma is mainly responsible for the notable shift during the past decade from routine surgical to nonsurgical management of blunt liver injuries. CT is the diagnostic modality of choice for the evaluation of blunt liver trauma in hemodynamically stable patients and can accurately help identify hepatic parenchymal injuries, help quantify the degree of hemoperitoneum, and reveal associated injuries in other abdominal organs, retroperitoneal structures, and the gastrointestinal tract. The CT features of blunt liver trauma include lacerations, subcapsular or parenchymal hematomas, active hemorrhage, juxtahepatic venous injuries, periportal low attenuation, and a flat inferior vena cava. It is important that radiologists be familiar with the liver injury grading system based on these CT features that was established by the American Association for the Surgery of Trauma. CT is also useful in the assessment of delayed complications in blunt liver trauma, including delayed hemorrhage, hepatic or perihepatic abscess, posttraumatic pseudoaneurysm and hemobilia, and biliary complications such as biloma and bile peritonitis. Follow-up CT is needed in patients with high-grade liver injuries to identify potential complications that require early intervention.

Contrast enhancement and contrast extravasation on computed tomography after intra-arterial thrombolysis in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: The goal of this study was to determine the CT findings and clinical consequences of contrast enhancement and contrast extravasation on CT scans obtained after intra-arterial thrombolytic therapy for treatment of acute ischemic stroke. METHODS: Sixty-two patients were treated with intra-arterial thrombolysis. All patients underwent nonenhanced CT scans immediately and 24 hours after thrombolytic therapy. Contrast enhancement was defined as a hyperdense lesion that disappeared on a 24-hour follow-up CT scan. Contrast extravasation was defined as a hyperdense lesion with maximum Hounsfield unit >90 that persisted on a follow-up CT scan. We evaluated the differences in the clinical and radiological data between 3 groups: contrast enhancement, contrast extravasation, and control groups. RESULTS: Contrast enhancement was found in 14 of 62 patients (22.6%); contrast extravasation was seen in 7 (11.3%). Compared with the control group, the contrast enhancement group had a lower recanalization grade (64.3% versus 34.1%, P=0.048) and a lower incidence of hemorrhagic transformation (14.3% versus 43.9%, P=0.047). The contrast extravasation group had a higher incidence of both hemorrhage (100% versus 43.9%, P=0.006) and symptomatic hemorrhage (100% versus 14.6%, P<0.001) than the control group. Poor outcomes were more frequent in the contrast extravasation group (100% versus 38.9%, P=0.003) than the control group. CONCLUSIONS: Contrast enhancement on CT scans obtained after intra-arterial thrombolysis is usually not associated with hemorrhagic complications. However, contrast extravasation is highly associated with parenchymatous hematoma and should be considered a negative prognostic sign.

Uterine cervical carcinoma after therapy: CT and MR imaging findings.

Cervical carcinoma is one of the most frequent causes of death in women. Computed tomography (CT) and magnetic resonance (MR) imaging are the primary modalities for follow-up of treated cervical carcinoma. A normal vaginal cuff after hysterectomy appears as a smooth, low-signal-intensity muscular wall on T2-weighted MR images. Early (2-3 months after treatment) and significant decreases in the signal intensity and volume of the tumor at MR imaging indicate a good response to radiation therapy. Sites of recurrence are the pelvis, lymph nodes, and distant sites. Pelvic recurrence appears as a heterogeneously enhancing mass at contrast material-enhanced CT and often appears as a heterogeneous, high-signal-intensity mass at T2-weighted MR imaging. Lymph node recurrence ranges from scattered, minimally enlarged nodes to large, conglomerate nodal masses. Determination of neoplastic infiltration of lymph nodes is based on size; most researchers consider nodes greater than 1 cm in short-axis diameter to be metastatic. Distant metastases are usually due to recurrent disease and occur in the abdomen, thorax, and bone. Knowledge of the normal therapeutic changes and the spectrum of recurrent tumor in patients with cervical carcinoma is important for accurate interpretation of follow-up CT and MR images.

Pelvic arterial hemorrhage in patients with pelvic fractures: detection with contrast-enhanced CT.

Arterial hemorrhage is one of the most serious problems associated with pelvic fractures, and it remains the leading cause of death attributable to pelvic fracture. At many trauma centers, contrast material-enhanced computed tomography (CT) is increasingly used for initial diagnosis in the evaluation of patients with pelvic fractures. Extravasation of contrast material in the pelvis at contrast-enhanced CT is an accurate indicator of ongoing arterial hemorrhage in patients with pelvic fractures. Detection of such extravasation on CT scans can lead to prompt performance of angiographic embolization, which can be lifesaving. Furthermore, the site of contrast material extravasation seen at CT corresponds well to the site of bleeding seen at angiography. This correspondence enables the interventional radiologist to selectively study the arteries most likely to be injured and therefore potentially reduce the patient's morbidity and mortality. Knowledge of the relevant pelvic anatomy, including the osseous, ligamentous, and especially axial vascular anatomy, is essential for understanding the relationship between a site of contrast material extravasation at CT and the specific injured artery visualized at angiography.