{"title":"Acute kidney graft rejection morphology and immunology.","authors":"C B Andersen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human kidney allo-transplantation is a successful treatment for end-stage renal failure. The main complication is acute rejection. Although much information has been accumulated on the genetic factors, the clinical and morphological features and the immunological mechanisms involved in acute rejection much remains to be learned. Histological evaluation of needle biopsies is considered one of the most valuable tools in monitoring the transplant. However, very few parameters specific for acute rejection exist and the histological evaluation is complicated by a limited knowledge of the morphology and immunology in well-functioning allografts. The study was undertaken to enlighten the morphological and immunological alterations in the renal allotransplant by biopsiing patients consecutively before and after transplantation. Special emphasis was by immunohistochemistry put on activated cellular infiltrates and adhesion molecules. Studies with cultured human tubular cells were performed to obtain information on mechanisms involved in the regulation of MHC molecules and the intercellular adhesion molecule-1 (ICAM-1). In situ hybridization formats were developed in order to investigate donor-recipient traffic of cellular components and to evaluate the possible influence of cytomegalovirus-infection. Finally, renal changes induced by cyclosporine was sought in a group of patients with chronic uveitis receiving long-term cyclosporine treatment. Arteritis and endocapillary glomerulitis was found to be the only reliable parameters specific to acute rejection. All other morphological parameters showed a continuum of changes from nonrejecting to rejecting patients. Thus, tubulitis and dense mononuclear cellular infiltrates were strongly indicative of acute rejection. Immunohistochemically, strong expression of ICAM-1, vascular cellular adhesion molecule-1 and MHC class II antigens on tubular and endothelial cells along with interleukin-2-receptor bearing infiltrates of T-lymphocytes and significant presence of macrophages were highly correlated with acute rejection. Contrarily, the phenotype of T-lymphocytes including the ratio of CD4+/CD8(+)-lymphocytes, the presence of B-cells or deposits of immunoglobulins and complement factors showed no significant correlation in patients with acute rejection. The in vitro studies confirmed that cytokines such as interleukin-1, tumor necrosis factor and gamma-interferon produced by inflammatory cells are involved in the regulation of ICAM-1 and MHC class II antigens on likely target cells such as tubular epithelial cells. Renal CMV-infection was rare. CMV was not found to induce any changes specifically associated with acute or chronic rejection. Cyclosporine induced tubular atrophy, interstitial fibrosis, glomerulosclerosis and hyaline arteriolar degeneration in kidneys from long-term treated uveitis patients but not in renal transplanted patients. Conclusively, the study confirms the value of pre- and postoperativ","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"67 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20021056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Avoidable cancers in the Nordic countries. Aims and background.","authors":"J H Olsen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In 1989, an action plan was adopted by the Nordic Council of Ministers with the aim of reducing cancer mortality in the Nordic countries by 15% around the year 2000. This was to be achieved by removing the causes of cancer, by the early diagnosis of cancer and by improving cancer treatment. The results so far have been disappointing. As the causes of many cancers have been identified over the past 40-50 years, the most efficient way of reducing cancer mortality on the basis of current knowledge would be to reduce the prevalence of exposure of the population to cancer-causing agents. Such preventive measures take time to implement, however; furthermore, since the process of carcinogenesis entails a lag period that varies from several years to decades, a decrease in cancer mortality will not be immediately evident. We review here the methodological background for estimating the numbers and proportions of cancers in the Nordic countries that could be avoided through primary prevention.