[Natural course and progression of liver cirhosis in patients with hepatitis C].
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Carcinoma, Hepatocellular↗
Biomedical subjects
S Zeuzem
Publications and source records attributed to S Zeuzem.
[Long-term follow-up and therapeutic control of a hepatic metastatic acinar cell carcinoma of the pancreas using FDG PET].
A 33 years old woman presented with cramp-like abdominal pain. Ultrasound examination revealed multiple lesions in the liver of hyper- and hypoechoic echogenicity which in accordance to subsequently performed computed tomography and dynamic hepatobiliary scintigraphy were considered to be a focal nodular hyperplasia (FNH). A severe increase of the serum lipase concentration, suspected to be an acute pancreatitis, was treated conservatively and led to a short improvement of symptoms. Some months later, a severe progression of the pain symptoms occurred, along with a measurable expansion of the abdominal circumference and palpable tumors of the liver. The dynamic hepatobiliary imaging and the static liver scan showed a decreased perfusion and function of the nodes as well as a reduced RES activity, respectively. A subsequently performed Positron Emission Tomography (PET) with F-18-Fluorodeoxyglucose (FDG) showed a massively increased glucose metabolism of the liver tumors. The histologic result of several biopsies of the tumors revealed metastases of an acinus cell carcinoma of the pancreas. Under systemic and local chemotherapy, a temporary remission could be obtained that was clearly detectable in a second FDG-PET. Nevertheless, during the further course of the disease, a progression occurred being detectable in an additional control PET-study by an increase in tumor size as well as in tumor glucose metabolism. The patient died in liver coma 15 months after the histologic diagnosis was obtained.
Adult↗
[Mutated serine-threonine kinase gene (STK11) is the cause of Peutz-Jeghers syndrome].
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Chromosomes, Human, Pair 19↗
Limited value of fluorine-18-fluorodeoxyglucose PET for the differential diagnosis of focal liver lesions in patients with chronic hepatitis C virus infection.
AIM: The differentiation of HCC from liver metastasis or benign disorders by imaging studies based upon morphological aspects may be difficult. METHOD: In order to evaluate the role of tumour metabolism, we performed FDG-PET (whole-body PET and transmission-corrected regional scans of the liver as well as the SUV determined 60 min after injection of FDG) in ten consecutive patients with HCV-associated focal liver lesions. Definite diagnosis was established after ultrasound-guided liver biopsy followed by histopathological examination. These results were compared with ultrasound, computed tomography, serum anti-p53, and p53 protein expression. RESULTS: The histologic examination revealed a HCC in five patients, regenerative nodules in three patients, and liver metastasis (primary malignancy: one adenocarcinoma and one neuroendocrine tumour) in the remaining two patients. Three of ten lesions were detectable by FDG-PET: two HCCs and one metastatic adenocarcinoma. Seven lesions were not distinguishable by FDG-PET (three HCCs, three regeneration nodules and one metastatic neuroendocrine tumour). In each patient hepatic lesions were visible either by ultrasound or CT. Both tumours (metastatic adenocarcinoma, moderately well-differentiated HCC) with the strongest expression of p53 also presented with highly increased FDG uptake. CONCLUSIONS: FDG-PET is not superior to ultrasound or CT and therefore does not allow the non-invasive differentiation of HCV-associated focal liver lesions. Tissue-diagnosis by means of liver-biopsy followed by histopathological examination remains the gold-standard for the differentiation of HCV-related liver lesions. The finding of the relationship of p53 protein overexpression with the SUV needs further confirmation.
Adult↗
[GB virus-C/hepatitis G virus--discovery, epidemiology, diagnosis and clinical relevance].
