Bacterial production of recombinant contraceptive vaccine antigen from CatSper displayed on a human papilloma virus-like particle.

CatSper is a voltage dependent calcium ion channel present in the principal piece of sperm tail. It plays a crucial role in sperm hyperactivated motility and so in fertilization. Extracellular loops of mouse sperm CatSper were used to develop a vaccine to achieve protection from pregnancy. These loops were inserted at one of the three hypervariable regions of Human Papilloma Virus (HPV) capsid protein (L1). Recombinant vaccines were expressed in E.coli as inclusion body (IB), purified, refolded and assembled into virus-like particles (VLP) in vitro, and adsorbed on alum. Four vaccine candidates were tested in Balb/C mice. All the constructs proved immunogenic, one showed contraceptive efficacy. This recombinant contraceptive vaccine is a non-hormonal intervention and is expected to give long-acting protection from undesired pregnancies.

Peri-ampullary duodenal diverticulum: effect on extrahepatic bile duct dilatation after cholecystectomy.

AIM: To investigate the effect of peri-ampullary duodenal diverticula (PAD) on extrahepatic bile duct (EHBD) dilatation before and after cholecystectomy. MATERIALS AND METHODS: During a 5-year period, a total of 860 consecutive patients with prior cholecystectomy were examined using abdominal computed tomography (CT). After exclusion of those with other obstructive EHBD lesions, 61 patients with PAD were recruited for evaluation of EHBD dilatation before and after cholecystectomy and were compared with a randomly sampled control group (n=113) without PAD. EHBD diameter was measured on coronal reconstruction CT using electronic callipers on the picture archiving and communication system monitors by two reviewers in consensus. RESULTS: There was no significant difference in EHBD diameter between PAD and non-PAD groups (8.2±2.8 versus 7.8±2.3 mm; p=0.276) before cholecystectomy. Compared with preoperative diameter, EHBD was significantly dilated after cholecystectomy (7.9±2.5 versus 9.8±3.4 mm, p<0.001), regardless of the presence of PAD; the degree of change was more prominent in the PAD group than in the non-PAD group (3.3±2.4 versus 1.1±1.6 mm; p<0.001) after surgery. The size of PAD did not affect the degree of EHBD dilatation after cholecystectomy (p=0.522). In the non-PAD group, the degree of EHBD dilatation was positively correlated with the follow-up interval after cholecystectomy (r=0.298; p=0.002), while the PAD group showed no significant correlation (r=-0.036; p=0.797). In patients with ≥2 mm postoperative EHBD dilatation, PAD incidence was higher than that in other patients (odds ratio, 8.739; p<0.001). CONCLUSION: Regardless of their size or postoperative follow-up duration, PAD induce marked post-cholecystectomy biliary dilatation.

High-flow haemangiomas versus hypervascular hepatocellular carcinoma showing "pseudo-washout" on gadoxetic acid-enhanced hepatic MRI: value of diffusion-weighted imaging in the differential diagnosis of small lesions.

AIM: To validate the usefulness of diffusion-weighted imaging (DWI) in the differentiation of high-flow haemangiomas showing pseudo-washout appearance on gadoxetic acid-enhanced hepatic MRI from small hypervascular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: DWI (b=50, 800 s/mm2) with apparent diffusion coefficient (ADC) maps for 50 haemangiomas (6.4±2.9 mm) showing intense enhancement on arterial dominant phase imaging and hypointensity on transitional and/or hepatobiliary phase imaging during gadoxetic acid-enhanced MRI were retrospectively analysed and compared with that of 113 hypervascular HCCs (12.8±3.7 mm). In addition to measurement of mean ADC values on DWI and contrast-to-noise ratio (CNR) on corresponding T2-weighted imaging, qualitative analysis of DWI was performed for each lesion by two independent observers using a five-point scale. RESULTS: Both of mean ADC value (1.902 versus 0.997×10-3 mm2/s) and mean CNR (119.2 versus 36.9) for haemangioma were significantly larger than for HCC (p<0.001). On receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.995 for ADC values was significantly larger than 0.915 for CNRs (p=0.002). When the ADC value of 1.327×10-3 mm2/s was used as the threshold for the diagnosis of haemangioma, the sensitivity and specificity were 98% and 97.3%, respectively. The mean sensitivity and specificity of qualitative analysis for the differentiation of haemangioma from HCC were 92% and 99.1%, respectively. CONCLUSION: For high-flow small haemangiomas showing pseudo-washout appearance during gadoxetic acid-enhanced hepatic MRI, high b-factor DWI including an ADC map may provide additional information to enhance the confidence to exclude small hypervascular HCCs.