</p>","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"76 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20389269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medullary carcinoma of the breast.","authors":"L Pedersen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"75 ","pages":"1-31"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20366389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The pituitary-gonadal function in postmenopausal women with epithelial ovarian tumors.","authors":"J Blaakaer","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"74 ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20323008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD73 (ecto-5'-nucleotidase) on blood mononuclear cells. Regulation of ecto-5'-nucleotidase activity and antigenic heterogeneity of CD73 on blood mononuclear cells from healthy donors and from patients with immunodeficiency.","authors":"L D Christensen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"73 ","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20323009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulator and effector functions of T-cell subsets in human Leishmania infections.","authors":"M Kemp","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Because of an increasing number of patients suffering from Leishmania infections and because of the serious consequences of these infections more thorough knowledge of the host factors responsible for resistance and susceptibility to the diseases is needed. In murine models of Leishmania infections the cytokine production by CD4+ T cells has been identified as a major factor in determining the outcome of the infection. In these models Th1 cells producing IFN-gamma provide protection against the infection whereas Th2 cells producing IL-4 and IL-10 aggravate the disease. The fatal outcome of Leishmania infections in humans with defects in T-cell functions illustrates that these cells are fundamental in the defence against Leishmania in humans also. However, as for many other infectious diseases (meningococcal disease and other septicaemic conditions, pneumonia, viral hepatitis, schistosomiasis) the immune reactions to Leishmania parasites in humans can be associated with both protection and pathogenesis. Many individuals without previous exposure to Leishmania parasites have T cells which can respond to Leishmania antigens. These cells have the potential to generate either Th1 or Th2 like responses. During infection with Leishmania parasites humans develop specific T-cell recognition of well-characterized parasite antigens. T cells producing disease-exacerbating factors such as IL-4 in response to Leishmania antigen stimulation have been identified in humans as well as in mice. Both Th1 like and Th2 like cells recognizing Leishmania antigens can be expanded during infection. At the polyclonal level Th1 like responses to Leishmania antigens are found in individuals who have had self-healing or asymptomatic infections. Factors secreted by such Leishmania specific Th1 like cells can induce killing of intracellular parasites in infected macrophages. In individuals who have been cured from uncontrollable disseminating disease both Th1 and Th2 like responses can be detected. A restriction in the antigen recognition to particular protein fractions could not be demonstrated in the Th1 or Th2 like responses. These findings suggest an association between the pattern of cytokines produced by parasite specific T cells and the clinical course of the infection similar to the one seen in mice. In the murine model the cytokine pattern present in the animal at the time of infection can determine whether a Th1- or a Th2 response will develop. In vitro studies on human and murine cells have confirmed that certain cytokines (e.g. IFN-gamma, IL-12) will favour maturation of Th1 responses whereas others (e.g. IL-4, IL-10) support Th2 development. If similar immunoregulatory mechanisms operate in mouse and man, design of vaccines against human leishmaniasis should aim at introducing powerful Th1 like responses. Importantly, once generation of either Th1 or Th2 has started, the immune response seems to be locked in this pattern, even when it is harmful to the host. ","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"68 ","pages":"1-33"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20021057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J F Winther, K Ulbak, L Dreyer, E Pukkala, A Osterlind
{"title":"Avoidable cancers in the Nordic countries. Radiation.","authors":"J F Winther, K Ulbak, L Dreyer, E Pukkala, A Osterlind","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Exposure to solar and ionizing radiation increases the risk for cancer in humans. Some 5% of solar radiation is within the ultraviolet spectrum and may cause both malignant melanoma and non-melanocytic skin cancer; the latter is regarded as a benign disease and is accordingly not included in our estimation of avoidable cancers. Under the assumption that the rate of occurrence of malignant melanoma of the buttocks of both men and women and of the scalp of women would apply to all parts of the body in people completely unexposed to solar radiation, it was estimated that approximately 95% of all malignant melanomas arising in the Nordic populations around the year 2000 will be due to exposure to natural ultraviolet radiation, equivalent to an annual number of about 4700 cases, with 2100 in men and 2600 in women, or some 4% of all cancers notified. Exposure to ionizing radiation in the Nordic countries occurs at an average effective dose per capita per year of about 3 mSv (Iceland, 1.1 mSv) from natural sources, and about 1 mSv from man-made sources. While the natural sources are primarily radon in indoor air, natural radionuclides in