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Biomedical subjects

G Hess

Publications and source records attributed to G Hess.

At least 109 records · Page 6Linked to original sources
PubMed1991

Interferon-alpha-2-induced stimulation of ACTH and cortisol secretion in man.

Short-term effects of interferon-alpha 2 on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol were measured in man in relation to interferon absorption. Interferon-alpha 2 was given subcutaneously at a dose of 3 x 10(6) IU at 17.00 h to 2 female and 5 male patients who suffered from chronic hepatitis B infection and who had not previously been treated with interferon. Plasma levels of ACTH, cortisol and interferon-alpha were determined at 30-min intervals between 16.00 and 24.00 h. In each patient a similar cortisol, ACTH and interferon-alpha profile was determined on a day, when no interferon-alpha treatment was given. Interferon-alpha plasma levels peaked around 21.30 h, i.e. 4.7 h after injection. In each patient ACTH and cortisol levels were increased. As calculated from the areas under the curves, ACTH release was increased by an average of 332% (maxima at about 22.00 h, i.e. 5.2 h post injection); cortisol release was increased by an average of 311% (maxima at about 23.00 h, 5.8 h post injection). These actions were not related to side effects like fever or other flu-like symptoms. Our findings confirm that in man as in animals interferon-alpha 2 can act as a mediator between the immune and endocrine system.

Adrenocorticotropic Hormone↗
PubMed1991

Hepatocellular expression of lymphocyte function-associated antigen 3 in chronic hepatitis.

T lymphocyte-mediated cytolytic immune reactions are considered a major cause of hepatocyte injury in chronic viral and autoimmune hepatitis. To further investigate local immune responses, we studied the expression of lymphocyte antigens and cell-cell interaction molecules known to be involved in effector-target cell interactions by light and electron microscopy in liver biopsy specimens from patients with chronic viral and autoimmune hepatitis. CD8+ lymphocytes were found to be the predominant population of cells in the inflammatory infiltrate in chronic hepatitis B and non-A, non-B hepatitis. In contrast, CD4+ cells constituted a comparably higher proportion of cells and were more numerous than CD8+ cells in chronic autoimmune hepatitis. In both viral and autoimmune hepatitis, a substantial portion of lymphocytes expressed activation antigens such as T11/3 (CD2R) and IL-2-R (CD25). Lymphocyte function-associated antigen-3 (CD58), which mediates lymphocyte adhesion and activation and is the natural ligand of the CD2/T11 lymphocyte surface receptor, could be demonstrated on endothelial cells and hepatocytes. Hepatocellular lymphocyte function-associated antigen-3 expression in chronic hepatitis showed membranous and cytoplasmic staining of hepatocytes and had a positive correlation with the degree of inflammatory activity. These results suggest that effector-target interactions between hepatocytes and lymphocytes mediated by the lymphocyte function-associated antigen-3/CD2 pathway play a role in chronic inflammatory liver disease. Possible functional consequences of this interaction include enhancement of antigen-specific immune reactions and antigen-independent mechanisms of T cell activation, which may contribute considerably to the degree of inflammatory activity and tissue damage in chronic hepatitis.

Antigens, Surface↗
PubMed1991

Improving a community preceptorship through a clinical faculty development program.

A department of family and community medicine has successfully used annual conferences to develop the teaching skills of clinical faculty. The conferences focus on specific topics each year, faculty are required to attend, and experienced preceptors are used as facilitators. These conferences have effectively improved the preceptors' abilities as teachers of medical students. This is dramatically illustrated by the increase in measurable objectives on the negotiated learning contracts.

Community Medicine↗
PubMed1991

Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B.

Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon was demonstrated only in lymphocytes. The expression of human leukocyte class I antigens on hepatocytes showed a close association with the number of interferon-producing cells, but not with the presence of virus particles and HBcAg in liver cells, when studied using electron microscopy and double-labeling. Interferon seems to be an important regulator of the local immune response in the liver in patients with chronic hepatitis B. Its functions may play a role in inducing the human leukocyte class I antigen expression on hepatocytes, thus enhancing the elimination of virus-containing hepatocytes by major histocompatibility complex-restricted cytotoxic lymphocytes.

Cytoplasm↗
PubMed1991

Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to pre-S- and S-encoded viral surface antigens.

