Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 91 records · Page 5Linked to original sources

PubMed1999

N-cadherin/catenin-based costameres in cultured chicken cardiomyocytes.

N-cadherin is a member of the Ca(2+)-dependent cell adhesion molecules and plays an important role in the assembly of the adherens junction in chicken cardiomyocytes. In addition to being present at the cell-cell junction, N-cadherin is associated with costameres in extrajunctional regions. The significance of the N-cadherin-associated costameres and whether catenins are components of costameres in chicken cardiomyocytes are not known. In this study, double-labeling immunofluorescence microscopy was used to determine the extrajunctional distribution of both N-cadherin and its cytoplasmic associated proteins, alpha- and beta-catenins, and their relationship to myofibrillar Z-disc alpha-actinin. N-cadherin, alpha-, and beta-catenins were all found to be present at the extrajunctional region and, in some cases, were codistributed with myofibrillar alpha-actinin exhibiting a periodic staining pattern. Confocal microscopy confirmed that both N-cadherin and beta-catenin colocalized with peripheral myofibrillar alpha-actinin on the dorsal surface of cardiomyocytes as components of the costameres. Intracellular application of antibodies specific for the cytoplasmic portions of N-cadherin, alpha-, and beta-catenin, either by electroporation or microinjection, resulted in myofibril disorganization and disassembly. These results suggest the existence of N-cadherin/catenin-based costameres in the dorsal surface of cultured chicken cardiomyocytes in addition to the integrin/vinculin-based costameres found in the ventral surface and indicate that the former set of costameres is essential for cardiac myofibrillogenesis.

Actinin↗

PubMed1999

The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.

BACKGROUND: In the initial stages of Fas-mediated apoptosis the cysteine protease caspase-8 is recruited to the cell receptor as a zymogen (procaspase-8) and is incorporated into the death-signalling complex. Procaspase-8 is subsequently activated leading to a cascade of proteolytic events, one of them being the activation of caspase-3, and ultimately resulting in cell destruction. Variations in the substrate specificity of different caspases have been reported. RESULTS: We report here the crystal structure of a complex of the activated human caspase-8 (proteolytic domain) with the irreversible peptidic inhibitor Z-Glu-Val-Asp-dichloromethylketone at 2.8 A resolution. This is the first structure of a representative of the long prodomain initiator caspases and of the group III substrate specificity class. The overall protein architecture resembles the caspase-1 and caspase-3 folds, but shows distinct structural differences in regions forming the active site. In particular, differences observed in subsites S(3), S(4) and the loops involved in inhibitor interactions explain the preference of caspase-8 for substrates with the sequence (Leu/Val)-Glu-X-Asp. CONCLUSIONS: The structural differences could be correlated with the observed substrate specificities of caspase-1, caspase-3 and caspase-8, as determined from kinetic experiments. This information will help us to understand the role of the various caspases in the propagation of the apoptotic signal. The information gained from this investigation should be useful for the design of specific inhibitors.

Amino Acid Sequence↗

PubMed1999

Paraneoplastic syndromes in patients with hepatocellular carcinoma in Taiwan.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in Taiwan. Some patients may manifest paraneoplastic syndromes during the clinical course of the disease. In this study, the authors evaluated the clinical significance of these paraneoplastic syndromes, compared the prevalence of these syndromes between cases of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related HCC, and estimated significant predictors associated with the syndromes. METHODS: Clinical data on 1197 HCC patients, including age, gender, Child-Pugh score, survival time, laboratory data (including liver biochemistry, hepatitis markers, and serum alpha-fetoprotein [AFP]), and tumor features (including tumor size, portal vein thrombosis, and histologic pictures), were retrospectively reviewed. RESULTS: A total of 232 of 1197 patients (19.4%) had paraneoplastic syndromes. HCC patients with paraneoplastic syndromes had significantly higher serum AFP; higher rates of initial main portal vein thrombosis, metastasis, and bilobal tumor involvement; larger tumor volume; and shorter survival than those without these syndromes. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than patients with HCV-related HCC (20.1% vs. 11.2%, P = 0.005). In a stepwise multivariate logistic regression analysis, AFP >50,000 ng/mL and tumor volume >30% were significant predictive variables associated with the presence of paraneoplastic syndromes in HCC patients. CONCLUSIONS: HCC patients with paraneoplastic syndromes usually had higher levels of serum AFP and larger tumor volumes than those without. Patients with HBV-related HCC had a significantly higher prevalence of paraneoplastic syndromes than those with HCV-related HCC.

