The 100 Most-Cited Articles Focused on Ultrasound Imaging: A Bibliometric Analysis.

Purpose The number of citations that an article has received reflects its impact on a particular research area. The aim of this study was to identify the 100 most-cited articles focused on ultrasound (US) imaging and to analyze the characteristics of these articles. Methods We determined the 100 most-cited articles on US imaging via the Web of Science database, using the search term. The following parameters were used to analyze the characteristics of the 100 most-cited articles: publication year, journal, journal impact factor, number of citations and annual citations, authors, department, institution, country, type of article, and topic. Results The number of citations for the 100 most-cited articles ranged from 1849 to 341 (median: 442.0) and the number of annual citations ranged from 108.0 to 8.1 (median: 22.1). The majority of articles were published in 1990 - 1999 (39 %), published in radiology journals (20 %), originated in the United States (45 %), were clinical observation studies (67 %), and dealt with the vessels (35 %). The Department of Internal Medicine at the University of California and the Research Institute of Public Health at the University of Kuopio (n = 4 each) were the leading institutions and Salonen JT and Salonen R (n = 4 each) were the most prolific authors. Conclusion Our study presents a detailed list and analysis of the 100 most-cited US articles, which provides a unique insight into the historical development in this field.

Loss of DAB2IP in RCC cells enhances their growth and resistance to mTOR-targeted therapies.

Targeted therapies using small-molecule inhibitors (SMIs) are commonly used in metastatic renal cell cancer (mRCC) patients; patients often develop drug resistance and eventually succumb to disease. Currently, understanding of mechanisms leading to SMIs resistance and any identifiable predictive marker(s) are still lacking. We discovered that DAB2IP, a novel Ras-GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. Loss of DAB2IP in RCC cells enhances their sensitivities to growth factor stimulation and resistances to SMI (such as mammalian target of rapamycin (mTOR) inhibitors). Mechanistically, loss of DAB2IP results in the activation of extracellular signal-regulated kinase/RSK1 and phosphoinositide-3 kinase/mTOR pathway, which synergizes the induction of hypoxia-inducible factor (HIF)-2α expression. Consequently, elevated HIF-2α suppresses p21/WAF1 expression that is associated with resistance to mTOR inhibitors. Thus combinatorial targeting both pathways resulted in a synergistic tumor inhibition. DAB2IP appears to be a new prognostic/predictive marker for mRCC patients, and its function provides a new insight into the molecular mechanisms of drug resistance to mTOR inhibitors, which also can be used to develop new strategies to overcome drug-resistant mRCC.

DAB2IP loss confers the resistance of prostate cancer to androgen deprivation therapy through activating STAT3 and inhibiting apoptosis.

Loss of DAB2IP, a novel tumor suppressor gene, is associated with the high risk of aggressive prostate cancer (PCa). Previously, we reported that DAB2IP modulated androgen receptor activation in the development of castration-resistant PCa; however, its direct action on the failure of androgen deprivation therapy (ADT) remains largely unknown. In this study, we showed that DAB2IP knockdown could significantly enhance in vitro growth and colony formation of PCa cells following ADT as well as tumorigenicity in pre-castrated nude mice. In addition, DAB2IP loss stabilized mitochondrial transmembrane potential, prevented release of cytochrome c, Omi/HtrA2 and Smac from the mitochondria to the cytoplasm and inhibited intrinsic apoptosis induced by ADT. Mechanistically, DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells. Moreover, the luminal epithelia in DAB2IP(-/-) mice with more activated STAT3 and survivin expression were resistant to castration-induced apoptosis. Consistently, DAB2IP expression inversely correlated with STAT3 phosphorylation and survivin expression in PCa patients. Together, our data indicate that DAB2IP loss reprograms intracellular signal transduction and anti-apoptotic gene expression, which potentiates PCa cell survival from ADT-induced cell death.

DAB2IP regulates cancer stem cell phenotypes through modulating stem cell factor receptor and ZEB1.

