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J J Chung

Publications and source records attributed to J J Chung.

35 records · Page 2Linked to original sources

Cellular localization of endothelin-1 and increased production in liver injury in the rat: potential for autocrine and paracrine effects on stellate cells.

Endothelin (ET) peptides have been implicated in the pathogenesis of several biological processes within the liver. ET levels are elevated in the circulation of patients with cirrhosis, and recent data suggest that ET may be overproduced in the liver itself in this condition. The aims of the current study were to elucidate the cellular source and expression of endothelin-1 (ET-1) in normal and injured liver, and to investigate its biological effects on stellate cells, the primary target of ETs in the liver. In normal hepatic cells, preproET-1 messenger RNA (mRNA) was detected in only nonparenchymal cells, predominantly in sinusoidal endothelial cells. After biliary fibrosis and early cirrhosis induced by bile duct ligation, preproET-1 mRNA and immunoreactive ET levels increased with progressive injury in whole liver extracts, as well as in isolated stellate and endothelial cell fractions. Eight days after bile duct ligation, the relative increase in preproET-1 mRNA was 1.6- and 7.6-fold above normal in sinusoidal endothelial and stellate cells, respectively. Additionally, immunoreactive ET peptide levels increased by 60% +/- 27% over basal values in sinusoidal endothelial cells and 98% +/- 40% in stellate cells. Cultured stellate cells responded dramatically to exogenous ET-1 by the spreading and up-regulation of smooth muscle alpha actin expression. Furthermore, in early culture before cellular activation, ET-1 (10 nmol/L) caused over a twofold increase in [3H]thymidine incorporation, while activated cells (i.e., those cultured for >1 week) exposed to ET-1 exhibited up to a fivefold decrease in [3H]thymidine incorporation. The data indicate that not only is ET-1 overproduced by both sinusoidal endothelial and stellate cells during liver injury, but that it also has potent effects on features of stellate cell activation. We conclude that autocrine and paracrine production of ET-1 is prominent and is likely to be important in the pathogenesis of hepatic diseases.

Actins↗

Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension.

BACKGROUND & AIMS: Intrahepatic vascular resistance is regulated in part by the vasoconstricting and relaxing effects of compounds such as endothelin and nitric oxide (NO). Although the hepatic endothelium is likely to be a prominent source of NO via production by endothelial cell NO synthase (ecNOS), this isoform has not been described in sinusoidal endothelial cells (SECs). The aim of this study was to determine whether ecNOS is produced by SECs, and, if so, to determine whether ecNOS- (mRNA/protein) or SEC-dependent production of NO varies after liver injury. METHODS: A cDNA encoding a 279-bp fragment homologous to bovine ecNOS was isolated and used to detect rat ecNOS mRNA. Liver injury and/or cirrhosis was induced by bile duct ligation or administration of CCl4. NOS activity was quantitated and the presence of NO was detected with highly sensitive nitrite and cGMP assays. RESULTS: ecNOS mRNA and protein (detected by immunoblot) were present only in SECs. Neither ecNOS mRNA abundance nor protein levels varied after liver injury induced by bile duct ligation or repeated CCl4 administration, including in animals with cirrhosis. Because inducible NOS is induced after bile duct ligation but not after CCl4-induced cirrhosis, we examined NOS activity and nitrite- and NO-dependent cGMP production after the latter form of injury. NOS activity and nitrite and cGMP production were significantly reduced in SECs from cirrhotic animals compared with controls (P < 0.05, n = 4-6). CONCLUSIONS: SECs are an important source of ecNOS in the liver; although ecNOS mRNA and protein levels in SECs do not seem to vary with liver injury, ecNOS function is altered, resulting in diminished NO release in SECs from cirrhotic livers. These data have important implications for the pathogenesis of intrahepatic portal hypertension as well as other disorders in which endothelia may be damaged.

Animals↗

Sonographic findings in tuberculous epididymitis and epididymo-orchitis.