Recently, two isolates of a new virus, designated GB virus C (GBV-C) and hepatitis G virus (HGV) were identified. Genomic organization place them in the family Flaviviridae, which includes HCV. A classification of GBV-C/HGV strains into at least three genotypes (West Africa, Europe/North America, Asia) has been proposed. GBV-C/HGV has a positive-stranded, linear RNA genome possessing a large open reading frame that encodes a single large polyprotein. As a possible genomic defect no core protein has yet been identified in GBV-C/HGV isolates. Whether GBV-C/HGV can be classified as a hepatotropic virus with replication in the liver is under discussion. The prevalence in the general population is high (2%). GBV-C/HGV is transmitted parenterally e.g., by transfusion of blood and blood products. Furthermore, cases of vertical and horizontal transmission are reported. Detection of GBV-C/HGV infection is exclusively possible by reverse transcription polymerase chain reaction (RT PCR). E2-specific antibodies are associated with loss of detectable GBV-C/HGV RNA and appear to indicate recovery from GBV-C/HGV infection. An acute icteric state with transient elevation of aminotransferases in association with GBV-C/HGV infection may exist. These cases are rare and approximately only 0.3% of persons with acute viral hepatitis are infected with GBV-C/HGV alone. Whether GBV-C/HGV is a cause of fulminant hepatic failure has not yet been proven. Persistent viremia of the GBV-C/HGV infection is frequent but is not related to chronic liver disease. Since no other chronic diseases associated with GBV-C/HGV infection could yet be identified, chronic GBV-C/HGV infections appear to be without clinical significance. GBV-C/HGV and hepatitis B or C virus (HBV, HCV) coinfection seem not to interfere with the outcome of HBV-respective HCV-related liver disease. The cause of the majority of cases with non-A-E viral hepatitis remains unknown and other yet undiscovered hepatic viruses must exist.
Cross-Sectional Studies↗
[Sonographic detection of lymph nodes in the hepatoduodenal ligament].
BACKGROUND AND OBJECTIVE: In patients with chronic inflammatory liver disease modern methods of ultrasound can visualize enlarged lymph nodes in the porta hepatis. Number, size and total volume of lymph nodes in the hepatoduodenal ligament in healthy subjects and in patients with chronic viral hepatitis without cirrhotic changes were investigated. PATIENTS AND METHODS: Sonographic localization of the perihepatic lymph nodes was validated at post-mortem and intraoperatively. Following this, 92 healthy persons (57 men, 35 women; average age 33 +/- 9 years) and 48 patients (30 men, 18 women; average age 35 +/- 8 years) with serologically and histologically confirmed chronic viral hepatitis (30 with hepatitis C, 18 with hepatitis B) were investigated by abdominal ultrasound (Acuson 128, 3.5 and 5 MHz). The hepatoduodenal ligament was assessed according to a standardized procedure with demonstration of the lymph node positions ventral to the portal vein and between the portal vein and the inferior vena cava. RESULTS: Satisfactory imaging of the hepatoduodenal ligament was achieved in 83 of the 92 healthy persons (90.2%) and in 44 of the 48 patients with chronic viral hepatitis (91.7%). Lymph nodes were demonstrated in 60 of the 83 healthy subjects (72.3%) and in 43 of 44 patients with chronic hepatitis (97.7%). The mean perihepatic lymph node volume was 2.8 +/- 2.6 cm3 (0-9.7 cm3) and was thus significantly smaller (P = 10(-9)) than in the patients with chronic viral hepatitis (19.8 +/- 15.7 cm3 [0-62.4 cm3]). There was no significant difference in lymph node volume between patients with hepatitis B and those with hepatitis C (23.1 +/- 14.9 cm3 vs 18.9 +/- 15.6 cm3; P = 0.16). CONCLUSIONS: With adequate ultrasound technique enlarged lymph nodes can be demonstrated in the porta hepatis of almost all patients with chronic hepatitis B or C. Lymph nodes of normal size can often be imaged also in healthy persons if their localization is known. The demonstration of lymph nodes in the hepatoduodenal ligament in the area of the porta hepatis and the determination of their volume can be helpful in the diagnosis of chronic inflammatory liver disease.
Adult↗
Synthetic peptides containing a BXBXXXB(B) motif activate phospholipase C-beta1.