Small hypervascular hepatocellular carcinomas: value of diffusion-weighted imaging compared with "washout" appearance on dynamic MRI.

OBJECTIVE: To compare the value of diffusion-weighted MRI (DWI) with the venous "washout" appearance during dynamic MRI for the assessment of small arterial hypervascular lesions in cirrhotic liver. METHODS: After exclusion of benign hypervascular lesions, including haemangiomas and subcapsular non-tumorous arterioportal shunts, indicated by typical imaging features, a total of 109 small arterial hypervascular lesions (0.5-3.0 cm in the longest diameter) in 65 patients with cirrhosis who underwent gadopentetate dimeglumine-enhanced dynamic MRI and DWI (b=50, 400, 800 s mm(-2)) at 1.5 T during a 16-month period were retrospectively analysed to determine the presence of venous washout during dynamic imaging or sustained hyperintensity upon increasing the b factor size on DWI. RESULTS: Among the 99 hypervascular hepatocellular carcinomas (HCCs), sustained hyperintensity on DWI (92/99, 93%) was more prevalent than the washout appearance (72/99, 72%) on dynamic MRI (p<0.001). Depending on the lesion size, subcentimetre-sized HCCs had a significantly lower prevalence of venous washout (13/30, 43%) than the sustained hyperintensity on DWI (27/30, 90%) (p=0.001). In all 10 hypervascular benign conditions, there was no venous washout on dynamic MRI and no sustained hyperintensity on DWI. Sensitivity and specificity for diagnosis of hypervascular HCCs were 92.9% and 100% in DWI and 72% and 100% in dynamic MRI, respectively. CONCLUSION: Compared with the venous washout during dynamic imaging, DWI provides more reliable information in the MRI assessment of small hypervascular HCCs, distinguishing them from atypical hypervascular benign or pseudolesions. DWI could complement the early diagnosis of small hypervascular HCCs that do not display venous washout during dynamic imaging.

Haemodynamic events and localised parenchymal changes following transcatheter arterial chemoembolisation for hepatic malignancy: interpretation of imaging findings.

Following transcatheter arterial chemoembolisation (TACE), the appearances on CT or MR images are largely related to the chemical and ischaemic insults to the portal tract. Understanding the mechanism of TACE-induced changes is essential for radiologists in order to determine the therapeutic effect as well as to distinguish these changes from recurrent tumours. This pictorial review illustrates the haemodynamic and substantial parenchymal changes related to TACE for hepatic malignancy.

Double contrast-enhanced MRI of viral hepatitis-induced cirrhosis: correlation of gross morphological signs with hepatic fibrosis.

The purpose of this study was to evaluate the diagnostic ability of the expanded gallbladder fossa and right posterior hepatic notch signs for hepatic fibrosis determined by double contrast-enhanced MRI. For patients with chronic viral hepatitis B (n = 96) or hepatitis C (n = 13) who underwent gadopentate dimeglumine-enhanced dynamic MRI followed by ferucarbotran-enhanced gradient-echo imaging, the degree of parenchymal fibrosis was categorised into three groups based on the extent of reticulation and nodularity: (1) pre-cirrhotic or minimal fibrosis; (2) mild to moderate fibrosis; (3) advanced cirrhosis. Each group was evaluated for the presence of a sharp notch in the posterior-medial surface of the right lobe of the liver and expanded gallbladder fossa. The expanded gallbladder fossa sign gradually increased with an increasing degree of fibrosis (Group 1, 50%; Group 2, 61%; Group 3, 78%), and there was no significant difference (p>0.5) between hepatitis B (67%) and C (73%). In the case of the right posterior hepatic notch sign, only 6% of Group 1 and Group 2 patients were positive; 27% of hepatitis B patients and 90% of hepatitis C patients in Group 3 exhibited the sign (p<0.05). Owing to its low prevalence, even in advanced cirrhosis, the right posterior hepatic notch sign is of little value in the diagnosis of cirrhosis due to chronic hepatitis B virus infection, whereas an expanded gallbladder fossa could be used as a non-specific indicator of early fibrosis before the gross appearance of advanced hepatic fibrosis.

