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Biomedical subjects

P Fowler

Publications and source records attributed to P Fowler.

At least 19 recordsLinked to original sources

Physicochemical characterization of cellulose from perennial ryegrass leaves (Lolium perenne).

In this study, we investigated the physicochemical properties of the cellulosic preparations obtained from both untreated perennial ryegrass leaves and de-juiced leaves. It was found that treatment at 22 degrees C with 18% NaOH and 18% KOH for 2h, and 10% NaOH and 10% KOH for 16 h yielded 28.2%, 28.8%, 22.7%, 23.4%, respectively, of 'cellulose' residue from untreated ryegrass leaves and 35.7%, 36.8%, 32.8% and 34.6%, respectively, from the de-juiced leaves. For each cellulosic fraction, the glucose content was 71.6%, 69.6%, 67.8%, 66.7%, 69.7%, 68.6%, 63.9% and 61.7%, respectively. The structure of the cellulose samples was examined using FTIR and CP/MAS (13)C NMR spectroscopy and X-ray diffraction. The cellulosic preparations were free of bound lignin except for noticeable amounts of residual hemicelluloses (28.4-38.3%), and had intrinsic viscosities between 275.1 and 361.0 mL/g, along with molecular weights from 144,130 to 194,930 g/mol. This study found that the cellulose samples isolated from both de-juiced ryegrass leaves and the untreated leaves had a much lower percent crystallinity (33.0-38.6%) than that from wood-based fibres (60-70%) and had much shorter fibres (0.35-0.49 mm) than those of either cereal straws, bagasse or wood. In addition, a partial disruption of the hydrogen bonds and microfibrils may occur during the de-juicing process by mechanical activity, which results in a decreased cellulose crystallinity and fibre length. These findings are significant in relation to hydrolysing ryegrass cellulose for bio-ethanol production.

Carbon Isotopes↗

Fractional and structural characterization of hemicelluloses from perennial ryegrass (Lolium perenne) and cocksfoot grass (Dactylis glomerata).

Sequential three-stage treatments with 80% EtOH containing 0.2% NaOH, 2.5% H2O2-0.2% EDTA containing 1.5% NaOH and 2.5% H2O2-0.2% TAED containing 1.0% NaOH at 75 degrees C for 3h released 8.0% and 10.4%, 79.1% and 77.0% and 12.9% and 12.5% of the original hemicelluloses from perennial grass and cocksfoot grass, respectively. It was found that the four alkaline peroxide-soluble hemicellulosic fractions contained higher amounts of xylose (33.4-38.2%), uronic acids (9.3-15.3%) and rhamnose (3.0-3.9%), but were lower in glucose (25.1-28.3%), galactose (13.3-15.3%) and mannose (0.4-1.5%) than those of the two alkaline EtOH-soluble hemicellulosic fractions in which glucose (32.9-36.0%), xylose (20.1-22.6%), arabinose (14.1-21.4%), galactose (16.6-19.9%), mannose (4.1-9.9%) and uronic acids (3.4-7.4%) were the major sugar components. 13C NMR spectroscopy confirmed that all the six hemicellulosic fractions were composed of galactoarabinoxylans, 4-O-methylglucuronoarabinoxylans and beta-glucan. In addition, the studies showed that the four alkaline peroxide-soluble hemicellulosic fractions were more linear and acidic and had larger molecular weights (Mw, 28,400-38,650 g mol(-1)) than those of the two alkaline EtOH-soluble hemicellulosic fractions (Mw, 16,460-17,420 g mol(-1)).

Chemical Fractionation↗

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori.

In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32,000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobacter pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagA- n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism.

Aged↗

Physicochemical characterisation of residual hemicelluloses isolated with cyanamide-activated hydrogen peroxide from organosolv pre-treated wheat straw.

Seven residual hemicellulosic preparations (19.6-45.0% of the original hemicelluloses) were extracted from wheat straw pre-treated with various organic solvents using 1.8% H2O2-0.18% cyanamide at 50 degrees C and pH 10.0 for 4 h. Their chemical compositions and physicochemical properties were determined using GC, HPLC, GPC, FT-IR and 13NMR spectroscopy. The results indicated that all the residual hemicellulosic preparations were heteropolysaccharides containing xylose, glucose, arabinose, galactose, mannose, rhamnose and 4-O-methyl-alpha-D-glucopyranosyluronic acid. The predominant monosaccharide was xylose, ranging between 67.7% and 81.9% of the total neutral sugars, composed mainly of L-arabino-(4-O-methyl-D-glucurono)-D-xylan. The content of contaminant lignin in the isolated residual hemicelluloses was 2.89-5.31%. The Mw values of the two residual hemicellulosic preparations H6 and H7 (42,710 and 44,080 g mol-1, respectively) obtained from the aqueous-alcohol pre-treated straw were much higher than those of H1-H5 (12,980-15,950 g mol-1) extracted from the organic acid pre-treated straw.