We have recently shown that synthetic peptides of the effector domain of the low-molecular-mass GTP-binding protein Rab3 stimulate inositol 1,4,5-trisphosphate production in various permeabilized cells. To investigate the mechanism of the peptide-induced activation of phospholipase C (PLC) and to identify the PLC isoenzyme(s) targeted by these peptides, isolated pancreatic acinar membranes and cytosol were preincubated with anti-PLC antibodies before examination of PLC activity in response to the Rab3B/D effector-domain peptide (VSTVGIDFKVKTVYRH, peptide P1). Western blot analysis revealed the presence of PLC-beta1, -beta3, -gamma1 and -delta1 in membrane and cytosolic fractions. P1 stimulated PLC activity in both membrane and cytosolic fractions. Anti-(PLC-beta1) antibody inhibited P1-induced PLC activity in both subcellular fractions almost completely. Moreover, P1-induced amylase release in digitonin-permeabilized pancreatic acini was also inhibited. Other immunoneutralizing anti-PLC antibodies had no effect, suggesting that P1 activates PLC-beta1 but not PLC-beta3, -gamma1 or -delta1. P1 also activated recombinant PLC-beta1, indicating direct activation of PLC-beta1 by Rab3 effector-domain peptides. To investigate further the structure-function relationship of the peptides, truncated peptides of P1 were tested for their ability to activate PLC in isolated pancreatic acinar membranes and to stimulate amylase release from digitonin-permeabilized pancreatic acini. Peptides containing a BXBXXXB(B) motif (where B represents a basic residue and X any residue)[KVKTVYRH (EC50 of 1 nM to stimulate amylase release) approximately TVGIDFKVKTVYRH > TVGIDFKVKTVYR] were potent stimulators of amylase release and PLC activity, whereas deletion of the C-terminus (VSTVGIDF), of the two basic C-terminal amino acid residues (VSTVGIDFKVKTVY and KVKTVY), or destruction of the BXB motif (VKTVYR) resulted in inactive peptides. In conclusion, the results of the present study show that short peptides containing a BXBXXXB motif represent promising pharmacological agents to activate the PLC-beta1 isoenzyme.
Amino Acid Sequence↗
Differential expression of Rab3 isoforms during differentiation of pancreatic acinar cell line AR42J.
Evidence is accumulating that low molecular weight GTPases of the Rab3 subfamily regulate exocytosis in secretory cells. The different isoforms of Rab3 (Rab3AD) probably have opposite roles in secretory processes. In the present study we have investigated differentiation-dependent expression of Rab3 isoforms in the pancreatic acinar carcinoma cell line AR42J. The data show that AR42J cells express all four different isoforms of Rab3. Dexamethasone treatment, which increases the number of secretory granules and secretagogue-induced exocytosis several-fold, was accompanied by down-regulation of Rab3A, Rab3C, and Rab3D mRNA, whereas Rab3B mRNA and Rab3 protein were found up-regulated at the mRNA and protein level, suggesting that Rab3B might be involved in the secretory function of AR42J cells.
Amino Acid Sequence↗
[Severe acute cholestatic viral hepatitis E in a non-pregnant woman].
HISTORY AND CLINICAL FINDINGS: During a journey in Germany a 25-year-old French woman, who had been living in India for 6 months, developed a severe acute hepatitis with marked jaundice and transitory liver failure. INVESTIGATIONS: Serum titres for anti-hepatitis E virus immunoglobulins G and M were markedly raised during hospitalisation, proving acute hepatitis E, a rare disease in Central Europe. TREATMENT AND COURSE: Within two weeks symptomatic treatment brought about almost complete regression of the initially greatly increased parameters of abnormal liver function (GPT 2277 U/l, GOT 1497 U/l, GLDH 39.2 U/l); reduction of the total bilirubin level from initially 11.7 to 1.0 mg/dl). Indicators of decreased liver synthesis, such as antithrombin III, partial thromboplastin time and coagulation factors II, V and VII, quickly became normal. Flue-like and gastrointestinal symptoms and arthralgia, improved within a few days. CONCLUSION: This case documents the sporadic occurrence in Germany and the course of severe acute hepatitis E, associated with marked liver damage. It demonstrates that the disease can take a fulminant course even in non-pregnant women, leading to severe impairment of liver function and the danger of hepatic coma.