Aged↗

PubMed1999

Intrastriatal transplantation of Sertoli cells may improve amphetamine-induced rotation and tyrosine hydroxylase immunoreactivity of the striatum in hemiparkinsonian rats.

This study investigated survival and neurotrophic effects of Sertoli cells transplanted in the striatum of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats. Primary cultures of Sertoli cells were established from 3-week old rats and characterized by associated marker, placental cadherin (P-cadherin). Two months after transplantation, amphetamine-induced rotations of rats transplanted with Sertoli cells were significantly lower than those of control rats. However, restoration of tyrosine hydroxylase (TH) immunoreactivity and Sertoli cells that expressed P-cadherin were only found in the striatum of the rat that showed full recovery from amphetamine-induced rotation 3 months after transplantation without immunosuppression. These results suggest that Sertoli cells transplanted in striatum of hemiparkinsonian rats may survive for at least 3 months, and improve amphetamine-induced rotation and restore TH immunoreactivity.

Amphetamine↗

PubMed1999

Characterization of novel inhibitors of cyclin-dependent kinases.

In epithelial cells progression through the G1 phase of the cell cycle and preparing the cell for the S phase is regulated by cyclin D1-cdk4. Cells that express the retinoblastoma protein (pRb) are dependent on cyclin D1-cdk4 activity for their proliferation while cells that do not express pRb are not. Overexpression of cyclin D1 and/or cdk4, and loss of expression of p16 (the natural inhibitor of cyclin D1-cdk4 activity), have been implicated in several cancers. These data suggest that the aberrant activity of cyclin D1-cdk4 correlates with the tumor phenotype. Hence, blocking cyclin D1-cdk4 activity may prove to be an effective anticancer therapy for pRb(+) tumors. In this paper, we report the identification of four novel compounds that selectively inhibit cyclin D1-cdk4 activity to various degrees. We further demonstrate that two of these compounds also selectively inhibit the target, pRb(+) tumor cells. The implications of these discoveries and their utility as anticancer agents are discussed.

Adenosine Triphosphate↗

PubMed1999

Activation of membrane-associated procaspase-3 is regulated by Bcl-2.

The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously activatable caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the caspase-3 zymogen was still associated with heavy membranes, its spontaneous activation was blocked. However, Bcl-2 expression had little effect on the levels of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane-associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to activation by exogenous cytochrome c. Our results demonstrate that intracellular membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and that control of caspase activation in membranes is distinct from that observed in the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in part by blocking the activation of membrane-associated procaspases.

Apoptosis↗

PubMed1999

Early metabolic inhibition-induced intracellular sodium and calcium increase in rat cerebellar granule cells.

1. Possible mechanisms responsible for the increases in intracellular calcium ([Ca2+]i) and sodium ([Na+]i) levels seen during metabolic inhibition were investigated by continuous [Ca2+]i and [Na+]i measurement in cultured rat cerebellar granule cells. An initial small mitochondrial Ca2+ release was seen, followed by a large influx of extracellular Ca2+. A large influx of extracellular Na+ was also seen. 2. The large [Ca2+]i increase was not due to opening of voltage-dependent or voltage-independent calcium channels, activation of NMDA/non-NMDA channels, activation of the Na+i-Ca2+o exchanger, or inability of plasmalemmal Ca2+-ATPase to extrude, or mitochondria to take up, calcium. 3. The large [Na+]i increase was not due to activation of the TTX-sensitive Na+ channel, the Na+i-Ca2+o exchanger, the Na+-H+ exchanger, or the Na+-K+-2Cl- cotransporter, or an inability of Na+-K+-ATPase to extrude the intracellular sodium. 4. Phospholipase A2 (PLA2) activation may be involved in the large influx, since both were completely inhibited by PLA2 inhibitors. Moreover, melittin (a PLA2 activator) or lysophosphatidylcholine or arachidonic acid (both PLA2 activation products) caused similar responses. Inhibition of PLA2 activity may help prevent the influx of these ions that may result in serious brain injury and oedema during hypoxia/ischaemia.

Animals↗

PubMed1999

Irreversible caspase inhibitors: tools for studying apoptosis.

