PubMed Health⌕ Search

Biomedical subjects

B J McMahon

Publications and source records attributed to B J McMahon.

At least 19 recordsLinked to original sources
PubMed2003

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers.

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

Base Sequence↗
PubMed2001

Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus.

BACKGROUND: Knowledge of the outcome of chronic hepatitis B virus (HBV) infection is limited. OBJECTIVE: To determine the incidence of and risk factors for adverse events (hepatocellular carcinoma and end-stage liver disease) and clearance of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) in carriers of HBV. DESIGN: Population-based cohort study of hepatitis B carriers who were observed for a median of 12.3 years as part of an active surveillance program to detect carriers with hepatocellular carcinoma. SETTING: 126 communities in Alaska. PATIENTS: 1536 Alaska Natives with chronic hepatitis B. MEASUREMENTS: Bivariate comparisons, multivariable models, and other statistical methods were used to examine the relationships of risk factors to outcomes and clearance of HBeAg and HBsAg. RESULTS: 1536 chronic HBV carriers were followed up for 19 430 person-years from their first HBsAg-positive test result. At the first serologic test, 641 were HBeAg positive and 893 were anti-HBe positive. Older carriers were more likely than younger carriers to clear HBeAg (P < 0.001). The observed probability of clearing HBeAg within 10 years of diagnosis was 72.5%. Clearance of HBsAg occurred in 106 (7%) of all carriers and was positively associated with older age and positive result on initial anti-HBe test. The incidence of adverse events was 2.3 per 1000 carrier-years, and the incidence of hepatocellular carcinoma was 1.9 per 1000 carrier-years (2.3 in men and 1.2 in women). Risk for hepatocellular carcinoma increased with age, among those of Yupik Eskimo ethnicity, and among carriers who reverted from anti-HBe to HBeAg. CONCLUSION: In HBsAg-positive carriers, observed clearance of HBeAg was more than 70% during the first 10 years of follow-up.

Adolescent↗
PubMed2001

Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers.

INTRODUCTION: Hepatitis B vaccination is recommended for all healthcare workers (HCW) at risk of exposure to infectious body fluids. However, the absolute duration of protection from immunization is unknown. The purpose of this randomized comparison trial was to determine how previously immunized HCW respond to different booster doses of hepatitis B vaccine. METHOD: Adult HCW (n=59) were classified by level of hepatitis B surface antigen (anti-HBs), either <10 milli-International Units per milliliter (mIU/ml) or 10-50 mIU/ml. Participants were then randomized to receive a 2.5 or 10 microg dose of hepatitis B vaccine. Evaluation of anti-HBs levels were conducted 10 to 14 days, one month and one year postbooster. RESULTS AND DISCUSSION: All participants responded to the booster dose with increased anti-HBs levels. At 14 days, mean anti-HBs levels were significantly higher for those with higher levels at baseline (P=0.004) and those receiving the 10 microg dose (P=0.016). At one month, those with higher anti-HBs levels at baseline and those receiving the 10 microg dose were significantly higher (P<0.01 for both). At one year, the increase for the higher dose was no longer statistically significant when examined by itself (P=0.081); statistical significance (P=0.021) was achieved after adjusting for anti-HBs level at baseline. For all participants, the geometric mean anti-HBs level was 2618 mIU/ml at 14 days, 2175 mIU/ml at one month and 88.9 mIU/ml at one year. At all time points the increase in anti-HBs levels represented an increase over the geometric mean baseline level of anti-HBs (7.4 mIU/ml). Hepatitis B immunized adults responded to a booster dose of hepatitis B vaccine from 3 to 13 yr postvaccination series. Data support current recommendations that immunized HCW do not require periodic antibody testing or vaccine boosters.

Adult↗
PubMed2001

Chronic hepatitis B.

Explore the source record for details and available documents.

Hepatitis B, Chronic↗
PubMed2000

Hepatitis B virions isolated with antibodies to the pre-S1 domain reveal occult viremia by PCR in Alaska Native HBV carriers who have seroconverted.