Acute Disease↗
Non-isotopic detection of hepatitis C virus quasispecies by single strand conformation polymorphism.
In patients infected with the hepatitis C virus (HCV), a heterogeneous population of viruses, so-called quasispecies exists in vivo. The hypervariable regions (HVR) within the second envelope gene (HCV-E2) show particularly highly intratypic variability and are considered to be the target of neutralizing antibodies. The aims of the study were to optimize a genotype-independent primer set for amplification of HVR-1 and to establish a sensitive SSCP analysis for rapid and non-isotopic detection of predominant serum HCV quasispecies. Using the optimized SSCP technique, changes of quasispecies composition were investigated in five chronically infected patients with HCV before and during interferon-alpha treatment. HCV genotyping was performed by sequence and phylogenetic analysis. In addition, serial viremia and serum alanine aminotransferase (ALT) levels were determined. The SSCP analysis was performed at two time points before and during interferon-alpha therapy, respectively. Four patients showed an alteration of the SSCP pattern during the first three months of interferon-alpha therapy, whereas in one patient the SSCP pattern changed before therapy and remained stable during treatment with interferon-alpha. The present approach for non-isotopic analysis of single strand conformation polymorphism provides a direct, rapid, and sensitive technique for detection of the heterogeneous population of HCV quasispecies of different genotypes. Using this test procedure, investigations of large cohorts of patients with chronic hepatitis C can be undertaken.
Alanine Transaminase↗
Mutations in the nonstructural 5A gene of European hepatitis C virus isolates and response to interferon alfa.
The response rate to interferon alfa (IFN-alpha) in patients infected with hepatitis C virus (HCV) genotype 1 isolates is poor. A region associated with sensitivity to IFN has been identified in subtype HCV-1b isolates from Japanese patients in the carboxyterminal half of the nonstructural protein NS5A (between codon 2209 and 2248). HCV-1b isolates with at least four amino acid changes in this region compared with the HCV-1b prototype sequence were sensitive, whereas isolates identical to the prototype sequence were resistant to IFN-alpha. Patients infected with HCV-1b isolates carrying 1 to 3 mutations in NS5A(2209-2248) showed an intermediate response pattern. Because of the large geographical differences observed for HCV it is unknown whether this putative IFN-alpha sensitivity determining region is also predictive for European isolates. We analyzed 32 patients chronically infected with HCV-1a or HCV-1b isolates who were treated with 3 million units of recombinant IFN-alpha three times per week for 1 year. Before initiation, during, and after treatment serum HCV-RNA levels were assessed by a quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay. The amino acid sequence of NS5A(2209-2248)was determined by direct sequencing of the PCR-amplified HCV genome and was compared with the reference sequence HCV-J. In patients chronically infected with subtype HCV-1a or HCV-1b the initial or sustained response to IFN-alpha was not related to the number of amino acid substitutions in the NS5A(2209-2248) region. In addition, the number of amino acid changes in NS5A(2209-2248) was not related to pretreatment HCV-RNA serum levels. In three patients with a pronounced initial decline of HCV-RNA levels (>3 log) sequence analyses of NS5A(2209-2248) were performed before and after therapy. Compared with the pretreatment amino acid sequence the HCV isolates of these patients revealed more mutations in the NS5A(2209-2248) region after therapy. These findings from European patients indicate that the NS5A(2209-2248) region of HCV does not represent a common interferon sensitivity determining region.
Adult↗
Enlargement of perihepatic lymph nodes in relation to liver histology and viremia in patients with chronic hepatitis C.
