PubMed Health⌕ Search

Biomedical subjects

H Dietrich

Publications and source records attributed to H Dietrich.

At least 19 recordsLinked to original sources
PubMed1996

Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma.

The mechanism that may cause degenerative fibrotic skin lesions was studied in situ using skin biopsies from patients with systemic sclerosis (SSc), localized scleroderma, or keloids, and at the initial disease stage in the University of California at Davis (UCD) lines 200/206 chickens, which develop a hereditary systemic connective tissue disease resembling human SSc and permit study of disease stages not accessible in humans. Frozen skin sections were analyzed simultaneously for apoptosis by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling and indirect immunofluorescence staining of cell markers with tetramethylrhodamine isothiocyanate conjugates. The results showed that endothelial cells are clearly the first cells to undergo apoptosis in the skin of UCD-200/206 chickens, a process that seems to be induced by anti-endothelial cell antibodies. In human fibrotic skin diseases, apoptotic endothelial cells could only be detected in early inflammatory disease stages of SSc and localized scleroderma.

Adolescent↗
PubMed1996

Analysis of the initiation period of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) of chickens.

The early, predictable, onset of spontaneous autoimmune thyroiditis (SAT) in Obese strain (OS) chickens provides a unique opportunity to analyse the mechanisms initiating autoimmunity which is virtually impossible to obtain in humans. In this study we focused on the respective roles of viruses and macrophages in the initiation of SAT. To analyse viruses, leukosis virus-free OS chickens were bred over three generations and reared under gnotobiotic conditions. By 2 weeks of age there were no differences in the levels of thyroid mononuclear cell infiltration between these and control animals. The role of mononuclear phagocytes in SAT was determined by their depletion via injecting newborn OS chicks with silica or carrageenan and dichloro-methylene diphosphonate encapsulated into liposomes. Although this treatment did not substantially change the amount of macrophages in primary lymphoid organs or blood, there was destruction of splenic architecture and, most importantly, mononuclear cell infiltration of the thyroids was significantly lower compared to controls. The role of activated macrophages in SAT is discussed.

Animals↗
PubMed1996

Regression of arteriosclerotic lesions induced by immunization with heat shock protein 65-containing material in normocholesterolemic, but not hypercholesterolemic, rabbits.

Previous studies in our laboratory have shown that arteriosclerotic changes can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp 65). To investigate the possible regression of such vascular lesions, 63 male New Zealand White rabbits were treated either by triple immunization with fortified Freund's complete adjuvant containing 5 mg/ml Mycobacterium tuberculosis, a hsp 65-rich material, by administration of a 0.2% cholesterol-rich diet only or by a combination of both immunization and cholesterol-rich diet. Sixteen weeks after the first immunization, half of the animals of each group were sacrificed, and as expected arteriosclerotic lesions in the intima of the aortic arch were found in 8 of 10 immunized animals. The remaining animals were sacrificed 16 weeks thereafter, having been maintained on a normal, non-cholesterol-enriched diet from week 16 to 32. Only 3 of 10 rabbits immunized showed moderate lesions in their aortae 32 weeks after the first immunization. On the other hand, atherosclerotic lesions induced by cholesterol-rich diet, or by immunization plus cholesterol-rich diet, showed no significant regression between 16 and 32 weeks. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp 65 can regress in the absence of additional risk factors for atherosclerosis, such as a cholesterol rich diet.

Animals↗
PubMed1995

Genomic analysis of collagen and endogenous virus loci in the UCD-200 and 206 lines of chickens, animal models for scleroderma.

