Biomedical subjects

T Radaszkiewicz

Publications and source records attributed to T Radaszkiewicz.

At least 73 records · Page 4Linked to original sources

PubMed1988

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes.

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.

Aged↗

PubMed1988

Primary high-grade malignant lymphomas of bone.

Five cases of primary high-grade malignant lymphoma of bone are presented. The tumours occurred at a single site in all the cases and produced osteopathic lesions. Histologically, they were large cell tumours characterized by round to irregularly shaped nuclei with finely distributed heterochromatin and small to medium-sized nucleoli. The cytoplasm was moderate and slightly to moderately basophilic. In one case, giant cells similar to Hodgkin and Sternberg-Reed cells occurred. The tumour cells bore B-cell markers but did not express immunoglobulin. Three of the bone tumours were polymorphic centroblastic lymphomas. The remaining two cases were also high-grade malignant B-cell lymphomas which may also be derived from germinal center cells but this could not be further substantiated.

Adult↗

PubMed1988

Autoreactive B-cell repertoire in mice with chronic graft versus host disease.

A quantitative analysis of the frequencies of autoantibody producing B-cells has been undertaken by producing and analyzing random hybridoma collections generated in fusions with activated B-cells. Activated B-cells were derived from mice injected with LPS and SRBC and normal mice. They were compared to those derived from mice undergoing chronic GVHD. The frequencies of successful fusion events correlate well with the number of activated B-cells used in the fusions, so that it is reasonable to conclude that the hybridoma collections reflect the activated B-cell repertoires in the different animals. The frequencies of hybridomas producing autoantibodies as well as their specificities for self-antigens, were not significantly different between the different collections of hybridomas. Moreover, no difference in VH gene family expression was found in the different collections of autoantibody producing hybridomas. So, the activated autoreactive B-cell repertoires in GVHF1 mice and in normal mice is similar. In contrast to the normal activated autoreactive B-cell repertoires, which make predominantly IgM antibodies, the GVH-activated autoreactive B-cells make predominantly antibodies of the IgG class. Therefore, we conclude that T-cell mediated graft versus host activation does not generally lead to selective expansion of autoreactive B-cells, but appears to play a crucial role in the switch from IgM to IgG production.

Animals↗

PubMed1988

Immunopathological signs in mice treated with mercury compounds--I. Identification by the popliteal lymph node assay of responder and nonresponder strains.

In the present study we screened mice from 22 different inbred strains for potential differences in their immunological reaction to HgCl2. As a rapid screening test, we used the popliteal lymph node assay (PLNA). Mice were injected s.c. into one hind footpad with 3-60 micrograms of Hg2+, given as HgCl2 in phosphate-buffered saline (PBS); contralateral hindfeet remained uninjected. Control mice received PBS alone. On day 6 the weights of the draining and contralateral PLN were determined and the PLN index calculated. While we found linear dose-response curves in some strains, these curves had a different shape in others. Out of the total of 21 euthymic strains tested only strain DBA/2 (H-2d) proved to be a nonresponder to HgCl2; it remained a nonresponder over the whole dose range (3-180 micrograms Hg2+) and period of time (days 2-12) studied. The other H-2d strains tested, i.e. NZB, BALB/c and B10.D2/n, showed absent or low PLN responses only in the lower dose range (3-30 micrograms Hg2+). F1 hybrids of strain DBA/2 and the responder strain C57BL/6 gave an intermediate response. While C3H nu/nu mice failed to respond to HgCl2, C3H +/nu mice did. The weight increase of the draining PLN after HgCl2 injection was preceded in time by an increased 3H thymidine uptake by the PLN. Histologically, enlarged PLNs revealed increased cellularity in both the T-cell and the B-cell areas. When CH3HgCl, instead of HgCl2, was injected all three strains tested, including DBA/2, responded by PLN enlargement. We conclude that (1) HgCl2 is an immunostimulatory agent in mice in that it induces T-cell-dependent enlargement of the draining PLN upon local injection, (2) there are striking genetic differences between inbred strains of mice in the PLN response to HgCl2, but these differences are not paralleled by similar differences in the response to CH3HgCl, (3) responsiveness to HgCl2 appears to be inherited in a codominant fashion, and (4) there is suggestive evidence that the observed genetic differences are determined by both H-2 and non-H-2 genes.

Animals↗

PubMed1988

Peripheral T cell lymphoma presenting primarily as lethal midline granuloma.

This clinicopathologic study reports seven patients who primarily presented with ulcerative and destructive lesions of the upper aerodigestive tract and face, clinically consistent with so-called lethal midline granuloma (LMG). Histologically, the infiltrates were composed of atypical lymphoid cells that displayed angiocentricity and angiodestruction. In five patients, involvement of distant sites such as skin, lungs, lymph nodes, and bone marrow occurred, and in two cases, the disease remained localized. Immunomorphologic analysis, using monoclonal antibodies to frozen and paraffin sections, provided evidence for the diagnosis of peripheral T cell lymphoma (PTL) in all cases. The midline tumors were classified as diffuse mixed or diffuse large cell lymphoma occurred at distant sites. According to modern PTL classification systems, the lesions could be classified as pleomorphic T cell lymphomas. Those five patients who presented with or progressed to large cell lymphoma died within 18 months (mean, 7 months), whereas the two patients with localized disease are alive after 10 and 36 months, respectively. The size of the atypical lymphoid cells may be of prognostic significance since the large cell compartment seems to represent the major growth fraction in these PTLs.

Adult↗

PubMed1988

The phenotypic spectrum of histiocytosis X cells.

Proliferating cells in histiocytosis X (histiocytosis X cells) share many structural and immunophenotypic features with Langerhans cells, leading to the assumption that histiocytosis X represents a proliferative disorder of Langerhans cells. Because, depending on their state of activation and/or differentiation, Langerhans cells exhibit a varying immunophenotype, we investigated whether histiocytosis X cells display a similar phenotypic heterogeneity and, if so, whether the heterogenous biological behavior of histiocytosis X is reflected by differences in the immunophenotype of the proliferating cells. In 21 patients suffering from different clinical manifestations of histiocytosis X, proliferating cells uniformly expressed class I and II alloantigens, T200, CD1, CD4, and S100 protein. In 12 of 21 cases, histiocytosis X cells additionally exhibited immunocytochemically detectable amounts of C3b and C3bi receptors and certain monocyte/macrophage antigens (CDw14, Ki-M1, Ki-M6). This immunophenotypic heterogeneity of histiocytosis X cells could not be correlated with clinical course, prognosis, and final outcome of the disease in a given patient. The capacity of histiocytosis X cells to immunophenotypically mimic various states of Langerhans cell activation and/or differentiation, however, underscores the concept of histiocytosis X as a proliferative disorder of Langerhans cell origin.

Adolescent↗

PubMed1988

Sequential immunohistologic analysis of the skin following allogeneic bone marrow transplantation.

Graft-vs-host disease is generally viewed as an immunologically mediated disease. In search of additional tools for early diagnosis and an elucidation of the pathogenic mechanisms we investigated the expression kinetics of hemopoietic differentiation and class II alloantigens on both resident and passenger skin cells after bone marrow transplantation. HLA-DR antigens, which are found normally on the dendritic epidermal Langerhans cells only, are synthesized and expressed by keratinocytes within lesions of acute and chronic cutaneous graft-vs-host disease. Within non-lesional skin, however, during the course of cutaneous graft-vs-host eruptions, no clear cut expression of keratinocyte-bound HLA-DR antigens can be identified, suggesting that this phenomenon is locally restricted rather than generalized. Furthermore, our data indicate that within lesions clinically suggestive of cutaneous graft-vs-host disease but lacking diagnostic histopathologic criteria, KC-bound HLA-DR antigens can be readily identified. The second class II alloantigens investigated within the epidermis, the HLA-DQ antigens, were seen on Langerhans cells only and were not or only rarely detectable on keratinocytes. Several subtypes of CD3+ T lymphocytes were present in the epidermis of acute graft-versus-host lesions: one portion of CD3+ T lymphocytes also displayed the CD8 antigen; one portion, mainly localized within the basal layer, displayed the CD8 and/or the CD4 antigen; and one portion did not allow identification of CD8, CD4, or Leu7 antigens. In chronic cutaneous graft-versus-host lesions CD3+/CD8+ T lymphocytes predominated. CD1+ epidermal Langerhans cells were reduced in number and appeared rounded with blunt dendrites both in acute and chronic cutaneous graft-vs-host disease, but also, though to a lesser extent, within normal appearing skin from bone marrow transplanted patients without cutaneous graft-vs-host disease.