Inflammatory processes in organs frequently lead to hyperplasia of regional lymph nodes. In the present study, we investigated whether lymph node enlargement within the hepatoduodenal ligament may reflect the inflammatory activity within the liver of patients chronically infected with the hepatitis C virus (HCV). In 114 patients with chronic hepatitis C and 49 healthy controls, the total lymph node volume within the hepatoduodenal ligament was prospectively investigated by ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the same occasion, and specimens were semiquantitatively evaluated by the histological activity index (HAI). Hepatitis C viremia was assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%) and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected in all patients with chronic hepatitis C and in 33 of 45 controls. The mean perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than in HCV-infected patients with mild to moderate inflammatory activity, severe inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4 mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P < 10(-6)). No correlation was found between the total lymph node volume within the hepatoduodenal ligament, HCV genotypes, and liver function test results. In conclusion, enlargement of perihepatic lymph nodes in patients with chronic hepatitis C is predictive for the presence of severe inflammatory activity. The mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown but appears to be related to viral replication within the liver and the immune-mediated inflammatory response of the host.
Adult↗
Evaluation and comparison of different hepatitis C virus genotyping and serotyping assays.
BACKGROUND/AIMS: Evidence that the geno/subtype of hepatitis C virus (HCV) is predictive of the response to interferon-alpha therapy suggests that typing methods are clinically useful. In the present study, HCV isolates obtained from 74 patients with chronic hepatitis C were used to evaluate three genotyping and two serotyping assays. METHODS: The reverse hybridization assay and the DNA immunoassay are based on immobilized type-specific probes for the 5'-noncoding and the core region, respectively. A third genotyping assay utilized type-specific primers for amplification of the core region. Serotyping assays detect type-specific antibodies of the nonstructural-4 region (enzyme immunoassay) or of the core and nonstructural-4 region (recombinant immunoblot assay). Gold standard geno/subtyping of HCV isolates was performed by sequence and phylogenetic analysis of the nonstructural-5B region. RESULTS: All genotyping systems amplified the respective target region of the HCV genome with high sensitivity. The reverse hybridization assay and the DNA immunoassay correctly identified HCV-1, -2, and -3. The DNA immunoassay misinterpreted all HCV-4 isolates as HCV-4 and -5 coinfection. In the type-specific amplification assay, coinfections of subtypes HCV-1a and HCV-3a with HCV-1b could not be excluded. The reverse hybridization assay misinterpreted 1/14 HCV-1a isolates as HCV-1h, and vice versa 3/36 HCV-1b isolates as HCV-1a. Furthermore, differentiation between HCV-2a and -2c was not possible using this assay. The DNA immunoassay correctly identified all HCV subtypes. The serotyping assays, recombinant immunoblot assay and enzyme immunoassay identified HCV-1, -2, and -3 in 93% and 89% of cases, respectively. HCV-4, however, could only be recognized by the enzyme immunoassay. CONCLUSIONS: The reverse hybridization assay and the DNA immunoassay specifically identified HCV genotypes 1, 2, and 3, while crossreactivity occurred in the primer-specific amplification assay. The DNA immunoassay achieved the best performance in HCV subtyping. Both serotyping systems correctly identified HCV-1, -2, and -3 in about 90% of cases, but lack the possibility of subtyping.
DNA, Viral↗
Prevalence and clinical and histological manifestation of hepatitis G/GBV-C infections in patients with elevated aminotransferases of unknown etiology.
