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Biomedical subjects

H Löhr

Publications and source records attributed to H Löhr.

At least 37 records · Page 2Linked to original sources

Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis.

Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P450dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+ CD8- T cell clones proliferated specifically in the presence of recombinant human LKM-1 antigen (rLKM). This reaction was restricted to autologous antigen-presenting cells and to HLA class II molecules. In order to see whether rLKM was also recognized by peripheral blood T lymphocytes (PBL) we tested the proliferative response of PBL from several individuals. PBL from three of the four patients with LKM-1 antibody-positive AI-CAH proliferated to rLKM, whereas no response was seen with PBL from patients with LKM-1 antibody-negative chronic liver diseases and from healthy blood donors. These data demonstrate that the LKM-1 antigen is recognized by liver-infiltrating T cells in LKM-1 antibody-positive AI-CAH. For further functional characterization, liver-derived T cell clones were tested for their cytotoxic activity. In the presence of phytohaemagglutinin 24 out of 26 CD4- CD8+ but also 20 out of 63 CD4+ CD8- T cell clones lysed autologous as well as allogenic EBV-transformed B cell lines or K562 cells. Five CD4- CD8+ T cell clones lysed autologous but not allogenic B cell lines spontaneously in a HLA class I-restricted manner. Although the antigen specificity of these clones is still unknown the data show the presence of autoreactive T cells at the site of inflammation that could contribute in the pathogenesis of AI-CAH.

Adolescent↗

[Retractile mesenteritis. Diagnostic and therapeutic aspects].

An 18-year-old boy, who had severe abdominal pain for 18 months associated with marked weight loss, was found to have a stenosed ileal sling on double-contrast radiology of the small intestine. At operation a plate-like tumour was extending from the pancreas to the aortic bifurcation. Histological examination of removed tissue revealed retractile mesenteritis (mesenteric panniculitis; liposclerotic mesenteritis). The symptoms regressed and the patient again gained weight under immunotherapy with 1 mg/kg of prednisone and 2 mg/kg of cyclophosphamide daily. Subsequently, under prednisone alone, there was a recurrence, which responded within five weeks to daily 60 mg prednisone and 125 mg cyclophosphamide. The patient remains symptom-free on 125 mg cyclophosphamide and 10 mg prednisone daily.

Abdominal Pain↗

The human hepatic asialoglycoprotein receptor is a target antigen for liver-infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis.

Autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50% of the sera of patients with autoimmune chronic active hepatitis and in 15% of patients with primary biliary cirrhosis. In this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for T cell-mediated immune responses. Peripheral blood lymphocytes of 37% (7 of 19) of patients with autoimmune chronic active hepatitis and 33% (2 of 6) of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor, whereas no proliferation was found with peripheral blood lymphocytes of patients with chronic viral hepatitis (0 of 13) and healthy blood donors (0 of 4). Moreover, we isolated T-cell clones from liver biopsy samples of two patients with autoimmune chronic active hepatitis and two patients with peripheral blood lymphocytes. Between 2.8% and 14.3% of these clones showed a specific proliferative response to purified human hepatic asialoglycoprotein receptor. The response was restricted to autologous antigen-presenting cells and could be blocked by monoclonal antibodies against human leukocyte antigen-DR molecules. The response of T cells to the human hepatic asialoglycoprotein receptor did not require the lectinlike activity of the asialoglycoprotein receptor. Thus the human hepatic asialoglycoprotein receptor could be identified as a major target antigen of humoral and cellular immune reactions in autoimmune-mediated liver diseases.

Adult↗

[Spontaneous intramural hematoma of the intestinal wall--an unusual hemorrhagic manifestation of hemophilia A].

Gastrointestinal bleeding is a well known event in patients suffering from blood dyscrasias. In contrast spontaneous nontraumatic hematoma of the bowel is a rare complication, requiring a different therapeutic management, which depends on localization and extent of the hematoma. We report about two hemophiliac patients presenting with acute abdominal pain caused by spontaneous intramural hematomas.

Adult↗

[Herman Hager (1816-1897)--the heights and depths of his life].

The "Hager", undoubtedly a practical, indispensable encyclopedia of more than 10,000 pages is to be found in every German pharmacy. The changeable life of his author, Hans Hermann Julius Hager, who was born in Berlin, is reflected in a contradictory way in pharmaceutical history. Although he never completed a study he reached the highest degree of pharmaceutical science as a genuine autodidact but was neglected and insulted during life time. He died in very poor circumstances at Neuruppin, where he had come to live at his son's place one year before his death.

Encyclopedias as Topic↗

[Cystic pancreas adenoma. On the clinical relevance of histologic typing].

Although pancreatic cystadenomas are rare neoplasms, they are found today in rising frequencies due to improvement of diagnostic tools. There exist two types of cystadenoma: microcystic serous cystadenoma and mucinous cystadenoma. Usually, histological distinction from cystadenocarcinoma is readily made, but it may be difficult in the case of the mucinous variant. This subtype is supposed to be potentially malignant, whereas microcystic serous cystadenoma is always benign. In order to elucidate the characteristics of both variants, 5 own cases are reported in this article.

Adult↗

A new hereditary bone dysplasia with characteristic bowing and thickening of the distal ulna.