Carbohydrates↗

Characteristics of degraded cellulose obtained from steam-exploded wheat straw.

The isolation of cellulose from wheat straw was studied using a two-stage process based on steam explosion pre-treatment followed by alkaline peroxide post-treatment. Straw was steamed at 200 degrees C, 15 bar for 10 and 33 min, and 220 degrees C, 22 bar for 3, 5 and 8 min with a solid to liquid ratio of 2:1 (w/w) and 220 degrees C, 22 bar for 5 min with a solid to liquid ratio of 10:1, respectively. The steamed straw was washed with hot water to yield a solution rich in hemicelluloses-derived mono- and oligosaccharides and gave 61.3%, 60.2%, 66.2%, 63.1%, 60.3% and 61.3% of the straw residue, respectively. The washed fibre was delignified and bleached by 2% H2O2 at 50 degrees C for 5 h under pH 11.5, which yielded 34.9%, 32.6%, 40.0%, 36.9%, 30.9% and 36.1% (% dry wheat straw) of the cellulose preparation, respectively. The optimum cellulose yield (40.0%) was obtained when the steam explosion pre-treatment was performed at 220 degrees C, 22 bar for 3 min with a solid to liquid ratio of 2:1, in which the cellulose fraction obtained had a viscosity average degree of polymerisation of 587 and contained 14.6% hemicelluloses and 1.2% klason lignin. The steam explosion pre-treatment led to a significant loss in hemicelluloses and alkaline peroxide post-treatment resulted in substantial dissolution of lignin and an increase in cellulose crystallinity. The six isolated cellulose samples were further characterised by FT-IR and 13C-CP/MAS NMR spectroscopy and thermal analysis.

Cellulose↗

Investigations into the biological relevance of in vitro clastogenic and aneugenic activity.

In the current study we present a view of events leading to chemically induced DNA damage in vitro from both a cytogenetic and molecular aspect, focusing on threshold mediated responses and the biological relevance of DNA damaging events that occur at low and high cellular toxicity levels. Current regulatory mechanisms do not take into account chemicals that cause significant DNA damage only at high toxicity. Our results demonstrate a defined threshold for micronucleus induction after insult with the alkylating agent MMS. Other results define a significant change in gene expression following treatment with chemicals that give rise to structural DNA damage only at high toxicity. Pairs of chemicals with a similar mode of action but differing toxicity levels were chosen, the chemicals that demonstrated structural DNA damage only at high levels of toxicity showed an increase in heat shock protein gene expression whereas the chemicals causing DNA damage events at all levels of toxicity did not induce changes in heat shock gene expression at identical toxicity levels. The data presented indicates that there are a number of situations where the linear dose response model is not appropriate for risk estimation. However, deviation from linear risk models should be dependent upon the availability of appropriate experimental data such as that shown here.

Alkylating Agents↗

Lack of association of the common immunologically anomalous LH with endometriosis.

BACKGROUND: Subfertile women with endometriosis have been reported to demonstrate impaired follicular growth, ovulatory dysfunction and disturbed LH patterns. In addition, abnormal LH and/or LH receptors have been linked with endometriosis-associated infertility. Carriers of a variant of the beta-subunit of luteinizing hormone (V-LH) are largely healthy; however, differences in their gonadal function such as alterations in gonadal steroidogenesis, ovarian reserve, pubertal development and predisposition to diseases such as infertility and polycystic ovarian disease have been found. METHODS AND RESULTS: To explore the possible relationship between endometriosis and V-LH, we examined its frequency in 230 women undergoing laparoscopic surgery for the investigation of infertility. For the entire study population, 185 (80.4%) were wild type; 42 (18.3%) were heterozygous; and three (1.3%) were homozygous for V-LH. No difference was found between women with (n = 85) and without (n = 145) endometriosis concerning the frequency of the type of LH. CONCLUSION: Our results do not support the hypothesis that the variant form of LH is associated with an altered risk of endometriosis in the population tested.

Adult↗

Hospital readmission after pulmonary resection: prevalence, patterns, and predisposing characteristics.