Irreversible inhibitors of caspase proteases are often used in studies of apoptosis. However, vigorous interpretation of data generated with irreversible inhibitors requires quantitative analysis of their effects on enzyme kinetics. A simple method for the quantitative analysis of affinity irreversible inhibitors is introduced. The method allows simultaneous measurement of the dissociation constant Ki for the reversible binding to a caspase and the first-order rate constant k3 for the subsequent in situ covalent reaction that follows the noncovalent binding. The Ki value provides information regarding the affinity of an inhibitor for the enzyme, whereas the k3 value provides a measure of the in situ reactivity between the reactive functional groups of the bound inhibitor and the nearby nucleophilic side chain at the protease active site. This two-step kinetic analysis offers a more complete description of the characteristics of an irreversible inhibitor than does the commonly used second-order rate constant. The method has been applied to a library of irreversible caspase inhibitors. We demonstrate how the resulting quantitative inhibitory constants can be used to identify key caspase activities responsible for apoptosis in specific cellular models.

Apoptosis↗

PubMed1999

One-week ranitidine bismuth citrate in combinations with metronidazole, amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection: the RBC-MACH study.

BACKGROUND: We have previously shown that ranitidine bismuth citrate (RBC)-based triple therapy is comparable to proton pump inhibitor-based triple therapy in eradicating Helicobacter pylori infection. AIM: To test the efficacy of different combinations of antimicrobials with RBC in the treatment of H. pylori infection. METHODS: Dyspeptic patients with H. pylori infection were prospectively randomized to receive one of the following regimens: (i) RBC 400 mg, amoxycillin 1 g, clarithromycin 500 mg [RAC]; (ii) RBC 400 mg, metronidazole 400 mg, clarithromycin 500 mg [RMC]; (iii) RBC 400 mg, metronidazole 400 mg, tetracycline 1 g [RMT] (all given twice daily for 1 week); or (iv) RBC 400 mg plus clarithromycin 500 mg twice daily for 2 weeks [RC-2]. Endoscopy (rapid urease test and culture) and 13C-urea breath test (UBT) were performed before randomization. Four weeks after finishing medication, the 13C-UBT was repeated in all cases and endoscopy was offered to patients with peptic ulcers. RESULTS: Four hundred patients were randomized but in two (one in the RAC group and one in the RMC group) H. pylori infection was not confirmed. Successful eradication of H. pylori (intention-to-treat analysis and 95% CI) of RAC (86% [79-93%]), RMC (90% [84-96%]), RMT (79% [71-87%]) and RC-2 (82% [75-90%]) were comparable, with a trend favouring clarithromycin-containing triple therapy regimens. Among 276 isolates tested for antibiotic sensitivity, primary resistance to metronidazole, clarithromycin and amoxycillin was found in 56%, 2% and 0.4%, respectively. When given RMC or RMT, patients infected by metronidazole-resistant H. pylori had success in eradicating H. pylori similar to patients infected by metronidazole-sensitive H. pylori. CONCLUSION: One-week RBC triple therapy is effective in curing H. pylori infection.

Adolescent↗

PubMed1999

A Boltzmann filter improves the prediction of RNA folding pathways in a massively parallel genetic algorithm.

RNA folding using the massively parallel genetic algorithm (GA) has been enhanced by the addition of a Boltzmann filter. The filter uses the Boltzmann probability distribution in conjunction with Metropolis' relaxation algorithm. The combination of these two concepts within the GA's massively parallel computational environment helps guide the genetic algorithm to more accurately reflect RNA folding pathways and thus final solution structures. Helical regions (base-paired stems) now form in the structures based upon the stochastic properties of the thermodynamic parameters that have been determined from experiments. Thus, structural changes occur based upon the relative energetic impact that the change causes rather than just geometric conflicts alone. As a result, when comparing the predictions to phylogenetically determined structures, over multiple runs, fewer false-positive stems (predicted incorrectly) and more true-positive stems (predicted correctly) are generated, and the total number of predicted stems representing a solution is diminished. In addition, the significance (rate of occurrence) of the true-positive stems is increased. Thus, the predicted results more accurately reflect phylogenetically determined structures.

Algorithms↗

PubMed1999

Expression of the cadherin-catenin complex in well-differentiated human thyroid neoplastic tissue.