The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of HBsAg-positive virus carriers using aliquots as small as 100 al. The detection limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different regions of the HBV genome resulted in different sensitivity. Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay. Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody-positive symptomatic HBsAg carriers and 57% of asymptomatic HBe antibody-positive HBsAg carriers were found to have hepatitis B virus DNA in the serum. During antiviral therapy hepatitis B virus DNA disappeared by the polymerase chain reaction assay in patients who became HBeAg negative, but polymerase chain reaction detected a relapse earlier than did the conventional dot blot. Pre-S antigens were assayed in serum and liver samples from most chronic carriers by enzyme-linked immunosorbent assay and/or immunoblot. Although most viremic carriers were strongly positive for pre-S1 and pre-S2 antigens, some hepatitis B virus DNA-positive HBsAg carriers did not have detectable pre-S antigens, and vice versa. Our data show that assay of hepatitis B virus DNA in the serum by polymerase chain reaction is by far more proficient than by dot blot and that it cannot be replaced by serological assays of HBeAg or pre-S antigen.

Base Sequence↗
PubMed1991

[Intestinal immune system].

The intestinal mucosa is the main barrier between a wide variety of potential antigens and human or animal beings. Beside of unspecific defense mechanisms there is a rather independently reacting gut associated lymphoid system (GALT), first described by Bienenstock. GALT is seen as part of a common mucosal immune system (MALT), the independency of which is based on morphological, functional and ontogenic reasons. The two main functional parts of GALT are Peyer's patches (with T-cells and B-cells) and the diffuse lymphoid tissue (DLT). The latter is found throughout the intestinal mucosa in two compartments, in the lamina propria and intraepithelially. However there is a network between different local immune systems and the humoral immune system which is demonstrated by the "homing" phenomenon of lymphocytes and "remote-site" stimulation. Although many basic mechanisms of intestinal immunity today are not completely understood, immunoprophylaxis against different enteropathogenic agents is successfully used either by active or by passive immunization methods.

Animals↗
PubMed1990

Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS.

Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV-infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.

AIDS-Related Complex↗
PubMed1990

T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): oligoclonality of PBC-derived T cell clones.

Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in both patients with primary biliary cirrhosis, T cell clones established were of limited diversity. Thus 5 out of 10 and 2 out of 10 T cell clones from one patient and 3 out of 9 and 2 out of 9 T cell clones from the second patient, respectively, showed identical TcR beta gene rearrangements. These data suggest that a clonal dominance is characteristic for local T cell responses in autoimmune liver disease such as primary biliary cirrhosis whereas in virus-induced chronic active hepatitis T cell activation occurs polyclonally.

Adult↗
PubMed1990

Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro.

The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the cells with prostaglandin E2 resulted in a reduced C.p.-mediated TNF-alpha production (p less than 0.001). Coincubation of interferon-gamma (IFN-gamma) together with C.p. led to an enhanced release of TNF-alpha, supporting the assumption that C.p. is a potent TNF-alpha inducer. The additive effect of IFN-gamma and TNF-alpha on the receptor level was demonstrated by addition of IFN-gamma antibodies to the PBMC cultures. Under these conditions TNF-alpha production, stimulated by C.p. and IFN-gamma, was decreased by 30%, compared to the production in assays supplemented with C.p. alone. From these data we conclude that C.p. is a new inducer of TNF-alpha in vitro and a useful tool to study TNF-alpha production of PBMC and BMo from either healthy donors or from patients.

Blotting, Northern↗
PubMed1990

Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis.

Autoantibodies to the human asialoglycoprotein receptor (anti-h-ASGPR) were studied with a solid-phase ELISA in the sera of 421 patients with inflammatory liver diseases, 288 patients with various other disorders and 31 controls. Anti-h-ASGPR were found predominantly in autoimmune chronic active hepatitis (44 of 88, 50%) and were closely related to inflammatory activity. In a subpopulation of these patients with untreated, biopsy-proven active disease or relapse, 15 of 17 were positive (88%). In contrast, only 11 of 204 patients (5.3%) with viral hepatitis were anti-h-ASGPR receptors-positive (chi 2 analysis; p less than 0.001). We also compared the occurrence of anti-h-ASGPR with antibodies to rabbit and rat asialoglycoprotein receptors in 352 sera. In contrast to the anti-human asialoglycoprotein receptor antibodies (3 of 107), anti-rabbit- or anti-rat-asialoglycoprotein receptor antibodies were found in 21 and 28 of 107 cases of viral hepatitis, indicating that different epitopes were recognized by these sera. In various other diseases anti-human asialoglycoprotein receptor antibodies were rarely found. Some sera from patients with connective-tissue diseases (8 of 73) and primary or secondary liver malignancies (6 of 55) exhibited anti-h-ASGPR. In autoimmune chronic active hepatitis the presence of anti-human asialoglycoprotein receptors did not correlate to other established autoantibody systems. Thus we conclude that anti-human asialoglycoprotein receptor antibodies can serve as diagnostic markers for inflammatory active cases of autoimmune chronic active hepatitis. Immune reactions to the asialoglycoprotein receptor, which is expressed on the hepatocellular membrane as a liver-specific antigen, might contribute to the pathogenesis of autoimmune chronic active hepatitis.