food, cosmic radiation and gamma radiation from soil and building materials, the man-made sources are dominated by the diagnostic and therapeutic use of ionizing radiation. On the basis of measured levels of radon in Nordic dwellings and associated risk estimates for lung cancer derived from well-conducted epidemiological studies, we estimated that about 180 cases of lung cancer (1% of all lung cancer cases) per year could be avoided in the Nordic countries around the year 2000 if indoor exposure to radon were eliminated, and that an additional 720 cases (6%) could be avoided annually if either radon or tobacco smoking were eliminated. Similarly, it was estimated that the exposure of the Nordic populations to natural sources of ionizing radiation other than radon and to medical sources will each give rise to an annual total of 2120 cancers at various sites. For all types of ionizing radiation, the annual total will be 4420 cancer cases, or 3.9% of all cancers arising in the Nordic populations, with 3.4% in men and 4.4% in women.</p>","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"76 ","pages":"83-99"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20391146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular and molecular effects of growth hormone and estrogen on human bone cells.","authors":"M Kassem","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of the present thesis is to examine some aspects of the biological effects of growth hormone (GH) and estrogen on bone cells in vitro. The first part of the thesis describes characterization of model systems to study normal human osteoblasts and osteoclasts in vitro. Three culture systems for human osteoblasts have been characterized, representing different stages of osteoblasts differentiation/maturation: (1) mature osteoblasts cultured from trabecular bone explants (trabecular osteoblasts), (2) less mature osteoblasts (stromal osteoblasts) cultured from bone marrow and (3) osteoblast precursor cells cultured also from bone marrow. This classification is based on quantitative and qualitative differences in the expression of osteoblast phenotypic markers by these cells. These systems are useful in studying the regulation of hormones and growth factors of different stages of osteoblast differentiation. Further characterization of the osteoblast differentiation pathway is still needed, especially the identification of surface markers that can definitively identify intermediate stages of osteoblast differentiation. Normal human osteoclasts were cultured from bone marrow mononuclear cells and exhibited the main characteristics of osteoclast phenotype: production of tartrate-resistant acid phosphatase, presence of a ruffled border and the ability to resorb mineralized matrix. This model is useful for studying factors regulating osteoclast commitment and differentiation. The second part of the thesis deals with the effects of GH on proliferation and differentiation of trabecular and stromal osteoblasts. Effects of GH on human osteoblasts were dependent on their degree of maturation. GH stimulated cell proliferation in both trabecular and stromal osteoblasts. While it increased the functional activity of trabecular osteoblasts, these effects were absent in stromal osteoblast cultures. Human trabecular osteoblasts produce mainly IGF-II, IGFBP-3 and minute quantities of IGF-I in culture. GH does not seem to regulate the local production of IGF-II or IGFBP-3. However, IGFs and their binding proteins may exert important regulatory effects on the biological effects of GH on human osteoblasts, and this role needs to be studied. Sincer GH exerted profound effects on the biological functions of human osteoblasts in vitro, the hypothesis that either decreased production of GH or decreased sensitivity of bone cells to its action leads to bone loss and osteoporosis was examined. No differences in the basal or GH-stimulated production of IGF-I, IGF-II or IGFBP-3 were found between osteoporotic patients and age-matched normals. Similarly, The response of bone cells to in vivo and in vitro stimulation by GH was similar in the two groups. These studies do not support the hypothesis of the presence of major defects in production of GH or the presence of resistance to its effects in bone cells in patients with osteoporosis. The last part of the thesis deal","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"71 ","pages":"1-30"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20290146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J F Winther, L Dreyer, K Overvad, A Tjønneland, M Gerhardsson de Verdier
