PubMed Health⌕ Search

Biomedical subjects

H J Radzun

Publications and source records attributed to H J Radzun.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sinus histiocytosis with massive lymphadenopathy: evidence for its relationship to macrophages and for a cytokine-related disorder.

AIMS: Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease is a rare histiocytic disorder of unknown origin. Immunophenotypically the histiocytes of SHML express intensively the S100 protein and in addition a panel of macrophage-associated antigens. Their exact relationship to either monocytes/macrophages or immune accessory dendritic cells is, however, still controversial. METHODS AND RESULTS: In this report recurrent nodal and extranodal manifestations of SHML of a 70-year-old patient were analysed by differential phenotyping using a panel of monoclonal and polyclonal antibodies to macrophage and immune accessory dendritic cell related antigens and by applying nonradioactive in-situ hybridization. CONCLUSIONS: We conclude that stimulation of monocytes/macrophages via macrophage colony stimulating factor (M-CSF) leading to immune suppressive macrophages represents a main mechanism for the pathogenesis of SHML. The study further provides evidence for the monocyte/macrophage but not dendritic cell differentiation of SHML histiocytes.

Biomarkers↗
PubMed1998

Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma.

Degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and MMP-9, are supposed to be key enzymes in this process. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 RNA using reverse transcriptase PCR technique with tumor stage in 17 samples of renal cell carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing TIMP-1 and TIMP-2 was defined to be 1 in normal kidney tissue. This MMP:TIMP ratio was significantly increased to 2.43 (standard deviation, SD = 0.8) in locally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIMP expression was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1997

Apoptosis in the small intestinal allograft of the rat.

BACKGROUND: Necrosis and apoptosis are different cell death mechanisms. Necrosis is a pathological process that occurs after destruction of the cell membrane. Apoptosis is a DNA-dependent cell death mechanism, which occurs under physiological and pathological conditions. Although necrosis is a well-defined phenomenon in an acute graft rejection, the occurrence and relevance of apoptosis during this process is largely unknown. METHODS: The enterocyte apoptosis rates in allografted (n=24) and isografted (n=24) small intestines of the rat were compared using the in situ end-labeling technique. RESULTS: In situ end-labeling showed a dramatically increased number of apoptotic enterocytes in allografted small intestines, whereas increased labeling could not be observed in isogeneic small intestinal grafts. CONCLUSIONS: We suggest that graft rejection-associated apoptosis, in addition to necrosis, plays an important role in the course of organ failure, and that the degree of apoptosis represents another reliable indicator for the diagnosis and prognosis of transplant rejection.

Animals↗
PubMed1997

Clinical, biochemical, and histological changes in hepatitis C virus infection-associated cryoglobulinemia.

The most common extrahepatic manifestation of HCV infection is mixed cryoglobulinemia (MC). 62 unselected patients with chronic HCV infection were prospectively evaluated for the presence of cryoglobulinemia and associated clinical and biochemical parameters. Furthermore, a putative relationship between the HCV genotypes and cryoglobulinemia was tested. Histological features typical for HCV infection were comparatively analyzed in cases with and without cryoglobulinemia. Whether an intrahepatic Th2-response is responsible for the strong antibody production causing cryoglobulinemia was also examined. Cryoglobulins were detected in sera of 30 patients (approximately equal to 48%). Patients with cryoglobulinemia were on the average elder, showed an apparent longer duration of infection, and suffered more frequently from arthralgia, accompanied by a significant increase of total serum IgM concentration and rheumatoid factor activity. The HCV genotype distribution among patients with cryoglobulinemia was not different from that found in patients without cryoglobulinemia. In cases with cryoglobulinemia, an increased activity of chronic hepatitis and a higher grade of liver fibrosis was noted. The prevalence of HCV-typical histological lesions among all patients were: Portal lymphocytic aggregates (40%), bile duct damage (35%), steatosis (47%), and intracellular acidophilic bodies (29%). A significant correlation, however, could not be found between cryoglobulinemia and the presence of HCV-typical histological lesions. An intrahepatic Th2-response causing an increased antibody production could not be observed in cases with cryoglobulinemia.

Adult↗
PubMed1997

Cell renewal, cell differentiation and programmed cell death (apoptosis) in pilomatrixoma.

Pilomatrixoma is a benign tumour of the cutaneous adnexa. Histologically, pilomatrixoma comprises masses of immature basophilic cells, small numbers of polygonal squamoid cells, few transitional cells, and clusters of 'shadow cells'. The mechanism leading to the formation of shadow cells is still unknown. Skin biopsy specimens of pilomatrixoma (n = 15) were studied histologically, immunohistologically, and by applying the in situ end-labelling technique. The basal layer of the basophilic cells induced most of the proliferating cells with high expression of bcl-2 and cytokeratin 19. The overlying basophilic cells showed a negligible mitotic activity, a high significant accumulation of p53 protein, and a heterogeneous, but progressive loss of bcl-2 and cytokeratin 19. They developed either into squamoid cells or into transitional cells. The squamoid cells were characterized as differentiated cells resembling mature keratinocytes of stratified mucosa. The transitional cells could be shown to represent apoptotic cells proceeding to shadow cells. The data suggest that apoptosis is the main mechanism leading to the development of the dead shadow cells and is most probably responsible for the banal biological behaviour of pilomatrixoma. Apart from that, pilomatrixoma represents a suitable biological model to study apoptosis in humans.

Apoptosis↗
PubMed1996

Optimization of restriction fragment length polymorphism and single strand conformation polymorphism analysis for the detection of point mutations of ras oncogenes in paraffin-embedded tissues.

69 samples of formalin-fixed and paraffin-embedded tumor tissues (colon carcinomas n = 15, colon adenomas n = 15, transitional cell carcinomas of the urinary bladder n = 17, transitional cell papillomas of the urinary bladder n = 22) were investigated for point mutations of ras oncogenes using polymerase chain reaction (PCR) and nested-PCR followed by restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP), respectively. Results were proved by sequence analysis. Nested-PCR combined with SSCP analysis revealed five mutations of the Ki-ras oncogenes in five colon tumors. RFLP analysis revealed one point mutation in one sample of invasive transitional cell carcinomas. Using optimized PCR protocols, the methods described are applicable to paraffin- embedded tissues and offer a tool for mutation analysis in retrospective and prospective studies.

Base Sequence↗
PubMed1994

Malignant histiocytosis and large cell anaplastic (Ki-1) lymphoma in childhood: guidelines for differential diagnosis--report of the Histiocyte Society.

A workshop of the Histiocyte Society was recently held, in order to discuss the problems and confusion of malignant histiocytosis (MH) and large cell anaplastic (Ki-1) lymphoma (LCAL). The aims of this workshop were to clarify the terminology for malignant histiocytic disorders and LCAL and to produce reliable criteria for diagnosis of both MH and LCAL. This article summarises the conclusions reached.

Antigens, CD↗
PubMed1993

Discrimination between immunoaccessory and phagocytic monocytes/macrophages of the skin in paraffin-embedded tissue by the monoclonal antibody Ki-M1P.

The variety of functions performed by monocytes and macrophages is reflected in their phenotypic diversity. Investigation of this complex system is facilitated by Ki-M1P, a new monoclonal antibody which recognizes a differentiation antigen on monocytes/macrophages in paraffin-embedded tissues. To test its usefulness as a pan-macrophage marker in the skin, we immunohistochemically analysed paraffin-embedded biopsy material from seven healthy individuals and 190 patients with a variety of dermatoses. Immunoreactivity was compared with results obtained with the antibodies KP-1, MAC-387, UCHL-1 and S-100. In normal skin, epidermal Langerhans cells were Ki-M1P-. Strong expression of this marker was detected on spindle-shaped as well as dendritic perivascular and intervascular macrophages. Pathological reaction forms such as giant cells and epithelioid cells in granulomatous dermatoses were also Ki-M1P+. The high specificity of Ki-M1P is reflected in the lack of reactivity with tumour cells in non-monocytic neoplasms and Langerhans cell histiocytosis. Thus, Ki-M1P is a useful marker for skin macrophages, discriminating between the immunoaccessory and the phagocytic compartments.

Antibodies, Monoclonal↗
PubMed1993

A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1.

A monoclonal antibody (Ki-S1) has been raised that reacts with the nuclei of proliferating cells. The antigen recognized is resistant to formalin fixation and can be detected in frozen tissues as well as in routinely processed specimens. In immunohistochemistry, nuclear staining can be seen in those tissues and cellular compartments known to be actively proliferating. Peripheral blood lymphocytes are negative but show a strong increase in antigen expression after mitogen stimulation. Flow cytometric determination of DNA content and antigen expression revealed negativity of G0 cells and positivity of G1 to G2/M cells. A cytoplasmic co-reactivity, not associated with proliferation, was confined to Langerhans islands of the pancreas. The nuclear localized antigen has a molecular mass of 160 kd and therefore seems to be different from all other known immunohistochemical markers of proliferating cells. We conclude that the monoclonal antibody Ki-S1 might provide a useful tool for studying cell proliferation in situ under normal and pathological circumstances.

Animals↗
PubMed1993

Expression of the monocyte-specific esterase gene in leukemia-lymphoma cell lines.

The expression of the monocyte esterase was examined in a panel of 77 continuous human leukemia-lymphoma cell lines representing all hematopoietic cell lineages and in 16 other cell lines. Accumulation of mRNA, determined by Northern blotting with the cDNA probe HMSE-1, and production of the protein, shown by isoelectric focusing on polyacrylamide gels, correlated with differentiation of the cells along the monocytic lineage. None of the lymphoid, erythroid, megakaryoblastic or Hodgkin's disease derived cell lines or the non-hematopoietic human tumor cell lines expressed the full-length mRNA of 2.0 kb. These results support the notion that this enzyme, a serine hydrolase with still unknown physiological functions, is specifically expressed in cells committed to the monocyte/macrophage cell lineage.

Animals↗
PubMed1992

Isolation of monocytic serine esterase and evaluation of its proteolytic activity.

Monocytes are characterized by high activity of alpha-naphthyl acetate esterase (ANAE), distinguishing them from all other blood cells. The physiological function of this monocyte marker enzyme has not yet been elucidated. In this study ANAE's potential proteolytic activity was analyzed because serine esterases/proteases can function as effector molecules in cell-mediated cytotoxicity and because monocytes-macrophages are known to exert cytotoxic effects on tumor cells. This enzyme was purified from the monocytic cell line U-937 by preparative isoelectric focusing and a three-step high-performance liquid chromatography that conserved its catalytic activity. It has a molecular mass of 60 kd, and partial amino acid sequence revealed that the enzyme is not identical to known serine esterases/proteases. The purified enzyme failed to digest a couple of peptides, indicating lack of protease activity. In addition, the esterolytic activity of ANAE was not inhibited by protease inhibitors. The isolation and purification of ANAE enable further studies concerning its function in monocytes-macrophages and its relation to monocytic cytotoxicity.

Amino Acid Sequence↗
PubMed1992

Detection of Epstein-Barr virus in lymphoid tissues of patients with infectious mononucleosis by in situ hybridization.

Although the immunological response during infectious mononucleosis (IMN) has been studied in detail, little is known about the spread of Epstein-Barr virus (EBV) in lymphoid organs or the topographical distribution of the infected cells. In this study, EBV was detected in 11 lymph nodes, 4 tonsils, and 1 spleen of 16 patients with IMN. The predominant cell type positive for the EBV genome was identified as small lymphocytes localized chiefly within typical T areas, preferentially in perifollicular and interfollicular regions of the lymph node. A few endothelia of epithelioid venules were also found to be positive. Furthermore, a small number of sinus lining cells of lymph nodes exhibited labelling. Altogether, only a small number of cells, not exceeding 1 per cent of all cells, were infected with EBV. Our results show that only a small number of lymphocytes carry the EBV and that besides B lymphocytes, other cell constituents of lymphatic tissues are infected by EBV during IMN.

Autoradiography↗
PubMed1992

Macrophage- and lymphocyte-subtypes in the endometrium during different phases of the ovarian cycle.

The presence of immunocompetetive cells in the endometrium during the proliferative and secretory phase of the ovarian cycle is demonstrated on the light and electron microscopic level using monoclonal antibodies (MoAb). Subtypes of monocytes, macrophages and T-lymphocytes appear during the different phases in variable extent and different localization. Some subpopulations of the monocyte/macrophage system and T-helper lymphocytes increase in number on day 21/22. Our observations indicate that cells with bone marrow origin take part in functional events of the endometrium during the ovarian cycle.

Antibodies, Monoclonal↗
PubMed1992

Immunohistochemical monitoring of plasmacytoid cells in lymph node sections of Kikuchi-Fujimoto disease by a new pan-macrophage antibody Ki-M1P.

The new monoclonal antibody Ki-M1P, which detects a formalin-resistant epitope on conventional paraffin sections, was applied in 20 cases of different stages of Kikuchi-Fujimoto disease. This new pan-macrophage immunoreagent detects plasmacytoid T cells, referred to as plasmacytoid cells, and renders a reliable delineation of these cells against other similar cell types, such as blasts of high-grade B- and T-cell lymphoma. Histiocytes as well as macrophages were strongly positive, and plasmacytoid cells showed a somewhat weaker and primarily granular, intracytoplasmic immunoreactivity. Plasmacytoid cells, being a diagnostic feature of the Kikuchi-Fujimoto disease, facilitate a clear distinction of this disease entity from large cell or high-grade lymphomas. These results may represent an additional argument favoring the histiocytic origin of plasmacytoid cells. Additionally, they may point to an immunohistochemical tool that facilitates the differential diagnosis between Kikuchi-Fujimoto disease, especially in early stages of the disease, and malignant lymphoma.

Antibodies, Monoclonal↗
PubMed1992

Heterogenous expression and putative structure of human monocyte/macrophage serine esterase 1.

Human monocyte serine esterase 1 (HMSE1) was purified from U937 cell extract. Since the N terminus of the enzyme was blocked, cleavage with trypsin was used to obtain several peptides accessible to amino acid sequencing. Based on partial amino acid sequence information, an oligonucleotide probe was synthesized and used to screen a U937 cDNA library. One clone was isolated and sequenced by us which contains an open reading frame of 503 amino acids that lacks about 50 amino acids at the N terminus relative to the protein. Computer analysis revealed an active site characteristic of known carboxylesterases with a catalytic active serine. Northern blot hybridization analysis revealed that the expression of HMSE1 is restricted to cells of the monocyte/macrophage system. In contrast to the moderate expression of HMSE1 in monocytes, alveolar macrophages showed very high amounts of the transcript. With the sequence features detected by computer analysis a structure model of HMSE1 as a dimeric, membrane-bound ectoenzyme was developed.

Amino Acid Sequence↗
PubMed1992

DNA analysis to aid in the diagnosis of chronic myeloproliferative disorders.

Diagnosing chronic myeloproliferative disorders (CMPD) can be difficult because of overlap and possible transitions between the different conditions and their similarity to reactive myeloproliferations. DNA analysis was applied to improve differentiation of CMPDs. All subtypes of CMPD analyzed, including chronic myeloid leukemia, agnogenic myeloid metaplasia, polycythemia vera, and essential thrombocythemia, had in common that granulocytes and bone marrow cells were clonal in origin, as shown by X chromosome-linked DNA polymorphism in conjunction with methylation patterns (n = 32). Reactive myeloproliferations, by contrast, showed polyclonal inactivation patterns. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome because the latter (n = 7) also exhibited clonal hematopoiesis. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 201) to detect bcr gene rearrangement. Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis. Chronic myeloproliferative disorders represent clonal hemopoietic diseases that probably have specific underlying genetic defects. Thus DNA analysis can aid substantially in the differential diagnosis of CMPD.

Adolescent↗
PubMed1992

[Sinus lining cells:morphology, function and neoplasia].

Lymph node sinuses consist mainly of sinus lining cells with clear dendritic morphology. Enzyme cytochemical and immune phenotypical analysis classify sinus lining cells as an intermediate cell type linking monocyte/macrophage to follicular dendritic cells, which are accepted immune accessory cells to humoral immune response. Labeling studies indicate sinus lining cells to hematogenous and possible monocytogenous in origin. In functional term sinus lining cells bind and present soluble antigen as the first cell type following antigen pulse. In addition sinus lining cells bind carcinoma cells and may play a role in metastasis. Sinus lining cells give rise to a well defined entity of neoplasia which is proposed to be termed sinus lining cell reticulosarcoma. In this presentation a case report exemplifies such a new entity.

Acid Phosphatase↗