Cancer stem cell (CSC), the primary source of cancer-initiating population, is involved in cancer recurrence and drug-resistant phenotypes. This study demonstrates that the loss of DAB2IP, a novel Ras-GTPase activating protein frequently found in many cancer types, is associated with CSC properties. Mechanistically, DAB2IP is able to suppress stem cell factor receptor (c-kit or CD117) gene expression by interacting with a newly identified silencer in the c-kit gene. Moreover, DAB2IP is able to inhibit c-kit-PI3K-Akt-mTOR signaling pathway that increases c-myc protein to activate ZEB1 gene expression leading to the elevated CSC phenotypes. An inverse correlation between CD117 or ZEB1 and DAB2IP is also found in clinical specimens. Similarly, Elevated expression of ZEB1 and CD117 are found in the prostate basal cell population of DAB2IP knockout mice. Our study reveals that DAB2IP has a critical role in modulating CSC properties via CD117-mediated ZEB1 signaling pathway.

Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women.

BACKGROUND: Recently, klotho has been proposed as a link between cardiovascular diseases and premature aging, but the relationship between KLOTHO genes and cardiovascular risk factors, especially glucose metabolism, in humans is unclear. OBJECTIVES: We investigate the relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women. MATERIAL AND METHODS: In 251 women (mean age 51.3+/-6.9 yr), body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, insulin and lipid profiles were measured. The genotyping of polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene was performed by allelic discrimination using a 5' nuclease polymerase chain reaction assay. RESULTS: Allele frequencies of G395A polymorphism was 0.829 for the G allele and 0.171 for the A allele and allele frequencies of C1818T polymorphism were 0.804 for the C allele and 0.196 for the T allele, both of which were in compliance with Hardy-Weinberg equilibrium and the two polymorphisms were in linkage disequilibrium (D'=0.43, p<0.01). Mean systolic blood pressure was significantly higher in A allele carriers of G395A polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Mean fasting plasma glucose was significantly higher in T allele carriers of C1818T polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Subjects without any minor allele from either single nucleotide polymorphisms (SNP) had significantly lower mean values for systolic, diastolic blood pressure and fasting plasma glucose levels compared with subjects with both minor allele from either SNP. CONCLUSIONS: We observed that KLOTHO G395A polymorphism was associated with blood pressure and KLOTHO C1818T polymorphism was associated with glucose metabolism in Korean women. Further studies are needed to clarify this relationship.

Benign breast diseases associated with cyclosporine therapy in renal transplant recipients.

PURPOSE: Our aim was to correlate the radiologic characteristics of cyclosporine-induced benign breast diseases with clinical and pathologic findings. MATERIALS AND METHODS: The clinical, mammographic, and ultrasonographic records of 33 female renal transplant recipients who received cyclosporine were retrospectively reviewed. Eleven patients had 46 breast masses on ultrasonography. We performed core needle biopsies on 20 masses and reviewed the pathologic findings. RESULTS: Among 33 female renal transplant recipients, 11 (33%) had 46 benign breast lesions detected on ultrasonography. We performed core needle biopsies on 20 of the 46 masses. On pathologic examination, 12 were fibroadenomas, 6 showed fibrocystic changes, and 2 revealed dense fibrosis. Regardless of the final pathologic diagnosis, more than half of the lesions revealed severe lymphatic and venular swellings. Among 11 patients with breast lesions on ultrasonography, 10/11 (91%) showed multiplicity, and 7/11 (64%) bilaterality. Mammographically, patients with breast lesions revealed heterogeneous or extremely dense breast patterns, and 8 of 11 patients, circumscribed masses. Twenty-two patients without breast lesions showed scattered fibroglandular densities (n = 7), or heterogeneously dense (n = 11) or extremely dense (n = 4) breast patterns, and 3 of 22 patients showed vague or asymmetric densities that needed further evaluation. CONCLUSION: The development of new breast lesions in patients after renal transplantation should suggest a diagnosis of cyclosporine-induced benign breast disease including fibroadenoma, fibrocystic changes, and dense fibrosis.

Gallbladder carcinoma and chronic cholecystitis: differentiation with two-phase spiral CT.

