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Biomedical subjects

H Uhlig

Publications and source records attributed to H Uhlig.

At least 19 recordsLinked to original sources
PubMed2006

Severe acute inflammatory reaction (SAIR) of the fetlock joint after intraarticular hyaluronate injection in a horse.

Hyaluronate (HA) was administered by intra-articular injection to a 13-year-old Haflinger mare for treatment of metacarpophalangeal osteoarthritis. Ten hours after the injection, a severe inflammatory reaction developed in the treated joint. While awaiting results of synovial fluid analysis, treatment for iatrogenic infectious arthritis was initiated, but the analysis did not confirm sepsis. Clinical signs improved significantly following systemic non-steroidal anti-inflammatory medication and the horse was discharged three days later. Following an intravenous hyaluronate injection, four days after discharge, the synovitis recurred. Synovial fluid analysis did not show any abnormalities, but the clinical signs were severe. The severe acute inflammatory reaction required systemic non-steroidal anti-inflammatory and intra-articular corticosteroid treatment in order to resolve the problem.

Adjuvants, Immunologic↗
PubMed2000

[Analysis of serum zinc level in patients with atopic dermatitis, psoriasis vulgaris and in probands with healthy skin].

BACKGROUND AND OBJECTIVE: The significance of zinc in the pathogenesis of different dermatological conditions is controversial. Using our own patient collective, the present study aimed to determine variations in serum zinc levels in patients with atopic dermatitis and psoriasis as compared to levels in the normal population. PATIENTS/METHODS: The serum zinc levels of 97 patients with atopic dermatitis and 88 patients with psoriasis were compared to those in 22 healthy subjects and subjected to statistical analysis. RESULTS: In contrast to the data given in the literature, no statistically significant difference was found between the populations investigated. CONCLUSIONS: Zinc replacement therapy in patients with atopic dermatitis and psoriasis appears to be indicated only in those with a documented zinc deficiency.

Adult↗
PubMed1998

Use of the phage display technique for detection of epitopes recognized by polyclonal rabbit gliadin antibodies.

A random phage heptapeptide library was screened with rabbit antibodies against wheat flour proteins comprising gliadins and a small amount of low molecular weight glutenins (gli/glu). Gli/glu antibodies isolated from the sera selected different consensus sequences (CS). All CS contained tri- to pentapeptide stretches homologous to gli/glu sequences (proposed epitopes). In alpha- and gamma-type gliadins, these sequences are clustered in the N-terminal region recently suspected to be toxic for humans with celiac disease. Peptides with CS were synthesized and checked for reactivity. Only immune and no control rabbit sera reacted with synthetic peptides. One of eight human sera containing gliadin antibodies was reactive as well (4/8 peptides) but control sera were negative. Thus the phage display technique is useful for epitope screening of polyclonal antibodies even in the case of a group of homologous but diverse antigens.

Amino Acid Sequence↗
PubMed1998

Role of tissue transglutaminase in gliadin binding to reticular extracellular matrix and relation to coeliac disease autoantibodies.

On different tissue sections, binding of gliadin to reticular matrix components was observed which was Ca2+-dependent, inhibited by Cu2+ and Zn2+ ions, by putrescine, and by preincubation with antibodies against tissue transglutaminase (tTG) suggesting that binding of gliadin is mediated by tTG. tTG was able to bind to gliadin and fibronectin fixed to microplates. Furthermore, tTG mediated binding of gliadin to fibronectin coated to microplates. On tissue sections, treatment with sera containing coeliac disease autoantibodies yielded staining patterns very similar to that of bound gliadin. Dual label experiments by means of conventional and laser scanning microscopy revealed that most of autoantibody binding sites are matched by bound gliadin. However, lack of competition between gliadin and autoantibody binding hints to ligands in very close vicinity of this enzyme. Furthermore, there were several autoantibody binding regions which did not bind gliadin. This implies the existence of further autoantigenic epitopes not related to tTG.

Animals↗
PubMed1997

Melatonin and 6-hydroxymelatonin sulfate excretion is inversely correlated with gonadal development in children.