An autosomal dominant hereditary bone dysplasia was observed in three members of a Sardinian family living in Germany--the father and two sons. The guiding clinical symptom is thickening of the wrist proximal to the styloid process of the ulna. The radiologically recognizable changes--non-calcified cartilaginous islands protruding like cones into the metaphysis--begin with the onset of puberty and are not always associated with pain. Varying degrees of thickening and bowing of the relatively poorly mineralized metaphyseal region, particularly of the distal ulna, occur at the end of skeletal development. Thickening of the dorsum sellae is also characteristic. Serum calcium levels remain slightly elevated throughout life. The metatarsals, metacarpals and the distal fibula are dysplastic to varying degrees. The two boys display a coxa valga. Skeletal development is retarded. A developmental disorder of the vertebral column may form part of the condition, which defied allocation to any of the acknowledged forms of skeletal disease.

Adolescent↗

Expression of c-myc in stimulated T lymphocytes of the helper/inducer phenotype producing lymphokine(s) supporting multilineage colony formation.

Phytohemagglutinin (PHA) renders human peripheral T lymphocytes competent to replicate their DNA and divide. The stimulation of peripheral T cells of the T4 phenotype by PHA, which appears to be a transcription-dependent event, leads to the production and release of lymphokines supporting proliferation and differentiation of human pluripotent stem cells (CFU-GEMMT). Supernatants of PHA-stimulated lymphocytes of the suppressor/cytotoxic phenotype (T8) failed to demonstrate reasonable activity to support the growth of CFU-GEMMT. Stimulation of T lymphocytes of the T4 but not of the T8 phenotype leads to an increased intracellular level of c-myc mRNA. This would be consistent with the c-myc gene product functioning as an intracellular mediator of the growth and lymphokine production response to PHA. Although the function of the c-myc gene product is not yet clear, it seems likely that it is involved in the control of cell proliferation. Such a contribution to control of cell proliferation by c-myc would probably be mediated by a family of genes inducing lymphokine production to stimulate proliferation of human pluripotent stem cells.

Gene Expression Regulation↗

[Radiation exposure and radiation risk in angiocardiography in adults].

In 100 patients, the X-ray exposure during routine angiocardiography was measured from which calculations were performed for the integral dose (the energy transferred to the body by the exposure), the mean body dose and the radiation risk (according to ICRP 26, 1977). Fluoroscopy contributed 21% and angiocardiography 79% of the total exposure. The mean body dose was 0.9 rd. The average of the area-dose product was 10,200 Rcm2 with a skin exposure in the central beam of 36.1 rd. The genetic risk (probability of X-ray-induced mutation in progeny) is 1 : 75,000 after average exposures and 1 : 7,700 at maximal doses. The somatic risk (probability of X-ray-induced lethal disease) in the patients studied is 1 : 11,000 after average exposures and approximately 1 : 4,400 at maximal doses. The genetic and somatic risks, thus, are small as compared with those of cardiac catheterization and contrast angiocardiography.

Adult↗

Survival time in cystinosis. A collaborative study.

In a retrospective study the overall survival time of 205 cystinotic patients of six countries was determined. The median survival time was 8.5 years. The median time for 'renal death' (age at death due to uraemia or age at starting renal replacement therapy) was 9.2 years. The youngest patient dying of renal death was 5.2 years. No sex difference in survival time was noticed. Furthermore no difference in survival time was noted between the different countries. The analysis of the overall survival curve indicates no clear differences between the infantile and adolescent types of cystinosis.

Adolescent↗

[Pathobiochemistry of minerals and trace elements. I. Metabolism of zinc in the mother and newborn during the perinatal period (author's transl)].

In 468 mothers and their newborns the zinc levels in blood and serum were measured after the birth. Zinc levels were low in normal and also in complicated pregnancies. The fall in the level was the same in primi and multipara. There was no correlation between the blood group or the Rhesus factor or Apgar score and zinc metabolism. In male newborns the zinc level was significantly lower than in female newborns. The Apgar score was not affected by the course of pregnancy or the sex of the foetus. We suggest that the recommendations of Mischel [19], Apgar [1,2] and Sandstead [20] to substitute zinc as well as calcium and iron to protect the physiological metabolism of mother and child during pregnancy should be investigated by further research.

Adolescent↗

[Fundamental facts on dosimetry in the assessment of radioexposure and risk of such exposure in children (author's transl)].

Various methods for determining exposure to radiation are critically reviewed on the basis of 358 x-ray examinations of children (218 cardiac catheters with angiocardiography, 39 gastrointestinal examinations, 101 urological examinations). It is shown that the surface dose is an insufficient parameter for the actual exposure of the child to radiation. Estimates of the radiation risk based thereon are misleading. Even the determination of the area dose product and the integral dose alone will not allow any valid comparison of the exposure in different age groups. The important factor for an accurate determination of the somatic radiation risk is the ratio of integral dose to the body mass (mean body dose), since this is the only factor which is independent of body variables, i.e. only this figure will yield the relation of radiation risks in different age groups. Independent of the examination methods, a higher radiation risk must be assumed in infants than in older children or adults. These relationships are demonstrated on the basis of the author's own measurements and calculations.

Adolescent↗