BACKGROUND: Our objective was to define the prevalence, patterns, and predisposing characteristics for hospital readmission after pulmonary resection. METHODS: Five years of pulmonary resections, excluding lung biopsies, were analyzed from a prospective, computerized database. Readmission was defined as inpatient or emergency department admission within 90 days of operation. Search of 1,173,912 admissions to the Providence Health System in Oregon identified readmissions. Readmission analysis excluded operative deaths. RESULTS: A total of 374 patients underwent pulmonary resections, of whom 8 died (2.1%). Of 366 patients discharged, 69 (18.9%) were readmitted a total of 113 times: 42 had only one readmission, 16 had two readmissions, 7 had three readmissions, 2 had four readmissions, and 2 had five readmissions. Slightly more than half (51%) were readmitted as inpatients. Causes of the 113 readmissions included pulmonary (27%), postoperative infection (14%), cardiac (7%), and other (16%). Mean time to readmission was 32.5 +/- 24.6 days. Inpatient readmission mean length of stay was 4.9 +/- 3.4 days. Readmission to hospitals other than the hospital of the operation was as follows: first readmission, 15.9%; second readmission, 14.8%; third readmission, 36.3%; fourth readmission, 25%; fifth readmission, 0%. Analysis revealed only pneumonectomy as a risk for readmission. Twelve of 33 (36%) pneumonectomies were readmitted (p = 0.005). Of the 297 patients discharged after pulmonary resection and not requiring readmission, 12 (4%) died over the study interval, whereas 8 of 69 patients (11.6%) requiring readmission died. CONCLUSIONS: Readmission after pulmonary resection is frequent and multiple readmissions are common. Causes are predominately pulmonary diagnoses and infections related to the operation. Pneumonectomy is a risk for readmission. An important portion of readmissions occurs outside the hospital of operation. The population requiring readmission after successfully undergoing pulmonary resection is at increased risk of subsequent mortality.

Adolescent↗

Brief report: Lack of correlation between age of symptom onset and contemporaneous presentation.

The parents/guardians of 50 individuals were surveyed using a semistructured interview to determine the feasibility of this method and to establish ages of symptom onset. Thirty-eight informants were able to recall sufficient detail to allow categorization of the age of symptom onset. Chi-square analysis confirmed a significant association between investigators' categorization and informants' categorization. Contemporaneous presentation was indexed using Childhood Autism Rating Scale, the Autism Behavior Checklist, the Conners Hyperactivity Index, and the Ritvo-Freeman Real Life Rating Scale for Autism. No significant correlations were determined between any of these indices of symptom severity and age of symptom onset.

Adolescent↗

Evaluation of ewe vaccination as a tool for increasing bighorn lamb survival following pasteurellosis epizootics.

We conducted field and laboratory experiments to evaluate whether treating pregnant bighorn ewes with a combination of an experimental Pasteurella trehalosi and Mannheimia haemolytica (formerly P. haemolytica) vaccine and a commercially-available bovine P. multocida and M. haemolytica vaccine would increase lamb survival following a pneumonia epidemic. Three free-ranging bighorn herds affected by pasteurellosis outbreaks between November 1995 and June 1996 were included in the field experiment. Post-epidemic lamb survival was low in all three herds in 1996, with November lamb:ewe ratios of < or = 8:100. In March 1997, thirty-six ewes (12/herd) were captured and radiocollared. Half of the ewes captured in each herd were randomly selected to receive both vaccines; the other half were injected with 0.9% saline solution as controls. Lambs born to radiocollared ewes were observed two or more times per week and were considered to have survived if they were alive in October 1997, about 6 mo after birth. Lamb survival differed among herds (range 22% to 100%), and survival of lambs born to vaccinated ewes was lower (P = 0.08) than survival of lambs born to unvaccinated ewes. Bronchopneumonia (pasteurellosis) was the dominant cause of mortality among lambs examined. We concurrently evaluated vaccine effects on survival of lambs born to seven captive ewes removed from the wild during the 1995-96 epidemic. Antibody titers were high in captive ewes prior to vaccination, and vaccines failed to enhance antibody titers in treated captive ewes. None of the captive-born lambs survived. These data suggest that, using existing technology, vaccinating bighorn ewes following pneumonia epidemics has little chance of increasing neonatal survival and population recovery.

Agglutination Tests↗

Tourniquet versus no tourniquet use in routine knee arthroscopy: a prospective, double-blind, randomized clinical trial.