PURPOSE: This paper presents the sonographic findings in scrotums of patients affected with tuberculous epididymitis or epididymo-orchitis. METHODS: Eighteen patients with a total of 22 abnormal hemiscrotums (4 patients had bilateral lesions) underwent scrotal sonography. Pathologic confirmation was obtained via epididymectomy in 10 cases, epididymo-orchiectomy in 7 cases, and scrotal exploration and biopsy in 3 cases. The histopathologic diagnosis was tuberculous epididymitis in 12 cases and epididymo-orchitis in 8 cases. RESULTS: Lesions involved the head of the epididymis in 8 cases, the tail in 5 cases, and the entire epididymis in 9 cases. The enlarged epididymis was hypoechoic in 13 cases, hyperechoic in 2 cases, and of mixed echogenicity in 7 cases. The echotexture was heterogeneous in 17 cases and homogeneous in 5 cases. Testicular involvement in 7 cases appeared as a diffusely enlarged hypoechoic testis in 2 cases, an ill-defined hypoechoic lesion in 1 case, a well-demarcated hypoechoic lesion in 2 cases, and multiple small hypoechoic nodules in an enlarged testis in 2 cases. Hydrocele, sinus tract, and extratesticular calcifications were seen in 12, 4, and 2 cases, respectively. CONCLUSIONS: The heterogeneous and hypoechoic swelling of the epididymis or the concomitant hypoechoic lesion of the testis with associated sinus tract or extratesticular calcifications may be helpful in the diagnosis of tuberculous epididymitis or epididymo-orchitis, especially in patients with known genitourinary tuberculosis.

Adolescent↗

Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis.

Nitric oxide (NO) production via inducible NO synthase (iNOS) is prominent in the liver after stimulation with cytokines and/or lipopolysaccharide. The aim of this study was to investigate the production of NO via iNOS in specific liver cell populations during toxin-mediated and obstructive hepatic injury and fibrogenesis. After a single dose of carbon tetrachloride, iNOS mRNA and nitrite (a metabolic product of NO) were detected only in Kupffer cells. They were not detectable in any cell type after recurrent administration of carbon tetrachloride, including in animals with far advanced cirrhosis (i.e., portal hypertension and/or ascites). After bile duct ligation, a mechanistically different form of liver injury and fibrogenesis, iNOS mRNA and nitrite were identified in all nonparenchymal cells but not in hepatocytes. Twenty-four hours after bile duct ligation, iNOS mRNA and NO production were greatest in Kupffer cells, but after prolonged bile duct ligation, iNOS was found predominantly in sinusoidal endothelial cells. These data indicate that iNOS expression varies temporally and spatially in the liver after injury and also varies with the type of insult.

Animals↗

Comparison of the use of the transrectal surface coil and the pelvic phased-array coil in MR imaging for preoperative evaluation of uterine cervical carcinoma.

OBJECTIVE: The purpose of this study was to compare the accuracy of fast spin-echo MR imaging that uses a transrectal surface coil with the accuracy of fast spin-echo MR imaging that uses a pelvic phased-array coil for preoperative local staging of uterine cervical carcinoma. MATERIALS AND METHODS: Sixty-two patients with pathologically confirmed invasive cervical carcinoma who underwent MR imaging using both a pelvic phased-array coil and a transrectal surface coil were retrospectively evaluated. Both sets of images were reviewed in random order by three observers who then reached a consensus opinion at a second session. Among the 28 patients who underwent radical hysterectomy, findings from MR imaging and pathologic staging were compared. In the remaining nonsurgical cases, findings from MR imaging using a transrectal surface coil and MR imaging using a pelvic phased-array coil were compared with findings from pelvic examinations under general anesthesia. RESULTS: MR imaging using a transrectal surface coil revealed 50 (88%) of the 57 tumors found at surgery, and MR imaging using a pelvic phased-array coil revealed 44 (77%) of the 57 tumors, resulting in a statistically significant (p < .05) difference. In patients who underwent surgery (n = 28), the accuracy of the overall staging and the parametrial evaluation were not significantly different for MR imaging using a transrectal surface coil and MR imaging using a pelvic phased-array coil (89% and 96%, respectively, on MR imaging using a transrectal surface coil; 89% and 93%, respectively, on MR imaging using a pelvic phased-array coil). For the patients who did not undergo surgery (n = 34), MR imaging using a transrectal surface coil and MR imaging using a pelvic phased-array coil corresponded in 82% for overall staging and in 92% for parametrial invasion. CONCLUSION: The use of a transrectal surface coil improved detection of small tumors of the uterine cervix but did not significantly improve the accuracy of overall staging or the accuracy of assessment of parametrial invasion.

Adult↗

Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing.