{"title":"Avoidable cancers in the Nordic countries. Diet, obesity and low physical activity.","authors":"J F Winther, L Dreyer, K Overvad, A Tjønneland, M Gerhardsson de Verdier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the early 1980s, Doll and Peto estimated that about 35% of all deaths from cancer in the United States were attributable to dietary factors, with a margin of uncertainty ranging from 10 to 70%. Since then, several dietary factors, e.g. fat and meat, have been suggested to increase the risk for cancer, while other factors, e.g. fibre, fruit and vegetables, have been suggested to decrease the risk. The case-control and cohort studies have, however, given ambiguous results, and the overall evidence is far from conclusive. The major findings on dietary factors that increase risk have been reported from case-control studies, but have not been confirmed in large population-based cohort studies. Although the research in this area indicates that diet is important in cancer prevention, current knowledge does not allow reliable estimates of the numbers and proportions of cancers that could be avoided through well-described modifications of dietary habits. During the last 10 years, low physical activity has been pinpointed as a risk factor for cancers at various sites, especially the colon; however, the causal mechanism is still unknown. Obesity, defined as a body mass index of 30 or more, is consistently associated with endometrial and gall-bladder cancers in women and renal-cell cancer in both men and women. As the prevalence of obesity was between 5 and almost 20% in the Nordic populations in 1995, 625 cancer cases (310 endometrial cancers, 270 renal-cell cancers in men and women and 45 gall-bladder and bile-duct cancers among women) can be predicted in the Nordic countries around the year 2000 to be caused by obesity. This implies that about 1% of all cancers in Nordic women and less than 1% of those in Nordic men could be avoided around the year 2000 if a healthy body weight could be maintained by all inhabitants.</p>","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"76 ","pages":"100-19"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20391147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ABH and related histo-blood group antigens in normal & malignant human endometrium in relation to genetic and hormonal factors.","authors":"V R Skovlund","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent immunohistochemical studies have shown that endometrial carcinomas are characterized by changes in glycosylation involving histo-blood group antigens. These carbohydrate determinants are present not only on erythrocytes but are also expressed by epithelial cells. Their expression herein has been shown to be related to the genetic status of the individual in terms of the ABO, Lewis and ABH-secretor type. Moreover, they show changes in expression relating to development, tissue-type, differentiation, cell-motility and malignancy. Meanwhile, most studies performed on endometrial tissue have not considered duly that histo-blood group antigen expression herein may be influenced by genetic and hormonal factors. Using immunohistochemistry and MABs with specificity to ABH- and related histo-blood group antigens with different peripheral core structures we have studied the expression of these carbohydrates in the human endometrium in relation to genetic and hormonal factors. The present paper presents a summary and a discussion of present knowledge on expression of histo-blood group antigens in the normal and malignant human endometrium. In addition, the possible regulatory mechanisms that control their expression in the endometrium are discussed. The histo-blood group phenotype of normal endometrial epithelial cells show great complexity. Variations in expression are related to the genetic status, i.e., the ABO, Lewis and ABH-secretor status. However, our findings suggest that the regulation of Lewis antigen expression in the endometrium differs from that in erythrocytes. Moreover, expression of histo-blood group and related carbohydrates varies with layer, mucosal histology, cell-type and hormone levels in serum. In glands in the functionalis and basalis, the histo-blood group phenotype is characterized by a predominant expression of sialylated types 2 and 3 chains. Expression of ABH determinants is, in general, low. However, the expression of fucosylated and terminal ABH determinants vary with the menstrual cycle, degree of proliferation and hormone levels in serum. The secretory phenotype is characterized by an increased expression of type-1 chain antigens, and by expression of sialylated chains as S-Tn, MS-Le(a), DS-Lac. A/B transferase protein expression was found to correlate with E2 levels in serum. These findings in conjunction with studies of glycosyltransferase activity in murine endometrial cell strongly suggest that the endometrial epithelial cell histo-blood group phenotype is also modulated by the ovarian hormones. The histo-blood group phenotype of endometrial carcinomas and precursor lesions is also influenced by the ABO, Lewis and secretor-status. Except for loss of A/B transferases and A/B antigens, which appear to be a late event, the changes are demonstrable also in preneoplastic endometrial cells. The malignant phenotype is characterized by an increased expression of type-1 chain carbohydrates. ABH-secretors express H an","PeriodicalId":77006,"journal":{"name":"APMIS. Supplementum","volume":"69 ","pages":"1-33"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20198351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}