Large (>or=2 cm) non-hypervascular nodules depicted on MRI in the cirrhotic liver: fate and implications.

AIM: To determine the fate and clinical implication of large (>or=2 cm), non-hypervascular nodules depicted on magnetic resonance imaging (MRI) in the cirrhotic liver. MATERIALS AND METHODS: In 21 patients with cirrhosis (14 hepatitis B, two ethanol abuse, four cryptogenic, one Wilson's disease), 25 large (>or=2 cm in the longest dimension) non-hypervascular nodules were identified on dynamic MRI. The implications for diagnosis of the initial size, contour, and signal characteristics on MRI in addition to patients' age and cause of cirrhosis were assessed in our analysis. RESULTS: Twelve (75%) out of 16 lesions were malignant or potentially-malignant from 14 hepatitis B patients, while seven (78%) of the nine lesions from other patients were benign (p=0.016). The mean age of the patients who had malignant or potentially malignant lesions (57 years) was older than that for the other patients (47 years; p=0.039). The ratio of the short-to-long diameter was higher in malignant or potentially malignant lesions (mean 0.86) than in benign lesions (mean 0.69; p=0.008). There was no discriminative signal intensity characteristic (p>0.2 for all factors) that indicated the malignant potential for each non-hypervascular nodule. For all 10 lesions in the hepatitis B patients who were older than 52 years with a short-to-long diameter ratio of more than 0.75, the positive predictive value for malignant potential based on these three combined factors was 100%. CONCLUSION: In older patients with cirrhosis from hepatitis B, large (>or=2 cm), non-hypervascular nodules with a spherical contour have a high malignant potential.

Small hypervascular hepatocellular carcinoma: limited value of portal and delayed phases on dynamic magnetic resonance imaging.

BACKGROUND: Characterization of small nodules in the cirrhotic liver is always challenging in clinical practice. In the differential diagnosis of small hypervascular lesions, it has been reported that portal venous or delayed hypointensity is a useful sign to characterize hepatocellular carcinomas (HCCs) during dynamic magnetic resonance (MR) imaging. However, few studies have assessed the diagnostic value of this sign. PURPOSE: To determine the diagnostic value of portal-phase (PP) and delayed-phase (DP) images for the diagnosis of small hypervascular HCCs during intravenous (IV) contrast-enhanced dynamic MR imaging of cirrhotic liver. MATERIAL AND METHODS: A total of 69 small (6-20 mm) hypervascular HCCs in 53 cirrhotic patients were subjected to a retrospective analysis of the signal intensities (hypo-, iso-, or hyperintense) and rim enhancement on PP and 5-min DP images from three-phased dynamic MR imaging according to the pre-contrast T1- and T2-weighted imaging features. After exclusion of 33 subcapsular wedge-shaped pseudolesions and three hemangiomas by typical imaging features, 74 centrally located small hypervascular benign or pseudolesions were used as a control group for comparative analyses. RESULTS: The sensitivities of PP hypointensity, DP hypointensity, and rim enhancement in the diagnosis were 11%, 29%, and 18%, respectively, for 6-10-mm hypervascular HCCs, and 42%, 63%, and 58%, respectively, for 16-20-mm lesions. After exclusion of the 48 lesions showing T2-weighted hyperintensity (HCCs, n = 39; benign lesions, n = 9), the overall sensitivity for diagnosis of small hypervascular HCCs decreased (8.3%, 25.0%, and 8.3%, respectively). CONCLUSION: Although DP provides a better sensitivity than PP, both PP and DP have very limited diagnostic value for diagnosis of small hypervascular HCCs during dynamic MR imaging of the cirrhotic liver.

A comparison of esophagography and esophageal transit scintigraphy in the evaluation of usefulness of endoscopic pneumatic dilatation in achalasia.