The liver's response to chronic injury is fibrosis, which is analogous to wound healing in other organs. Hepatic wounding is characterized by the "activation" of resident stellate cells (lipocytes, Ito cells) to myofibroblast-like cells that produce increased amounts of smooth muscle alpha-actin and extracellular matrix. Stellate cells possess abundant endothelin (ET) receptors (ETA/B) and, therefore, are subject to the effects of ET-1 and 3. In this study, we investigated whether ETs contribute to the activation of stellate cells and consequently, fibrogenesis. In cultured stellate cells, ET-1 and sarafotoxin S6C (a potent ETB receptor agonist) stimulated stellate cell activation, as assessed by expression of smooth muscle alpha-actin. Furthermore, the mixed ETA/B receptor antagonist, bosentan, blocked this process. Next, we administered bosentan during the induction of liver injury in two mechanistically distinct forms of hepatic wounding. Bosentan reduced levels of type I collagen and cellular fibronectin mRNAs in whole-liver tissue extracts in both models. In freshly isolated stellate cells from injured livers, bosentan reduced expression of activation markers, including smooth muscle alpha-actin and extracellular matrix mRNAs. We further demonstrate that endothelin antagonism after establishment of fibrosing injury reduced stellate cell activation and matrix production. These data indicate that ET contributes to stellate cell activation and fibrogenesis. Because ET is upregulated in diverse forms of parenchymal injury, we speculate that ET may play an important role in the wound-healing response.

Actins↗

Regulation of inducible nitric oxide synthase in hepatic sinusoidal endothelial cells.

Nitric oxide (NO) has many important physiological effects that depend in part on its cellular source(s). In liver, NO is produced by all major cell types, including hepatocytes, Kupffer, stellate, and sinusoidal endothelial cells (SECs). Although endothelial cells have been commonly associated with constitutive NO production, recent evidence suggests that NO is inducible in this cell type. Here, we investigated the regulation of inducible NO synthase (iNOS) in SECs. Interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) as individual compounds induced iNOS mRNA in SECs. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) had no effect when used alone but enhanced iNOS mRNA upregulation by IFN-gamma. iNOS transcription after LPS was present only for 4 h after exposure yet was more sustained after IFN-gamma/TNF-alpha, LPS was unique in that it transiently induced iNOS mRNA, whereas IFN-gamma/TNF-alpha resulted in prolonged increases in iNOS mRNA. Both LPS and IFN-gamma/TNF-alpha caused prolonged elevation of immunoreactive protein. However, when stimulated by LPS, iNOS remained enzymatically active for only 24-48 h. After IFN-gamma or IFN-gamma/TNF-alpha, iNOS activity declined only moderately. LPS added to IFN-gamma alone or IFN-gamma/TNF-alpha did not result in more rapid decay of iNOS enzymatic activity. These data indicate that induction of iNOS by sinusoidal endothelial cells is prominent and that it is regulated both transcriptionally and by its inactivation. Such complex regulation of iNOS has important implications for NO biology in liver disease.

Animals↗

Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility.

In liver injury, perisinusoidal cells known as lipocytes (Ito cells) undergo "activation," acquiring smooth muscle-like features and a contractile phenotype. To assess whether contraction of these cells is regulated by nitric oxide (NO), we examined the production of NO by lipocytes and the effect of NO on lipocyte contractility. Cultured lipocytes were exposed to cytokines and/or LPS. Single agents had little or no effect on the level of inducible NO synthase (iNOS) mRNA. However, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), or LPS in combination with interferon-gamma (IFN-gamma) stimulated iNOS mRNA, which was present within 4 h after exposure. iNOS mRNA levels were paralleled by changes in nitrite (a metabolic product of NO). Intraperitoneal administration of IFN-gamma, TNF-alpha, and LPS led to rapid induction of iNOS mRNA in lipocytes, confirming in vivo the culture findings. Ligation of the common hepatic bile duct, which induces periportal-based liver injury, stimulated iNOS mRNA in lipocytes. Transforming growth factor-beta 1 decreased IFN-gamma/TNF-alpha--stimulated iNOS mRNA and nitrite. Finally, the effect of NO on lipocyte contractility was examined. In cells incubated with IFN-gamma and TNF-alpha, the contractile response to either serum or endothelin-1 was blocked. Contraction was restored entirely by an inhibitor of NO synthase, NG-monomethylarginine. Furthermore, 8-bromoguanosine 3':5'-cyclic monophosphate and sodium nitroprusside inhibited lipocyte contractility, consistent with the effect of NO induced by cytokines. We conclude that NO is a potent modulator of lipocyte contractility and may regulate this function by autocrine (or intracrine) mechanisms. Moreover, NO may play an important role in liver injury, countering the effect of contractile agonists on lipocytes.