To delineate the development of melatonin (MLT) production during childhood, we measured the excretion of MLT and 6-hydroxymelatonin sulfate (MLTS) in the urine of children (n = 134) from the 26th week of gestation until the age of 20 years. MLTS excretion showed a diphasic pattern with declining values in preterm babies with lowest values around term. After birth, the values remained low for the first 6 months of life. The highest values were reached between 4 and 7 years of age with a smooth but steady decline thereafter. A night-day difference was not detectable before the age of 6 months; the greatest night-day variations occurred at the time of the highest MLTS excretions. The MLT values showed an identical pattern but with amounts 1,000 times smaller; the ratio of MLTS to MLT increased from 40:1 in preterm babies to 900:1 in prepubertal children. In summary, the MLT/MLTS excretion exhibits the highest activity with respect to total secretory capacities as well as night-day differences at the time of gonadal quiescence during childhood. The strong inverse correlation of MLT and MLTS excretion with the hypothalamic-pituitary-gonadal activity points to a causal relationship between pineal gland activity and pubertal development.

Adolescent↗
PubMed1996

[Surgical therapy of severe colitis].

Severe colitis, eventually complicated by toxic megacolon, perforation or massive hemorrhage still represents a potentially life threatening complication during the course of inflammatory bowel disease reaching a mortality of almost 40% if not operated in time. From 1.1.1973 until 30.4.1994 22 patients (13 men, 9 women, mean age 29 years) with either ulcerative colitis or Crohn's disease of the colon were operated on for severe colitis. Indications for operative treatment were as follows: 7 patients relapsed conservative medical treatment, 8 developed toxic megacolon and in 7 patients perforation occurred. Diagnosis was based on the clinical criterias first described by Turnbull. In 11 (50%) cases subtotal colectomy with an ileostomy and intrapelvic Hartmann's pouch was performed, in 4 (18%) patients a Turnbull's procedure was carried out with loop ileostomy and colostomies and in 3 (14%) cases a left hemicolectomy and transversostomy was applied. In two patients with Crohn's disease an ileocolic resection was done because of perforation, one received a subtotal colectomy and ileorectal anastomosis and one patient was operated by a right hemicolectomy and ileostomy. One patient with ulcerative colitis died, reaching a post-operative mortality of 4.5%. After an intervall of approximately 18 months in the 16 surviving patients with ulcerative colitis an ileal pouch-anal procedure could be done. Of the 5 patients with Crohn's disease one had to be operated on for recurrence, the other patients have been free of recurrent Crohn's disease for a follow-up time between 3 and 11 years. We conclude, provided early operative treatment is intended, that subtotal colectomy with Hartmann's pouch and ileostomy is the procedure of choice in patients with severe colitis.

Adult↗
PubMed1995

A sulfatide-reactive human monoclonal antibody obtained from a multiple sclerosis patient selectively binds to the surface of oligodendrocytes.

In a previous paper, we described the production of a sulfatide-reactive IgM antibody-secreting B cell line that was obtained by Epstein-Barr virus transformation of peripheral B cells from a patient with multiple sclerosis (MS) (Uhlig and Dernick, 1989). In the present study, we demonstrate that this human monoclonal antibody (humAb) DS1F8 selectively binds to the surface of living oligodendrocytes in mixed brain cell cultures of newborn rats. Since a mouse mAb reactive with sulfatide was shown to inhibit oligodendrocyte progenitor differentiation, autoantibodies with binding specificities similar to DS1F8 could play a role in the demyelinating process in the CNS.

Animals↗
PubMed1993

A monoclonal antibody against an activation epitope on mouse integrin chain beta 1 blocks adhesion of lymphocytes to the endothelial integrin alpha 6 beta 1.

We have generated a monoclonal antibody (mAb), 9EG7, against mouse endothelial cells that blocks adhesion of lymphocytes to endothelial cells. Sequencing of four tryptic peptides of the purified antigen revealed its identity with the integrin chain beta 1. The only beta 1 integrin that is known to mediate cell-cell adhesion is alpha 4 beta 1 (VLA-4). This is not the integrin that is functionally defined by the mAb 9EG7 on endothelial cells. First, alpha 4 is not present on the analyzed endothelial cells. Second, mAb 9EG7 does not block the cell-adhesion function of alpha 4 beta 1 on the nonactivated mouse lymphoma L1-2. Thus, the mAb 9EG7 can functionally distinguish between different beta 1 integrins and defines a beta 1 integrin other than alpha 4 beta 1 as a newly discovered cell-cell adhesion molecule. This integrin is most likely alpha 6 beta 1, since an antibody against the alpha 6 chain blocks lymphocyte adhesion to the same degree as the mAb 9EG7, the effect of both antibodies is not additive, and the alpha 6 chain is coprecipitated with beta 1 in 9EG7 immunoprecipitations. Surprisingly, activation of alpha 4 beta 1 on L1-2 cells with phorbol ester or Mn2+ allows blocking of alpha 4 beta 1-mediated adhesion of L1-2 cells to endothelial cells with mAb 9EG7. Furthermore, only the activated alpha 4 beta 1 heterodimer, but not the unactivated complex, is detectable with 9EG7 in immunoprecipitations and by flow cytometry. Thus, mAb 9EG7 defines an epitope on integrin chain beta 1, which is accessible on the alpha 4 beta 1 heterodimer only after activation of this integrin.

