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Biomedical subjects

G Hess

Publications and source records attributed to G Hess.

At least 163 records · Page 9Linked to original sources

Demonstration of antibodies to the surface (anti-p41) and core proteins (anti-p24) of the human immunodeficiency virus (HIV) in individuals positive for anti-HIV.

Diagnosis of infection with the human immunodeficiency virus (HIV) relies on the demonstration of antibody to this virus. Occasionally, the combined analysis of sera using ELISA and western blot reveals false-positive results. We have compared a newly developed test to detect antibodies to the core (anti-p24) and surface (anti-p41) proteins of HIV with the established tests described above. Anti-p24 and anti-p41 were negative in three individuals positive for anti-HIV by ELISA and immunoblot; they had a low risk to acquire HIV infection and were clinically and immunologically normal and suspected false positive previously. In 62 individuals at risk, anti-p41 was always positive while anti-p24 was negative in 24/62 individuals including all but one patient with AIDS. The data indicate that this new test may replace the western blot as a reliable, widely available, and standardized confirmatory assay. In addition, preliminary evidence needs to be confirmed that quantitative analysis of anti-p24 might be of prognostic value in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗

Quantal analysis of paired-pulse facilitation in guinea pig hippocampal slices.

Intracellular excitatory postsynaptic potentials (EPSPs) were recorded in area CA1 of hippocampal slices from guinea pigs. With paired-pulse stimulation of stratum radiatum, the second stimulus (interval of 40-50 ms) produced an EPSP with enlarged amplitude. Two methods of quantal analysis showed an increase in quantal content of the facilitated EPSP and a smaller increase in quantal size. The correlation between amplitudes of the first and second EPSP was usually insignificant. The results favour a presynaptic location of the mechanisms of the paired-pulse facilitation and suggest increases in the average of transmitter quanta released by presynaptic volley as well as increases in the amount of transmitter in each quantum.

Animals↗

Pre-S encoded surface proteins in relation to the major viral surface antigen in acute hepatitis B virus infection.

The role of pre-S encoded viral surface proteins in acute hepatitis B virus infection is still poorly understood. Binding sites for polymerized human serum albumin have been found to be encoded by the pre-s2 region of the hepatitis B virus genome. Recently, murine monoclonal antibodies against pre-s1 and pre-s2 encoded hepatitis B virus gene products were generated and used for their specific detection in serum. In sera from patients with acute hepatitis B, pre-s1 and pre-s2 antigen occurred in 16 of 20 and 15 of 20 patients, respectively. In the initial stage of the disease, pre-S gene products correlated with binding sites for polymerized human serum albumin, but not with hepatitis B surface antigen. Subsequently, pre-s1 and pre-s2 antigens were cleared from the serum of patients with acute hepatitis B before binding sites for polymerized human serum albumin and hepatitis B surface antigen. Possibly, the early clearance of pre-S markers can be of prognostic value in acute hepatitis B. The mechanisms of the early clearance of the pre-S antigens in acute hepatitis B remain to be elucidated. However, elimination by immunologic mechanisms appears likely.

Acute Disease↗

Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection.

Pre-S1 and pre-S2 encoded antigens of hepatitis B virus were localized in liver tissue using monoclonal antibodies. They were found to be exclusively expressed in the cytoplasm of liver cells. Cell bound pre-S1 encoded protein was often detected in patients with chronic liver disease and viremia. Only a small number of the HBsAg positive cells also contained pre-S1 antigen. There was no correlation with nuclear HBcAg. Livers of non-viremic HBsAg carriers contained many HBsAg expressing liver cells, that were frequently also positive for pre-S2 encoded protein but contained no detectable pre-S1 encoded protein at all. It remains open whether cell bound pre-S2 containing proteins of middle size have a significance for pathogenesis, as they are present in individuals with chronic liver disease as well as in healthy HBsAG carriers, and may be associated with both increased and normal liver enzymes. Cell bound pre-S1 antigen with viremia may, however, be involved in the maintenance of viremia and liver disease.

Biopsy↗

Rotavirus isolate WI61 representing a presumptive new human serotype.

A virus (strain WI61) representing a presumptive new human serotype was isolated from an 18-month-old child with gastroenteritis admitted to Children's Hospital of Philadelphia in February 1983. The WI61 virus was clearly distinguished by cross-neutralization tests from human rotaviruses of serotypes 1, 2, 3, and 4, human 69M, and representative bovine (NCDV), porcine (OSU), and chicken (Ch2) rotaviruses. Antisera generated in guinea pigs hyperimmunized to WI61 virus displayed a partial cross-reactivity with rotaviruses of human serotypes 1, 2, 3, and 4. By means of studies with reassortant rotaviruses, it was presumptively determined that the WI61 virus cross-reactive antigenic determinants are localized on the vp3 surface polypeptide coded by gene segment 4. The characteristic RNA genome electropherotype of WI61 virus was observed in 5 of 59 cases of infant gastroenteritis detected in 1983 and 1984 but has not been observed in a subsequently at Children's Hospital. Serotype WI61-specific neutralizing antibodies were observed in a majority of sera of normal adults and infants of less than 4 or greater than 12 months of age collected in the Philadelphia area. Median antibody titers to WI61 equaled or exceeded those to rotaviruses of serotype 1 or 3. Each of seven samples of commercial cow's milk exhibited neutralizing antibodies to WI61 virus at a titer greater than or equal to that to serotype 1 or 3 or bovine (strain NCDV) rotavirus. However, WI61 rotavirus did not induce disease or a specific serum-neutralizing antibody response when fed to a caesarean-derived colostrum-deprived newborn calf. WI61 rotavirus caused diarrhea in newborn mice with a 50% diarrhea-inducing dose of 10(7.0) PFU.