BACKGROUND: Esophageal transit scintigraphy and barium esophagography have been used for evaluation of therapeutic results in patients with achalasia. It remains to be determined which method is most useful, and whether both studies are necessary before and after treatment for achalasia. PURPOSE: To evaluate the usefulness of both esophagography and esophageal transit scintigraphy (ETS) to determine the efficacy of endoscopic pneumatic dilatation (EPD) in patients with achalasia. MATERIAL AND METHODS: Seventeen patients (6 M, 11 F) with achalasia underwent both esophagography and ETS before and after EPD. Esophagographic findings were reviewed to determine the length and caliber of stenosis in the esophagogastric channel. Dynamic images of ETS were evaluated on time-activity curves. Changes in the clinical symptom score were evaluated. Statistical analyses of esophagography and ETS before and after EPD were performed. RESULTS: After EPD, the mean symptom score improved (P<0.05). The mean residue of radioisotope in ETS also improved after EPD, with a statistically significant correlation (P<0.05). There was a statistically significant correlation between the improved symptom scores and the change in ETS after EPD (P<0.05). There was no statistical correlation between clinical symptom scores and esophageal caliber, regardless of EPD (P>0.05). With an 8-mm diameter of the esophagogastric channel as a benchmark for successful treatment, there was no statistical correlation between esophagography and ETS at 15 s after EPD (P>0.05). CONCLUSION: Esophagography was useful for the evaluation of morphology and caliber of the esophagogastric channel, while ETS was useful for the functional evaluation of esophageal emptying. Both studies may therefore be considered necessary to evaluate the efficacy of EPD in patients with achalasia.

Gallbladder lymphangioma: MR findings.

Intraabdominal lymphangiomas are rare lesions that can be difficult to diagnose. We report ultrasonographic (US), computed tomographic (CT), magnetic resonance (MR) imaging, and pathologic findings in a patient with cavernous lymphangioma originating in the gallbladder. US and CT showed a multiseptated cystic mass in the gallbladder fossa. T2-weighted MR images and MR cholangiopancreatography depicted the lumen of the gallbladder and thin septations of the cystic mass, which originated in the gallbladder. Endoscopic retrograde cholangiopancreatography showed no apparent communication between the cyst and the gallbladder. Histologic findings obtained during the operation were consistent with cavernous lymphangioma. Its characteristic histology was observed in the subserosal layer of the gallbladder. This case is a rare instance of cavernous lymphangioma originating in the gallbladder preoperatively diagnosed by MR and MR cholangiopancreatography.

Acute renal failure: common occurrence of preservation of corticomedullary differentiation on MR images.

The purpose of this study was to evaluate the relationship between renal corticomedullary differentiation (CMD) on MR imaging and serum creatinine (sCr) level in patients with acute renal failure (ARF). Twenty-one patients with ARF were retrospectively investigated. In all 21 patients, sCr levels were obtained on the same date as the MR study, and within 8 days before and after the MR study. CMD was assessed on non-contrast T(1)-weighted images and immediate post-gadolinium spoiled gradient echo (Gd-SGE) images. Presence of CMD was graded into 3 groups as 'preserved', 'intermediate', or 'loss'. On non-contrast T(1)-weighted images, 12/21 (57%) showed loss of CMD and 9/21 (43%) showed preserved CMD. On immediate Gd-SGE images, 5/21 (24%) showed loss of CMD, 12/21 (57%) preserved CMD, and 4/21 (19%) intermediate CMD. The sCr levels of 9 patients with preserved CMD on non-contrast T(1)-weighted images ranged from 1.4 to 10.5 mg/dl (mean 4.6 mg/dl), while those of 12 patients with loss of CMD ranged from 1.6 to 7.6 mg/dl (mean 4.8 mg/dl), which was not statistically significant (p > 0.2). Renal CMD can remain preserved on non-contrast T(1)-weighted or immediate Gd-SGE images in patients with acute presentation of ARF, independent of sCr level.

Recurrent pyogenic cholangitis: comparison between MR cholangiography and direct cholangiography.