Animals↗
PubMed1993

Detection of growth hormone, prolactin and human beta-chorionic gonadotropin mRNA in growth hormone-secreting pituitary adenomas and in prolactin-secreting pituitary adenomas by in situ hybridization using a non-isotopic detection method.

A non-isotopic in situ hybridization method with digoxigenin-labelled probes was used to examine growth hormone (GH), prolactin (PRL) and human beta-chorionic gonadotropin (beta-hCG(LH)) gene expression in 63 pituitary tumours in acromegaly and 20 adenomas in hyperprolactinaemia. hCG and LH were detected simultaneously because of the extensive homology (more than 90%) of their mRNA sequences (1). A comparison with former results obtained with 35S-labelled probes shows the value of the easier and faster non-isotopic method. Additionally, immunohistochemical data are included to give even more evidence for the synthesis of the respective hormones by the tumour cells. In all 63 adenomas in acromegaly, GH mRNA was revealed in 59 PRL mRNA and in 36 beta-hCG(LH) mRNA. A positive immunostaining for GH was found in all, for PRL in 40, and for beta-hCG(LH) in 34 adenomas. The comparison of the two in situ hybridization methods revealed no differences concerning GH mRNA detection, but not all tumours positive after non-isotopic PRL and beta-hCG(LH) mRNA detection showed signals with the radioactive method. Referring to the 20 PRL-secreting adenomas, PRL gene expression was demonstrable in all, GH mRNA in 12, and beta-hCG(LH) mRNA in 2 cases. Comparing the positive results of immunohistochemistry with those of in situ hybridization, correspondence was found in 19 cases for PRL, in 5 cases for GH and in no case for beta-hCG(LH).

Acromegaly↗
PubMed1991

HGH, PRL and beta HCG/beta LH gene expression in clinically inactive pituitary adenomas detected by in situ hybridization.

Within our surgical collection clinically inactive pituitary adenomas represent 30.7% of all pituitary tumours. To characterize their endocrine activity we studied 40 clinically inactive pituitary adenomas with in situ hybridization (ISH) using cRNA probes labelled with 35S encoding growth hormone (GH), prolactin (PRL) and chorionic gonadotrophin (beta HCG). No tumour was associated with clinical evidence of elevated hormone secretion. A mild hyperprolactinaemia not correlated with hormone or the mRNA content of the cells was interpreted to be incidental in 11 patients. By histological analysis, immunohistochemistry (IH) and electron microscopy the adenomas were diagnosed as small cell chromophobic (n = 16) and large cell chromophobic (n = 8) adenomas, and oncocytomas (n = 16). Gene expression of one or more hormones was identified by ISH in 18 of 40 adenomas in few cells. GH and PRL gene expression was rare (GH mRNA in 3 of 40 tumours and PRL mRNA in 8 of 40 tumours) whereas in 14 of 40 adenomas beta HCG/beta LH gene expression was identified in scattered cells. Five of 40 adenomas lacking hybridization signals revealed hormones by IH. The detection of mRNA was accompanied by positive immunostaining for the respective hormones in 72%. The combination of ISH and IH reveals good evidence that the hormones are synthesized in the tumours and not taken up from the serum and stored in the cells. The two methods used together permit a more precise analysis of tumour biology than each alone.

Adenoma↗
PubMed1991

Detection of growth hormone, prolactin and human beta-chorionic gonadotropin messenger RNA in growth-hormone-secreting pituitary adenomas by in situ hybridization.