PURPOSE: The purpose of this study was to determine the effects of tourniquet use for routine knee arthroscopy based on both subjective and objective functional outcome measures. TYPE OF STUDY: The study was a prospective, double-blind, randomized clinical trial. MATERIALS AND METHODS: There were 120 patients randomized to tourniquet inflation (300 mm Hg) or no tourniquet inflation during routine knee arthroscopy. Patients recorded their average pain on a visual analog scale and their narcotic use for the previous 24 hours, for the first 5 postoperative days. Patients also completed a preoperative and postoperative (2 week, 6 week, 3 month) Western Ontario and McMaster University Osteoarthritis Index (WOMAC), 6-minute walk, 30-second stair climb, 1-leg standing vertical leap, range of motion, and isokinetic strength testing. Time to return to work and sport was documented. RESULTS: No statistically significant difference was found between tourniquet-up and tourniquet-down groups for the WOMAC quality of life measure, functional tests, isokinetic muscle strengthening, or time to return to work or sport (t test/repeated measures analysis of variance). However, there was a trend for less early postoperative pain and slightly better isokinetic strength testing at 2 weeks in the tourniquet-down group. Visualization was rated by surgeons to be 3 times better in the tourniquet-up group, although mean operative time did not differ between the groups. CONCLUSION: The use of a pneumatic tourniquet at 300 mm Hg does not significantly effect overall patient quality of life or functional outcome following routine knee arthroscopy.

Adult↗

The efficacy of femoral nerve block in pain reduction for outpatient hamstring anterior cruciate ligament reconstruction: a double-blind, prospective, randomized trial.

The purpose of this study was to assess the efficacy of intraoperative femoral nerve block (FNB) in the reduction of postoperative pain following anterior cruciate ligament (ACL) hamstring reconstruction. Patients undergoing primary ACL reconstruction with hamstring tendon graft under general anesthetic who had signed an informed consent were included in the study. Patients were stratified to 4 surgeons and randomized to FNB with 0.25% bupivacaine or placebo of normal saline injected into the femoral nerve sheath before reversal of the general anesthetic. All patients received an intra-articular injection of bupivacaine at the beginning of their operative procedure. A single technique that included the use of a peripheral nerve stimulator was used for all FNBs. All patients were discharged on the day of surgery and given prescriptions for Tylenol 3. The Short-Form McGill Pain Questionnaire (SF-MPQ), a visual analog scale (VAS) for pain, and a medication diary recording Tylenol 3 usage were completed by patients in the recovery room, on the night of surgery, and on postoperative days 1, 2, and 3. There were complete data for 61 patients (FNB, 29; placebo, 32). An analysis of variance (ANOVA) test of the data showed no significant difference between the FNB and placebo group for pain reduction over the combined study period for both the SF-MPQ and VAS. However, the ANOVA does suggest that, on the night of surgery, there was a significant reduction in pain as measured with the VAS in the FNB group. A Student t test performed on the night of surgery data (SF-MPQ, P = .131; VAS, P = .0114; Tylenol 3, P = .076) showed a statistically significant difference between the FNB (39.4+/-21.0 mm) and placebo (56.8+/-24.6 mm) measured by VAS. Because this represented a difference of only 1.74 cm on a 10-cm VAS, it is unlikely to be clinically relevant. No difference was found in the amount of analgesic required on any day postoperatively. In conclusion, FNB may reduce pain on the night of surgery. However, this may not be clinically significant. FNB is not recommended at this time for use in outpatient ACL reconstruction with hamstring graft.

Adolescent↗

Compartment pressure monitoring during anterior cruciate ligament reconstruction.

A prospective double blind randomized study was carried out using 20 healthy males with anterior cruciate ligament (ACL) insufficiency undergoing bone-patellar tendon-bone ACL reconstruction. The subjects were randomized into either water or saline irrigation and then underwent identical reconstructive procedures using an arthroscopic pump. Continuous preoperative, intraoperative, and postoperative pressures were monitored using the slit catheter technique. Blood pressure and compartment pressure measurements were continuously recorded and noted at all stages of the procedure. Mean preoperative anterior and posterior compartment pressures were similar in both groups. No significant differences were noted between the anterior and posterior compartments of each group. No difference between water and saline irrigation was identified throughout the procedure. In both groups, postoperative pressures were slightly lower in the anterior and posterior compartments compared with preoperative pressures, but not significantly.

Adolescent↗

The effect of bracing on varus gonarthrosis.

