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Biomedical subjects

G Pallesen

Publications and source records attributed to G Pallesen.

At least 91 records · Page 5Linked to original sources

Stages in LAV/HTLV-III lymphadenitis. II. Correlation with clinical and immunological findings.

The aim of the present study was to investigate the relation between the histopathological findings in LAV/HTLV-III lymphadenitis and immunological, clinical, and serological variables. The study group included 38 consecutive homosexual men with persistent generalized lymphadenopathy (PGL) in whom lymph node biopsy was performed. The histopathological lymph node changes were grouped into three stages. Opportunistic infections at the time of biopsy and their development during follow-up were significantly associated with stage III histology (follicular depletion). Analysis of blood from 10 patients with stage III histology revealed significantly (P less than 0.01) decreased proliferative responses of lymphocytes to mitogens and reduced absolute number of CD5+ and CD4+ lymphocytes compared with 17 patients with stage I histology (follicular hyperplasia), whereas patients with stage II histology (follicular involution) had intermediate values. The absolute number of CD8+ lymphocytes was increased in all three stages, as was IgG, while increase in IgM and IgA was restricted to stage III. No difference was observed between the different histopathological stages with respect to the specificity of the anti-LAV/HTLV-III antibody as measured by immunoblotting. In conclusion, the defects of lymphocytes from the blood of LAV/HTLV-III infected persons reflect alterations in secondary lymphoid tissue. Further, there is a close correlation between these alterations and the clinical status of the patients.

Acquired Immunodeficiency Syndrome↗

Histopathology and immunohistology of HTLV-III/LAV related lymphadenopathy and AIDS.

Fifty-nine lymph node biopsies from homosexual men with serum antibodies to HTLV-III/LAV were the subject of a detailed histopathological and immunohistochemical study. The histological findings were correlated to the patients clinical status, and the T4/T8 ratios in blood and lymph nodes. Four histological patterns predominated and were defined as follicular hyperplasia (FH), follicular fragmentation (FF), follicular atrophy (FA), and follicular depletion (FD). Immunocytochemical studies indicated that destruction of follicular dendritic cells is related to the initiation of follicular involution from FH to FF, but the possible role of follicular infiltrating T-cells cannot be excluded. Marked individual variations in lymph node angiogenesis increasing during involution were observed, which suggests that the degree of angiogenic host response may predispose for evolution of Kaposi's sarcoma. The majority of the patients with the clinical diagnosis of persistent generalized lymphadenopathy (PGL) were morphologically staged as FH or FF (89%), whereas most of the AIDS patients showed lymph node changes compatible with FA and FD (89%). Patients with AIDS-related complex (ARC) had a wider spectrum of morphological lymph node changes but a majority of cases (62%) were also classified as FA or FD. Clinical follow-up showed progression from PGL to ARC in seven of 21 cases with the FF pattern and only in three of 19 cases with FH, indicating a possible prognostic value in differentiating between FH and FF. Three cases with FD and one with FA progressed to AIDS during the time of observation. T4/T8 ratios in blood and lymph nodes were significantly lower in patients with FD histology compared to patients of the other histological groups. At autopsy, all AIDS cases showed the FD pattern of lymphadenopathy. Autopsy findings in seven patients emphasized the importance of post-mortem studies in clarifying the spectrum of opportunistic diseases, including tumors which afflict the AIDS patients.

AIDS-Related Complex↗

Quantification of CD8-positive lymphocytes in lymph node follicles from HIV-infected male homosexuals and controls.

The number of CD8-positive cells in follicular centres of hyperplastic lymph nodes from 20 Danish and Swedish homosexual men with persistent generalized lymphadenopathy and 43 control patients were enumerated in frozen tissue sections immunostained with monoclonal antibody reactive with the CD8-antigen ("cytotoxic-suppressor" T-cell antigen). All the homosexuals were seropositive for HIV and histology showed changes characteristic of the early stage of HIV lymphadenitis. A significant increase (p much less than 0.001) of CD8-positive cells was demonstrated (mean 1,307 per mm2 follicular centre, SD 639) in HIV-related lymphadenopathy compared with the controls (mean 161 CD8-positive cells per mm2 follicular centre, SD 169). The results of this study show that the immunohistological demonstration of a significant increase of CD8-positive cells in the follicles of hyperplastic lymph nodes is suggestive of HIV-related lymphadenopathy.

Acquired Immunodeficiency Syndrome↗

Unusual immunophenotype displayed by histiocytes in haemophagocytic lymphohistiocystosis.

Extensive immunophenotypic studies in a 2 1/2 month old girl with haemophagocytic lymphohistiocytosis were performed to characterise the proliferating histiocytes of the disease. The cells strongly expressed conventional macrophage antigens, but unexpectedly, there was a dissociated expression of the CD1a antigen (reacting with the monoclonal antibody NA1/34 but not with OKT6) and intracellular S-100 protein by the haemophagocytic lymphohistiocytosis histiocytes. These findings indicate that there is a "hybrid" phenotype between the two main arms of the mononuclear phagocyte system--namely, Langerhans' cells and phagocytic macrophages.

Antibodies, Monoclonal↗

Immunophenotypic analysis of neoplastic cells in follicular dendritic cell sarcoma.

The existence of a sarcoma derived from the antigen-presenting follicular dendritic cells (FDCs) has been assumed but never confirmed. This report describes a tumor from axillary lymph nodes of a 39-year-old male in which the morphologic, enzyme histochemical, and immune phenotypic data are consistent with the malignant cells being of FDC origin. Morphologically, the tumor showed a tendency toward bi- and polynucleation with areas of storiform growth pattern, resulting in an initial diagnosis of malignant fibrous histiocytoma. However, the tumor cells had interconnections with well-developed desmosomes. Enzyme histochemistry revealed strong 5'-nucleotidase activity. Immunohistologic analysis showed that tumor cells expressed two of three FDC-specific antigens (Ki-M4, BU-10, and R4/23) strongly. Virtually all myelomonocytic markers were absent. Like normal FDCs, the leukocyte antigens CD35, CD19, CD21, and CD23 were expressed strongly and CD4 antigen weakly. No staining was evident for CD45 antigen, and no nonhemopoietic cell markers were expressed. The origin of the normal FDC is obscure. Given some evidence suggesting a bone marrow origin for the FDC, this cell may represent a lineage distinct from other known cell lineages derived from bone marrow stem cells since its immune phenotype differs considerably from them.

Antigens, Differentiation, T-Lymphocyte↗

T-cell origin of Lennert's lymphoma.

The arrangement of the T-cell receptor and immunoglobulin genes has been analysed in five cases of Lennert's lymphoma. All cases showed rearrangement of the gene coding for the beta chain of the T-cell receptor and a germline configuration of the immunoglobulin genes. This provides strong evidence that Lennert's lymphoma is a T-cell lymphoma.

Antibodies, Monoclonal↗

Use of a panel of monoclonal antibodies for the diagnosis of hairy cell leukaemia. An immunocytochemical study of 36 cases.

The phenotype of 36 cases of hairy cell leukaemia has been investigated using a panel of monoclonal antibodies reactive with normal human lymphoid cells and with hairy cells. Staining was performed on frozen sections and/or cell smears by the recently developed APAAP immuno-alkaline phosphatase procedure. In about 90% of cases, neoplastic cells reacted strongly with antibodies against HLA-DR, leucocyte common antigen, B-cells (antibodies B1 and To15), hairy-associated antigens (antibodies KB-90, S-HCL3, HC2) and activated T-lymphocytes (antibodies anti-Tac and Tü69). The phenotype of 10% of cases was clearly different in that the neoplastic cells were negative or only weakly positive for one or more of the antigens recognized by HC2, anti-Tac and Tü69. Antibody HC1 reacted with tumour cells of only 50% of the hairy cell leukaemia cases investigated. Monoclonal antibody Ki-67 (which selectively detects proliferating cells) stained only a low percentage of cells in all but three of the cases studied. The neoplastic cells in all cases were unreactive with monoclonal antibodies anti-Leu1, Tü1, Tü33 and a meshwork of follicular dendritic cells was consistently absent from tissues infiltrated by hairy cells. The immunological phenotype associated with hairy cell leukaemia was not observed in any case of non-Hodgkin's lymphoma, suggesting that it represents a unique type of B-cell neoplasm.

Antibodies, Monoclonal↗

The preservation and loss of various non-haematopoietic antigens in human post-mortem tissues as demonstrated by monoclonal antibody immunohistological staining.

Immunohistological methods using monoclonal antibodies have proved to be valuable in the differentiation between cells of various origins. We have previously shown most leucocyte differentiation antigens to be very resistant to post-mortem disintegration (Pallesen & Knudsen 1985). In the present study we have examined the preservation of several non-haematopoietic antigens in tissue samples of human skin, kidney, liver, pancreas, lung, thyroid gland, uterine tissue, female breast and brain from 30 autopsies performed at specific intervals after death. Frozen tissue sections were stained using monoclonal antibodies and an immunoperoxidase method. A total of 17 monoclonal antibodies against various intermediate filament proteins, epithelial antigens, various hormones and factor VIII related antigen were tested. We found surprisingly good preservation and staining of tissue antigens--even 3 d after death--in all organs except pancreas. It is concluded that many tissue antigens are fairly resistant to post-mortem disintegration and that immunohistology may be applied to diagnostic problems in human autopsy material.

Antibodies, Monoclonal↗

Erythema elevatum diutinum and pre-AIDS.

Erythema elevatum diutinum (EED) is a chronic disease with symmetrical persistent erythematous nodules and plaques primarily in an acral distribution. EED is often associated with infections, especially of streptococcals. An immunological reaction has been proposed as pathogenetic mechanism. We describe a patient, who developed EED secondary to a LAV/HTLV III positive lymphadenopathy syndrome. Immunological investigation of a skin lesion and a lymph node biopsy is described.

Adult↗

Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders.

The arrangement of the T-cell-receptor and immunoglobulin genes has been analysed in 77 cases of lymphoproliferative disorder. All 6 T-cell leukaemias and 16 of 19 T-cell lymphomas showed rearrangement of the gene coding for the beta chain of the T-cell receptor, associated in all cases with a germline arrangement of the immunoglobulin genes. All 36 B-cell leukaemias and all 16 B-cell lymphomas showed rearrangement of immunoglobulin genes; the T-cell-receptor gene was in the germline configuration in most of these cases but showed a rearranged pattern in 3 cases (2 chronic lymphatic leukaemias and 1 immunoblastic lymphoma). The combined use of T-cell-receptor and immunoglobulin gene probes promises to be a valuable means of identifying and classifying T-cell neoplasms.

Autoradiography↗

Leucocyte antigens in human post mortem tissues: their preservation and loss as demonstrated by monoclonal antibody immunohistological staining.

The development of monoclonal antibodies and of techniques for demonstrating antigens in situ in frozen tissue sections has been responsible for remarkable progress in diagnostic histopathology. We explored the potential of these techniques when applied to post mortem tissues that were frozen at various intervals after death and stained by monoclonal antibodies using immunoperoxidase technique. The monoclonal antibodies were selected according to their reactivity with essential markers of the lymphatic system and also to their availability. Lymph nodes and splenic tissue from 30 autopsy cases were stained in addition to thymic tissue from eight deceased infants. The antigens proved to be surprisingly well preserved. Staining could be precisely evaluated with UCHT1, OKT6 and anti-Leu-7 antibodies at least 72 h after death; staining with DAKO-pan-B, DAKO-LC and anti-Leu-3a was also very reliable. Antigens expressed by T-suppressor lymphocytes and dendritic reticulum cells were less well preserved. The T8-antigen of suppressor lymphocytes was usually demonstrable in the lymph nodes but less frequently in the splenic tissues. It is concluded that most leucocyte antigens are very resistant to post mortem disintegration, and that they can be reliably interpreted by immunohistological staining using monoclonal antibodies. We therefore recommend this in autopsy specimens in cases where in-vivo examination was not feasible.

Adult↗

The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease-derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio-immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large-cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell-related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an "activation state." In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

Adolescent↗

Further evidence for the B-cell nature of hairy cells. A study using immunostaining of splenic tissue with a wide panel of monoclonal antibodies.

Phenotypic characterization of neoplastic cells from 5 patients with hairy cell leukemia (HCL) was performed with 29 monoclonal and 6 polyclonal (anti-Ig) antibodies using immunoperoxidase staining of fresh frozen splenic tissue. Monotypic Ig was expressed in 4 cases, one case was non-expressive. Strong staining was obtained in all cases by monoclonal antibodies (MAs) specific for 3 pan-B-lymphocyte antigens (by anti-B 1, To 15, anti-Leu 12). Five other B-cell related antigens detectable with appropriate MAs (BA-1, anti-B2, DAKO-C3 b R, Tü 1, 38.13) were absent in all cases. The stainings with 13 T-cell associated MAs (OKT 3, OKT 4, anti-Leu 3 a, OKT 6, OKT 8, Tü 68, OKT 10, anti-Lyt 2, Tü 71, OKT 11, anti-Lyt 3, Tü 14, Tü 33) were all negative. Stainings with 4 MAs recognizing myelocytic and/or monocytic antigens (OKM 1, anti-Mo 1, anti-Mo 2, 3 C4) were also negative. We included 14 frozen biopsies with B-type chronic lymphatic leukemia (B-CLL) into our immunohistological study in order to establish phenotypic differences between HCL and B-CLL. Five MAs (Tü 1, anti-Lyt 2, Tü 71, BA-1 and anti-B2) gave consistently negative staining in HCL cases but positive staining in most or all B-CLL cases. The study provides significant evidence for the B-cell nature of HCL and also establishes important phenotypic differences between HCL and B-CLL.

Adult↗

Nature of non-B, non-T lymphomas: an immunohistological study on frozen tissues using monoclonal antibodies.

In a previous study employing conventional immunological marker analysis we found that 17% of high grade malignant lymphomas were devoid of cytoplasmic and membrane immunoglobulin and also sheep erythrocyte receptors. Cryostat sections from 24 of these cases (four of low grade and 20 of high grade malignancy) were stained with a panel of 30 monoclonal antibodies and six polyclonal antisera using a sensitive immunoperoxidase method. All tumours expressed the leucocyte common antigen (detected by monoclonal antibody 2D1) and all lacked epithelial cytokeratin (monoclonal antibody LE61), confirming their haematopoietic origin. All but one of the lymphomas expressed antigens characteristic of either B cells (17 cases) or T cells (six cases), while one case (morphologically a centroblastic lymphoma) had an unusual dual phenotype in which strong staining for T6 (marker of immature T cells) was associated with expression of the pan B lymphocyte antigens detectable with To15, anti-B1, anti-Leu12. This case was therefore classified as a B cell lymphoma showing aberrant expression of the T6 antigen. The pan B cell antibodies (To15, anti-B1, anti-Leu12) all appeared highly specific and sensitive, but the simultaneous use of all three monoclonal antibodies was necessary to detect the B cell nature in each of the 18 lymphomas. A wider panel of monoclonal antibodies was required to detect T lymphomas since these often disclosed atypical and restricted phenotypes. To15 and UCHT1 were the most reliable antibodies for the detection of B and T cell neoplasms, respectively. We conclude that most, if not all, "non-B, non-T" lymphomas are of either B or T lymphocyte origin and that monoclonal antibodies provide indispensable tools in their classification and diagnosis.

Antibodies, Monoclonal↗

Immune marker expression in 53 lymphomas of high-grade malignancy.

Tissue from 53 non-Hodgkin's lymphomas of high-grade malignancy according to the Kiel classification were analysed for cellular immunological markers. In most cases studies were performed in parallel on cell suspensions and cryostat sections. Histologically, the lymphomas were classified as anaplastic centrocytic (four), centroblastic (seven), Burkitt type (three), convoluted-cell type (five) lymphoblastic-unclassified (10), immunoblastic (IBL) (19) and pleomorphic T-cell type (five). Immunological phenotyping resulted in 60% B lymphomas characterized by monotypic surface membrane Ig (SmIg) and/or cytoplasmic Ig (CIg), and 23% T lymphomas with detectable E receptors; 17% of cases were non-expressive (O-type). Unusual SmIg-types were noticed in some monoclonal proliferations. Gamma (gamma) and mu chains occurred simultaneously in four cases; delta chain was the only heavy-chain in one case and a heavy-chain was absent in one case. Cases of IBL were of T-cell type in two cases, and two other cases were non-expressive. The cases of B-IBL expressed CIg in 93%, but the B lymphomas other than B-IBL only in 38%. Receptors for Fc-IgG and C3 were expressed by all major immune phenotypes (B, T, O), but were infrequent in lymphoblastic lymphoma unclassified (O-type). Adoption of immunological techniques to include frozen tissue studies was necessary in order to reach a conclusion regarding the immune phenotype in several cases.

Adolescent↗