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Biomedical subjects

J J Chung

Publications and source records attributed to J J Chung.

At least 19 recordsLinked to original sources

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.

Animals↗

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.

Adenoma↗

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.

Adolescent↗

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.

Animals↗

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.

Acute Kidney Injury↗

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.

Aged↗

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.

Alitretinoin↗

Functional impairment of lens aquaporin in two families with dominantly inherited cataracts.

Opacities in the crystalline lens of eye appear with high frequency in the general population. Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP). Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life. To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R. Both substitutions cause loss of membrane water channel activity due to impaired trafficking of the mutant proteins to the oocyte plasma membrane. Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour. To our knowledge, these studies represent the first in vitro demonstration of functionally defective AQP0 protein from humans with congenital cataracts. Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts.

Amino Acid Sequence↗

Colon diseases: MR evaluation using combined T2-weighted single-shot echo train spin-echo and gadolinium-enhanced spoiled gradient-echo sequences.

This study demonstrates the appearance of large bowel diseases on magnetic resonance (MR) images using breath-hold T2-weighted half-Fourier acquisition snapshot turbo spin-echo (HASTE), breath-hold T1-weighted spoiled gradient-echo (SGE), and breath-hold gadolinium-enhanced T1-weighted SGE with and without fat-suppression sequences. The study represents a collective experience using a generalized combined abdominal-pelvic imaging protocol. Of 29 patients, 27 had surgical, endoscopic, microbiological, and/or histopathological correlation, and 2 had a diagnosis based on characteristic imaging findings. Fifteen patients had neoplastic disease including colon adenocarcinoma (n = 11), rectosigmoid carcinoid (n = 1), familial adenomatous polyposis (n = 2), and cecal lipoma (n = 1). Fourteen patients had non-neoplastic disease including diverticulosis (n = 6), ischemic colitis (n = 2), pseudomembranous colitis (n = 2), acute appendicitis with periappendiceal abscess (n = 2), Mycobacterium avium intracellulare (MAI) colitis (n = 1), and Crohn's proctocolitis (n = 1). In all 15 patients with neoplastic diseases, MR imaging depicted the primary lesions and demonstrated local extent. Mass lesions were best shown on T2-weighted HASTE and gadolinium-enhanced fat-suppressed SGE images. Of 14 patients with non-neoplastic diseases, inflammatory changes were best shown on gadolinium-enhanced fat-suppressed T1-weighted SGE images in all cases. MR imaging with fast scanning breath-hold techniques and intravenous gadolinium enhancement provided good depiction and characterization of large bowel diseases.

Adolescent↗

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.

Adult↗

Osteoma cutis coexisting with cutis laxa-like pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disorder of elastic fibers characterized by yellowish, coalescing papules on the loose and wrinkled flexural area. There have been no reports of osteoma cutis associated with PXE. A 17-year-old Korean girl presented cutis laxa-like marked wrinkling on the flexural area, and a skin biopsy specimen revealed multiple foci of ossification with irregularly clumped, basophilic-stained elastic fibers in the reticular dermis and calcium deposits along the elastic fibers. Ultrasonographic evaluation showed multiple tiny osteomas diffusely scattered along the entire abdominal wall, axillae, and medial aspect of the upper arms. We report the first case of osteoma cutis coexisting with cutis laxa-like PXE.

Adolescent↗

Radiologic findings of Mirizzi syndrome with emphasis on MRI.

We have reported a case of Mirizzi syndrome preoperatively diagnosed using MR cholangiopancreatography. MRCP and T2-weighted image using a single-shot fast spin-echo sequence accurately depicted all components of Mirizzi syndrome, including impacted stone in the neck of the gallbladder compressing the common hepatic duct and wall-thickening of the gallbladder without any evidence of malignancy. The combination of MRCP and T2-weighted image can be counted on to replace conventional modalities of diagnosing Mirizzi syndrome without any loss of diagnostic accuracy.

Bile Duct Diseases↗

T2-weighted fast spin-echo MR findings of adenocarcinoma of the uterine cervix: comparison with squamous cell carcinoma.

The purpose of this study was to investigate the differences in MR findings of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix and to compare MR findings with pathologic findings. MR images of 17 patients with pathologically proven AC, using a fast spin-echo (FSE) T2-weighted image (T2WI) with pelvic phased-array coil on a 1.5-T unit, were retrospectively evaluated. After measurement of the signal intensity (SI) ratios of the region of interest between tumors and gluteus maximus muscle, we compared the ratios of AC with those of 16 patients with SCC. AC showed relatively high SI on FSE T2WI with multiseptated lesions in four cases and hydrometrocolpos in three cases. The mean SI ratio was 3.82 +/- 1.68 in AC and 2.35 +/- 0.42 in SCC (p < 0.0001, t-test). Multiple tumorous glands with cytoplasmic and intraglandular mucin or serous fluid were pathologically found in AC, but SCC revealed the compact cellularity of stratified squamous tumor cells. The cervical AC showed higher SI than SCC on FSE T2WI with occasional multiseptated lesions and hydrometrocolpos. If the SI ratio of the tumor was more than 3.0, AC could be diagnosed with a sensitivity of 68.8% and a specificity of 100%.

Adenocarcinoma↗

Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments.

Hepatic injury and chronic wounding are characterized by increased synthesis of extracellular matrix proteins including hyaluronan (HA). Recently, it has been recognized that low-molecular-weight fragments of HA, but not native HA (e.g., high-molecular-weight HA), induce inflammatory gene expression, and activate the transcriptional regulator, nuclear factor kappaB (NF-kappaB). The inducible isoform of nitric oxide synthase (iNOS) is induced by cytokines and/or lipopolysaccharide (LPS) through the NF-kappaB signal transduction pathway. Because of this association, we hypothesized that HA fragments might also stimulate iNOS gene transcription. The aims of this study were therefore to determine whether HA or HA fragments induced iNOS in hepatic cells, and to characterize the signaling pathway. HA fragments (100 microg/mL) markedly stimulated iNOS messenger RNA (mRNA) in endothelial and Kupffer cells, but minimally induced this mRNA in hepatocytes and stellate cells. High-molecular-weight HA (200 microg/mL) had no effect on iNOS mRNA in any cell type. The addition of interferon gamma (IFN-gamma) to HA fragments resulted in stimulation of iNOS mRNA 2-, 3-, 4-, and 10-fold above that for HA fragments alone in hepatocytes, endothelial, Kupffer, and stellate cells, respectively. The combination of HA fragments and LPS did not result in an incremental increase in iNOS mRNA induction. iNOS protein and nitrite levels (used as a measure of NO production and NOS enzymatic activity) paralleled closely iNOS mRNA expression and increased proportionally to HA fragment concentration in a dose-dependent fashion. At 1 hour following stimulation, NF-kappaB DNA binding activity was detected in extracts from Kupffer cells stimulated with HA fragments, but not in those exposed to media alone or to high-molecular-weight HA. Finally, inhibitors of NF-kappaB blocked HA fragment-dependent iNOS mRNA induction in Kupffer and sinusoidal endothelial cells. The data indicate that HA fragments, but not high-molecular-weight HA, induce iNOS in liver, having the greatest effects on endothelial and Kupffer cells. We speculate that HA fragments may be an important stimulus for NO production in various forms of liver disease, particularly as a cofactor with inflammatory cytokines.

Animals↗