University of California at Davis (UCD) lines 200 and 206 chickens develop a hereditary systemic scleroderma-like connective tissue disease characterized by severe lymphocytic infiltration and excessive accumulation of collagen in skin and internal organs. The immune system seems to play an important role in the development and/or perpetuation of this condition. The main goal of our work with this strain is the investigation of interactions between endothelial cells, lymphocytes, macrophages and fibroblasts leading to the proliferation of the latter and to excessive collagen synthesis and/or deposition. One aim of the present study was to clarify whether UCD-200 and 206 chickens have a defect of collagen genes at the genomic level by means of restriction fragment length polymorphism (RFLP) analysis using non-radioactively labelled cDNA probes specific for chicken alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III), alpha 1(VI), alpha 2(VI), and alpha 3(VI) (pro) collagens. As in the human disease, no gross alteration at the genomic level of collagen genes has been found, thus providing the UCD-200/206 model to be appropriate for studying the altered collagen metabolism in systemic sclerosis (SSc). In addition to the RFLP analysis of procollagen genes, we investigated the endogenous avian leukosis virus loci (ev) of UCD-200 and 206 chickens by means of Southern blot analysis of Sac I and BamH I digested DNA samples using pRAV-2, a Rous sarcoma virus specific probe, for hybridization. Most UCD-200 and 206 chickens harbour evs 1, 3 and 10 similar to the healthy control UCD-058, but they also contain a novel ev characterized by a 4.2 kb Sac I fragment and a 6.1 kb BamH I fragment, which we would like to designate ev 23. So far, the role of ev 23 in the development of avian scleroderma is unclear; for further analysis classical crossbreeding experiments are necessary and are underway.

Alpharetrovirus↗
PubMed1995

Atherosclerosis as an autoimmune condition.

Atherosclerosis is a multifactorial vascular disorder responsible for the highest rate of mortality in the western world. During the last decades, research on this disease has primarily focused on the role of lipids, which are essential to the formation of lesions in the vascular intima that ultimately leads to clinically apparent atherosclerotic plaques. More recently, several anecdotal findings have indicated the possible involvement of the immune system in the process of atherogenesis. In particular, the appearance of immunocompetent cells as well as humoral antibodies in the intima in the early stages of disease development supports the view of an inflammatory component in this disorder. In addition to the search for lipid-associated antigens that might entail full-blown atherosclerosis, other candidate antigens capable of inducing an immune response in the vascular wall have also been explored. Within the probable group of antigens for immune responsiveness, heat shock protein (hsp) 60/65 became a serious candidate, upon observation that immunization of rabbits with this protein led to arteriosclerotic changes of the aortic intima. In the last few years we have established this rabbit model for immunologic investigations of atherosclerosis and, in parallel, examined the pathogenesis of human atherosclerosis with regard to hsp 60/65 immune reactivity. Currently available data point to an autoimmune induction of early inflammatory arteriosclerotic changes triggered by a cellular and humoral immune reaction to stress-induced hsp 60-expressing areas of the endothelial cells.

Animals↗
PubMed1995

Allogeneic liver transplantation for hepatic veno-occlusive disease after bone marrow transplantation--clinical and immunological considerations.

Veno-occlusive disease (VOD) is a frequent complication early after bone marrow transplantation. In cases of severe liver failure treatment by allogeneic liver transplantation is possible. We report the clinical and immunological course of a patient after bone marrow transplantation for AML and subsequent allogeneic liver transplantation for severe hepatic VOD. After liver transplantation the patient recovered well clinically. Early after liver transplantation he had large numbers of liver donor T and NK lymphocytes in his circulation. He had no liver graft rejection, but he developed mild acute GVHD which was caused by liver graft-derived T lymphocytes. Two years after transplantation he had persistent microchimerism with donor liver cells detectable in his bone marrow. Now 36 months after transplantation, the patient has no evidence of recurrent leukemia, stable liver function, and no signs of graft-versus-host disease or bone marrow dysfunction.

Acute Disease↗
PubMed1994

Subcellular location of enzymes involved in core histone acetylation.

