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P Resnitzky

Publications and source records attributed to P Resnitzky.

At least 19 recordsLinked to original sources
PubMed2003

A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

OBJECTIVES: Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. PATIENTS AND METHODS: Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. RESULTS: Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. CONCLUSIONS: A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

Anemia↗
PubMed1998

Ultrastructural characteristics and lysozyme content in hypergranular and variant type of acute promyelocytic leukaemia.

We investigated the electronmicroscopic (EM) features and cellular lysozyme (LZ) content in 16 cases of acute promyelocytic leukaemia (APL): 11 cases of the hypergranular form (M3) and five cases of the microgranular variant (M3-V). The main EM features in all cases were: irregular, folded or bilobed nuclei, many cytoplasmic granules, distended rough endoplasmic reticulum (RER) cisternae which, in some cases, presented as stellate forms (more frequent in M3-V), and bundles of cytoplasmic microfilaments. Many Auer rods were present in M3 cases and few in M3-V; most of these disclosed parallel tubular arrays (PTA) with a varied periodicity ranging from 13 to 26 nm. There was a significant difference between M3 and M3-V (P<0.0001) in both the number of granules per cell section (62.9 +/- 34.5 v 38.0 +/- 23.6) and in the granule section area (0.044 +/- 0.033 v 0.026 +/- 0.015 microm2). In some cases, mainly in M3-V, we found cells with large granules containing PTA which probably represent poorly developed Auer rods. Intracellular LZ content assayed by a post-embedding immunogold method, showed high granular LZ density (in the range of that found in M4 and M5) in M3 cells and very low granular LZ content in M3-V. This study adds new objective parameters for the diagnosis of these two types of APL and provides new information on their LZ pattern of expression.

Endoplasmic Reticulum, Rough↗
PubMed1998

Localization of the gene for congenital dyserythropoietic anemia type I to a <1-cM interval on chromosome 15q15.1-15.3.

Congenital dyserythropoietic anemias (CDA) are a rare group of red-blood-cell disorders of unknown etiology that are characterized by ineffective erythropoiesis, pathognomonic cytopathology of the nucleated red blood cells in the bone marrow, and secondary hemochromatosis. In CDA type I, bone-marrow electron microscopy reveals characteristic findings in erythroid precursors, including spongy heterochromatin and enlarged nuclear pores. Since the genetic basis of CDA type I is not evident, we used homozygosity and linkage mapping to localize the genetic defect responsible for CDA type I in 25 Bedouins from four large consanguineous families. We report the linkage of this disease to markers on chromosome 15 located at q15. 1-q15.3. Fourteen markers within a 12-cM interval were typed in the relevant family members. Nine of the markers yielded maximum LOD scores of 1.625-12.928 at a recombination fraction of .00. Linkage disequilibrium was found only with marker D15S779. Haplotype analysis revealed eight different carrier haplotypes and highlighted the existence of a founder haplotype. Identification of historical crossover events further narrowed the gene location to between D15S779 and D15S778. The data suggest localization of the CDA type I gene within a 0.5-cM interval. The founder mutation probably occurred >/= 400 years ago. Sequence analysis of the coding region of protein 4.2, the only known erythroid-specific gene in the locus, did not reveal any change in the CDA type I patients. Future analysis of this locus may lead to the identification of a gene essential to normal erythropoiesis.

Anemia, Dyserythropoietic, Congenital↗
PubMed1996

Clinical features and studies of erythropoiesis in Israeli Bedouins with congenital dyserythropoietic anemia type I.

