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Biomedical subjects

R Engle

Publications and source records attributed to R Engle.

At least 19 recordsLinked to original sources
PubMed1998

Experimental infection of chimpanzees with hepatitis C virus of genotype 5a: genetic analysis of the virus and generation of a standardized challenge pool.

Six major genotypes (genotypes 1-6) of hepatitis C virus (HCV) have been identified. These genetic variants are being transmitted to chimpanzees, the only recognized animal model for the study of HCV. Genotype 5a (strain SA13), a variant found primarily in South Africa, has been transmitted to chimpanzees for the first time. Experimental infection of 2 chimpanzees was characterized by early appearance of viremia and peak virus titers of 10(5)-10(6) genome equivalents/mL. The HCV infection was resolved by week 15 after inoculation in 1 chimpanzee and persisted in the other. Both chimpanzees became anti-HCV-positive by week 14 after inoculation. Both chimpanzees developed viral hepatitis. The infectivity titer of a genotype 5a challenge pool prepared from the first passage of HCV in a chimpanzee was approximately 10(4) infectious doses/mL. Finally, sequence analysis of strain SA13 confirmed that genotype 5a is genetically distinct from other genotypes of HCV.

Animals↗
PubMed1995

Acute viral hepatitis in Saudi Arabia: seroepidemiological analysis, risk factors, clinical manifestations, and evidence for a sixth hepatitis agent.

We conducted a prospective, descriptive cohort study of all 217 cases of acute viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with infectious disease departments in the second and third largest cities in the Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study. Our goals were (1) to determine the causes, demographics, risk factors, and clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative importance, characteristics, and risk factors of a sixth hepatitis agent, non-A-E. All cases and controls completed a questionnaire. Cases provided blood samples for studies of serum bilirubin, alanine and aspartate aminotransferases, and antibody to hepatitis viruses as well as genome detection studies. The results of serological and molecular tests were used to categorize each case as hepatitis A, B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were statistically analyzed by comparisons between groups with different types of AVH and controls. Analysis of risk factors suggested that hepatitis C and D were parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route of transmission of hepatitis B was unclear. Hepatitis E was strongly associated with living or traveling on the Indian subcontinent. The clinical disease caused by all six agents was indistinguishable. The putative sixth agent caused 13% of cases. The second-generation tests for antibody to HCV and HEV were relatively reliable for the diagnosis of AVH.

Acute Disease↗
PubMed1994

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma. Development of an effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV.

Animals↗
PubMed1993

Physician frustration in communicating with patients.

In this study, the nature of practicing physicians' "frustrating" visits was explored and a guide to help physicians identify problems in communicating with patients was developed. The study included 1,076 practicing physicians who attended a voluntary workshop on physician-patient communication. The physicians were from multiple specialties and diverse work settings geographically dispersed throughout the United States. The method included development of a preliminary item pool (descriptions of frustrating patients and occasions) by experienced physicians and teachers of medical communication, additions/deletions/revisions of items within the pool, empirical analyses to reduce redundancy and group-like items, and construct validation of the final 25-item questionnaire. Factor analysis was used to identify subscales. Physicians most often attributed communication problems to the patient rather than to their own limitations. Seven types of communication problems (subscales) were identified, including: 1) lack of trust/agreement, 2) too many problems, 3) feeling distressed, 4) lack of understanding, 5) lack of adherence, 6) demanding/controlling patient, and 7) special problems. Primary care physicians reported greater problems than specialists on four subscales. Physicians practicing in health maintenance organizations reported greater problems than physicians in fee-for-service practice on five subscales. Seven sources of frustration physicians experience in their work with patients were identified. Understanding these frustrations will allow physicians to reflect on their own experiences and potentially improve the quality of their patient visits.

Adult↗
PubMed1993

Communication techniques for HMO physicians.

A program utilizing a council of health professionals found three areas of significant importance in physician/patient communication: inquiry, instruction and empathy. Attention to these three areas can improve patient adherence and decrease patient anxiety. The result can be more satisfied patients.

Communication↗
PubMed1992

Lack of protective immunity against reinfection with hepatitis C virus.

Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.

Acute Disease↗
PubMed1992

The natural history of infection with hepatitis C virus (HCV) in chimpanzees: comparison of serologic responses measured with first- and second-generation assays and relationship to HCV viremia.

The sensitivity of first- and second-generation tests for antibody to hepatitis C virus (HCV) and the relationship among the patterns of antibody response and HCV viremia were examined in serial serum samples from 6 chimpanzees experimentally infected with HCV and followed less than or equal to 3 years. HCV infection was transient in 4 chimpanzees and became chronic in 2. All chimpanzees developed antibodies to HCV detectable by second-generation assays, while only 5 of the 6 became positive by first-generation assay. Second-generation were consistently more sensitive than first-generation assays for the early diagnosis of primary HCV infection. The pattern observed with second-generation assays was not influenced by the outcome of HCV infection, since antibodies remained persistently detectable throughout follow-up regardless of whether viremia was transient or persistent. In contrast, the first-generation antibody response was variable: It usually disappeared after loss of viremia, whereas its presence paralleled HCV viremia in chimpanzees with chronic infection.