BACKGROUND: Occult viremia occurring before the appearance of HBsAg or after the disappearance of HBsAg is detectable by gene amplification technologies whose efficiency depends on nucleic acid preparation. STUDY DESIGN AND METHODS: To isolate HBV DNA from viremic plasma, immunoaffinity capture (IAC) of intact HBV with biotinylated pre-S1 antibodies coupled to streptavidin-coated magnetic beads was evaluated. IAC was compared with a silica-gel method (Qiagen [QSG]) and its two modifications wherein the samples were heated with lysis buffer at 60(o)C for 10 minutes (QSG-60) or at 58 degrees C for 60 minutes with proteinase-K (QSG-PK). Each HBV DNA sample was tested by heminested PCR amplification of the HBV gene sequences. A total of 36 coded serum samples were tested, including three HBsAg-positive controls and 33 former chronic HBV carriers who had seroconverted (developed antibody to HBsAg [anti-HBs]). Commercially available seroconversion panels (PHM 907, 911, and 922) were similarly tested for window-period viremia. RESULTS: In the 33 former chronic HBV carriers who had seroconverted, IAC revealed HBV DNA in 17 samples, whereas it was revealed in only 11 samples by QSG-PK (p = 0.031), 10 by QSG-60 (p = 0.016), and 9 by QSG (p = 0.0078). However, HBV DNA was not amplified from the 17 samples at 1-in-10 dilutions; thus, they were considered to have low-level viremia. IAC revealed HBV DNA as early as or earlier than the other methods in PHM 907, 911, and 922 panels. CONCLUSION: IAC is apparently an optimal method of sample preparation for amplification of HBV DNA in patients in the pre-HBsAg window period, and for detecting low-level viremia persistent in several individuals who were former chronic HBV carriers who had seroconverted (developed anti-HBs).

Alaska↗
PubMed2000

Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study.

The benefits of screening hepatitis B surface antigen (HBsAg)-positive carriers for hepatocellular carcinoma (HCC) in terms of long-term survival have not been established. We conducted a prospective 16-year, population-based cohort study to determine the impact of screening for HCC in 1,487 HBsAg-positive Alaska native carriers with alpha-fetoprotein (AFP) determinations every 6 months. Men and nonpregnant women with an elevated AFP level were evaluated for the presence of HCC by ultrasound (US) examination. The long-term survival rate for patients whose HCC was detected by the screening program was compared with a historical control group of Alaska native patients with HCC from the same population who were clinically diagnosed with HCC between 1969 and October 1982, through a National Cancer Institute-sponsored Cancer Registry. Between October 1982 and December 1998, 26,752 AFP determinations in HBsAg carriers were performed. One or more AFP elevations were found in 61 men and 39 nonpregnant women. HCC was diagnosed in 32 patients (24 men and 8 women). HCC tumors less than 6 cm were found in 23 patients; 22 patients had resections, and 1 patient refused a resection. Compared with 12 patients with hepatitis B virus (HBV)-related HCC diagnosed from 1969 to October 1982, before this program, the 5- and 10-year survival rate for the 32 patients with HCC were 42% (P =.008) and 30% (P =.07), respectively. Five- and 10-year tumor-free survival rates for carriers who had a normal AFP level on initial screening and subsequently developed HCC were 29% (P =.004) and 24% (P =.024), respectively. Screening of HBsAg carriers with semiannual AFP was effective in detecting most HCC tumors at a resectable stage and significantly prolonged survival rates when compared with historical controls in this population.

Adolescent↗
PubMed2000

Elimination of new chronic hepatitis B virus infections: results of the Alaska immunization program.

An immunization assessment and a serologic survey were conducted to evaluate the effectiveness of a hepatitis B immunization program in eliminating hepatitis B virus (HBV) transmission among Alaska Natives in a region in which HBV infection is endemic. Hepatitis B vaccine coverage was 93% among 567 children </=10 years old residing in the study villages, and catch-up vaccine coverage among 582 susceptible persons 11-30 years old was 62%. None of 271 tested children </=10 years old were chronically infected with HBV, and just 4 (1.5%) had evidence of resolved infection. In contrast, 16% of 332 persons 11-30 years old (those born before implementation of routine infant hepatitis B vaccination) were chronically infected. A hepatitis B immunization program that includes prevention of perinatal HBV infection, routine infant vaccination, and catch-up vaccination of older children and adults can eliminate new chronic HBV infections in a population with a high rate of chronic infection.

