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Biomedical subjects

P Biberfeld

Publications and source records attributed to P Biberfeld.

At least 127 records · Page 7Linked to original sources
PubMed1987

Blood clonal B cell excess (CBE) at diagnosis in patients with non-Hodgkin lymphoma (NHL). Relation to clinical stage, histopathology and response to treatment.

Untreated non-leukemic (lymphocytes less than or equal to 4.0 X 10(9)/l) patients with non-Hodgkin lymphoma (NHL) of B cell type often show an excess of B cells in peripheral blood bearing the same light chain isotype as the lymph node tumor cells which may indicate a leukemic spread of the disease. The ratio between kappa- and lambda-bearing lymphocytes (normal range 1.0-3.3) was studied to evaluate the prognostic significance of clonal B cell excess (CBE) at diagnosis in 110 NHL patients. In total 43% had a CBE in peripheral blood. Fifty-two per cent of the patients in clinically advanced stages had CBE and 30% of the patients in stages I and II. CBE was detected in 49% of all patients with low-grade malignant lymphoma and in 32% with high-grade malignancy. Patients with a normal kappa:lambda ratio at diagnosis entered complete remission more often than those with CBE (P less than 0.01). In patients with high-grade but not with low-grade malignant lymphomas remission duration was longer for those with normal kappa:lambda distribution than for the patients with an abnormal ratio (P less than 0.01). Survival was not statistically significantly influenced.

Adult↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Ultrastructural characterization of a new human B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease.

A new DNA virus, designated "human B lymphotropic virus" or "human herpesvirus 6" (HBLV), has been isolated from the peripheral blood leukocytes of patients with various lymphoproliferative disorders, in some instances also associated with human immunodeficiency virus (HIV-1) infection. HBLV, propagated in vitro in human cord blood lymphocytes, was found to be ultrastructurally similar to members of the herpesvirus family. It is an enveloped virus with an icosahedral nucleocapsid made up of 162 capsomeres. Unenveloped nucleocapsids in the cytoplasm wee always coated with a tegument, a feature also described for human cytomegalovirus (HCMV). However, the nucleoprotein core of HBLV does not have the beaded appearance as that of HCMV, nor do HBLV-infected cells contain the skein-like structure. Immune electron microscopy demonstrated the presence of specific antibodies to viral envelope and internal antigens in sera of infected patients, indicating that this virus is a possible human pathogen. These and previously reported characteristics are consistent with the HBLV being a new and unique DNA virus morphologically belonging to the herpesvirus family.

Cytomegalovirus↗
PubMed1986

Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders.

A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features.

Animals↗
PubMed1986

Cell proliferation and DNA content in non-Hodgkin's lymphoma. Flow cytometry in relation to lymphoma classification.

Flow cytofluorometric (FCF) DNA analysis was performed on specimens from 154 patients with non-Hodgkin's lymphoma (NHL) and correlated to histopathology according to the Rappaport classification and the Working Formulation of NHL for clinical usage (WF). NHL associated with unfavorable prognosis (UP) had significantly higher proportions of cells in S-phase as compared to the favorable prognosis (FP) group. The proportion of S-phase cells also differed significantly between the low-, intermediate-, and high-grade malignancy groups of the WF. Aneuploidy was significantly more frequent in the UP (41%) than in the FP (15%) group. By stepwise discriminant analysis, the S-phase frequency was a stronger discriminator between prognostic groups than DNA content. Classification by discriminant analysis showed that over 90% of the low grade/FP lymphomas were allocated to the good prognosis group by their S-phase and DNA values. Due to the variation in the proportion of S-phase cells in the intermediate grade and high grade, as well as the UP lymphomas, only approximately 50% of the UP and 60% of the high-grade lymphomas were identified as such by this discriminant model, while almost one half of the intermediate-grade lymphomas were allocated to the low-grade group. The results suggest that S-phase analysis can be of value in distinguishing intermediate- and high-grade lymphomas with high and low proportions of proliferating cells, which may be prognostic importance.

Adult↗
PubMed1986

Specificity and diagnostic implications of the reactivity pattern of a panel of monoclonal antibodies against myeloid leukemia cells.