Multiple enzyme forms of histone deacetylase and histone acetyltransferase exist in germinating maize embryos. We analyzed the association of the different enzymes to chromatin by ion exchange chromatography of subcellular fractions from different time points of embryo germination. The vast majority of histone deacetylase HD-1A was not bound to chromatin, since it was solubilized during chromatin isolation, regardless of its phosphorylation state and the phase of embryo germination. In contrast, HD-2 was chromatin bound during the entire germination pathway. Histone deacetylase HD-1B was present in a chromatin-bound and a soluble form; the ratio between these two forms changed during germination. Both nuclear histone acetyltransferases, HAT-A1 and HAT-A2, were tightly chromatin-bound and could only be released from chromatin by salt extraction. To test whether histone acetyltransferases or deacetylases are associated with the nuclear matrix, we analyzed nuclear matrix preparations from yeast, Physarum, and maize step by step for both enzyme activities. This analysis confirmed that part of the activity is chromatin bound, but no significant enzyme activity could be found in the final nuclear matrix, regardless of the preparation protocol. This result was further substantiated by detailed analysis of histone deacetylases and acetyltransferases during cellular fractionation and nuclear matrix preparation of chicken erythrocytes. Altogether our results suggest that the participation of these enzymes in different nuclear processes may partly be regulated by a distinct location to intranuclear components.

Acetylation↗
PubMed1994

Ultrastructural analysis of thymic nurse cell epithelium.

Thymic nurse cells (TNC), a paradigmatic cell type of cortical epithelium, are large lymphoid-epithelial cell complexes of thymocytes enclosed within vacuoles lined by the epithelial cell membrane. TNC express major histocompatibility complex (MHC) class I and class II molecules on their surface and vacuole-lining membranes at high density and it was suggested that TNC provide an optimal microenvironment for positive selection of T cells. In this report we present electron microscopical data demonstrating that chicken TNC display morphological structures of exocytosis previously shown for hormone-secreting cells. In TNC, however, exocytosis is restricted to the capillary cleft between the epithelial cell and engulfed thymocytes. Thus, besides physical contact between the epithelial cell and enclosed thymocytes, TNC may additionally influence the development of thymocytes through release of soluble factors in a restricted microenvironment. By employing the 3-(2,4-dinitroanilino)-3'-amino-N-methyl-propylamine technique which at the ultrastructural level detects acidic organelles involved in processing of antigens presented by MHC class II molecules, we also show that TNC contain acidic compartments similar to classical antigen-presenting cells, i.e. early and late endosomes and lysosomes, albeit in a lower amount than in thymic dendritic cells. This fact provides evidence that TNC not only are capable of antigen presentation but also possess the intracellular machinery for antigen processing.

Animals↗
PubMed1994

Genetically determined target organ susceptibility in the pathogenesis of spontaneous autoimmune thyroiditis: aberrant expression of MHC-class II antigens and the possible role of virus.

Considerable controversy exists concerning the role of aberrant MHC-class II antigen expression in the pathogenesis of organ-specific auto-immune disease. Since Obese strain (OS) chickens are afflicted with a spontaneously occurring autoimmune thyroiditis (SAT), we have readdressed this pivotal question by investigating the chronical appearance of MHC-class II antigens on thyroid epithelial cells (TEC) of OS and normal healthy CB chickens before onset of overt clinical symptoms in the former. Among the candidates as potent inducers of aberrant MHC-class II antigen expression, interest in our studies focussed on the potential role of viruses in the development of SAT. Since aberrant MHC-class II antigen expression could prove to be an epiphenomenon of virally afflicted TEC, we determined 2,5-oligoadenylate synthetase and 2,5-oligoadenylatepolymer cytosol levels in both chicken lines. Our results indicate that the presence of infiltrating lymphocytes does not necessarily represent a prerequisite for the aberrant expression of MHC-class II antigens but coincides in most cases. However, the phenomenon seems to play a perpetuating rather than a causative role. Moreover, in support of a possible viral involvement, elevated levels of the 2,5-oligoadenylate synthetase and 2,5-oligomers could be demonstrated in TEC cytosol of OS chickens.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Interleukin-1 receptor deficiency in brains from NZB and (NZB/NZW)F1 autoimmune mice.