Congenital dyserythropoietic anemia (CDA) type I is a rare macrocytic anemia of unknown etiology. In the present study, we redefined the clinical and laboratory picture of CDA type I, some of its pathogenic aspects, and the association with thalassemia-like features in 20 patients, all of whom belong to one Bedouin tribal group and are probably descended from a common ancestor. In each case ultrastructural studies of bone marrow (BM) erythroblasts showed the classic morphological findings of CDA type I. Serological tests for CDA type II were negative. The clinical picture was variable, but mostly benign. Some patients displayed elevated hemoglobin A2 levels or high ratio of alpha- to non-alpha- globin. However, neither family studies nor complete sequence analysis of the beta-globin was compatible with beta-thalassemia. Increased erythropoiesis was manifested by a high number of BM erythroid burst-forming units. Serum erythropoietin was also elevated. BM flow cytometry studies demonstrated arrest of erythroid precursors in the S phase of the cell cycle. The ultrastructural morphological features of the erythroid precursors, showing peripheral chromatin condensation, suggest apoptosis. Additional studies are indicated to define the molecular basis of this disease.

Adolescent↗
PubMed1996

The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32).

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.

B-Lymphocytes↗
PubMed1995

A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8:16)(p11:p13), in a patient with the variant t(8:19)(p11:q13)--case report and review of the literature.

Acute myeloblastic leukemia (AML) with t(8:16) or its variant t(8:V) has been rarely reported. A high proportion of patients are infants and children, often with a bleeding tendency and disseminated intravascular coagulopathy (DIC). Only one-third of the de novo patients remain in the first complete remission following multiagent chemotherapy and bone marrow transplantation (BMT). Morphocytochemically, the disorder is classified as an M5, M4, or M4/M5 variant. In the presented case, with the variant t(8:19)(p11:q13), comprehensive light and electron microscopic blast cell characterization showed monocytic and granulocytic features compatible with the M4 subtype (on the monocytic predominance range of the French-American-British classification scale). Although hemophagocytosis, one of the hallmarks of the disease, was rare in our patient, numerous autophagic vacuoles were present. Immuno- and genotyping showed a myelomonocytic phenotype with no evidence of early progenitor antigen expression or mixed leukemia. These results and those of previous reports support the high specificity of t(8:16) or its variants to the unique M4/M5 type leukemia and the role of a gene on 8p11 in this specific transformation.

Adolescent↗
PubMed1995

The effects of passive anti-viral immunotherapy in AKR mice: II. Susceptibility to B cell lymphomagenesis.

Prevention of high frequency spontaneous T cell lymphoma development in AKR mice by mAb 18-5 treatment was shown to involve inhibition of the recombinant Class I MCF virus formation and elimination of the early occurring potential lymphoma cells (PLCs). A low B cell lymphoma incidence (16% at a mean latency of 540 days) and a low level of PLCs (yielding 12% B cell lymphoma development following lymphoid cell transfer) was observed in mAb 18-5 treated mice (in contrast to a high PLC level in thymectomized AKR mice that could be experimentally triggered to progress to overt CD5+ B cell lymphomas). Administration of anti CD8 mAb or IL-4 to 12-month-old mAb 18-5 pre-treated mice only slightly increased B cell lymphoma incidence (up to 30-40%). Exposure to split-dose irradiation resulted in 26% B cell lymphomas at a 250 day mean latency. The phenotypes of the B lymphomas developing in mAb 18-5 treated mice were: B220+ (14.8+, 6B2+), 6C3+, Mac2+, CD5-. Most lymphomas expressed l-a and surface IgM, pointing to their mature B cell characteristics. Moreover, in some of the lymphomas, high levels of IgM production and secretion were determined. A comparison of the morphological characteristics (based on light and ultrastructure microscopy) of CD5+ and CD5- B cell lymphomas developing in AKR mice indicated marked differences. Analysis of the IgH locus of representative CD5- B lymphomas showed an identical pattern of IgH rearrangement in some tumors (similar to previous findings among CD5+ lymphomas). The virological analysis of the CD5- B cell lymphomas (similar to those observed in the CD5+ B cell lymphomas of AKR origin) showed that their development did not require formation of the pathogenic MCF recombinant viruses. The differences observed between the CD5+ and CD5- B cell lymphomas developing in AKR mice (following prevention of spontaneous T cell lymphomagenesis) may be due to their origin of different B cell precursors or from B cells at different levels of differentiation.

