Overview of the NASA 70-day Bed Rest Study.

Purpose: The purpose of this article was to provide an overview of the National Aeronautics and Space Administration (NASA) 70-day Bed Rest Study. The integrated complement of investigations and the standardized bed rest environment that served as the platform for this study complement are described. Outcomes of the studies will not be presented here but will be reported in separate publications.

Ophthalmological Evaluation of Integrated Resistance and Aerobic Training During 70-Day Bed Rest.

Introduction: We evaluated ophthalmic changes in healthy individuals who underwent integrated resistance and aerobic training (iRAT) during 70-d 6° head-down tilt (HDT) bed rest (BR).

Methods: Participants were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented.

Ocular Outcomes Comparison Between 14- and 70-Day Head-Down-Tilt Bed Rest.

Purpose: To compare ocular outcomes in healthy subjects undergoing 14- and/or 70-day head-down-tilt (HDT) bed rest (BR).

Methods: Participants were selected by using NASA standard screening procedures. Standardized NASA BR conditions were implemented.

Ocular outcomes evaluation in a 14-day head-down bed rest study.

Introduction: We evaluated ocular outcomes in a 14-d head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body.

Methods: Healthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.

Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1.

Background: We wished to determine the safety and anti-human immunodeficiency virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4 monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected subjects.

Methods: Sequential cohorts of 6 HIV-1-infected subjects each received infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4+ T cell count, TNX-355 coating of CD4+ T cells, and serum TNX-355 levels.

Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay.

We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and to enable vaccine evaluations. Five antigen lots were characterized; we used a reference antiserum to standardize antigen potency. We defined Walter Reed antibody units (WR U) with a reference antiserum by using the four-parameter logistic model, established other reference pools as assay standards, and determined the conversion factor: 1 WR U/ml = 0.

Hepatitis E virus infection in chimpanzees: a retrospective analysis.

Different patterns of disease were observed among 11 chimpanzees who were inoculated intravenously with hepatitis E virus (HEV) positive fecal specimens from four different outbreaks (Nepal 1981, Uzbekistan 1981, Pakistan 1985, and Mexico 1986). Five chimpanzees had marginal or no liver enzyme elevations within 70 days of inoculation. Two of the chimpanzees had limited viremia, but did not produce detectable antibody.

Hepatitis E seroconversion in United States travelers abroad.

Sporadic cases of symptomatic hepatitis E virus (HEV) infection have been reported in United States travelers to developing countries, including Mexico and Pakistan. To evaluate the risk of exposure in United States travelers, 356 patients seen in our Travel Clinics were tested for antibodies to HEV before and 6 weeks after traveling. Samples obtained 6 months after traveling were available for 211 travelers.

Hepatitis E virus. Advances in HEV biology and HEV vaccine approaches.

Hepatitis E, previously known as enterically transmitted, enteric, or epidemic hepatitis, is a worldwide public health problem. The causative agent, the hepatitis E virus, is involved in epidemic, sporadic, and fulminant hepatitis cases worldwide. This review describes the advances in the biology of the hepatitis E virus and the progress made to develop simple and robust serologic assays for the diagnosis of HEV infection.

Hepatitis E virus infection in eastern India.

Most cases of enterically transmitted non-A, non-B hepatitis in India have so far been attributed to hepatitis E virus (HEV) infection. Most of the documented studies of hepatitis have focused on the incidence of this disease in northern, western, and south central India. A small seroprevalence study was conducted in the eastern Indian city of Patna to assess the degree of HEV infection among acute sporadic hepatitis cases.

Comparison of tests for antibody to hepatitis E virus.

The results of serologic tests for hepatitis E virus have varied widely from laboratory to laboratory, making interpretation of seroepidemiologic studies difficult. The present study compares serologic results with different antigens and tests developed in two laboratories for their ability to diagnose hepatitis E and measure antibody prevalence in a high risk population in Saudi Arabia. The results confirm that tests based upon open reading frame (ORF) 3 of HEV are of limited value for seroepidemiologic studies, whereas ORF2-based antigens have broad utility and yield data that are reproducible in more than one laboratory.

In vitro infection and replication of hepatitis E virus in primary cynomolgus macaque hepatocytes.

An in vitro model was developed to replicate hepatitis E virus (HEV) in normal primary cynomolgus macaque hepatocytes using a hormonally defined, serum-free medium formulation. Primary hepatocytes were infected in tissue culture following isolation by collagenase treatment of liver wedge biopsy material. Viral replication was monitored by a highly strand-specific reverse transcription-polymerase chain reaction (RT-PCR) assay, which could detect the positive- and negative-strands of HEV RNA independently in a sensitive and specific manner.