Adolescent↗
PubMed1999

Hepatocellular carcinoma not related to hepatitis B virus infection among Alaska natives.

Chronic infection with hepatitis B or C viruses is a common underlying condition in patients with hepatocellular carcinoma worldwide. We studied serum and liver tissue from a cohort of Alaska natives with hepatocellular carcinoma (HCC) for evidence of hepatitis B, C and G viral infection using conventional serological tests as well as the sensitive polymerase chain reaction. Evidence of HBV infection was found in 25 and possible HCV infection in two cases. Among the remaining 11 patients, four had a history of recent or remote alcoholism while seven had no recognizable risk factors for HCC. Only one was seropositive for HGV RNA and that was an individual with a history of alcoholism. Non-tumorous liver tissue was available for study in six of these seven cases. Histological features of chronic hepatitis were present in five. Thus, at least five of 38 (13%) Alaska natives with HCC appeared to have chronic hepatitis not related to HBV or HCV infection, suggesting the possibility of some form of previously unrecognized chronic liver disease predisposing to HCC.

Adolescent↗
PubMed1998

Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease.

Acute hepatitis A superimposed on chronic liver disease (CLD) has been associated with severe or fulminant hepatitis. An open, multicenter study was performed to compare the safety and immunogenicity of an inactivated hepatitis A vaccine in patients with CLD with that in healthy subjects. A secondary objective was to compare the safety of the hepatitis A vaccine with that of a commercial hepatitis B vaccine in subjects with chronic hepatitis C. A total of 475 subjects over the age of 18 years were enrolled into 1 of 5 groups according to history, serological data, and previous diagnosis. Patients in groups 1 (healthy adults), 2 (chronic hepatitis B), 3 (chronic hepatitis C), and 5 (other CLD not caused by viral hepatitis) were vaccinated with two doses of inactivated hepatitis A vaccine, 6 months apart. Patients in group 4 (chronic hepatitis C) received 3 doses of a recombinant hepatitis B vaccine, according to a 0-, 1-, and 6-month schedule. Local injection-site symptoms were the most common reactions reported following vaccination in all groups (35.5% of all doses), with the hepatitis B vaccine eliciting fewer injection-site symptoms than the hepatitis A vaccine (19.8% compared with 37.5%). Although a higher percentage of healthy subjects (93%) seroconverted after a single dose of the hepatitis A vaccine than did subjects with chronic hepatitis C (73.7%) or CLD of nonviral etiologies (83.1%), more than 94% of all vaccinees were seropositive for anti-HAV after the complete vaccination course. At each time point, a lower geometric mean concentration of anti-HAV was observed for each group of CLD patients compared with the healthy control subjects. In conclusion, hepatitis A vaccine was well tolerated and induced a satisfactory immune response in patients with chronic hepatitis B, chronic hepatitis C, and miscellaneous CLD.

Adolescent↗
PubMed1998

Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine.

Serum samples from 133 persons who were positive only for antibody to hepatitis B core antigen (anti-HBc) by enzyme immunoassay (EIA) were retested for seromarkers of hepatitis B virus (HBV) by radioimmunoassay and for HBV DNA by polymerase chain reaction analysis. All persons were subsequently vaccinated with hepatitis B vaccine. HBV DNA was found in only five persons, four of whom remained positive during retesting. Most persons had a primary antibody response with three doses of hepatitis B vaccine. Evidence of HBV DNA was not detected in 96% of persons with isolated anti-HBc by EIA.

DNA, Viral↗
PubMed1998

Increases in levels of antibody to hepatitis B surface antigen in an immunized population.