The objective of the present study was to determine whether an analysis of two-phase spiral computed tomographic (CT) features provides a sound basis for the differential diagnosis between gallbladder carcinoma and chronic cholecystitis. Eighty-two patients, 35 with gallbladder carcinoma and 47 with chronic cholecystitis, underwent two-phase spiral CT. We reviewed the two-phase spiral CT features of thickness and enhancement pattern of the gallbladder wall seen during the arterial and venous phases. Mean wall thicknesses were 12.6 mm in the gallbladder carcinoma group and 6.9 mm in the chronic cholecystitis group. The common enhancement patterns seen in gallbladder carcinoma were (a) a highly enhanced thick inner wall layer during the arterial phase that showed isoattenuation with the adjacent hepatic parenchyma during the venous phase (16 of 35, 45.7%) and (b) a highly enhanced thick inner wall layer during both phases (eight of 35, 22.9%). The most common enhancement pattern of chronic cholecystitis was isoattenuation of the thin inner wall layer during both phases (42 of 47, 89.4%). In conclusion, awareness of the wall thickening and enhancement patterns in gallbladder carcinoma and chronic cholecystitis on two-phase spiral CT appears to be valuable in differentiating these two different disease entities.

Clinical application of NMP22 in the management of transitional cell carcinoma of the bladder.

The combination of a noninvasive, quantitative immunoassay, NMP22, with voided urinary cytology prior to cystoscopy was evaluated in patients with urothelial transitional cell carcinoma. Fifty-six patients with a history of transitional cell carcinoma were evaluated. Voided urine was obtained for NMP22 and cytology prior to cystoscopy. One hundred and twenty-three NMP22 assays, 124 cytologies, and 124 cystoscopies were performed. The type of anesthesia used for cystoscopic evaluation was determined by the NMP22 value in 30 patients. Cystoscopy results were considered positive on biopsy-confirmed malignancy. The reference value used for NMP22 was 10.0 U/ml. NMP22, cytology, and the combination of NMP22 and cytology were compared to cystoscopy and to pathologic grading and staging. Thirty-four recurrent transitional cell carcinoma episodes occurred; 22 were low-grade (I-II), and 12 were high-grade (III-IV). Twenty-seven were stage Ta; four were T1; and three were T3b or 4. Within this group, NMP22 detected low- and high-grade tumors equally, as compared to cytology, which was sensitive only to high-grade tumors. Nineteen patients were NMP22-negative and underwent cystoscopy under topical anesthesia; 17 were tumor-free. Eleven patients were NMP22-positive and had anesthesia, and all had visible lesions, which were subjected to biopsy and were resected. Six lesions were tumors, five were inflammatory. Overall sensitivity of combined NMP22 and cytology was 70%; specificity was 72%; positive predictive value was 54%; and negative predictive value was 77%. An accurate assessment of the risk of a bladder cancer can be obtained with NMP22, cytology, and cystoscopy in patients with a history of bladder cancer. NMP22 values can be used to determine the level of anesthesia for cystoscopy in patients with a history of bladder cancer.

Production of two different catalase-peroxidases by Deinococcus radiophilus.

The production of two kinds of catalase-peroxidase, viz. catalase-2 and catalase-3 of Deinococcus radiophilus varied depending upon growth phases and oxidative stress. A gradual increase in total catalase activity occurred during exponential and stationary phase. Electrophoretic resolution of these catalases in Deinococcal cell extracts revealed the uniform occurrence of catalase-2 and the appearance of catalase-3 only during the late exponential and stationary phase. A substantial increase in total catalase was observed in either hydrogen peroxide- or UV-treated cells. Monitoring of D. radiophilus catalase activity in the oxidative stressed and non-treated cells by gel electrophoresis followed by densitometry revealed the several-fold increase in catalase-3, which is above the constant level of catalase-2. The occurrence of catalase-3 and catalase-2 revealed by fractionation of sucrose-shocked cells suggests that catalase-3 is a cytosolic inducible enzyme whereas catalase-2 is the membrane-associated constitutive enzyme.

Hepatic hemangioma: contrast-enhancement pattern during the arterial and portal venous phases of spiral CT.