PURPOSE: To compare the accuracy of magnetic resonance (MR) cholangiography with that of direct cholangiography for the evaluation of recurrent pyogenic cholangitis. MATERIALS AND METHODS: Twenty-four patients with recurrent pyogenic cholangitis underwent MR cholangiography before surgery, and 18 of these 24 also underwent direct cholangiography. Two reviewers evaluated MR cholangiograms and direct cholangiograms and focused on identifying intrahepatic ductal dilatation, stricture, and calculi, as well as coexistent parenchymal abnormalities, on the basis of the classification of the internal lobes and segments of the liver. These observations were compared with surgical findings. RESULTS: According to examination results in the surgical specimens, 24 patients had 46 segmental abnormalities. MR cholangiography depicted all 46 (100%) segments with ductal dilatation, 22 (96%) of 23 segments with focal ductal stricture, and 43 (98%) of 44 segments with ductal calculi. Eighteen patients who underwent direct cholangiography had 32 segmental abnormalities according to examination results in the surgical specimens. Direct cholangiography depicted 15 (47%) of 32 segments with ductal dilatation, eight (44%) of 18 segments with focal ductal stricture, and 14 (45%) of 31 segments with ductal calculi. CONCLUSION: MR cholangiography is superior to direct cholangiography for accurate topographic evaluation of recurrent pyogenic cholangitis because it is able to depict all of the biliary tree, despite obstruction or stenosis.

Intestinal Behçet's disease: breath-hold MR imaging.

BACKGROUND: To determine the feasibility of magnetic resonance (MR) imaging in the evaluation of intestinal Behçet's disease. METHODS: Eight patients diagnosed to have intestinal Behçet's disease prospectively underwent MR imaging. Five patients had previously undergone abdominal surgery for intestinal Behçet's disease 27-81 months previously. Breath-hold T2-weighted single-shot fast spin echo, T1-weighted multiplanar spoiled gradient recalled echo, and postgadolinium-enhanced fat-suppressed T1-weighted opposed-phase multiplanar spoiled gradient recalled echo images were obtained. MR findings were analyzed by three independent radiologists in terms of the presence and location of bowel wall thickening and ulcer, maximal bowel wall thickness, grade of bowel wall enhancement, and presence and nature of extraluminal manifestations. K statistics were used to evaluate interobserver variability. RESULTS: Seven cases (88%), including the five cases with previous operations, demonstrated bowel thickening of more than 9 mm and increased enhancement. Ulcer was depicted in four cases (50%) in the terminal ileum or an anastomosis site. Three cases (38%) showed extraluminal manifestation, such as mesenteric infiltration around the involved bowel (two cases) and a sinus tract to subhepatic abscess from perforation (one case). CONCLUSION: Breath-hold MR imaging is useful for the evaluation of bowel wall thickening, enhancement, mesentery infiltration, and abscess formation. Characteristic ulcerative lesions may be also depicted on T1- and T2-weighted breath-hold images. MR imaging is a useful method for postoperative follow-up study for the evaluation of recurrence.

Chronic hepatitis: correlation of early patchy and late linear enhancement patterns on gadolinium-enhanced MR images with histopathology initial experience.

The purposes of our study were to describe the early and late enhancement patterns of the liver on gadolinium-enhanced dynamic magnetic resonance (MR) images in patients with chronic hepatitis and to correlate these findings with histopathology. Patients were entered into the study based on the presence of chronic hepatitis, imaging evaluation with MR imaging (MRI), including early and late postgadolinium images, and histopathologic correlation. Early and late dynamic postgadolinium MR images of 29 consecutive patients with a pathologically proven diagnosis of chronic hepatitis were retrospectively evaluated for the presence of three types of enhancement, i.e., homogeneous, linear, and patchy. Correlation was made between the enhancement patterns on MR images and blinded retrospective interpretation of the histopathologic specimens, which were obtained within 3 months of the MR examination. Of the 29 patients, 16 (55.2%) patients showed patchy enhancement on the early gadolinium-enhanced MR images. In 11 (68.8%) of these 16 patients, histopathology demonstrated numerous macrophages, variable hepatocyte necrosis, and increased steatosis. The remaining 13 (44.8%) patients showed homogeneous enhancement on the early gadolinium-enhanced MR images. In 11 (84.6%) of these 13 patients, histopathology demonstrated few or no macrophages, little or no hepatocellular necrosis, and little or no steatosis. The correlation between patchy enhancement and acute liver inflammation was significant (P = 0.005). On the late gadolinium-enhanced MR images, 20 (69.0%) of 29 patients showed prominent linear enhancement. In 19 (95.0%) of these 20 patients, histopathology revealed hepatic fibrosis. We concluded that in patients with chronic hepatitis, the presence of early patchy enhancement indicates either concurrent or recent hepatocellular damage, whereas the presence of late linear enhancement indicates the presence of fibrosis, with a high degree of correlation with histopathologic findings.