Animals↗

Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: effect on viral replication and on liver cell damage.

Immunosuppressive therapy was stopped in 12 individuals positive for hepatitis Be antigen (HBeAg) and hepatitis B surface antigen (HBsAg) and in 4 individuals positive for HBsAg but negative for HBeAg. Discontinuation of immunosuppressive therapy in HBeAg-positive patients was always associated with a bout of hepatitis and elimination of HBeAg in 8/12 patients. One patient died from liver failure and 2 patients experienced a decompensation of their liver disease indicating that this approach might be harmful if used therapeutically. A bout of hepatitis was not noted in any of the individuals negative for HBeAg when the immunosuppressive therapy was stopped, implying that this event is not potentially harmful to the patient.

Adult↗

Virus-associated receptors for polymerized human serum albumin (RpHSA) in patients with chronic active hepatitis B treated with recombinant leukocyte A interferon.

Hepatitis B surface antigen (HBsAg)-associated receptors for polymerized human serum albumin (RpHSA) are assumed to mediate viral attachment to hepatocytes in hepatitis B virus (HBV) infection. RpHSA was found to be coded by the pre-S region of HBV genome. Recently, the antiviral effect of recombinant leukocyte alpha-interferon was shown in patients with hepatitis B. Our study evaluated the detection and the clinical implications of RpHSA in patients with chronic active hepatitis B under treatment with recombinant alpha-interferon. Two out of nine patients eliminated all HBV markers including RpHSA. Four out of nine patients became negative for markers of viral replication but remained positive for HBsAg and in part for RpHSA. In three out of nine patients HBV markers including RpHSA remained unchanged. In summary, the titer for RpHSA is a reliable indirect marker for infectivity and of prognostic value in patients with chronic active hepatitis B during interferon treatment. Future studies should evaluate a putative immune response to RpHSA-containing viral surface proteins, which could be relevant for viral clearance in HBV infection.

Adult↗

Detection of hepatitis B virus markers in sera of asymptomatic hepatitis B surface antigen carriers with special emphasis to pre-S-encoded proteins.

Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.

Carrier State↗

Effects of halothane, enflurane, and nitrous oxide on colon motility.

Previous work from this laboratory has demonstrated that the colon, particularly the left colon, is the major site of persistent postoperative ileus after both minimal and more extensive abdominal operations. Inhalation anesthetics have been implicated in the past as a possible cause of altered postoperative bowel function, but direct evidence of such a role in postoperative ileus is lacking. In this investigation, the effects of three inhalation anesthetic agents, halothane, enflurane, and nitrous oxide, on contractile function of the right and left colon were investigated in monkeys. Enflurane and halothane administration caused cessation of contractions in both the left and right colon; suppression of motor activity continued throughout the period of anesthetic administration. Recovery of normal contractile function occurred relatively promptly after cessation of anesthesia with these drugs. Return of normal contractions was more prompt in the right than in the left colon. Administration of nitrous oxide was not associated with significant suppression of contractile function of either the the right or left colon. None of the three agents studied appear to have any role in typical postoperative ileus.

Animals↗

Treatment of hepatitis B surface antigen (HBsAg)-positive chronic hepatitis with recombinant leucocyte alpha-A interferon.

A total of 32 individuals with HBsAg-positive and anti-delta-negative chronic hepatitis were treated with recombinant alpha-A interferon in phase I and phase II studies. In 5/32 patients HBsAg could be eliminated and in 19/32 individuals HBeAg became negative including all those who also eliminated HBsAg. Side-effects were tolerable in most patients and were readily reversible upon discontinuation of interferon therapy. In conclusion, treatment of HBsAg-positive chronic hepatitis with interferon seems to be a promising therapeutic approach. Future studies will have to establish the optimal dose, duration of treatment and factors predicting a favourable outcome of the treatment.

Drug Evaluation↗

Modification of hepatitis B virus infection by recombinant leukocyte alpha A interferon.

A defect in alpha interferon production in patients with chronic type B hepatitis offers a rationale principle for treating this disease with interferon. Two trials with interferon in chronic type B hepatitis indicate that this therapy achieves an elimination of HBsAg and HBeAg significantly higher than spontaneous. Our study and that of others indicate, however, that the response to interferon therapy is dependent on many variables including: the type of interferon, the interferon dose, duration of interferon treatment, sex, sexual preference in men and coinfection with other viruses. As of the multiple modes of action of interferon, a better understanding of viral replication, of the antiviral action of interferon in hepatitis B virus (HBV) infection and of the immunomodulatory action of interferon in HBV infection will help to improve the treatment of chronic HBV infection with interferon.

Antibodies, Viral↗

Hepatitis B virus and delta infection in male homosexuals.

Six hundred and sixty-six homosexuals were analysed in respect of hepatitis B virus and delta infections. Evidence of ongoing or recent hepatitis B virus infection was found in 450/666 (67.6%) homosexuals; 44 were HBsAg positive. Anti-delta was found in two HBsAg-positive homosexuals. Both individuals had a non-replicative form of HBV infection and biochemical evidence of liver disease. The study confirms that HBV infection is frequent in homosexuals and indicates that delta-infection is rare in male homosexuals.

Berlin↗