Hepatitis B vaccine is effective in preventing infection with hepatitis B virus (HBV), but its duration of protection is unknown. To examine the effect of exposure to HBV on an immunized population, data were analyzed from a cohort of Alaska Natives who were immunized and then followed up annually for 10 years. A boost in antibody to hepatitis B surface antigen (anti-HBs) was defined as a fourfold rise in levels to > or = 20 mIU/mL that was not accompanied by the presence of antibody to hepatitis B core antigen or attributable to interim vaccination. During 10 years of follow-up, 8.2% of 1,595 vaccines had boosts in anti-HBs. Persons with boosts did not differ significantly from those without boosts in terms of age, gender, village, initial level of anti-HBs, or level of anti-HBs before the boost. These results underscore the continued exposure to HBV among vaccinees and the continued protection against disease that the vaccine provides.

Adolescent↗
PubMed1998

Evolution of hepatitis C virus quasispecies in hypervariable region 1 and the putative interferon sensitivity-determining region during interferon therapy and natural infection.

To study hepatitis C virus (HCV) genetic mutation during interferon (IFN) therapy, the temporal changes in HCV quasispecies heterogeneity were compared before and after treatment for nine patients infected with HCV genotype 1, including four nonresponders, four responders who relapsed after therapy, and one responder who experienced a breakthrough of viremia during therapy. Nine untreated patients with an average time between specimens of 8.4 years served as controls. Sequences from the second envelope glycoprotein gene hypervariable region 1 (HVR1) and the putative IFN sensitivity-determining region (ISDR) of the nonstructural NS5A gene were analyzed by heteroduplex mobility assays and nucleotide sequencing. A strong positive correlation was found between the percent change in a heteroduplex mobility ratio (HMR) and percent change in nucleotide sequence (r = 0.941, P < 0.001). The rate of fixation of mutations in the HVR1 was significantly higher for IFN-treated patients than for controls (6.97 versus 1.31% change in HMR/year; P = 0.02). Similarly, a higher rate of fixation of mutations was observed in the ISDR for IFN-treated patients than for untreated controls, although the result was not significant (1.45 versus 0.15 amino acid changes/year; P = 0.12). On an individual patient basis, IFN therapy was associated with measurable HVR1 and ISDR mutation in nine of nine (100%) and two of nine (22.2%) patients, respectively. Evolution to IFN-resistant ISDR sequences was observed in only one of nine IFN-treated patients. These data suggest that IFN therapy frequently exerts pressure on the HCV envelope region, while pressure on the ISDR was evident in only a subset of patients. Thus, the selection pressures evoked on HCV genotype 1 quasispecies during IFN therapy appear to differ among different patients.

Amino Acid Sequence↗
PubMed1998

Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population.

Hepatitis B virus (HBV) is major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. Serologic surveys performed in the 1970s and 1980s have demonstrated that Alaskan Eskimos, Canadian Inuit, and Greenland Inuit have very high prevalence rates of HBV. In Alaska, a high incidence of HCC in Eskimos, especially males, has been reported. Alaska Natives chronically infected with HBV have a relative risk of HCC of 148 compared to Alaska Natives who are not chronically infected. In Canada the incidence of HCC is six times more frequent in elderly Inuit than in Canadians in general. However, an elevated rate of HCC has not been found in Greenland. Primary prevention programs to prevent HCC by vaccination against HBV are being conducted in Alaska, Canada, and Greenland. In addition, in Alaska a program to detect HCC earlier by screening persons chronically infected with HBV, using semiannual alpha-fetoprotein testing, has resulted in detecting over 60% of HCC early enough for surgical resection.

Adolescent↗
PubMed1997

Protection provided by hepatitis B vaccine in a Yupik Eskimo population--results of a 10-year study.

A hepatitis B virus vaccine demonstration project was conducted in southwest Alaska in 1981-1982 to determine the immunogenicity and efficacy of the vaccine. A total of 1630 susceptible persons in the Alaskan Native population were vaccinated with the recommended three-dose regimen of plasma-derived hepatitis B vaccine, and 94% demonstrated antibody to hepatitis B surface antigen (anti-HBs) at levels > or = 10 mIU/mL. After 10 years of follow-up, 76% of those immunized had anti-HBs levels > or = 10 mIU. During the 10 years following the first dose of vaccine, 13 study participants developed antibody to hepatitis B core antigen (10 vaccine responders, 3 nonresponders), and none developed sustained HBs positivity or had clinical hepatitis. These data suggest that immunization with hepatitis B vaccine continues to provide high levels of protection from clinical disease for at least 10 years.