Expression, characterization, and immunoreactivities of a soluble hepatitis E virus putative capsid protein species expressed in insect cells.

The hepatitis E virus (HEV) open reading frame-2 (ORF-2) is predicted to encode a 71-kDa putative capsid protein involved in virus particle formation. When insect Spodoptera frugiperda (Sf9) cells were infected with a recombinant baculovirus containing the entire ORF-2 sequence, two types of recombinant proteins were produced; an insoluble protein of 73 kDa and a soluble protein of 62 kDa. The 62-kDa species was shown to be a proteolytic cleavage product of the 73-kDa protein.

Seroreactivity to hepatitis E virus in areas where the disease is not endemic.

If the occurrence of hepatitis E virus antibody (anti-HEV) in regions where the disease is not endemic represents infection, rates may be greater in high-risk populations and behavioral correlates may reflect recognized transmission modes. Serum samples from 300 homosexual males, 300 injection drug users (IDUs), and 300 blood donors from Baltimore, Md., were tested for anti-HEV by enzyme immunoassay.

The role of hepatitis E virus infection among patients with acute viral hepatitis in southern Saudi Arabia.

We investigated the etiology of acute sporadic viral hepatitis in southern Saudi Arabia in a series of 132 patients admitted with acute viral hepatitis. Of these cases, 108 (81.8%) were due to acute hepatitis A virus infection, of which 11 (8.

Purification and characterization of a recombinant hepatitis E protein vaccine candidate by liquid chromatography-mass spectrometry.

A protein with a molecular mass of approximately 62.10(3), derived from open reading frame 2 (ORF-2) of the hepatitis E virus (HEV: Burma strain), was expressed in a baculovirus expression vector and purified to homogeneity. The recombinant 62 kDa protein appeared to be a doublet, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Purification of a soluble hepatitis E open reading frame 2-derived protein with unique antigenic properties.

The second open reading frame (ORF2) of hepatitis E virus (HEV) is predicted to encode a 73-kDa capsid protein (1). When full-length ORF2 was expressed in insect cells (Spodoptera frugiperda (Sf9)) using a recombinant baculovirus, two distinct HEV polypeptides were observed: a full-length insoluble 73-kDa protein, and a soluble 56.5-kDa protein.

Purification of a baculovirus-expressed hepatitis E virus structural protein and utility in an enzyme-linked immunosorbent assay.

We report on the purification of the full-length structural protein encoded by open reading frame 2 (ORF-2) of hepatitis E virus. The ORF-2 protein, expressed in Sf9 cells by using a recombinant baculovirus vector system, was successfully purified to homogeneity. Gel electrophoresis of the purified ORF-2 protein showed a single polypeptide of 75 kDa by Coomassie blue staining and by Western blot (immunoblot) analysis.

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.

The risk of viral hepatitis A, B, C, and E among North American missionaries.

The seroprevalence and incidence of hepatitis A, B, C, and E virus infection were determined among North American missionaries (n = 328) serving in various geographic locations between 1967 and 1984. The mean age of subjects at entry into the study was 39.7 years (range 5-73 years); 65% were female; 89% had lived outside the United States before the study began.

Detection of hepatitis E virus genome and gene products in two patients with fulminant hepatitis E.

Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards hepatitis E virus ORF1) and immunohistochemistry (against hepatitis E virus ORF2 and ORF3) were applied to detect hepatitis E virus genome and gene product in the liver tissue of two patients with fulminant hepatitis E seropositive for hepatitis E virus RNA. Both hepatitis E virus RNA and hepatitis E virus antigens were detected exclusively in the cytoplasm of hepatocytes and not detected in other cell types. In both patients, more than 50% of the hepatocytes were positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of which showed degenerative changes.

Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive.

Expression of hepatitis E virus putative structural proteins in recombinant vaccinia viruses.

Hepatitis E virus (HEV) is a polyadenylated, positive-stranded RNA virus which is a major cause of enterically transmitted non-A, non-B hepatitis in many developing countries. The viral genome contains three different open reading frames (ORFs): ORF1, which is believed to encode nonstructural proteins, and ORF2 and ORF3, which are believed to encode structural proteins. The full-length putative structural proteins encoded by ORF2 and ORF3 of HEV have been cloned and expressed in recombinant vaccinia virus.

Non-A, non-B fulminant hepatitis is also non-E and non-C.

Objectives: to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis.

Methods: we utilized the polymerase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients.

Results: none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera.