In situ monitoring of caspase activation in hepatobiliary diseases.
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Publications and source records attributed to P Ruck.
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BACKGROUND: Extramedullary plasmacytomas (EMP) are plasma cell tumors in which by definition the primary tumor is extramedullary. Most of them are found in the upper aerodigestive tract. PATIENTS: In this study we describe 3 patients with EMP. The first case is a locally recurrent EMP with recurrent involvement of cervical lymph nodes. The first manifestation of EMP was 31 years ago. Hence, this is one of the longest clinical courses of recurrent EMP ever described in the literature. Case 2 is a locally aggressive recurrent EMP. Case 3 is a localized solitary EMP that could be successfully treated by surgery alone. RESULTS AND CONCLUSIONS: Different classifications of EMP described in the literature are discussed. If these classifications are applied to our cases neither the tumor stage nor the histological picture allow definite conclusions about the prognoses to be drawn. Metastases in regional lymph nodes do not necessarily mean a worse prognosis. Overall, compared to MM with a ten year survival rate of 18% the prognosis is more favorable in EMP with a ten year survival rate of 50%. After a generalized plasma cell neoplasia has been excluded EMP in the head and neck should be treated like a locally aggressive and potentially metastatic tumor. From our experiences we recommend a primary surgical therapy followed by radiation therapy if necessary.
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Adrenocortical insufficiency (Addison's disease) is a functional diagnosis. At the beginning of this century, tuberculosis was recognized as the main etiological cause (50-70%). Today, however, tuberculosis represents only 10% of the cases. Adrenocortical insufficiency is mainly caused by autoimmune adrenalitis (more than 50%). Unilateral adrenocortical disease is usually asymptomatic or presents, as in the case described, with minor symptoms. This case report of adrenal tuberculosis illustrates the current challenges of diagnosis and therapy.
OBJECTIVE: The objective of this study was to quantify the extent of neutrophil infiltration and the concentrations of enzymes involved in collagenolysis in the lower uterine segment in relation to the degree of cervical dilatation and the duration of labor. STUDY DESIGN: Biopsy specimens of the lower uterine segment were obtained from 62 women undergoing cesarean section at term. The number of extravascular neutrophils was assessed with enzyme histochemical evaluation, and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 by were assessed by enzyme-linked immunosorbent assay. RESULTS: The neutrophil count and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 increased with increasing cervical dilatation. At >6 cm the neutrophil count and the concentrations of matrix metalloproteinase-8, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 were significantly higher than at <2 cm. An association with the duration of labor was found for the neutrophil count and the concentrations of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1. Multiple linear regression analysis showed that the degree of cervical dilatation is more closely related to the 4 laboratory parameters investigated than to the duration of labor. CONCLUSION: The findings support the hypothesis that local changes (ie, collagenolysis) in the lower uterine segment unrelated to uterine activity play a crucial role in cervical dilatation at term.
OBJECTIVE: To determine whether the unusually high number of CD56+ large granular lymphocytes (LGL) in the decidua of early human pregnancy arises from selective migration or in situ proliferation. DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Thirty healthy women undergoing therapeutic abortion of an intact pregnancy at 5-11 weeks' gestation. INTERVENTION(S): Decidua was obtained by suction curettage; tissue and isolated cells were subjected to immunohistochemical and flow cytometric investigation. MAIN OUTCOME MEASURE(S): Proliferation rate of LGL. RESULT(S): The proportion of CD56+ cells positive for the proliferation-associated Ki-67 antigen was found to be 7%-23.5% by three different methods of investigation. These findings are consistent with those of flow cytometric analysis of the nuclear phase, which revealed 6%-22% of the LGL nuclei to be in the phases S+G2+M. CONCLUSION(S): The various methods of investigation revealed marked proliferative activity in the LGL of early pregnancy decidua. This finding suggests that in situ proliferation may be responsible for the high density of these cells in the decidua.
AIMS: It is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver. The aim of this study was to investigate whether cells with ultrastructural and immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia. METHODS AND RESULTS: Liver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes. CONCLUSIONS: The findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.
A relationship was sought between the tissue concentrations of interleukin (IL)-8, matrix metalloproteinase (MMP)-8 and MMP-9, and the numbers of the various leukocytes infiltrating the lower uterine segment stroma during parturition. Biopsy specimens of the lower uterine segment were obtained from 63 women undergoing Caesarean section at various stages of cervical dilatation at term. The concentrations of IL-8, MMP-8 and MMP-9 were determined with enzyme-linked immunosorbent assays, and the leukocytes were quantified immunohistochemically. The median IL-8 concentration (pg/mg total protein) rose significantly from 17.2 at < 2 cm dilatation, to 26.5 at 2 to < 4 cm dilatation, and 1954.0 at 4-6 cm dilatation, and remained at approximately this concentration at > 6 cm dilatation. The median MMP-8 concentration (ng/mg total protein) increased significantly from 32.2 at < 2 cm dilatation to 114.2 at > 6 cm dilatation. The median MMP-9 concentration (ng/mg total protein) rose significantly from 15.4 at < 2 cm dilatation to 102.1 at > 6 cm dilatation. The number of neutrophils was significantly higher at 4-6 cm and > 6 cm dilatation than at > 2 cm, reaching maximum values at > 6 cm dilatation. The findings in this study support the hypothesis that IL-8-induced infiltration of the cervical stroma by neutrophils and subsequent release of proteinases may play a key role in parturition.
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In this survey, findings relating to the control of infiltration by the cytotrophoblast during human placentation are reviewed, with particular reference to immunology and tumour biology. Possible effects on pregnancy and parturition due to failure of the regulatory processes involved in placentation are discussed.
Complications after BCG vaccine (bacilli Calmette-Guérin) occur rarely. They can reach from a local acute abscess to chronic ulceration's. Therapeutically concepts of these complications range from conservative to operative treatment. In the following case history recurrent soft tissue infections occurred after accidental inoculation with BCG vaccine. The time course of these recurrent infections with its therapeutic options is discussed and a treatment strategy is suggested. Currently, radical excision combined with antituberculotic treatment seems to be the most promising therapy of this specific soft tissue infection.
OBJECTIVE: Our purpose was to determine whether the expression of certain adhesion molecules by endothelium in the human lower uterine segment at term varies with the degree of cervical dilatation. STUDY DESIGN: Biopsy specimens of the lower uterine segment of 34 women undergoing cesarean section at term at various stages of cervical dilatation were immunostained for endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-endothelial cell adhesion molecule. RESULTS: The expression of endothelial leukocyte adhesion molecule-1 was significantly greater at more than 6 cm dilatation than at less than 2 cm (p = 0.00031) as was that of vascular cell adhesion molecule-1 (p = 0.033). Expression of intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule did not vary with the degree of cervical dilatation. CONCLUSION: Cervical dilatation is associated with up-regulation of certain endothelial cell adhesion molecules. The findings support the hypothesis that certain processes associated with cervical dilatation at term resemble those involved in the acute inflammatory reaction.
The incidence and pattern of liver involvement in 127 liver specimens (2 biopsy and 125 autopsy specimens) from cases of acute myelogenous leukaemia (25), chronic myelogenous leukaemia (7), acute lymphatic leukaemia (5), chronic lymphatic leukaemia (9), multiple myeloma (25), low-grade non-Hodgkin's lymphoma (25), high-grade non-Hodgkin's lymphoma (24) and myeloproliferative diseases (7) were investigated histologically and immunohistochemically. Liver infiltration was found frequently in chronic leukaemia and myeloproliferative diseases (80-100%), acute leukaemia (60-70%) and non-Hodgkin's lymphoma (50-60%), but was significantly less common in multiple myeloma (32%) than in any of the other diagnostic groups. Hepatomegaly was found in over 50% of cases in all the diagnostic groups, but was not always associated with infiltration. Diffuse, non-destructive infiltration was most common: in acute myelogenous leukaemia, both the portal triads and sinusoids were usually involved; in chronic myelogenous leukaemia, multiple myeloma and myeloproliferative diseases, infiltration was mainly sinusoidal; and in lymphatic leukaemia and non-Hodgkin's lymphoma the portal triads were mainly involved. Nodular infiltration was seen in multiple myeloma and non-Hodgkin's lymphoma. The primary tumours and liver infiltrates generally exhibited the same immunophenotype, although reactivity with the antibody L26 (CD20) was only found in the primary lesion in many high-grade B-cell lymphomas. Thus, liver involvement is common in haematological malignancies, but the incidence and pattern of infiltration vary amongst the different types.
AIMS: In a recent study we described a population of small epithelial cells (SEC) in human hepatoblastoma that exhibit ultrastructural features of the oval cell of rodents. Both SEC and oval cells are immunoreactive for cytokeratin 7, a marker of biliary differentiation, and it was postulated that SEC, like oval cells, are closely related to hepatic stem cells. This study was undertaken to investigate whether SEC also exhibit immunolabelling for albumin, a marker of hepatocytic differentiation, and to determine whether other antigens typical of oval cells are detectable in hepatoblastoma. METHODS AND RESULTS: Hepatoblastomas of various subtypes were investigated by electron microscopy, and by immunohistochemistry with the monoclonal antibodies OV-1 and OV-6, which recognize antigens associated with oval cells. Double-labelling for cytokeratin 7 and albumin was carried out by immuno-electron microscopy. OV-1 stained scattered cells in seven of 12 tumours investigated and OV-6 in nine. On immunoelectron-microscopic investigation, SEC exhibited labelling for both cytokeratin 7 and albumin. CONCLUSIONS: The results demonstrate that antigens associated with oval cells are found in certain cells in hepatoblastoma. SEC, like oval cells, co-express markers for hepatocytic and biliary differentiation. The findings further support the hypothesis that SEC are closely related to the putative bipotent hepatic stem cell, which, by definition, gives rise to both hepatocytes and biliary epithelial cells.
PURPOSE: Percutaneous radiofrequency interstitial thermal ablation is a new method in local tumour therapy. The aim of this study was to define the relations between the variable parameters and local efficacy in vitro and to evaluate optimal parameter combinations for this system. Furthermore, we studied the feasibility of increasing the volume of destroyed tissue using perfusion electrodes. MATERIAL AND METHODS: Thermal lesions were produced with radiofrequency in ex vivo pig livers. In separate experiments the parameters wattage (5-30 watts), exposure time (1-15 minutes) and tip exposure were varied. The resulting areas of tissue necrosis coagulation were measured; in 30 of 90 cases the macroscopic findings were compared to the histological findings. RESULTS: Lesion size correlated with tip exposure, wattage and procedure duration up to 10 minutes. For a tip exposure of 2 cm (3 cm) the maximal lesion volume was 18.8 cm3 (33.2 cm3) at a wattage of 20 watts (30 watts) and a procedure duration of 10 minutes. The maximal cross- (length-) diameter of these lesions was 3 cm (4 cm) for 2 cm tip exposure and 3.6 cm (4.9 cm) for 3 cm tip exposure. CONCLUSION: The parameters wattage, procedure duration and tip exposure affect the size of lesions created with radiofrequency under ex vivo conditions. Perfusion electrodes make it possible to produce larger lesions than described for non-perfused electrodes. The ablation of hepatic neoplasms up to a size of 3 cm seems to be possible with a single electrode.
BACKGROUND: Inverted papilloma is a benign sinunasal tumor, characterized by aggressive nature and tendency to recur. This tumor also has a significant malignant potential (10%). In spite of extensive research in the past the origin of inverted papilloma is not known. METHODS: A retrospective analysis of the clinical data of 28 patients suffering from inverted papilloma of the nose and paranasal sinuses with regard to symptoms, clinical examination, computed tomography findings, and operative management was performed. Furthermore, immunohistochemical examinations of the cytokeratin profile of 12 specimens were carried out. RESULTS: The most presenting symptoms were unilateral nasal obstruction (17.61%) and rhinorrhea (7.25%). Polyposis was seen endoscopically in 19 cases (68%), so that in many patients in inverted papilloma became suspicious in the CT scan. The surgical therapy was dictated by the extent of the tumor, so that the tumor was treated by lateral rhinotomy (n = 17), midfacial degloving (n = 5), endonasal endoscopic surgery (n = 5), and craniofacial resection due to an infiltration of the frontal skull base (n = 1). An immunohistochemical analysis of the cytokeratin profile revealed for the first time that the inverted papilloma, when compared to the normal surface epithelium of the nasal cavity and the paranasal sinuses, exhibits increased expression of cytokeratin 5, typical for basal cells, and cytokeratin 13, typical for squamous epithelial cells. CONCLUSIONS: Based on our results we recommend that the endonasal approach is reliable for processes restricted to the middle nasal meatus and the anterior and middle ethmoid cells. Inverted papilloma of the frontal sinus, retrobulbar and supraorbital ethmoid cells, and laterocaudal parts of the maxillary sinus should be resected via lateral rhinotomy or midfacial degloving. The findings of immunohistochemical examinations suggest that inverted papilloma is derived from a cytokeratin 5-immunoreactive cell of the basal layer of the mucosa.
Numerous studies have suggested that interferon-gamma (IFN-gamma) exhibits an inhibitory effect on conceptus development during pregnancy, and recent investigations have shown that decidual CD56++, CD16- large granular lymphocytes (LGL) contain mRNA for IFN-gamma. We have investigated the influence of exogenous interleukin-12 (IL-12) and interleukin-2 (IL-2) on IFN-gamma secretion by cultivated LGL and macrophages isolated from first trimester human decidua. The effect of decidual macrophages on IFN-gamma secretion by LGL was also assessed using co-incubation experiments. Neither IL-12 nor IL-2 stimulated the secretion of IFN-gamma by decidual macrophages. IL-12 alone, but not IL-2 alone, stimulated the release of IFN-gamma by LGL. However, IL-2 acted synergistically with IL-12 to enhance the release of IFN-gamma by LGL. Unstimulated and IL-12- and IL-2-stimulated LGL incubated with macrophages exhibited a marked increase in secretion of IFN-gamma compared to those in monoculture. This effect was also seen when the LGL and macrophages were separated by a semi-permeable membrane. The results suggest that interactions between decidual LGL and macrophages, possibly mediated by soluble factors, could play a role in regulating IFN-gamma secretion at the materno-fetal interface and thus contribute to the control of invasion by the trophoblast.