BACKGROUND/AIMS: Hepatitis G virus (HGV) and hepatitis GB virus-C (GBV-C) are recently identified non-A-E hepatitis-associated viruses. The prevalence of HGV/GBV-C in the general population is high (1.0-1.7%), but data on the clinical and histological manifestations of the new viruses are sparse. In the present study we investigated the prevalence and clinical and histological manifestation of HGV/GBV-C infections in patients with elevated aminotransferase levels of unknown etiology. METHODS: In 52 of 630 consecutive patients referred for evaluation of elevated aminotransferases the underlying liver disease remained unknown. Serum samples of these 52 patients with elevated aminotransferase levels of unknown etiology were tested for HGV/GBV-C RNA by reverse transcription-polymerase chain reaction (RT-PCR) using primers deduced from nonstructural regions. Cloned PCR products were sequenced and compared by phylogenetic analysis. RESULTS: HGV/GBV-C RNA was consistently detected in 7 of the 52 patients (13%). Sequence and phylogenetic analysis revealed the presence of only one subtype, with nucleotide sequence homologies between 86 and 91%. All seven patients had persistent viremia for at least 9 months. In six patients liver function test results normalized, and alanine aminotransferase levels remained persistently elevated in only one patient. Four HGV/GBV-C positive and ten HGV/GBV-C negative patients consented to a liver biopsy, which revealed similar results with minimal to mild chronic hepatitis and mild portal fibrosis. CONCLUSIONS: The prevalence of HGV/GBV-C infections in patients with elevated aminotransferases of unknown etiology is low. Since clinical, biochemical and histomorphologic features of patients with elevated aminotransferases of unknown etiology with and without HGV/GBV-C infection are indistinguishable, the role of HGV/GBV-C in the pathogenesis of chronic liver disease appears insignificant.
Adult↗
Dynamics of hepatitis B virus infection in vivo.
BACKGROUND/AIMS: Information on the kinetics of the pretreatment steady-state of HBV can be obtained from serial measurements of serum hepatitis B virus (HBV) DNA concentrations following lamivudine ((-)enantiomer of 3'-thiacytidine)-induced perturbation of the balance between virus production and clearance. METHODS: In a placebo-controlled, dose-ranging trial, lamivudine (5 to 600 mg per day) was administered for 4 weeks to 17 patients with chronic replicative hepatitis B. Serum HBV DNA levels were quantified by standard liquid hybridization techniques. The time-dependent concentrations of serum HBV DNA following lamivudine administration were subjected to iterative least-squares regression in order to obtain kinetic data on HBV life-time and viremia. RESULTS: In patients with stable HBe-antigen positive chronic hepatitis B responding to lamivudine, HBV DNA declined exponentially with a half-life of approximately 2-3 days. The minimum virus production and clearance per day in patients with chronic hepatitis B was calculated to be 6.09 x 10(11) virions/day (range 0.26 to 21.06 x 10(11) virions/day). Compared to the HBeAg levels before treatment, relative amounts of HBeAg were 1.00 +/- 0.16 and 0.96 +/- 0.20 at days 22 and 28 of treatment, respectively. Four weeks after termination of lamivudine treatment, the relative amount of HBeAg was 1.04 +/- 0.19. CONCLUSIONS: The half-life of HBV in chronically infected patients is longer and in vivo turnover rates are higher compared to recently published data on the human immunodeficiency virus type 1 and the hepatitis C virus. The constant expression of HBeAg observed in the present study during a 28-day lamivudine treatment period does not allow calculation of a definite decay rate for virus-producing cells. Our data, however, imply that the minimum half-life of infected cells may exceed 100 days.
Adolescent↗
Prevalence of hepatitis G virus and its strain variant, the GB agent, in blood donations and their transmission to recipients.
BACKGROUND: Hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) are independent isolates of a recently identified non-A through -E hepatitis virus. Prevalence in United States volunteer blood donors is 1.5 to 1.9 percent, but no data on European blood donors are available. Epidemiologic data suggest a preferred parenteral transmission route. The prevalence of HGV/GBV-C in European blood donors and the efficiency of transmission to transfusion recipients were investigated. STUDY DESIGN AND METHODS: Plasma samples from unpaid volunteer German blood donors were tested for HGV/GBV-C by in-house reverse transcription-polymerase chain reaction. Positive donors were independently retested and interviewed for parenteral transmission risks. Amplification products were sequenced and subjected to phylogenetic analysis. Recipients of reverse transcription-polymerase chain reaction-positive donations were traced and tested for HGV/GBV-C infection. RESULTS: A total of 14 (1.34%) of 1048 donors (alanine aminotransferase < 45 IU/L) were repeatedly positive for HGV/GBV-C with 9 (2.18%) of 413 urban and 5 (0.78%) of 635 rural donors (chi 2-test; p = 0.04). Isolates differed in nucleotide sequence homology over a range of 12.5 to 19.6 percent. All but one positive donor reported parenteral transmission risks. Transmission of HGV/GBV-C was detected in 4 of 9 transfusion recipients. The prevalence of HGV/GBV-C in donors with an alanine aminotransferase level > 45 IU per L was 3 percent (3/100). Two mother/child pairs were identified with highly homologous isolates. CONCLUSION: A significantly greater prevalence of HGV/GBV-C was detected in urban volunteer blood donors than in rural donors. The high prevalence in urban donors (2.18%) suggests specific transmission risks for this group. The less than 50-percent efficiency of HGV/GBV-C transmission via blood components may indicate the presence of defective viruses with reduced infectivity. There is evidence for vertical transmission.
Adult↗
Epidermal growth factor inhibits bombesin-induced activation of phospholipase C-beta1 in rat pancreatic acinar cells.
BACKGROUND & AIMS: Epidermal growth factor (EGF) inhibits bombesin-induced activation of phosphoinositide-specific phospholipase C (PLC) in pancreatic acini. The aim of this study was to investigate the mechanism by which EGF inhibits bombesin-induced activation of PLC. METHODS: Intact pancreatic acini were pretreated with pertussis toxin to study the role of Gi/o-type heterotrimeric guanosine triphosphate-binding regulatory proteins (G proteins) in EGF-induced modulation of PLC activity. To identify the PLC isoenzyme(s) and Gi/o protein subtype(s) involved in EGF-induced signaling, PLC activity was measured in isolated pancreatic acinar membranes that had been preincubated with immunoneutralizing antibodies raised against various PLC-beta isoenzymes or G protein alpha-subunits. The association of PLC-beta1 and Gi/o-type G proteins was studied by pertussis toxin-catalyzed [32P]adenosine diphosphate ribosylation of PLC-beta1 immunoprecipitates. RESULTS: Pertussis toxin pretreatment of pancreatic acini abolished the inhibitory effect of EGF on bombesin-induced PLC activation and amylase release. Anti-PLC-beta1, -beta3, and Gq/11alpha antibodies inhibited bombesin-induced PLC activity by 50%, 35%, and 65%, respectively. Anti-Gi1-2alpha, but not a Gi3alpha-specific antibody, abolished the inhibitory effect of EGF on bombesin-induced PLC activity. Pertussis toxin-sensitive G proteins coimmunoprecipitated with PLC-beta1 in an EGF-dependent fashion. CONCLUSIONS: EGF inhibits bombesin-induced activation of PLC-beta1 by a mechanism involving activation of Gi1-2 proteins in pancreatic acinar membranes.
Amylases↗
Heterosexual transmission of GB virus-C/hepatitis G virus infection.
GB virus-C (GBV-C) and hepatitis G virus (HGV) are recently identified non-A-E hepatitis-associated viruses belonging to the family Flaviviridae. The prevalence of GBV-C/HGV in the general population is high (1.2-3.0%), but data on possible transmission routes are sparse. In this report GBV-C/HGV RNA was detected in a couple by reverse transcription polymerase chain reaction (RT-PCR) using primers deduced from non-structural regions. Neither partner was coinfected with hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV). The child of the couple tested repeatedly negative for GBV-C/HGV by RT-PCR. The couple had lived in a stable monogamous relationship for 10 years and had never used barrier contraception. Other than sexual risk, factors for transmission were carefully excluded. GBV-C/HGV isolates obtained from the couple were sequenced and phylogenetically analysed together with control GBV-C/HGV isolates. The evolutionary distance between the sequences obtained from the couple (1%) was smaller than between any other GBV-C/HGV sequence. Taken together, the clinical and molecular data provide strong evidence for heterosexual but not vertical transmission of GBV-C/HGV in non-coinfected individuals.
Adult↗