A functional retinoic acid response element (RARE) is present within the distal promoter of the rat gonadotropin-releasing hormone (GnRH) gene.

We previously demonstrated that all-trans-retinoic acid (all-trans-RA) regulates gonadotropin-releasing hormone (GnRH) release and gene expression in rat hypothalamic fragments and GT1-1 neuronal cells. Promoter analysis of rat GnRH gene revealed that the enhancing effect of all-trans-RA on GnRH transcription is mediated by cis-elements localized within --1640/--1438 of the rat GnRH promoter. In the present study, we attempted to localize functional retinoic acid response elements (RAREs) within the all-trans-RA-responsive region of the rat GnRH gene. Sequence analysis showed that there exist three putative repeats of AGGTCA-related sequences (--1637/--1617, --1579/--1562, and --1494/--1470) within this promoter sequence. Among them, only the --1494/--1470 sequence could compete the specific binding of GT1-1 nuclear extracts to the consensus RARE (direct repeat of AGGTCA with a 5-bp spacer, DR-5) and vice versa in electrophoretic mobility shift assays. In addition, like consensus RARE, the --1494/--1470 sequence could confer all-trans-RA responsiveness when inserted into the upstream region of SV40 promoter. Treatment of GT1-1 cells with all-trans- or 9-cis-RA increased the specific bindings of GT1-1 nuclear extracts to the consensus RARE and to the --1494/--1470 sequence while not affecting the specific binding to the cAMP response element (CRE). Both retinoids induced RARbeta gene expression in GT1-1 cells. The --1494/--1470 sequence (5'-TCTTAGGACTCTGTGTGACCTAAGA) is similar to the direct repeat of TGACCT (complementary sequence of AGGTCA) with a spacer of 5 bp (i.e. DR-5 in the reverse orientation). A mutation of the second core recognition motif of the --1494/--1470 sequence to a more divergent one from consensus RARE (from TGACCT to TTACAT) abolished the responsiveness to all-trans-RA, whereas a mutation of first core recognition motif to a more TGACCT-like sequence (from AGGACT to TGAACT) increased the responsiveness to all-trans-RA. These results indicate that the --1494/--1470 sequence is indeed a weak but functional RARE of the modified DR-5 type. Taken together, these data indicate that all-trans-RA enhances GnRH transcription via functional RARE present in the distal region of the GnRH promoter.

Partial purification and characterization of a hemolysin (CAH1) from Hawaiian box jellyfish (Carybdea alata) venom.

We have isolated and characterized a novel hemolytic protein from the venom of the Hawaiian box jellyfish (Carybdea alata). Hemolysis of sheep red blood cells was used to quantitate hemolytic potency of crude venom extracted from isolated nematocysts and venom after fractionation and purification procedures. Hemolytic activity of crude venom was reduced or lost after exposure to the proteolytic enzymes trypsin, collagenase and papain. The activity exhibited lectin-like properties in that hemolysis was inhibited by D-lactulose and certain other sugars. Activity was irreversibly lost after dialysis of crude venom against divalent-free, 20mM EDTA buffer; it was optimal in the presence of 10mM Ca2+ or Mg2+. Two chromatographic purification methods, size fractionation on Sephadex G-200 and anion exchange with quaternary ammonium, provided fractions in which hemolytic activity corresponded to the presence of a protein band with an apparent molecular weight of 42kDa by SDS-PAGE. We have designated this protein as CAH1. The N-terminal sequence of CAH1 was determined to be: XAADAXSTDIDD/GIIG.

Adrenal adenomas: characteristic postgadolinium capillary blush on dynamic MR imaging.