E-cadherin is a member of the cadherin family that plays a major role in epithelial integrity and tumorigenesis. Catenins are a group of cytoplasmic proteins that regulate the intracellular anchorage of cadherin and are required for the linkage between cadherin and the actin cytoskeleton. Loss of E-cadherin contributes to the pathogenesis in tumor invasion and gives a poor prognosis. In order to investigate the adhesion property of intercellular junctions in thyroid tumors, expression of alpha-,beta, and gamma-catenin should also be studied. A correlation between these molecular markers and malignancy would be useful as a preoperative diagnostic test for thyroid neoplasms. The expression of E-cadherin, alpha-, beta-, and gamma-catenin were studied in normal and neoplastic thyroid tissue by immunofluorescence microscopy and Western blot analysis. In the normal thyroid and in nodular goiter, and follicular adenoma, staining for E-cadherin, alpha-, beta-, and gamma-catenin was seen mainly at the lateral surface of epithelial cells in the follicle and the presence of these molecules was confirmed by Western blot analysis. Follicular carcinoma tissue stained positive for E-cadherin and alpha-catenin, but the results of beta- and gamma-catenin immunostaining were highly variable, with beta-catenin being absent in most follicular carcinomas (8/10) and gamma-catenin being absent in some follicular carcinomas (3/10). These results suggest that E-cadherin expression was not reduced during the pathogenesis of differentiated thyroid malignancies. Impairment of the cadherin-catenin complex at the cell junction may contribute to the malignant progression of differentiated thyroid neoplastic tissue.

Adult↗

PubMed1999

Recombination of hepatitis D virus RNA sequences and its implications.

Recombination between RNA sequences plays a role in the fast evolution of a few viruses. There has been no report on hepatitis D virus (HDV) recombination. In this study, we analyzed genetic recombination of HDV and its possible impact on evolution and clinical course. The aligned HDV sequences allowed us to construct a phylogenetic tree which supported the notion of distinct lineages of HDV. The tree was also used in the analysis of recombination using partial likelihoods assessed through optimization. Nine segments of the HDV genome with significant levels of genetic recombination were detected. Five segments were in the hypervariable region, and four were in the delta-antigen- coding region. None could be found in the well-conserved autocleavage region that is essential for replication. Recombination occurred both between and within types. The results of this study indicated that the remarkable variation in HDV genomic sequences, particularly in the hypervariable region, among different genotypes may at least partly result from multiple episodes of genetic recombination during evolution. Genetic recombination may play a significant role in increasing genetic diversity. Importantly, a genetic recombination (nt 1082-1093) occurred in one of the immunogenic domains of hepatitis delta virus antigen recognized by human and woodchuck antibodies (amino acids 174-195). Genetic recombination also occurred at another segment between nt 1517 and 1535, which was close to one of the predicted T-cell epitopes (amino acids 26-41). In longitudinal analysis of HDV genomes at different time points during chronic infection, novel dominant HDV strains with amino acid changes at these epitopes usually emerged after severe hepatitis attacks. In the comparison of HDV clones during or shortly after flare-up of liver disease, Ka/Ks ratios of > 1 were frequently found, suggesting Darwinian positive selection. Therefore, recombination in these two segments may play an important role for HDV in the evasion of immunity.

Amino Acid Sequence↗

PubMed1999

Supportive treatment, resection and transcatheter arterial chemoembolization in resectable hepatocellular carcinoma: an analysis of survival in 419 patients.

OBJECTIVE AND DESIGN: Both surgical resection and transcatheter arterial chemoembolization (TACE) are effective treatments for hepatocellular carcinoma (HCC). Few reports have compared the different treatment modalities for resectable HCC based on clinically matched groups. The aim of this study was to compare the survival rate after surgery, TACE or supportive treatment in resectable HCC patients, and also in elderly patients (> or = 70 y/o). METHODS: From 1984 to 1993, 419 consecutive patients with resectable HCC were included in this study. Of these, 311 (74%) underwent resection of tumours and 46 (11%) refused operation, opting instead for TACE. The remaining 62 (15%) who refused both methods of treatment were given supportive care. Univariate and multivariate analyses for prognostic factors and the 5-year survival rate among the groups were studied. RESULTS: Both surgical resection and TACE groups had a better 5-year survival rate than the supportive treatment group (43% and 34% vs. 7%). There was no difference in survival between the surgery and TACE groups. However, the 5-year survival rate was 11% in TACE and 41% in the surgical group when the patients were > or = 70. In multivariate analysis, female sex (P = 0.0466), tumour size < or = 3 cm (P = 0.0001), alpha-fetoprotein (AFP) < 400 U/l (P = 0.0036), single tumour (P = 0.0474), serum creatinine < or = 1.5 mg/dl (P = 0.0006) and alkaline phosphatase (AP) < or = 100 U/l (P = 0.0007) are associated with good prognosis for resectable HCC. CONCLUSION: TACE is an alternative for resectable HCC. Tumour size, tumour number, AFP level, renal function, AP level and female sex are prognostic factors. In elderly people, TACE must be used prudently and has a worse prognosis.