BACKGROUND: The purpose of this study was to compare a custom-made valgus-producing functional knee (unloader) brace, a neoprene sleeve, and medical treatment only (control group) with regard to their ability to improve the disease-specific quality of life and the functional status of patients who had osteoarthritis in association with a varus deformity of the knee (varus gonarthrosis). METHODS: The study design was a prospective, parallel-group, randomized clinical trial. Patients who had varus gonarthrosis were screened for eligibility. The criteria for exclusion included arthritides other than osteoarthritis; an operation on the knee within the previous six months; symptomatic disease of the hip, ankle, or foot; a previous fracture of the tibia or femur; morbid obesity (a body-mass index of more than thirty-five kilograms per square meter); skin disease; peripheral vascular disease or varicose veins that would preclude use of a brace; a severe cardiovascular deficit; blindness; poor English-language skills; and an inability to apply a brace because of physical limitations such as arthritis in the hand or an inability to bend over. Treatment was assigned on the basis of a computer-generated block method of randomization with use of sealed envelopes. The patients were stratified according to age (less than fifty years or at least fifty years), deformity (the mechanical axis in less than 5 degrees of varus or in at least 5 degrees of varus), and the status of the anterior cruciate ligament (torn or intact). The patients were randomly assigned to one of three treatment groups: medical treatment only (control group), medical treatment and use of a neoprene sleeve, or medical treatment and use of an unloader brace. The disease-specific quality of life was measured with use of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), and function was assessed with use of the six-minute walking and thirty-second stair-climbing tests. The primary outcome measure consisted of an analysis of covariance of the change in scores between the baseline and six-month evaluations. RESULTS: One hundred and nineteen patients were randomized. The control group consisted of forty patients (thirty-one men and nine women; mean age, 60.9 years); the neoprene-sleeve group, of thirty-eight patients (twenty-seven men and eleven women; mean age, 58.2 years); and the unloader-brace group, of forty-one patients (twenty-eight men and thirteen women; mean age, 59.5 years). Nine patients withdrew from the study. At the six-month follow-up evaluation, there was a significant improvement in the disease-specific quality of life (p = 0.001) and in function (p< or =0.001) in both the neoprene-sleeve group and the unloader-brace group compared with the control group. There was a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to pain after both the six-minute walking test (p = 0.021) and the thirty-second stair-climbing test (p = 0.016). There was a strong trend toward a significant difference between the unloader-brace group and the neoprene-sleeve group with regard to the change in the WOMAC aggregate (p = 0.062) and WOMAC physical function scores (p = 0.081). CONCLUSIONS: The results indicate that patients who have varus gonarthrosis may benefit significantly from use of a knee brace in addition to standard medical treatment. The unloader brace was, on the average, more effective than the neoprene sleeve. The ideal candidates for each of these bracing options remain to be identified.

Bone Diseases, Developmental↗

Polyclonality and multispecificity of the CTL response to a single viral epitope.

The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site will not usually lead to viral escape from all CTL clones of the same epitope specificity. Given these constraints and the fact that the CTL response is usually directed against several different epitopes during most viral infections, mutational inactivation of a single epitope is not likely to be sufficient to cause viral persistence.

Amino Acid Substitution↗

Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice.

Hepatitis B virus (HBV) transgenic mice that are immunologically tolerant to HBV-encoded Ags represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies before testing in humans. Five lineages of HBV transgenic mice were immunized with plasmid DNA that encodes hepatitis B surface Ag (HBsAg) or with cytokine-activated bone marrow-derived dendritic cells (DCs) in an attempt to break tolerance to HBsAg at the B and T cell levels. DNA immunization stimulated an Ab response but not a cytotoxic T lymphocyte response to HBsAg in two of the five transgenic lineages studied. In contrast, infusion of activated transgenic or nontransgenic DCs stimulated a splenic CTL response in all three transgenic lineages immunized in this manner at precursor frequencies comparable to those in nontransgenic mice, indicating that DC function is normal, and HBsAg-specific CTLs are present but functionally silent in these transgenic animals. Importantly, none of the animals developed hepatitis or displayed suppressed viral gene expression or replication following either DNA immunization or DC administration even in the presence of anti-hepatitis B surface (HBs) Abs and HBs-specific CTLs. These results indicate that Ag presentation by cytokine-activated DCs can break tolerance and trigger an anti-viral CTL response in HBV transgenic mice, and they suggest that this strategy is more efficient than DNA immunization in this setting. Nonetheless, more efficient immunization strategies are needed to stimulate an immune response of sufficient quality and magnitude to achieve an immunotherapeutic antiviral effect.

Adoptive Transfer↗

Immune pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanisms potentially responsible for HCC during chronic HBV infection are not well defined. This study demonstrates that chronic immune-mediated liver cell injury triggers the development of HCC in the absence of viral transactivation, insertional mutagenesis, and genotoxic chemicals. These results strongly suggest that the immune response to HBV is both necessary and sufficient to cause liver cancer during chronic HBV infection, and that all other procarcinogenic events associated with HCC are probably dependent on this process.

Animals↗