Animals↗
PubMed1990

Detection of SIV antigens by HIV-1 antigen capture immunoassays.

We tested three commercially available HIV-1 antigen capture systems for their ability to detect simian immunodeficiency viruses (SIV). All three kits detected antigens from six distinct SIV isolates, but with varying degrees of sensitivity. For the overall detection of SIV in cell culture, our assay for reverse transcriptase was more sensitive than HIV-1 antigen capture. HIV-1 antigen capture systems were useful for the detection of SIV antigenemia in experimentally infected macaques. The limited sensitivity of HIV-1-specific antigen capture suggests that SIV-specific antigen capture reagents should be developed.

Animals↗
PubMed1987

Hepatitis B virus produced by transfected Hep G2 cells causes hepatitis in chimpanzees.

We have reported that clonal cells derived from Hep G2 cells transfected with a plasmid containing hepatitis B virus (HBV) DNA secrete spherical and filamentous forms of hepatitis B surface antigen (HBsAg), core particles, and virions into the culture medium. Here we describe the development of typical hepatitis in two chimpanzees following intravenous inoculation with the medium in which the transfected cells had grown. The liver biopsies from these animals showed characteristic lesions in parenchyma and portal tracts, more conspicuous at an earlier time in the chimpanzee that had received a greater number of virions. The amount of HBsAg in the serum of one infected chimpanzee increased with time after the initial inoculation and then decreased concomitantly with the appearance of antibodies against HBsAg and core antigens. HBsAg remained detectable in the other animal throughout the course of the experiment. The levels of hepatitis B "e" antigen in both animals peaked at week 5, signifying the acute phase of the infection. The activities of serum enzymes that are markers for necroinflammation also increased. The hepatitis HBsAg subtype of the virions isolated from the patient whose DNA was cloned and then used for transfection of the Hep G2 cells was the same as that found in the chimpanzees. Furthermore, the restriction enzyme analysis of the viral DNA isolated from the chimpanzees was identical to the cloned DNA. Thus, HBV DNA-transfected Hep G2 cells can support the replication of virions that, in turn, produce hepatitis in chimpanzees.

Animals↗
PubMed1987

Titration of the infectivity of hepatitis D virus in chimpanzees.

The infectivity of hepatitis D virus (HDV) was evaluated by intravenous inoculation of chimpanzees. HDV was present in the inoculum at a titer of 10(11) chimpanzee infectious doses (CID). In contrast, the titer of hepatitis B virus (HBV) in the same inoculum was 10(6) CID. All HBV-infected chimpanzees inoculated with less than or equal to 10(-11) dilutions of the HDV-positive plasma were superinfected; an animal receiving a 10(-12) dilution did not develop markers of HDV replication in serum or liver. All HDV-infected chimpanzees had marked elevations of serum alanine aminotransferase activities. The incubation period from exposure to development of hepatitis was inversely related to the dose of HDV inoculum, although the severity and duration of hepatitis were independent of it. All animals recovered and rapidly developed antibody to hepatitis D antigen.

Alanine Transaminase↗
PubMed1986

Fulminant hepatitis in asymptomatic hepatitis B surface antigen carriers in Greece.

Eleven male fulminant hepatitis (FH) patients (mean age: 47.7 +/- 16 years) positive for hepatitis B surface antigen (HBsAg) but negative for IgM antibody to hepatitis B core antigen (IgM anti-HBc) were admitted consecutively to the Athens Hospital for Infectious Diseases between May 1981 and November 1983. Because of the absence of IgM anti-HBc, determined by an enzyme immunoassay, these patients were considered to be HBsAg carriers with a superimposed acute hepatitis. Three of the 11 patients received immunosuppressive chemotherapy during the six months before the onset of the acute hepatitis. None of the patients was homosexual or a drug addict. Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis delta virus (HDV) was detected with serologic markers and/or molecular hybridization techniques. Fulminant hepatitis was attributed to spontaneous reactivation of chronic hepatitis B in four patients, chemotherapy-induced reactivation of chronic hepatitis B in three patients, HDV superinfection in one patient and possible superinfection by non-A, non-B agent(s), HDV, or HDV-like agents in three patients. Reactivation of chronic hepatitis B was an important cause of apparent acute hepatitis in heterosexual male HBsAg carriers from an area with a high prevalence of HBV infection.

Acute Disease↗
PubMed1986

Serologic markers of hepatitis B virus (HBV) and hepatitis D virus infection in carriers of hepatitis B surface antigen who are frequently exposed to HBV.