Adolescent↗
PubMed1990

Hepatic expression patterns of the large and middle hepatitis B virus surface proteins in viremic and nonviremic chronic hepatitis B.

The envelope of hepatitis B virus consists of large, middle, and small hepatitis B surface proteins. Recent data from in vitro studies suggest that intracellular expression and distribution of the three polypeptides may be variable. These observations in artificial expression systems prompted this analysis of the occurrence and distribution of the three hepatitis B surface proteins in the liver tissue of substantial viremic (hepatitis B virus DNA- and hepatitis B e antigen-positive) and low-viremic or nonviremic (hepatitis B virus DNA-negative, anti-hepatitis B e antigen-positive) carriers by specific monoclonal antibodies against large, middle, and small proteins. Patients with an active form of viral replication showed a prevalence of middle and small hepatitis B surface proteins in the liver. In nonviremic carriers, the large hepatitis B surface protein was the predominant intrahepatic antigen, a finding that was confirmed at the ultrastructural level by staining of the entire filaments of the viral envelope material in ground glass hepatocytes. The present data are thus consistent with observations in hepatitis B virus-transgenic mice and in transfected cell systems, suggesting that the different patterns of the envelope proteins in the liver may be due to different processing at the translational level.

Antibodies, Monoclonal↗
PubMed1990

Changes in field excitatory postsynaptic potential shape induced by tetanization in the CA1 region of the guinea-pig hippocampal slice.

The present paper contains a description of a prolonged potentiation of the field excitatory postsynaptic potential in the CA1 region of the hippocampal slice preparation following afferent tetanization. In contrast to long-term potentiation, this novel potentiation is not specific to the activated synapses, and manifests itself as a change in the shape of the field excitatory postsynaptic potential with a prolongation of the rising phase and an increased peak amplitude. The potentiation is fully developed within minutes after tetanization and shows no decrement for at least an hour. Although it can appear together with long-term potentiation following tetanization at moderate strength (single volley excitatory postsynaptic potential below threshold for spike initiation), it is more readily seen following tetanization at higher strengths. The N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate prevents the induction but not the maintenance of the shape modification. The potentiation is observed in the presence of the GABAA antagonist picrotoxin (100 microM) and is thus not secondary to changes in postsynaptic inhibition. 4-Aminopyridine (50-100 microM) produced changes in the field excitatory postsynaptic potential resembling the shape modification produced by afferent tetanization, suggesting that the potentiation may be due to a blockade of potassium channels, pre- or postsynaptically located. The potentiation is also found to be associated with an increase in the population spike for a given initial slope of the field excitatory postsynaptic potential, and may thus contribute to the excitatory postsynaptic potential-spike potentiation that can be observed following afferent tetanization.

2-Amino-5-phosphonovalerate↗
PubMed1990

Immunosuppressive function of hepatitis B antigens in vitro: role of endoribonuclease V as one potential trans inactivator for cytokines in macrophages and human hepatoma cells.

The mRNAs of transiently expressed cytokine genes contain AUUUA-rich sequences in the 3' untranslated regions. In order to examine whether the AU-specific endoribonuclease V (EC 3.1.27.8) described previously by us transinactivates those mRNA species, we introduced a 51-nucleotide ATTTA sequence from tumor necrosis factor into the 3' untranslated region of beta-globin gene. Transcripts of that construct, synthesized in vitro, were prone to endoribonuclease V digestion at those AU-rich sequences. Stimulation of human macrophages with lipopolysaccharide resulted in a shift of the association state of the enzyme from the nuclear matrix-associated to the free form. This shift was strongly prevented by the hepatitis B surface antigen (HBsAg) and more weakly by hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region. HBsAg and, to a lesser extent, hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region inhibited the release of alpha interferon, tumor necrosis factor alpha, and granulocyte-macrophage colony stimulating factor, while it had no effect on interleukin-1 production from stimulated macrophages. Using the human hepatoma cell line PLC/PRF/5, we provide further experimental evidence that endoribonuclease V acts in trans as a posttranscriptional inactivator for nuclear matrix-associated cytokine transcripts. These results suggest that those cytokine transcripts which contain reiterated (overlapping) AUUUA sequences are degraded by nuclear matrix-associated endoribonuclease V. This degradation was comparably high in cells incubated with HBsAg or cells which produced this antigen.

Animals↗