Age Factors↗

PubMed1999

Localization of isoprenylated antigen of hepatitis delta virus by anti-farnesyl antibodies.

Hepatitis delta virus (HDV) is a subviral pathogen that requires pre-existing or concurrent infection with hepatitis B virus (HBV). HDV expresses two forms of a single protein, the delta antigen (HDAg), which are identical except for an additional 19 residues at the C terminus of the large form. Within this C-terminal extension a cysteine residue is isoprenylated; this isoprenylation is critical for interaction with HBV envelope proteins to enable virus assembly and release into the medium. Therefore, large HDAg must be recruited to an extracellular compartment. However, immuno-staining with HDAg-specific antibodies has localized the large antigen mainly to the nucleus and supports the notion that large HDAg suppresses virus replication in the nucleus. Since isoprenylation would increase the hydrophobicity of the protein and may favour transport towards specific membranes, the question remains whether the large HDAg detected in the nucleus carries an isoprenyl group. To address this issue, antibodies against the farnesyl modification were generated to allow direct visualization of the antigen by immunofluorescence microscopy. The anti-farnesyl antibodies specifically stained large HDAg expressed in Huh-7 cells, and the signal was largely restricted to the nucleus; the staining pattern could be superimposed on those of cells stained for large HDAg. The large HDAg translocated into the nucleus was therefore isoprenylated. In addition, antibodies specific for the farnesyl modification should be applicable to the study of other similarly isoprenylated proteins.

Amino Acid Sequence↗

PubMed1999

Clinical significance of portal lymphoid aggregates/follicles in Chinese patients with chronic hepatitis C.

OBJECTIVE: Portal lymphoid aggregates/follicles (lymphoid A/F) is a characteristically histological finding in patients with chronic hepatitis C. We assessed the prevalence of lymphoid A/F in Chinese patients with chronic hepatitis C and evaluated the correlation of this phenomenon with clinical, biochemical, immunological, virological, and other histological features of these patients. METHODS: Eighty-nine Chinese patients with chronic hepatitis C were enrolled and portal lymphoid A/F was evaluated in liver biopsy. Clinical, biochemical, immunological, histological, and virological data, including serum HCV RNA titer and HCV genotype and the response to interferon therapy, were compared between patients with and without portal lymphoid A/F. RESULTS: Twenty-nine (33%) of 89 patients with chronic hepatitis C had portal lymphoid A/F. Patients with lymphoid A/F had a significantly higher frequency of HCV genotype 1b infection (p = 0.039) and had a significantly higher mean score of bile duct damage, periportal necroinflammation, and portal inflammation in liver histologies when compared with patients without lymphoid A/F. No significant difference in sex distribution, mean age, history of blood transfusion, serum liver biochemistry, presence of serum autoantibodies/cryoglobulinemia, serum viral titer, and response to interferon therapy was noted between the two groups. Multivariate logistic regression analysis showed HCV genotype 1b infection and periportal necroinflammation were significant independent predictors associated with portal lymphoid A/F. CONCLUSIONS: The presence of portal lymphoid A/F in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection and periportal necroinflammation.

Biopsy↗

PubMed1999

Prevalence and distribution of Helicobacter pylori in gastroesophageal reflux disease: a study from the East.