Adipocytes↗

Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis.

BACKGROUND: A central feature of liver injury involves activation of hepatic lipocytes (perisinusoidal cells), a process characterized by their morphologic transformation to myofibroblast-like cells. Important features of this process include new expression of smooth muscle alpha actin and production of increased amounts of extracellular matrix. Interferon gamma is a cytokine with immunomodulatory and antifibrotic properties that has potent effects on lipocytes in a culture model of activation. The aim of this study was to determine if interferon gamma inhibited lipocyte activation in an in vivo model of liver injury and whether this effect resulted in an overall reduction in hepatic fibrosis. METHODS: Liver injury (with ensuing fibrosis) was induced by carbon tetrachloride. Interferon gamma was infused continuously by osmotic pump during the induction of liver fibrosis, after which lipocytes were isolated and features of lipocyte activation were examined. Finally, whole liver type I collagen mRNA was quantitated. RESULTS: Carbon tetrachloride caused histological fibrosis, which was significantly reduced on a quantitative basis by interferon gamma. Immunocytochemical analysis of livers from animals treated with interferon gamma demonstrated a significant reduction in the number of desmin positive cells (lipocytes) in portal and noncentral lobular areas as well as in bands of fibrosis, consistent with reduced lipocyte proliferation. Using discontinuous density centrifugation, two populations of lipocytes were isolated and characterized: one migrating in the upper layer of the gradient and another to the lower layer. Interferon gamma markedly reduced smooth muscle alpha actin expression (by immunoblot) in upper layer lipocytes and had significant inhibitory but less dramatic effects on lower layer lipocytes. Interferon gamma also reduced collagen I mRNA to 36% (p < 0.001, interferon gamma versus control) and 46% (p < 0.01) of control values in upper and lower layer lipocyte samples, respectively. Effects of interferon gamma on expression of cellular fibronectin mRNA were similar. Smooth muscle actin as well as type I collagen and cellular fibronectin mRNA were more abundant in lower than upper layer lipocytes in both control and interferon gamma treated animals. Finally, interferon gamma reduced collagen I mRNA in whole liver specimens to 36% of control values (p < 0.005, for interferon gamma compared to control, n = 6). CONCLUSIONS: The data indicate that interferon gamma inhibits lipocyte activation and extracellular matrix production in vivo during liver injury, which results in an overall decrease in hepatic fibrosis. Further, the data demonstrate heterogeneity in lipocytes during activation and identify a novel population of markedly activated lipocytes.

Adipocytes↗

Abdominal tuberculous lymphadenopathy: MR imaging findings.

BACKGROUND: The purpose of this study was to evaluate the utility of magnetic resonance imaging (MRI) as a diagnostic tool in abdominal tuberculous lymphadenopathy. METHODS: MRI studies of 11 patients with histologically proven abdominal tuberculous lymphadenopathy were reviewed with regard to anatomic distribution, size, shape, degree, and pattern of enhancement and relation of the lesions to adjacent structures. RESULTS: The most common site of involvement was the periportal area (n = 6), followed by the peripancreatic (n = 5), mesenteric (n = 1), and paraaortic (n = 1) areas. Eight patients were readily diagnosed as having tuberculous lymphadenopathy on abdominal computed tomography. Three patients had a heterogeneously enhancing masslike lesion adjacent to the pancreas and were initially diagnosed as having cystic tumor of the pancreas. On MRI, 11 lesions showed T1 iso- or hypointensity and central T2 hyperintensity. Two lesions showed T1 iso- or hypointensity and central T2 hypointensity. The lesions with different T2 signal intensities showed different patterns of enhancement on contrast-enhanced dynamic studies. The relations between the enlarged lymph nodes and adjacent bile ducts or vascular structures were well depicted on MRI. CONCLUSION: MRI was useful in differentiating enlarged lymph nodes abutting the pancreas initially diagnosed as cystic neoplasms on abdominal computed tomography.

Abdomen↗

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.

Adult↗

Focal eosinophilic infiltration of the liver: a mimick of hepatic metastasis.

