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Biomedical subjects

G Eder

Publications and source records attributed to G Eder.

At least 19 recordsLinked to original sources

Dual tropism of HIV-1 IIIB for chimpanzee lymphocytes and monocytes.

In humans, macrophages serve as a major reservoir of human immunodeficiency virus (HIV-1) in the infected host and may play a role in the pathogenesis of the disease. In HIV-1-infected chimpanzees, however, virus could not be recovered from cells of the monocyte/macrophage lineage, leaving the question of macrophage tropism of HIV-1 in this species unresolved. The data reported that HIV-1 IIIB shows dual tropism and is infectious for both chimpanzee monocytes and lymphocytes in vitro. Viral replication in chimpanzee monocytes was clearly demonstrated by infection of allogeneic phytohemagglutinin (PHA) blasts in vitro and by electron microscopy (EM). EM revealed HIV particles associated with 10-15% of the HIV-1 IIIB-infected chimpanzee monocytes. Viral particles budding from the monocyte surface in the typical crescent form were noted as well. This is in contrast to the human situation, where monocytotropic HIV strains preferentially bud into and accumulate in cytoplasmic vacuoles. These results indicate that both lymphocytes and cells of the monocyte/macrophage lineage replicate virus in the chimpanzee; the cell tropism of viral strains, however, is different in chimpanzees and humans.

Animals

Ultrastructure of normal and hepatitis virus infected human and chimpanzee liver: similarities and differences.

Ultrastructure of liver biopsy specimens obtained from normal and hepatitis B (HBV) and hepatitis C virus (HCV) infected livers of patients and chimpanzees were compared. Nuclear alterations (glycogen particles, nuclear bodies, "vermicellar bodies", etc.), intracytoplasmic crystalloid inclusions were observed before and after the HBV and HCV infections both in human and chimpanzee hepatocytes, however, some of them were more common during the viral infection. Extreme endoplasmic reticulum dilatation characterized the human, while the presence of membranous cytoplasmic inclusions the hepatocytes of chimpanzees during HCV infection. Interferon-associated membrane alterations were noted during acute or chronic hepatitis, however, in slightly different forms in humans and chimpanzees. Data suggest to be precautions in the interpretation of the ultrastructural alteration observed in different species even to be so closely related as humans and chimpanzees especially during infection with hepatotropic viruses.

Animals

Immunization of chimpanzees with the HIV-1 glycoprotein gp160 induces long-lasting T-cell memory.

The goal of the present study was to investigate the antigen-specific T-cell response to the recombinant HIV envelope glycoprotein (gp160) and to test the effect of various adjuvant formulations on the efficiency of T-cell priming as well as on magnitude and longevity of the gp160-specific T-cell response. Our studies revealed that, in combination with an appropriate adjuvant (lipid-based adjuvant or mineral carrier complex), immunization with recombinant gp160 led to the appearance of gp160-primed T cells. The T-cell response obtained was substantial (proliferative response of greater than 100,000 delta dpm after one primary and two booster immunizations), gp160-specific (proliferation only in response to gp160, no proliferation after addition of a mock gp160 preparation), and long-lasting (T cell responses of greater than 50,000 delta dpm were observed more than one year after the last booster). The results presented here differ from those of previous studies in that they show the presence of substantial and long-lasting T-cell memory toward the immunogen gp160. Therefore further investigations on the use of these preparations as HIV candidate vaccines appear to be justified.

Adjuvants, Immunologic

Characterization of a vaccinia-derived recombinant HIV-1 gp160 candidate vaccine and its immunogenicity in chimpanzees.

The human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 was produced in large-scale microcarrier cultures of Vero cells, using a system involving coinfection with two recombinant vaccinia viruses. The immunogenicity of this material was studied in conjunction with a number of different adjuvant formulations, and chimpanzees were then immunized with gp160 in conjunction with Al(OH)3, Al(OH)3 and sodium deoxycholate, and a lipid-based adjuvant. The Al(OH)3-gp160 vaccine formulation elicited very poor immune responses in two chimpanzees, and these animals were further immunized with gp160 in conjunction with a lipid-based adjuvant. Immunization with the latter formulation lead to induction of high-titer neutralizing antibodies, and, following challenge with HIV-1, one chimpanzee demonstrated no evidence of virus infection over a period of 3 years. The second chimpanzee, which had previously been infected with non-A, non-B hepatitis, and two animals immunized with gp160 with Al(OH)3 and deoxycholate were not protected against challenge.