OBJECTIVES: The relationship between Helicobacter pylori infection and gastroesophageal reflux (H. pylori) disease (GERD) is controversial. In Asian populations, the prevalence of H. pylori infection is high and GERD is relatively uncommon. The aim of this study was 1) to test the hypothesis that H. pylori protects the esophagus against GERD, and 2) to study the pattern of H. pylori colonization and gastritis in GERD. METHODS: We conducted a prospective case-control study in which patients with GERD and asymptomatic controls were compared for the prevalence of H. pylori infection. Diagnosis of GERD was based on symptoms of heartburn that improved with acid-suppressive therapy and/or endoscopic evidence of erosive esophagitis. H. pylori status was determined by serology and, when endoscopy was indicated, was confirmed by rapid urease test and histology. Gastric biopsies were examined under hematoxylin and eosin and Giemsa stains. Density of H. pylori colonization and activity of gastritis at different parts of stomach were graded and compared according to Updated Sydney system. RESULTS: A total of 106 patients with GERD and 120 age- and sex-matched, asymptomatic controls were enrolled. The prevalence of H. pylori infection was significantly lower in GERD patients (31%) compared with controls (61%, p < 0.001, odds ratio 0.229, 95% confidence interval 0.13-0.41). H. pylori-infected GERD patients showed significantly more severe gastritis in the antrum than in other parts of stomach (mean inflammatory scores: antrum; 3.3 +/- 1.63*, body; 1.85 +/- 1.31; fundus; 1.65 +/- 0.58; cardia, 1.65 +/- 1.39; *p < 0.005). H. pylori colonization was found less commonly and at lower density at the cardia compared with other parts of the stomach. CONCLUSIONS: H. pylori infection protects against the development of GERD, and carditis is unlikely to play an important role.

Adult↗

PubMed1999

Phylogenetic analysis to document a common source of hepatitis D virus infection in a mother and her child.

BACKGROUND: Spread of hepatitis D virus (HDV) from mother to infant is rare and nucleotide evidence to document such transmission is lacking. The aim of this study was to screen the children of HDV-infected parents and compare the HDV nucleotide sequence between children and parents by phylogenetic analysis. METHODS: Fifty-seven children of 28 HDV-infected parents (23 fathers and 5 mothers, including two couples) were enrolled. HDV genomes from sera of HDV-infected parents and their children were cloned and sequenced. Comparison and phylogenetic analysis of HDV genomes were based on a region from nucleotide 911 to 1260. The homology to nucleotide sequence among different genotypes was estimated by phylogenetic analysis. RESULTS: One of the eight children whose mothers were anti-HDV positive was positive for anti-HDV. Mean heterogeneity among different HDV clones from a single subject ranged from 0.29% to 1.15%. HDV sequences from the mother and her child (referred from southern Taiwan) were nearly identical (99.7%), both showed 92.2-93.4% homology with other genotype II isolates from north Taiwan and 76.3-77.1% homology with genotype I isolates. CONCLUSIONS: Genotype II HDV is most prevalent in Taiwan. There are significant variations up to 8% in nucleotide sequence among different genotype II HDV clones isolated from patients in northern and southern Taiwan. Phylogenetic analysis revealed that HDV clones from the mother and her child form a monophyletic group, supporting a common source of infection. Susceptible children of HDV-infected mothers should be protected by hepatitis B virus vaccination and active education.

Female↗

PubMed1999

Serum levels of cytokines in hepatitis C-related liver disease: a longitudinal study.

BACKGROUND: Elevated serum cytokine levels are found in patients with acute and chronic hepatitis B. However, little is known about the development and progression of cytokines in hepatitis C infection. We conducted this study to evaluate the change and clinical significance of cytokines in the different stages of hepatitis C infection. METHODS: Circulating interleukin-1 beta (IL-1 beta), interleukin-2 receptor (IL-2r), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay in 29 patients with acute hepatitis C (AHC), 43 patients with chronic hepatitis C (CHC), 40 patients with liver cirrhosis (LC) and positive serum anti-hepatitis C antibody (anti-HCV), 36 patients with hepatocellular carcinoma (HCC) and positive anti-HCV and 30 normal controls. A cohort of patients with chronic hepatitis C was monitored for a median of seven years. RESULTS: Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels were significantly elevated in all patient groups compared with controls (p < 0.05). The serum IL-1 beta, IL-2r and TNF-alpha levels in patients with LC or HCC were higher than that in patients with AHC or CHC (p < 0.05). In the longitudinal follow-up, 12 patients with chronic hepatitis at enrollment in the study developed liver cirrhosis. For these patients, serum levels of IL-1 alpha, IL-2r and TNF-alpha were higher in liver cirrhosis than in chronic hepatitis (p < 0.05). In addition, the serum concentrations of these cytokines correlated better with indices of hepatic dysfunction (prothrombin time and indocyanine green retention ratio) than with parameters of hepatic inflammation (alanine aminotransferase and aspartate aminotransferase). CONCLUSIONS: Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels are elevated in patients with hepatitis C-related liver diseases, especially in LC and HCC patients. These levels reflect hepatic dysfunction better than liver inflammation parameters, which might explain the higher serum concentrations of cytokines in LC patients.

Adult↗