Adolescent↗
PubMed1996

A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine.

OBJECTIVE: To stop an epidemic of hepatitis A in rural Alaska by mass immunization of susceptible persons with 1 dose of an inactivated hepatitis A vaccine. DESIGN: Nonrandomized, uncontrolled trial. Hepatitis A vaccine was offered to all persons in susceptible age groups in villages with documented cases of hepatitis A. Immune globulin was not offered at the time of vaccination. SETTING: Twenty-five rural communities located in interior Alaska and along the northwest coast of the Bering Sea and Arctic Ocean. PARTICIPANTS: Persons without a history of acute hepatitis A in age groups selected by applying results of a previous serosurvey conducted on serum collected before the epidemic. INTERVENTION: One dose of a formalin-inactivated hepatitis A vaccine was given to each participant. Adults 20 years of age and older received 1440 enzyme-linked immunosorbent assay units and persons younger than 20 years received 720 enzyme-linked immunosorbent assay units. Prevaccination and postvaccination levels of antibody to hepatitis A IgG were obtained from 136 participants. MAIN OUTCOME MEASURES: An active surveillance system was established to detect persons with symptomatic illnesses compatible with hepatitis A; persons who met the illness criteria were tested for antibody to hepatitis A IgM. One area (the Kotzebue region), where all communities were offered vaccine, was selected for intensive surveillance and analysis. RESULTS: During the 12-month period before the vaccine trial, 529 cases of icteric hepatitis A were reported, and 443 were confirmed to be positive for antibody to hepatitis A IgM. Hepatitis A vaccine was administered to 4930 persons, 3517 of whom were younger than 20 years. After vaccination began, 237 persons positive for antibody to hepatitis A IgM were identified during a 60-week surveillance period; 46 were vaccines and 191 were unvaccinated susceptible persons. In the Kotzebue region, in communities in which more than 80% of persons considered susceptible were vaccinated, the outbreak ceased in 4 to 8 weeks, whereas in 1 large community in which less than 50% of susceptible persons were vaccinated, the outbreak continued for more than 50 weeks. More than 90% of seronegative persons developed antibody to hepatitis A IgG 3 to 4 weeks after vaccination. CONCLUSION: This trial suggested that by providing both short-term and long-term protection, hepatitis A vaccine used without immune globulin halted an established epidemic of hepatitis A in rural Alaska.

Adolescent↗
PubMed1996

Detection of alpha-fetoprotein and hepatitis-B surface antigen in blood spotted on filter paper: use as a screen for hepatocellular carcinoma in Alaska Natives.

A program of twice yearly testing of Alaska Native carriers of hepatitis-B surface antigen (HBsAg), for alpha-fetoprotein elevations as an indicator of early hepatocellular carcinoma has been established in Alaska. Because many HBsAg carriers live in remote regions of Alaska, logistical and cost considerations complicate the efficiency of this program. We evaluated the feasibility of using blood spotted onto mail-in cards as a system of blood collection and commercial assays for alpha-fetoprotein and HBsAg testing. We compared alpha-fetoprotein levels and the detection of HBsAg in both plasma and blood spots from HBsAg-positive carriers, normal volunteers, and pregnant females. There was good correlation between serum and blood spot AFP levels (r = 0.94, p < 0.001) over a wide range of serum alpha-fetoprotein levels. alpha-fetoprotein and HBsAg remained detectable in blood spots stored at room temperature for more than 8 weeks. The sensitivity of detection of HBsAg in blood spots was not as great in blood spots when compared to plasma levels. This system has been incorporated into the hepatocellular carcinoma screening program in Alaska. It should also prove feasible and economical for such screening to be undertaken in developed countries and possibly make alpha-fetoprotein screening affordable in those developing countries where the prevalence of hepatitis-B virus infection is high.

Alaska↗