The immunological phenotypes of leukemia cell samples from 60 patients, of whom 54 had acute myeloid leukemia (AML), were assessed with a panel of monoclonal antibodies (Mabs) with specificity for the following epitopes: Epitopes associated with myeloid leukemia cells, Epitopes expressed only on immature myeloid cells (or subsets) and on monocytes, Epitopes only expressed on granulocytes or on granulocytes and mature myeloid cells (promyelocytes, myelocytes and monocytes), Epitopes on HLA-class II (DR) and HLA-class I molecules and on insulin receptors. This panel of Mabs proved useful to identify leukemia cells in blood and to assess their myeloid origin. The panel of Mabs was found also to be useful for immunophenotyping of leukemia cells. Furthermore, the analysis revealed considerable variations in the immunological phenotype of AML cells, reflecting antigenic heterogeneity within the individual leukemia cell population as well as abnormal or no expression of histocompatibility antigens and insulin receptors in some samples. Some of the Mabs bound preferentially to subgroups in the French-American-British (FAB) classification.

Antibodies, Monoclonal↗
PubMed1986

Activation of malignant B-lymphocytes: pathophysiologic and clinical importance.

Recent advances in clarifying the activation mechanisms of the normal immune system have provided the basis for successful experiments concerning the activation of malignant lymphocytes. Such studies with malignant cells, freshly sampled from patients with lymphoproliferative diseases, can be used for pathophysiological considerations, analysis of tumor evolution, classification of malignant subsets, and karyotyping. Of particular interest is the possibility of abrogating the maturation arrest in some clonally-restricted cells. This might lead to therapeutical implications, since the differentiation blockage plays a fundamental role in the clonal expansion and pathogenesis of tumors. Recently, it has been shown that interferon (IFN) can be a potent inducer of various degrees of transformation, differentiation and even proliferation in different subsets of normal and malignant B cells. This may be important in explaining the divergent results of IFN treatment in various malignant B-cell disorders.

B-Lymphocytes↗
PubMed1986

Unmasking antigen determinants in amyloid.

Rehydrated paraffin sections of formalin-fixed, amyloid-containing tissues were treated with denaturing agents (guanidine and urea) and reducing agents (DDT and mercaptoethanol) before immunostaining, in an attempt to expose antigenic determinants hidden in the rigid structure of amyloid fibrils. Pre-treatment overnight with 6 M guanidine or urea was found beneficial, especially in specimens from familial amyloid polyneuropathy of the Portuguese type. Addition of reducing agents had no major effect. Modifications of this method may be useful in unmasking other antigens that are polymerized or considered destroyed by fixation and paraffin embedding.

Amyloid↗
PubMed1986

Chronic B-lymphocytic leukemia cells proliferate and differentiate following exposure to interferon in vitro.

The ability of interferon (IFN) to induce proliferation and differentiation in malignant B cells from 29 patients with chronic lymphocytic leukemia (CLL) and in lymphoid cells from 11 healthy donors was investigated. IFN induced transformation and plasmacytoid differentiation in B cells from 19 of 29 CLL patients. The transformed cells belonged to the malignant clone as indicated by the immunoglobulin (lg) light chain restriction. Cells exposed to IFN expressed intracellular lg to a varying degree, which was correlated to the level of plasmacytoid differentiation. IFN gave rise to proliferative responses in cells from three patients. Cytogenetic studies on lymphoid cells from one patient showed that proliferation occurred in the malignant B cells. Induction of proliferation and differentiation was observed with various alpha-IFN and gamma-IFN preparations, as well as with a completely pure beta-IFN, showing that IFN and not contaminants in the preparations were responsible for the observed effects. Maximal transformation and proliferation usually occurred after four days of incubation at an IFN concentration of 500 to 5,000 U/mL. The ability of IFN to induce differentiation in CLL cells may be of importance for the reported antitumoral effects observed in some B cell malignancies during IFN therapy.

Adult↗
PubMed1986

HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy.

In situ hybridization with a 35S-labeled probe of cryosections from 14 lymph nodes of HTLV-III/LAV-seropositive individuals with lymphadenopathy showed the presence of rare cells containing HTLV-III RNA at levels consistent with virus replication. Positive cells were observed at a frequency of only 1-10 per section. In all lymph nodes studied, including those showing follicular hyperplasia or involution, most of the cells expressing viral RNA were present in the follicular areas. Only a minority of such cells were found outside the follicles. The nature of the follicular, virus-replicating cells was not evident from the processed cryosections. After prolonged autoradiography, another pattern of hybridization was observed, suggesting low levels of viral RNA diffusely distributed throughout most, but not all, follicles. This may represent extracellular virus and/or virus-antibody complexes, but was not consistent with intracellular viral RNA or phagocytosed virus particles. Comparison of hybridization levels in relation to histology suggested a decrease in both the number of HTLV-III replicating cells as well as in the diffusely distributed viral RNA with progression of follicular involution. Our observations indicate that in HTLV-III-infected subjects, lymph node follicles are an important site of virus replication and trapping, suggesting a decisive role of the virus in the characteristic reactive and cytopathogenic changes of HTLV-III-associated lymphadenopathy.

AIDS-Related Complex↗
PubMed1986

Haematological remission of leukaemic polymorphic immunocytoma following splenectomy. Case report with longitudinal immunological and cytogenetic studies.

A 56-year old man with a Rai stage IV B-cell chronic lymphocytic leukaemia (polymorphic immunocytoma according to the Kiel classification) of mu kappa-phenotype with a clonal chromosomal abnormality in cells from peripheral blood, bone marrow, and spleen is reported on. Following splenectomy (without further therapy) the blood lymphocytosis gradually decreased to normal and the patient entered a remission, assigned 42 months after splenectomy by immunological and cytogenetic studies that revealed no cells of clonal origin in blood or bone marrow. Utilizing cellular markers of clonality, we thus confirm that haematological remissions may follow splenectomy. A subsequently developed orbital lymphoma (without leukaemia) consisted of tumor cells derived from the initial leukaemia cell clone as indicated by their immune and cytogenetic phenotype. The case report is discussed in relation to previous reports on "spontaneous" remissions of lymphoid leukaemias.

Antigens, Neoplasm↗
PubMed1986

Treatment of patients with metastasizing colo-rectal carcinoma with mouse monoclonal antibodies (Moab 17-1A): a progress report.

Eight patients with metastasizing colo-rectal carcinoma have been treated with Moab 17-1A. Before infusion the antibodies were incubated in vitro with isolated autologous blood mononuclear cells (AMC) enriched for monocytes/macrophages. Treatment was given in repeated courses (2-4 times) up to a maximum amount of 1000 mg Moab 17-1A. Two patients had an objective tumor reduction. In further four patients a period of stable disease varying between 3-6 months on was observed. Therapy was well tolerated. Out of 24 treatment courses only on one occasion an anaphylactoid reaction occurred at the third infusion. All patients developed anti-mouse antibodies of IgG and IgM class with increasing levels during the course of therapy. Repeated tumor biopsies and immunohistochemical analyses showed no antigenic modulation, a weak staining for mouse IgG, no deposits of complement components but no obvious increases in the number of cells infiltrating the tumors 24 h after infusion of antibody-armed AMC.

Adult↗
PubMed1985

Del(3)(p13) in B-prolymphocytic leukemia--a new nonrandom chromosomal aberration possibly related to the c-ras oncogene.

Cytogenetic analysis was performed on the leukemic cells from two patients with B-prolymphocytic leukemia. Both patients had del(3)(p13) chromosomal abnormality, as well as other clonal aberrations. Del(3p) was previously reported in one case of B-cell prolymphocytic leukemia, and is known to be a specific aberration in small-cell carcinoma of the lung. In B-cell prolymphocytic leukemia, as in other B-lymphocytic leukemias/lymphomas, the karyotype often involves chromosomes #3, #6, #11, and #12. All of these chromosomes are suggested sites for the c-ras oncogene family.

Aged↗
PubMed1985

Cytotoxicity of monoclonal antibodies against individually immunophenotyped human leukemic cells.

Peripheral blood and bone marrow mononuclear cells from 12 patients with acute myeloid leukemia (AML), 2 patients with acute lymphatic leukemia, and 1 patient with chronic myeloid leukemia in blastic crisis were taken at diagnosis or in relapse. Cells were immunophenotyped with a panel of monoclonal antibodies (Moab) (OKIa, Leu M1, Leu M2, Leu M3, Leu M4, B1, Okt 11, J5) and the same antibodies were used in an in vitro cytotoxicity test. Of the 14 patients, 10 had antibody-binding cells, and the percentage of lysed cells was almost equal to that of blasts. The other 4 patients had few binding cells and little lysis. Acute leukemia with and without preceding myelodysplastic features did not differ in immunophenotype. Mean spontaneous release of 51Cr was 12.7% and complement alone caused an additional average release of 11.8%. Four single antibodies together with complement showed a mean 51Cr release of 0.7-32.4% above that found with complement alone. Combinations of Moabs resulted in 51Cr release at least 10% above the single most efficient Moab in 8 out of 12 patients. Not all blast cells showed antibody binding, nor were all antibody-binding cells susceptible to cytotoxicity. Normal bone marrow growth in vitro seemed to be stimulated by factors in complement and in the Moab. When this stimulation was compensated for by adding fetal calf serum, cytotoxicity tests prior to CFUc assays resulted in a mean decrease of 46% of colonies and 25% of clusters in normal bone marrow. CFUc are thus sensitive to the cytotoxicity, although CFU may also be resistant.

Antibodies, Monoclonal↗
PubMed1985

Autoantibodies to the basal cells of squamous epithelium react with thymic epithelial cells.

Sera from carriers of hepatitis B surface antigen (17 out of 21), which reacted in immunofluorescence with the basal cell layer (BCL) of squamous epithelium, were also shown to react with a thymic stellate epithelial cell (SEC) characterized by long, dendritic-like cytoplasmic processes. Absorption of the autoantibodies against BCL of squamous epithelium (BCL-Ab) with a thymic homogenate abolished the reactivity with BCL and SEC, demonstrating that the same antigenic determinant was recognized in both cells. In the human thymus, SEC were present both in the cortex and in the medulla. In the outer cortex SEC delineated the septal spaces. SEC were also stained by anti-HLA-DR (Ia) but not by antiactin monoclonal antibodies. The morphology and distribution of SEC were similar to those of the previously described thymic epithelial cells containing alpha-1 thymosin (K. Hirokawa, J. E. McClure, and A. L. Goldstein, Thymus 4, 19, 1982). BCL-Ab were also found to react with five human epithelial thymomas. BCL-Ab seemed to be useful for further characterization of the thymic epithelial cells and for the immunodiagnosis of thymoma.

Actins↗
PubMed1985

Specificities and binding properties of 2 monoclonal antibodies against carcinoma cells of the human urinary bladder.

Mice were immunized with cultured cells derived from transitional cell carcinoma of the human urinary bladder (TCC). Spleen cells were fused with mouse myeloma cell line Sp2/0-Ag14 and the hybridomas obtained screened for antibody production against a panel of human cells. Two hybridomas were selected for further studies. The antibodies from one of these hybridomas (P7A5-4) could clearly discriminate between malignant and normal cells from the bladder, both when tested with cultured cells and fresh tissue. The P7A5-4 antibodies, however, also reacted with some non-TCC cultured carcinoma and melanoma cells but to a lesser extent. This difference in reactivity was even more pronounced in the fresh tumours tested, thus indicating a quantitative difference in antigen expression between TCC and other cells. From extracts of TCC cells, P7A5-4 bound three polypeptides of mol. wts 92Kd (ConA+), 23 and 17Kd (ConA-). The antibody derived from hybridoma SK4H-12 bound a ConA reactive glycopeptide of 100Kd mol. wt, the expression of which was almost entirely restricted to urothelial cell lines and tissue of TCC origin, as shown by immunocytochemical studies. The finding in this study of new antigens associated with urinary bladder carcinoma, extend the results obtained previously in our laboratory (Koho et al., 1984; Paulie et al., 1984) and further delineate the heterogeneity of tumour-associated antigens in this human tumour system.

Animals↗