AIDS Vaccines

Multiple infusions of human intravenous immunoglobulin in chimpanzees do not lead to immune elimination.

Administration of human i.v. immunoglobulins was shown to lead to a permanent increase in IgG1 and IgG2 levels in chimpanzees. Half-lives of human IgG1 and IgG2 in chimpanzees were comparable to those found in humans, and no signs of immune elimination were observed. Furthermore, long-term treatment of chimpanzees had no effect on the percentage of immunoregulatory T cells (CD2+, CD4+ and CD8+ T cells) as determined by FACS analysis. In addition, serum IgM levels in chimpanzees were found to be comparable to those in humans, whereas the chimpanzees' IgG levels are slightly elevated due to higher concentrations of IgG2 and, in particular, IgG4.

Animals

Neopterin as discriminating and prognostic parameter in healthy homosexuals, ARC and AIDS patients.

Urinary neopterin, a sensitive marker for activation of cell mediated immunity, is compared to clinical and laboratory data in 5 patients with AIDS, in 15 patients with ARC and in 40 male subjects without AIDS-related clinical signs attending an AIDS outpatient clinic. The sensitivity of neopterin for AIDS-related diseases was higher than that of the CD4+/CD8+ subset ratio. The differences in neopterin levels between the controls, ARC and AIDS patients were found to be more significant than the T-cell subset data. The observation that the 3 AIDS patients with the highest neopterin levels have died whereas the two others with the lower levels are still alive also underlines the prognostic potential of urinary neopterin level determinations. Measurement of urinary neopterin is thus recommended as an additional criterion for monitoring ARC and AIDS patients.

AIDS-Related Complex

[Vertical hepatitis B transmission by anti-HBe positive hepatitis B carrier mothers].

5 infants (3 boys and 2 girls) were infected vertically with hepatitis B virus by their healthy anti-HBe positive HBsAg carrier mothers. First sign of infection in the infants occurred 1 to 6 months after birth. The course of the disease was as follows: subclinical hepatitis B (1 case), acute hepatitis B with complete resolution (1 case), fatal fulminant hepatitis B (1 case), chronic persistent hepatitis B (1 case), and chronic active hepatitis with rapid progression to cirrhosis. We conclude that anti-HBe positive hepatitis B carrier mothers may be infective and thus may cause serious, eventually fatal disease in their infants. Passive-active immunization must be given to infants of all hepatitis B carrier mothers irrespective if they are anti-HBe positive or not.

Carrier State

[Epidemiology and clinical course of perinatally acquired hepatitis B infection].

A report is presented on 10 children with perinatally-acquired hepatitis B virus infection. In 9 cases the mother was most probably the source of infection (vertical transmission of hepatitis B), whilst one child was infected via repeated blood transfusion. 7 mothers were of south-eastern European and/or Anatolian origin. Only 2 mothers suffered from clinically apparent liver disease (one had chronic-aggressive hepatitis with positive HBs-antigen and the other had acute hepatitis B). All the others were healthy hepatitis B carriers. Of 7 mothers examined 2 were HBe-antigen positive, and 5 were anti-HBe positive. The clinical course of infection in children varied: 2 children developed subclinical infection, 2 developed acute hepatitis B, which was fulminant with a fatal outcome in one. 6 children showed antigen persistence (HBs-antigen carriers) over the whole period of observation. In one child this antigen persistence is associated with cirrhosis of the liver, 3 children suffer from chronic-persistent hepatitis B, 2 children are healthy carriers; all children are HBe-antigen positive and, thus, seem to be highly infectious. Apart from the risk to the individual, perinatal hepatitis B infection in a certain population. Hence, preventive measures are indicated and should be carried out in form of HBs-antigen screening of pregnant women - at least of high-risk groups - and active-passive immunization of the newborns at risk. The indication for immunization should not depend on the HBe-antigen status of HBs-antigen positive mothers.

Austria

[The need for hepatitis B immunoprevention in families with vertical hepatitis B infected children].