Serum hepatitis B e antigen (HBeAg) and HBV DNA are indicators of active replication of HBV, whereas IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to chronic HBV infection. Fifty-eight carriers of hepatitis B surface antigen (HBsAg) who had frequent parenteral exposures were studied for the presence of HBeAg, HBV DNA, IgM anti-HBc and hepatitis delta virus (HDV) serologic markers. Active replication of HBV was detected in 36.2% (25% of drug addicts, 16.7% of thalassemia patients, and 46.9% of hemodialysis patients) and seropositivity for IgM anti-HBc in 55.2% of the HBsAg carriers. Among the 39 HBsAg carriers who were negative for HBeAg, IgM anti-HBc was detected significantly more frequently than HBV DNA (46.1% vs. 5.1%, p less than 0.001). Serologic evidence of HDV infection was detected in 35% of drug addicts, 50% of thalassemia patients and in 9.4% of hemodialysis patients. These data revealed that continued replication of HBV was more frequent in hemodialysis patients than in drug addicts and thalassemia patients who are HBsAg carriers and the opposite was true for the prevalence of HDV infection.

Adolescent↗
PubMed1985

Radioimmunoassay and characterization of woodchuck hepatitis virus core antigen and antibody.

Solid-phase radioimmunoassays for woodchuck hepatitis virus core antigen (WHcAg) and antibody (anti-WHc) were developed. WHcAg in woodchuck liver homogenates was characterized by ultracentrifugation in CsCl gradients; both heavy (1.35 g/cm3) and light (1.31 g/cm3) cores were obtained from the liver of an animal during acute WHV infection, which is consistent with observations in hepatitis B virus infection in man. Endpoint titers of anti-WHc were higher in chronic WHV carriers than in animals recovered from acute infections. Both IgM and IgG anti-WHc antibodies were produced by infected woodchucks. A survey of colony woodchucks demonstrated that 88/89 animals having one or more markers of past or ongoing WHV infection were positive for anti-WHc. Thus, serum anti-WHc appears to be a sensitive marker of WHV infection.

Animals↗
PubMed1985

Double infections with hepatitis A and B viruses.

Ten (2.8%) asymptomatic carriers of HBsAg and four (1.1%) patients with acute hepatitis B virus (HBV) infection were detected among 356 adults with acute viral hepatitis A (HAV) consecutively admitted to the Athens Hospital for Infectious Diseases from May 1981 to March 1984. These patients did not differ in clinical, epidemiologic (except in age), biochemical or serologic characteristics from patients acutely infected with HAV alone. Transient suppression of the HBV replication and disappearance of the HBV DNA accompanied by seroconversion from HBeAg positive to anti-HBe positive were detected in one and two carriers respectively. The titer of non-class-specific anti-HBc was low (less than or equal to 10(-2)) in all cases. These data suggest that superinfection of HBsAg carriers with HAV does not cause more severe disease or influence adversely the course of chronic hepatitis B disease. However, accurate diagnosis of double infections is necessary for prognosis of the liver disease and appropriate management of the patient's environment. This is quite important in areas with a high prevalence of HBV infections, like Greece, where double infections are relatively common.

Acute Disease↗
PubMed1983

Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees.

Synthetic peptides, predicted from the nucleotide sequence of the S gene of hepatitis B virus were analyzed in terms of the established specificities of the hepatitis B surface antigen. The analysis indicated that the group-specific alpha antigen is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the surface antigen protein, spanning amino acid residues 110-137, specifies the major d and y subtype system. The d/y subtype appears to depend on changes in one or more variable amino acids at positions 127, 131, and 134 of the hepatitis B surface antigen protein. Peptide 49 (consisting of amino acid sequences of the y subtype for the region 110-137), coupled to a carrier protein and mixed with an adjuvant, stimulated a brisk anti-y response in chimpanzees, the relevant model of human response to hepatitis B virus immunization and infection. Experimental challenge with homologous hepatitis B virus resulted in a pattern of partial protection. The results offer promise for the application of chemically synthesized peptides as vaccines in the prophylaxis of hepatitis B virus disease.

Amino Acid Sequence↗
PubMed1981

Induction of persistent infection in mice and oncogenic transformation of mouse macrophages with infectious bovine rhinotracheitis virus.

Infectious bovine rhinotracheitis virus (IBRV) established long-term persistent infection in intracerebrally inoculated athymic nude mice. After intraperitoneal injection into outbred mice, virus was isolated for only 3 days from spleens and livers. In vitro inoculation of outbred mouse spleen fragments with IBRV resulted in persistent infection and subsequent transformation of spleen macrophages. The IBRV-specific membrane and intracellular antigens were detected by indirect immunofluorescence techniques in transformed cells in early in vitro passages. The presence of IBRV genetic formation was confirmed by in situ hybridization. The IBRV-transformed mouse macrophages induced fibrosarcomas and cystic tumors in athymic nude mice. Infective virus could not be rescued from transformed cells by cocultivation with rabbit kidney cells, treatment with iododeoxyuridine, or ultraviolet irradiation.

Animals↗
PubMed1975

Pupillary measurement and release from proactive inhibition.

One of the explanations of release from proactive inhibition in short-term memory is that the subjects re-attend to the items on the release trial because the items are different from the previous ones. It is further assumed that this increase in attention causes the relase items to be learned better than the preceding items. This experiment measured the pupils of the subjects' eyes while they were participating in a proactive-inhibition release-type task. The results showed no increase in attention, as indexed by pupil size, on the release trial. This did not support the attentional explanation of the proactive-inhibition release phenomenon.

Attention↗