We present three cases of focal eosinophilic infiltration in the liver that mimicked hepatic malignancy on computed tomography during hepatic arteriography (CTHA) and computed tomography during arterial portography (CTAP). In all patients, focal eosinophilic liver infiltration appeared as a solitary nodule or as two nodules without hepatosplenomegaly and showed homogeneous hyperattenuation on CTHA and hypoattenuation on CTAP.

Diagnosis, Differential↗

Gallbladder adenomyomatosis: findings on MRI.

BACKGROUND: To describe the characteristic magnetic resonance imaging (MRI) findings of gallbladder adenomyomatosis in two cases. METHODS: Two patients had abdominal MRI findings of gallbladder adenomyomatosis confirmed at cholecystectomy. RESULTS: The surgical specimen showed findings typical of adenomyomatosis, including marked thickening of both epithelial and muscular elements with multiple Rokitansky-Aschoff sinuses. On gadolinium-enhanced spoiled gradient-echo images and single-shot fast spin-echo images, mild gallbladder wall thickening with multiple intramural cystic components from Rokitansky-Aschoff sinuses were readily visualized. CONCLUSION: Adenomyomatosis of the gallbladder can be detected and diagnosed from MRI findings.

Aged↗

Long-term experience with polyurethane, pail handle, coiled tip peritoneal dialysis catheters.

Long-term experience with 63 polyurethane, pail handle, coiled tip peritoneal dialysis catheters surgically implanted in 57 consecutive patients with renal failure is presented. One hundred percent follow-up of the study group represented 1,248 patient-months of observation. Cumulative catheter survival rates were 80.8% at 12 months, 62.3% at 24 months, and 48.1% through 51 months. Catheter half-life was 32.6 months. Infection was the most frequent catheter related complication. Incidence rate of peritonitis was 0.73, and exit site/tunnel infection was 0.42 episodes per patient-year. Median time to first episode was 11.7 months for peritonitis, and 26.3 months for exit site/tunnel infection. Infection led to removal of 28.6% of implanted devices, mechanical blockage resulted in 6.4% loss, and pericatheter leak and tubing break each accounted for 1.6% of catheter removals. The polyurethane, pail handle, coiled tip peritoneal catheter was found to be a reliable long-term access device compared with reported performances of other catheter types. An adverse outcome was identified in the current clinical series with a model design using a permanently attached catheter adapter that caused large exit site wounds that were predisposed to infection and catheter loss.

Adolescent↗

Perirectal cystic paragonimiasis: endorectal coil MRI.

We report the transrectal ultrasonographic (TRUS) and endorectal surface coil MR findings for paragonimiasis involving the perirectal space. The patient presented with voiding difficulty. TRUS showed a well demarcated, oval-shaped hyperechoic mass in the perirectal space. On endorectal MR images, the lesion was depicted as a well defined cystic mass with homogeneous intermediate signal intensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. Ectopic paragonimiasis can appear as a well defined cystic mass in the peritoneum and should be included in the differential diagnosis of cystic mass in the abdomen and pelvic cavity, including the perirectal space.

Aged↗

Colorectal mucinous carcinoma: findings on MRI.

PURPOSE: The purpose of this work was to define the characteristic MR features of colorectal mucinous carcinomas and to correlate the mucin pool with the signal intensity of this tumor. METHOD: MRI of 12 cases of pathologically proven colorectal carcinoma containing mucin was evaluated. We analyzed the signal intensity of tumor on T1- and T2-weighted MR images and correlated the area of intratumoral high signal intensity on T2-weighted images with the mucinous pool on the pathologic specimens. Two radiologists independently estimated the area of high signal intensity in the tumor on T2-weighted images and one pathologist estimated the amount of mucinous pool in the pathologic specimen. RESULTS: In 9 (75%) of 12 cases, focal or diffuse high signal intensity areas were detected on T2-weighted fast spin echo images. In seven cases in which mucin pools were seen macroscopically, partial (n = 3) or diffuse high signal intensity areas were noted on the T2-weighted images. Among the five cases in which microscopic mucinous pools were detected on the pathologic slides, three cases showed no high signal foci on MR images, and in the remaining two cases, high signal intensity areas were noted as small foci. CONCLUSION: Intratumoral high signal intensity on T2-weighted fast spin echo MR images occurs in mucinous carcinomas and correlates with the mucin pools on pathologic specimens.

Adenocarcinoma, Mucinous↗