Adolescent↗

PubMed1988

Recombinant gamma interferon and in vivo induction of HLA-DR antigens.

Recombinant human IFN-gamma, used for treatment of melanoma and renal carcinoma, was found to induce HLA-DR expression on human keratinocytes in vivo. HLA-DR antigens bound to keratinocytes of the basal and suprabasal layers of the epidermis were observed after intramuscular or intravenous injections of 0.5 mg/kg body weight IFN-gamma, 3 times a week. Keratinocyte-bound HLA-DR antigens were first observed at the beginning of the third or fourth week of treatment, but HLA-DQ and HLA-DP antigens were never detected on keratinocytes. The intracytoplasmic constant (gamma) chain of the class II molecules was also not detectable within the keratinocytes. Patients who received IFN-alpha 2 therapy, did not exhibit keratinocyte-bound HLA-DR antigens.

Female↗

PubMed1988

Monoclonal autoantibodies specific for kidney proximal tubular brush border from mice with experimentally induced chronic graft-versus-host disease.

Nine hybridomas producing monoclonal autoantibodies specific for kidney proximal tubular brush border were found in 600 hybridomas derived from (C57BL/6J X DBA/2)F1 mice injected with DBA/2 T cells. None of the 1100 hybridomas derived from nonautoimmune (C57BL/6J X DBA/2)F1 mice produced antibodies with a similar specificity. Four of these nine monoclonal antibodies were characterized further. They did not bind to cryosections of liver, lung, stomach, or intestine. Three bound to kidney proximal tubular brush border of mouse, cattle, sheep, pigs, rabbits, rats, and humans, whereas the fourth was specific only for murine brush border. All four precipitated from mouse kidney microvilli, a protein with an apparent molecular weight of 160,000 under reducing as well as nonreducing conditions. Removal of asparagine-linked carbohydrate with EndoF reduced the molecular weight of the 160,000 protein by about 20,000. One of the three multi-species-specific antibodies bound to pig kidney aminopeptidase, a glycosylated enzyme located on the microvilli of kidney proximal tubular brush border. Three antibodies have a heavy-chain variable region encoded by VH genes of the J558 family, whereas the heavy-chain variable region of the fourth is encoded by a VH gene of the 7183 family. Attempts to passively transfer immune complex glomerulonephritis to normal mice by injection of the purified monoclonal antibodies or by growth of the corresponding hybridoma cells in mice have so far been unsuccessful. However, antibodies recognizing the 160,000 molecule are present in the serum of mice with chronic graft-versus-host disease and can be eluted from kidneys with immune complex glomerulonephritis.

Aminopeptidases↗

PubMed1988

Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas.

We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of T- and B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B10.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I-Ab/k [(B10.A x B10)F1 and (B10 x B10.A)F1], and H-2 I-Abm12 (bm12) mice were resistant against T-cell lymphomagenesis, but 65% of these H-2 I-Ab, b/k, bm12 animals developed B-cell lymphomas (mean latency, 71 weeks). Animals of T-cell lymphoma-susceptible strains that escaped from T-cell lymphomagenesis developed B-cell lymphomas with similar frequency as animals of T-cell lymphoma-resistant strains, but with a shorter latency. H-2 class II-determined regulation of antiviral immunity was reflected in the presence of high titers of antiviral envelope antibodies in T-cell lymphoma-resistant B-cell lymphoma-susceptible H-2 I-Ab, b/k, bm12 mice, whereas in T-cell lymphoma-susceptible H-2 I-Ak,d mice no antiviral antibodies were found. At week 4 after neonatal MCF 1233 infection, a high percentage of thymocytes were virally infected in both T-cell lymphoma-susceptible and -resistant mice. However, T-cell lymphoma-resistant animals cleared the thymic infection between weeks 4 and 10 of age, coinciding with a sharp rise in serum levels of antiviral antibodies. We conclude that the pleiotropic effects of MCF 1233 infection in H-2-congenic mice result from MHC class II I-A-determined T-cell response differences.