UNLABELLED: We investigated the scope of hepatitis B infection in 11 families (family contacts: fathers, siblings) in which the mother transmitted (vertical) hepatitis B infection to the child. RESULTS: The initial examination demonstrated an acute hepatitis B infection in one of the 11 fathers and former hepatitis B infection in 8 fathers. In 2 fathers no hepatitis B markers were found (susceptible for hepatitis B). In 3 of the 10 siblings examined an acute hepatitis B infection was demonstrated, one child showed signs of a former hepatitis B infection, and in 6 no hepatitis B markers were demonstrable. Current checks made in 5 families over a period of about 6.2 years showed another hepatitis B infection in one father and one child. These observations stress the importance of immunisation in such families.

Adult

[Vertical transmission of hepatitis B. Results of a prospective study 1978 to 1981].

From June 1978 until August 1981 4400 pregnant women were consecutively investigated in Vienna for the presence of hepatitis B. 23 women (0.52%) were HBs-antigen positive; 15 of these were foreigners (from Yugoslavia, Turkey, Philippines, Rumania),22 pregnant women were healthy HBs-antigen carriers. One woman had an unspecific reactive hepatitis. Three pregnant women were HBe-antigen positive, 18 anti-HBe positive. Hepatitis B infection was detected in three children of HBs-positive mothers. The highest risk of infection existed in children of HBe-antigen positive mothers. There was no connection between the infection of the children and HBs-antigen in cord blood, delivery and breast-feeding habits. Hepatitis infection took a different course in the three children: one child was an HBs-antigen carrier with a healthy liver, whilst in two children seroconversion took place and anti-HBs was formed without clinical-biochemical signs of hepatitis. Measures for the prevention of vertical hepatitis B transmission are discussed.

Carrier State

Ultrastructural alterations in hepatocytes and sinus endothelia in experimental non-A, non-B hepatitis in chimpanzees with and without immunoglobulin prophylaxis.

Three chimpanzees were inoculated with an infectious factor VIII preparation. Two of the chimpanzees received in addition a human immunoglobulin preparation as used for prophylaxis in humans. All three chimpanzees developed an acute limited non-A, non-B hepatitis as judged from light and electron microscopic markers after an incubation period of two weeks. The use of immunoglobulin did not prevent the infection. A prolonged incubation of 15 weeks, however, was observed in one animal when alanine aminotransferase (ALT) elevation was used as criterion of infection. In the electron microscope, non-A, non-B hepatitis was characterized by tubular structures, spongelike inclusions and attaching curved membranes, in the absence of nuclear viruslike particles. An additional finding were viruslike particles in crystalline arrays which were found in the cytoplasm of sinusoidal-lining endothelial cells and tubuloreticular complexes.

Animals

Experimental non-A, non-B hepatitis in chimpanzees: light, electron and immune microscopical observations.

Two chimpanzees (Pan troglodytes) were inoculated and cross-challenged with a fibrinogen and factor VIII preparation, respectively. Successful non-A, non-B (NANB) infection was documented by biphasic elevations of aminotransferases (ALT), concomitant hepatitic reactions and typical electron microscopic alterations, the most consistent being dilatation of the endoplasmic reticulum, as well as tubular and sponge-like cytoplasmic inclusions in the absence of nuclear virus-like particles. An anti-nuclear (anti-DNA) antibody of the IgM class in one of the chimpanzees simulating an antiviral antibody is described.

Animals

Effects of serial resin hemoperfusion in fulminant hepatic failure.

Resin hemoperfusion using an albumin coated Amberlite XAD-7 column was performed in 19 patients in coma due to fulminant hepatic failure. The procedure was clinically well tolerated, with good blood compatibility, platelet and white cell levels being 97.3 +/- SE 3.2% and 105 +/- 3.8% of the respective initial values after four hours hemoperfusion. No significant changes were observed in beta-thromboglobulin, screen filtration pressure, plasma electrolytes, calcium, protein or albumin. The total plasma bilirubin fell by a mean of 24 mumol/l, with a reduction in 21 of the 25 perfusions studied of up to 104 mumol/l during perfusion. Mean plasma levels of total bile acids were 137 +/- 19 mumol/l and 115 +/- 16 mumol/l respectively before and after four hours hemoperfusion. The amount of bile acids recovered by elution of the resin column was over three times greater than that apparent from the change in plasma levels. Column chromatography on Sephadex G-25 of material eluted from the resin column showed various peaks to be removed, including substances in the middle molecular weight range (1000-5000 daltons). Of the patients treated, eight (42%) survived to leave hospital.

Acrylic Resins