In a series of 39 adenomas from patients with the clinical hyperfunction syndrome of acromegaly and in one from a case of prolactinoma we studied the mRNA expression of growth hormone (GH), prolactin (PRL) and beta-human chorionic gonadotropin (HCG) by using this technique of in situ hybridization (ISH). This technique allows the direct identification and localization of cells expressing mRNA and thus synthesizing the respective hormone. The aim of our study was to demonstrate the frequent co-expression of PRL mRNA and HCG mRNA in pituitary adenomas of acromegalic patients. Probes for ISH of the above-mentioned hormones were obtained by subcloning cDNA fragments into pGEM plasmids. Subsequent Sp6-polymerase catalysed in vitro transcription with 35S-CTP revealed radiolabelled single-stranded antisense RNA probes [the probe for beta HCG detects beta-luteinizing hormone (beta LH) simultaneously because of a sequence homology of 90%]. To localize the labelled hybrids, autoradiography was carried out. Light microscopical evaluation of the tissue sections demonstrated positive signals in all cases for GH, in 80% of cases for PRL and in 25% of cases for HCG [LH] mRNA. The comparison of mRNA content shown by ISH with immunocytochemical (ICC) hormone detection revealed that in all cases the detection of GH corresponded to GH mRNA content of the cells. For PRL and HCG [LH] positive mRNA detection (ISH) and negative hormone detection (ICC) occurred in some cases (PRL 17.5%; HCG [LH] 15%). In contrast, negative mRNA detection (ISH) and positive hormone content (ICC) was also demonstrated (PRL 5%; HCG [LH] 37.5%). The remaining adenomas showed both mRNA and the respective hormone, as well as negative ISH and ICC.

Acromegaly↗
PubMed1991

Dissection of murine lymphocyte-endothelial cell interaction mechanisms by SV-40-transformed mouse endothelial cell lines: novel mechanisms mediating basal binding, and alpha 4-integrin-dependent cytokine-induced adhesion.

Lymph node-derived endothelial cells were immortalized by infection with SV40 virus and subclones expressing the marker MECA 325 specific for high-endothelial venules (HEV) were selected. These transformed mouse endothelial (TME-) cell lines grow permanently without requirement for special growth factors. Staining of the selected clones with endothelium-specific antibodies and with anti-von Willebrand factor antiserum and uptake of acetylated low-density lipoprotein provide evidence for their endothelial origin. The vascular addressins identified by mAbs MECA 79 and MECA 367 on HEV are not detectable, indicating that the phenotype of the cells differs from that of HEV-type endothelium. The TME cells display a constitutive capacity to bind lymphocytes. An additional binding component is induced by treatment of the TME cells with TNF alpha. Antibodies against the homing receptor LECAM-1 (lectin-related leucocyte-endothelial cell adhesion molecule 1), alpha 4-integrins, vascular addressins, LFA-1, or ICAM-1 known to block lymphocyte interaction with particular types of HEV were unable to inhibit the basal adhesion to TME cells, indicating that a further binding mechanism in mice is displayed by this cell type. The adhesion component induced by TNF alpha is mediated by alpha 4-integrins since enhanced binding could be blocked by an antibody against mouse alpha 4 (lymphocyte-Peyer's patch adhesion molecule 1/2). TME cell lines therefore seem to be a useful model for the dissection and analysis of hitherto poorly characterized murine lymphocyte/endothelial cell interaction mechanisms.

Animals↗
PubMed1991

In situ hybridization for different mRNA in GH-secreting and in inactive pituitary adenomas.

In a series of 40 pituitary adenomas in acromegaly all tumors showed mRNA for GH by in situ hybridization (ISH). The signals were mostly very strong and found in more than 80% of adenoma cells by using frozen sections. In paraffin sections the number of positive cells and the intensity of signals are lower. Prolactin mRNA was found in 87% of adenomas. In 27% more than 80% of cells were marked. beta-HCGmRNA (with 90% hormology for LH-mRNA) was demonstrable in very sparse cells of 25% of adenomas. Comparing ISH with immunohistology (IH) we found a correlation between signals and hormone content in 100% of adenomas for GH, in 60% for Prolactin and in 10% for Gonadotropins. In 18% Prolactin mRNA but not the hormone was demonstrable and in 5% Prolactin was immunostained but no hybridization signals were detected. In a series of 40 clinically inactive adenomas sparse cells of three tumors expressed GHmRNA and two of these contained also the hormone, whereas in one adenoma GH but not GHmRNA was demonstrable. Prolactin mRNA was found in 8 adenomas. 7 of these also contained the hormone. In two cases Prolactin but not Prolactin mRNA was present. Beta-HCG(LH)mRNA and the respective hormones were shown in very sparse cells of 6 adenomas, whereas only beta-HCG(LH)-mRNA was found in 8 cases. The significance of the findings is discussed.