Animals↗

PubMed1988

Defective intralesional interferon-gamma activity in patients with lepromatous leprosy.

Cryostat sections of full-thickness skin biopsies from 21 patients along the whole spectrum of leprosy were subjected to immunohistological examination with special regard to defective lymphokine production. There was an inverse relationship between intra-lesional IL-1 reactivity and IL-2R expression, in that the latter was markedly observed in tuberculoid lesions. Whenever epithelioid cell containing granulomas were present in paucibacillary forms, significant reactivity within the central phagocytic cells with the monoclonal antibody directed against interferon-gamma was detectable. The keratinocytes covering tuberculoid lesions abundantly expressed class II alloantigens (HLA-DR antigens), indicating high intra-lesional interferon-gamma activity. In contrast, multibacillary forms revealed significant anti-IL-1 reactivity within the cellular infiltrate. IL-2R bearing cells were virtually absent as was anti-HLA-DR reactivity of the keratinocytes, underlining a defective intra-lesional interferon-gamma activity.

Epidermal Cells↗

PubMed1988

T cell receptor alpha mRNA transcription in T-lymphoblastic transformation of chronic myelocytic leukemia.

Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were obtained from immunological phenotyping. Blasts were found to be CD7+, CD1+, CD3+, CD4+, CD8+, and TdT- and classified as common/mature thymocytes. The presence of the breakpoint cluster region gene on chromosome 22 excluded the possibility of a second neoplastic process.

Adult↗

PubMed1988

[T- and B-cell double lymphoma: immunologic characterization using monoclonal antibodies].

The coexistence of two non-Hodgkin lymphomas in one patient is extremely rare. We describe a patient who suffered for 17 years from chronic lymphocytic leukemia of B-cell origin with bone marrow and peripheral blood involvement until he developed clinically typical mycosis fungoides of the skin. The neoplastic lymphatic cells in the skin infiltrates were T-cells of the helper/inducer phenotype and thus differed morphologically and by immunological markers from the neoplastic cells in peripheral blood and bone marrow. The clonal B-cell expansion was controlled well over many years by cytotoxic drug therapy, the cutaneous T-cell lymphoma only with limited success by oral photochemotherapy owing to lack of compliance. The patient died 3 years after the diagnosis of MF from a parallel exacerbation of both diseases. Extensive immunohistochemical studies verified the nature of both lymphomas in vivo and at autopsy.

Aged↗

PubMed1987

The autoantigen-binding B cell repertoires of normal and of chronically graft-versus-host-diseased mice.

A quantitative analysis of the frequencies of autoantibody-producing B cells in GVHD and in normal mice has been undertaken by generating collections of hybridomas of activated B cells. These hybridomas secreted sufficient quantities of Ig to allow binding analyses on a panel of autoantigens. B cells have been activated in a variety of ways. In vivo they were activated by injection of alloreactive T cells of one parent, leading to GVHD by a foreign antigen, sheep erythrocytes, in a secondary response, or by the polyclonal activator LPS. B cells from an experimentally unstimulated animal were used for an analysis of the normal background. In vitro B cells were activated by alloreactive T cells or by LPS. The frequencies of hybridomas and, therefore, of activated B cells producing autoantibodies to DNA or to kidney were not significantly different in mice activated by a graft-vs.-host T cell response as compared with B cell populations activated by any of the other procedures. They were found to compose 7.1-17.1% of the total repertoire of activated B cells. Moreover, the frequencies of autoantibody-producing activated B cells does not change with time after induction of the graft-vs.-host reaction. The pattern and frequencies of autoantigen-binding specificities to cytoskeleton, smooth muscle, nuclei, mitochondria, and DNA were not found to be different in any of the groups of hybridomas. The single notable exception, found in GVHD mice, were hybridomas producing autoantibodies to kidney proximal tubular brush border. These results allow the conclusion that autoantigen-binding B cells exist in an activated state in GVHD mice, as well as in mice activated by a foreign antigen or by a polyclonal activator, in B cell populations activated in vitro either by alloreactive T cells or by a polyclonal activator, and even in the background of experimentally unstimulated animals. T cell-mediated graft-vs.-host activation, in large part, does not lead to a selective expansion of autoantigen-binding B cells. The main difference between the graft-vs.-host-activated B cell repertoire and all others is that approximately 90% of teh autoantibodies were of the IgG class, whereas al autoantibodies found in the other groups were IgM.