The objective of the present study was to evaluate contrast-enhancement patterns of hepatic hemangioma according to size during hepatic arterial (30-s delay) and portal venous (65-s delay) phases of spiral computed tomography (CT). During a 10-month-period, 73 patients with 118 hemangiomas underwent two-phase spiral CT examination. The enhancement patterns of tumors were divided into four types based on the attenuation of surrounding liver parenchyma: peripherally nodular high, uniform high, iso, and low. The diameter of the tumors were <10 mm (n = 39), 11-20 mm (n = 33), and >21 mm (n = 46). Overall, the most common enhancement patterns of hemangioma were peripherally nodular high (66/118, 55. 9%) during the arterial and portal venous phases. The second most common contrast-enhancement patterns of hemangioma were uniform high (15/118, 12.7%) during the arterial and portal venous phases. In tumors smaller than 20 mm, 11 (9.3%) had low-low attenuation and two (1.7%) had iso-low attenuation during the arterial and portal venous phases, respectively. In conclusion, at two-phase spiral CT, the most common contrast-enhancement patterns of hemangioma are peripherally nodular high and/or uniform high during the arterial and portal venous phases. However, hemangiomas smaller than 2 cm may have atypical enhancing patterns including low and iso-attenuation.

Cytomegalovirus proctitis in a diabetic.

We describe an unusual case of cytomegalovirus (CMV) proctitis in an elderly adult with uncontrolled diabetes mellitus, who had not received immunosuppressive therapy. Barium study and computed tomography showed large ulceration and sinus tract involving the rectum. CMV colitis is thought to occur almost exclusively in immunosuppressed persons. In a nonimmunosuppressed host, the infection is rarely reported.

Hepatocellular carcinoma: power Doppler US with a contrast agent--preliminary results.

PURPOSE: To investigate the value of contrast material-enhanced power Doppler ultrasonography (US) in the demonstration and characterization of tumor vascularity in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty patients with HCC were prospectively evaluated with power Doppler US before and after injection of the contrast agent SH U 508 A. The grade and pattern of tumor vascularity at power Doppler US were analyzed, along with the degree of tumor staining at angiography. RESULTS: Intra- and peritumoral flow signals were detected in 19 HCCs (95%) at unenhanced power Doppler US. After injection of contrast agent, flow signals increased in 19 lesions (95%). At contrast-enhanced power Doppler US, two tumors demonstrated grade 1 vascularity; four, grade 2; three, grade 3; and 11, grade 4. At angiography, two tumors demonstrated grade 1 staining; four, grade 2; eight, grade 3; and six, grade 4. The correlation between vascularity grades at contrast-enhanced power Doppler US and at angiography was statistically significant (P < .0001). Seventeen HCCs (85%) showed the intratumoral or basket pattern of vascularity at unenhanced power Doppler US; after injection of contrast material, 15 HCCs (75%) showed the mixed pattern. CONCLUSION: Contrast-enhanced power Doppler US is superior to unenhanced power Doppler US in the demonstration and characterization of tumor vascularity in HCC.

Atypical small hemangiomas of the liver: "bright dot" sign at two-phase spiral CT.

PURPOSE: To determine if a tiny enhancing dot is characteristic of small hemangiomas with low attenuation during the hepatic arterial phase (HAP) and portal venous phase (PVP) of two-phase spiral computed tomography (CT). MATERIALS AND METHODS: Among 249 consecutive patients with 377 hemangiomas who underwent two-phase spiral CT (performed 30 and 65 seconds after the start of injection), 34 hemangiomas in 20 patients were less than 2 cm in diameter, had low attenuation during the HAP and PVP, and showed characteristic findings on dynamic contrast material-enhanced magnetic resonance (MR) images. The CT scans were retrospectively reviewed for tiny enhancing dots and correlated with the MR images. RESULTS: Tiny enhancing dots were found in 26 of 34 hemangiomas (76%). The dots were seen during the HAP and PVP in 15 lesions (58%) and during the PVP alone in 11 lesions (42%). The lesions showed a tendency toward slow fill-in at MR imaging (only four lesions completely filled with contrast material within 5 minutes). The dots seen at CT corresponded to the initial enhancing area at MR imaging. CONCLUSION: Small hemangiomas with persistent low attenuation at two-phase spiral CT can be diagnosed with the "bright dot" sign.