Interleukin-1 receptors (IL-1R) are expressed in the brain and the anterior pituitary of normal mice (C3H/He, Swiss), and appear to be involved in the neuroendocrine control of the immune response. Here we have studied the IL-1R density in the brain and the pituitary from several strains of autoimmune mice (NZB, (NZB/NZW)F1, MRL/MP-lpr), using quantitative autoradiography with recombinant human [125I]IL-1 alpha as a ligand. IL-1R was similar in the brain of C3H/He, Swiss and NZW (controls) and MRL/MP-lpr mice. In NZB mice a profound deficit (10% of control mice) in IL-1R was observed exclusively in the dentate gyrus. In (NZB/NZW)F1 the deficit was about 50%. These observations were independent of sex and age. Pituitary receptors were not affected in all the strains except NZW (30% increase). Competition experiments demonstrated that the affinity of IL-1R was not modified in dentate gyrus of (NZB/NZW)F1 and NZW mice. Thus, the number of IL-1R was the only parameter affected. This deficit was not reversed by corticosterone treatment (0.2 mg/20 g body weight, i.p.) and was poorly modified by lipopolysaccharide treatment (0.1 mg/20 g body weight, i.p.) compared to C3H/He mice. In conclusion, this central IL-1R deficit is unlikely to be the consequence of occupancy by abnormal synthesis of brain IL-1. This abnormality is tissue-specific with hereditary autosomal transmission. The role of central IL-1R in neuroimmunoendocrine interactions and in autoimmunity remains to be clarified.

Age Factors↗
PubMed1994

[Objective vernier acuity testing in adults, children and infants. Possibilities and limits of a new method].

BACKGROUND: Recently, a method of objective Vernier acuity testing using a modified Catford drum was presented. A tight correlation between the objective Vernier acuity and the Snellen acuity was reported (Hopkisson et al. 1991). PATIENTS AND METHODS: In 41 cooperative patients with strabismic amblyopia and 20 normal subjects were compared the subjective Landolt acuity with the objective Vernier acuity and the individual interocular differences of the objective Vernier acuity. The Vernier method was then tested in 44 healthy 6- to 36-months-old infants. In 39 of the amblyopic and 15 of the normal subjects we compared the Landolt acuity with the grating acuity as measured with the Teller-acuity-card-test, and the interocular differences of the grating acuity. The Vernier target was a black line with an offset of one fifth of its thickness. In a distance of 1 m the offset appeared under visual angles of 15.9' to 0.3' corresponding to acuities of 0.06 to 3.2. The line was moving back and forth in its longitudinal direction. The objective Vernier acuity was defined by the smallest offset causing pursuit eye movements. RESULTS: Strabismic amblyopia was detected by the Vernier method with a sensitivity of 54%. In infants, however, the sensitivity would be less than 30%. In both eyes only 45% of the infants could be tested at all. The sensitivity of the Teller-acuity-card-test was 28%. CONCLUSION: Many cases of strabismic amblyopia will escape detection by the described method of Vernier acuity testing.

Adolescent↗
PubMed1994

Immunohistochemical analysis of cells infiltrating Rous sarcoma virus-induced tumors in chickens.

The aim of our experiments was the analysis of peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) in chicken inbred congenic lines, CB line with regressing and CC line with progressing RSV-induced sarcomas. For serological analysis, monoclonal antibodies to CD4, CD8, TCR1, TCR2, MHC class I and class II antigens were used. Significant differences determined by flow cytometry in CD4+ and CD8+ populations of PBL between CB chickens with tumors in progressive phase and CC chickens were not confirmed by means of TIL analysis. TIL were analysed either in suspension prepared from tumors by means of flow cytometry or on cryostat section of tumors. But using the histochemical method we observed more non-specific esterase positive cells in cryostat sections from CB than CC tumors. The role of macrophages in the regression of RSV-induced tumors in CB chickens has to be further analysed.

Animals↗
PubMed1993

Fragrance compounds and essential oils with sedative effects upon inhalation.

Fragrance compounds and essential oils with sedative effects influence the motility of mice in inhalation studies under standardized conditions. A significant drop in the motility of mice was registered following exposure to these fragrances. The same results were achieved when the mice were artificially induced into overagitation by intraperitoneal application of caffeine and subsequently subjected to inhalation of fragrance compounds and essential oils. These results proved the sedative effects of these fragrants via inhalative exposure in low concentrations. Blood samples were taken from the mice after a 1-h inhalation period. Chromatographic and spectroscopic methods were used to detect and characterize the actual effective compounds after solid-phase extraction. Serum concentrations of 42 different substances, including fragrance compounds, were found in low ranges (ng/mL serum). The results contribute to the correct interpretation of the term aromatherapy (i.e., a stimulating or sedative effect on the behaviour of individuals only upon inhalation of fragrance compounds).