Animals↗

PubMed1987

Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders.

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.

Aged↗

PubMed1987

In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders.

Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.

Bone Marrow↗

PubMed1987

Refinement and precision in the classification of murine lymphomas by genotyping with immunoglobulin and T cell receptor probes.

Of 114 murine leukemia virus induced lymphomas and 12 lymphoid hyperplasias, T cell receptor beta-chain gene and immunoglobulin gene constellation (immunogenotype) was compared with histology and surface marker expression (immunomorphology). In 53 out of 114 lymphomas (45%), definite conclusions concerning cell lineage were possible only after genotyping. Fifteen follicular center cell lymphomas with a clear phenotype (13 tumors with B and 2 tumors with T cell markers) were genotypically classified in agreement with their phenotype. Of another 21 follicular center cell tumors (12 null cell tumors lacking T or B cell-specific antigens and 9 tumors phenotypically composed of mixtures of T and B cells), B cell lineage was determined upon genotyping in 17 cases. All 41 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a B cell phenotype, upon DNA analysis were indeed classified as T and B cell tumors, respectively. Of another 10 lymphoblastic tumors (phenotypically 4 null cell lymphomas, 6 mixtures of T and B cells) genotyping established lineage in 9 cases. Fifteen lymphoblastic neoplasms showing lineage infidelity because of simultaneous expression of a T (Thy-1) and a B cell (B220) marker were clearly of T cell genotype. Only 4 out of 114 lymphomas tested retained both Ig and T cell receptor genes in germline configuration, although 6 lymphomas in these series had both Ig and T cell receptor genes rearranged. Four of twelve lesions histologically classified as hyperplasias nevertheless contained a monoclonal B cell population at the DNA level. Immunogenotypic evaluation of lymphomas allows precise lymphoma lineage determination even in cases where marker analysis falls short, and is clearly superior in detecting mono- or oligoclonality in lymphomas versus polyclonality in benign lesions.

Animals↗

PubMed1986

Acute leukemia with mediastinal mass, lymphadenopathy, and monocytic precursor cells.

Cell marker analysis with monoclonal antibodies (MoAb) as well as differentiation studies with the chemical inducer TPA were used to identify a population of apparently lymphoid cells as monocytic precursor cells in a patient with acute leukemia. The initial manifestation of the disease with mediastinal mass and lymphadenopathy was followed by the appearance of small lymphocyte-like blast cells in bone marrow (BM) and peripheral blood (PB). Although a lymph node biopsy revealed an infiltration with monoblasts, the leukemic cells in BM and PB were not classifiable. However, when the patient relapsed after chemotherapy with large monoblasts and again with morphologically lymphoid blast cells, the latter could be classified by treatment with TPA. After incubation with the inducer (12-48 hr) the cells became positive with the MoAB VIM-D5, showed a strong reaction with alpha-naphthyl-acetate-esterase and developed macrophage like morphology, as well as phagocytic properties. During the terminal phase of the disease, small, lymphocyte-like blast cells predominated. These cells could be classified by a panel of MoABs. They expressed myeloid determinants (VIM-D5, VIM-2, MY 9, VIM-12, VIM-13) but showed no reactivity with MoABs specific for lymphocytic cells.

Adult↗