Acromegaly↗
PubMed1991

From host components of virus particles to anti-myelin human monoclonal antibodies obtained by Epstein-Barr virus transformation of lymphocytes from multiple sclerosis patients.

Human monoclonal antibodies against viruses and host components were obtained after transformation of human B cells by Epstein-Barr virus, their cloning and propagation. B cells were mainly obtained from peripheral blood of healthy individuals or patients with neurological diseases, especially with multiple sclerosis (MS). The obtained autoantibodies reacted with cell components, i.e. with the nucleus, cytoplasm or cytoskeleton. Using myelin in the screening procedure, about 30 monoclonal antibodies were obtained reacting with human brain cells or myelin components. Anti-myelin antibodies were further examined to determine their antigenic targets in a liposome agglutination assay and an anti-lipid ELISA. Most of these antibodies reacted with phospholipids, some reacted with glycolipids. Some of the tested autoantibodies were obtained only from MS patients. Differences in their reaction with galactocerebroside between MS- and non-MS-persons were observed. The regression of transformed B cells was more pronounced and faster in MS-patients than in healthy individuals. The idea that host components in enveloped viruses could be responsible for autoimmune diseases, especially for MS, is put into a historical perspective and discussed in the paper.

Antibodies, Monoclonal↗
PubMed1989

N-AgIB of poliovirus type 1: a discontinuous epitope formed by two loops of VP1 comprising residues 96-104 and 141-152.

Analysis of resistant mutants to neutralizing monoclonal antibodies revealed a discontinuous neutralization epitope on VP1 of poliovirus type 1, Mahoney. The epitope has the unique property of being also part of a sequential epitope within neutralization antigenic site I (N-AgI). It is formed by residues in the loop 96-104 connecting the B and C strand and in the loop 141-152 connecting the D and E strand of VP1. Because of strong analogy to neutralization immunogen IB (NImIB) of human rhinovirus 14 (HRV-14) we have called this site N-AgIB of poliovirus type 1.

Amino Acid Sequence↗
PubMed1989

Monoclonal autoantibodies derived from multiple sclerosis patients and control persons and their reactivities with antigens of the central nervous system.

Peripheral blood B lymphocytes of multiple sclerosis (MS) patients and control persons were transformed with Epstein-Barr virus. Antibody production of transformed cells against isolated human myelin was investigated by enzyme-linked immunosorbent assay (ELISA). Cells producing reactive antibodies were cloned and propagated to produce monoclonal antibodies (mAbs). These mAbs did also react with acetone fixed frozen sections of normal human white matter, as determined by indirect immunofluorescence staining. Some of the mAbs derived from MS patients and a control person with a central nervous system cyst agglutinated liposomes made from lipids of a chloroform/methanol extract of human myelin, whereas mAbs derived from four glioma patients were negative in these tests. The reactive antibodies were investigated further using agglutination tests with liposomes made from pure auxiliary lipids (cholesterol and lecithin) or containing in addition either galactocerebroside, sulfatide or a mixture of bovine brain gangliosides. The great majority of myelin liposome agglutinating antibodies reacted with all types of liposomes, including those made from pure auxiliary lipids. Investigations by ELISA suggest that phospholipids are the reactive components, at least for some of these mAbs. Some antibodies reacted with liposomes containing galactocerebroside or sulfatide, others only with sulfatide containing liposomes. Antibodies showing these specificities were only obtained from MS patients.

Adult↗
PubMed1989

[Cytochrome P-450 dependent drug metabolism--use of an in vitro test system in multiple chemical exposure].

Investigations of the influence of an actual exposure on the in-vitro-activities and the inducibility of cytochrom P-450 dependent enzymes have not been described in the literature until now. First results gained from mitogen-stimulated lymphocytes of exposed and not-exposed individuals suggest such an influence of the given mixture of noxious agents on the basic deethylational ability of the examined cells acting in the sense of inhibition. Possible causes for this phenomenon are discussed.

Air Pollutants, Occupational↗