We sought to evaluate dynamic post-gadolinium contrast enhanced magnetic resonance (MR) imaging characteristics of adrenal adenomas with comparison to those of malignant adrenal tumors. MR images, including in- and out-of-phase spoiled gradient echo (SGE) and dynamic gadolinium enhancement, of 35 adrenal adenomas in 34 patients, and 12 malignant adrenal tumors in 12 patients, were reviewed retrospectively. MR images were assessed for the presence of a capillary blush on immediate postgadolinium SGE images, and for rapid washout of contrast on 45-second postgadolinium SGE images. Thirty-five adrenal adenomas (mean size, 3.1 cm) and 12 malignant adrenal tumors (mean size, 7.4 cm) were assessed. Of 35 adrenal adenomas, 25 (71%) showed a homogeneous capillary blush on immediate postgadolinium images. Thirty-three (94%) adrenal adenomas demonstrated rapid washout on 45-second postgadolinium images (P < 0.001). Of 35 adrenal adenomas, 30 (86%) showed diminished signal intensity (SI) on out-of-phase images. Of 12 malignant adrenal tumors, none showed a homogeneous capillary blush on immediate postgadolinium images. Six (50%) malignant tumors showed negligible enhancement, four (33%) showed irregular patchy enhancement, and two (17%) showed peripheral enhancement (P < 0.001). On 45-second postgadolinium images, 11 (92%) of 12 malignant adrenal tumors showed irregular enhancement. In the majority of adrenal adenomas, an initial homogeneous capillary blush and rapid washout are demonstrated on gadolinium-enhanced dynamic MR imaging. Our preliminary results suggest that this may provide useful complementary information to the appearance of adrenal masses on in- and out-of-phase images.

Sequential use of gadolinium chelate and mangafodipir trisodium for the assessment of focal liver lesions: initial observations.

The purpose of this study was to assess the feasibility of sequential administration of 2 different MR imaging contrast agents using a single visit protocol to image focal liver abnormalities. Twenty-one patients with known or suspected liver lesions were included in the study. All patients received a bolus intravenous injection of gadolinium chelate (Gd) and dynamically enhanced imaging performed. The patients then received an injection of mangafodipir trisodium (Mn) contrast and a second scan performed with an average delay of 62 min after the Gd bolus injection. The images were evaluated to determine the appearance of liver lesions after administration of each contrast agent, and for evidence of prior Gd administration adversely affecting evaluation of images acquired after Mn administration. Focal liver lesions were present in 19 patients, including 8 with liver metastases, 1 with liver lymphoma, 6 with hemangiomas, 3 with focal nodular hyperplasia (FNH), and 1 with hepatic abscess. In 2 other patients no liver lesions were identified in either the post-Gd or post-Gd-post-Mn scans. All malignant lesions identified on the post-Gd scan were also identified on post-Gd-post-Mn scans. Although the potential benefit for increasing detection sensitivity for hepatic metastases was not demonstrated, this is a preliminary series. This study does demonstrate the practicality for use a single visit sequential Gd-Mn protocol described here, with possible application of this technique for further assessment of the utility of combining Gd and Mn for detection of liver metastases.

Activation of retinoic acid receptor gamma induces proliferation of immortalized hippocampal progenitor cells.

In the present study, we report evidence that activation of RARgamma promotes cell proliferation in immortalized hippocampal progenitor cell line HiB5. We found that treatment of HiB5 cells with all-trans- (all-trans-RA) or 9-cis-retinoic acid (9-cis-RA) significantly increased the number of dead floating cells as well as viable cells in serum-free defined medium (N2). Flow cytometric analysis of DNA contents revealed that the proportion of apoptotic cells over the whole cell population was not affected by both retinoids. Instead, the proportion of S phase cells was significantly increased by retinoids. Under this condition, bcl-2 mRNA levels were significantly increased over time by retinoid treatment, whereas bax mRNA levels were not affected. This suggests that retinoids increase viable cells by enhancing proliferation rather than by suppressing apoptosis. In an attempt to dissect the molecular mechanism underlying retinoid-induced HiB5 cell proliferation, we examined the expression patterns of retinoid receptors following retinoid treatment. Retinoids induced RARgamma mRNA, which paralleled the increase in the transactivation of strong retinoic acid response element (RARE) reporter construct. Accordingly, treatment of HiB5 cells with RARgamma-selective agonist (CD666) increased HiB5 cell number in a dose-dependent manner, which was blocked by co-treatment with RARgamma-selective antagonist (CD2665). Taken together, these data clearly indicate that activation of RARgamma increases proliferation of immortalized hippocampal progenitor cells.