Administration, Inhalation↗
PubMed1993

Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease.

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.

Animals↗
PubMed1993

Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65.

We have shown previously that atherosclerotic lesions can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp65), which has a high degree of sequence homology with mammalian hsp60. To investigate a possible relationship between hsp60 expression and the antigenic specificities of infiltrating T cells in the lesion, 38 New Zealand White rabbits were treated either by immunization with recombinant mycobacterial hsp65 or by administration of a 0.2% cholesterol diet. Atherosclerotic lesions were observed after 16 wk, particularly in the aortic arch and arterial bifurcations of rabbits immunized with hsp65 or fed with a cholesterol-rich diet. Hsp65 staining of aortas showed a heterogeneous distribution, and significantly increased staining intensity in atherosclerotic lesions compared to aortic media or adventitia. This abundantly expressed hsp65 was observed in atherosclerotic lesions induced by hsp65 immunization as well as those induced by cholesterol-rich diet alone. Interestingly, a population of the T lymphocytes isolated from all forms of atherosclerotic lesions specifically responded to hsp65 in vitro. IL-2-expanded T cell lines derived from atherosclerotic lesions showed a significantly higher hsp65 reactivity than those developed from peripheral blood of the same donor. Furthermore, levels of circulating antibodies and numbers of spleen cells specifically reacting against hsp65 were elevated in all experimental animals. Flow cytometric analysis of spleen cells showed elevated immune response-associated antigen expression in treated animals. In conclusion, increased hsp65 expression in intimal cells and the presence of hsp65-specific T cells in blood and in atherosclerotic lesions may be important in initiating the development of atherosclerosis and perpetuating the lesions.

Animals↗
PubMed1992

The substance P (NK1) receptor antagonist (+/-)-CP-96,345 causes sedation and motor impairment in Swiss albino mice in the black-and-white box behavioral paradigm.

In order to test the suggested involvement of substance P (NK1) receptors in anxiety, the non-peptide NK1 antagonist (+/-)-CP-96,345 was tested in Swiss albino mice using the black-and-white box behavioral paradigm. Intraperitoneal (+/-)-CP-96,345 dose-dependently decreased the motor activity and the number of exploratory rearings in both the brightly lit and dark compartment as well as the transitions between the compartments, whereas it increased the latency of the initial movement into the dark compartment as well as the time spent in the light section. ED50 or ID50 values ranged from 1.9 to 3.6 mg/kg and Hill slopes from 1.4 to 5.0. (+/-)-CP-96,345 also produced rotatory behavior of no preferred lateralization as well as the Straub phenomenon in some animals. The effects of (+/-)-CP-96,345 (5 mg/kg) were not affected by 2 mg/kg naloxone (i.p.) which was also ineffective when given alone. Thus, (+/-)-CP-96,345 does not display any anxiogenic effect but causes dose-dependent sedation and motor impairment.

Animals↗
PubMed1992

Investigation of ACTH responses of chickens with autoimmune disease.

An altered immunoendocrine feedback regulation within the hypothalamo-pituitary-adrenal axis may modulate the pathogenesis of an avian autoimmune disease. To date studies have been hampered by a lack of reliable, specific, and sensitive methods for determining adrenocorticotropic hormone (ACTH) in chickens. The present study describes the determination of ACTH in plasma of chickens with a commercial radioimmunoassay, the antibody of which binds to the midregion of human ACTH 1-39. The chickens, kept on a 12-hr day and 12-hr night shift with artificial light, showed changes in plasma ACTH concentrations during the light phase with maximum values 8 hr after the light was turned on. ACTH was not measurable after treatment with dexamethasone. Intravenous administration of supernatants from concanavalin A-stimulated spleen cells increased basal plasma ACTH concentrations more than 20-fold within 1 hr. This increase in plasma ACTH was higher and longer lasting in UCD 200 chickens, an animal model for scleroderma, compared with outbred and inbred normal White Leghorn chickens.

Adrenocorticotropic Hormone↗