Animals↗
PubMed1994

Distinct lysozyme content in different subtypes of acute myeloid leukaemic cells: an ultrastructural immunogold study.

Using an ultrastructural immunogold method, we performed a quantitative study on cellular lysozyme (LZ) content in young normal bone marrow cells and in 14 cases of acute myeloid leukaemia (AML) of the M2, M3, M4 and M5 types. In five cases of M2 we found significantly lower LZ content than in normal promyelocytes and than in nine cases of M3, M4 and M5. In M3, M4 and M5 cells a very high LZ content was observed whereas the serum LZ activity was high in M4 and M5 and normal in M3. The intragranular LZ content was especially high in M5 and in most granules of M4 cells. The immunogold reaction (IGR) for LZ was also performed in cells previously reacted for myeloperoxidase (MPO). In M2 the granules showed definite positive MPO reactivity and low LZ density (granulocytic pattern), whereas in M5 we found high granular LZ content and weak or almost negative MPO activity (monocytic pattern). In M4 we found 'granulocytic' and 'monocytic' type of granules in the same cell. The IGR for LZ performed in post-embedded M5 cells which were previously subjected to phagocytosis of latex particles, showed granules that had moved toward the phagosome, releasing LZ without degranulation. The above findings and those showing normal serum LZ in M3 despite their high cellular LZ content, definitely indicate that only leukaemic M4 and M5 cells secrete LZ into their environment, explaining the high serum LZ observed in those leukaemias.

Acute Disease↗
PubMed1994

Distinct intracellular lysozyme content in normal granulocytes and monocytes: a quantitative immunoperoxidase and ultrastructural immunogold study.

Using two different immunological methods, we performed a quantitative estimation of lysozyme (LZ) in normal mature granulocytes and monocytes. An immunoperoxidase reaction for LZ in granulocytes and monocytes of 10 healthy donors measured by a scanning microdensitometer as arbitrary units showed a significantly higher LZ content in granulocytes than in monocytes. An ultrastructural immunogold reaction (IGR) for LZ performed on post-embedded thin sections showed a higher number of total gold grains in neutrophilic granulocytes than in monocytes. In monocytic granules we found a high density of gold grains per micron 2, whereas in granulocytic granules lower values were obtained. In granulocytes, LZ was found in both primary myeloperoxidase (MPO)-positive and secondary MPO-negative granules, and in monocytes the granules showed weak MPO reactivity and high LZ content. Granulocytes previously subjected to phagocytosis of bacteria and latex particles showed release of LZ on degranulation inside the phagosome, whereas in monocytes the granules remained outside the phagosome and released LZ without degranulation. Our study demonstrated a significantly higher total LZ content in granulocytes, a higher granular LZ content in monocytes, and release of LZ from intact monocyte granules during phagocytosis.

Densitometry↗
PubMed1994

Left pleural hemorrhagic effusion. A presenting sign of thoracic aortic dissecting aneurysm.

Left hemorrhagic pleural effusion was the presenting sign of painless aortic dissecting aneurysm in two elderly hypertensive patients. Computed tomography (CT) of the chest revealed the aneurysmal dilatation of the thoracic aorta and an intimal flap connecting its descending part with the left pleural space. The patients were treated conservatively with blood transfusions and drugs directed to control blood pressure. The first reported 71-year-old patient remains in stable condition for 16 months without evidence of recurrent active aortic dissection. The second 85-year-old patient remained in stable condition for 28 days, but finally had a second fatal episode of dissection into the left pleural space. The differential diagnosis of nontraumatic left hemorrhagic pleural effusion in an elderly hypertensive patient should include dissecting aneurysm of the descending thoracic aorta and CT of the chest should be performed as the next preferable diagnostic procedure.

Aged↗
PubMed1993

Wegener's granulomatosis with peripheral eosinophilia. Atypical variant of a classic disease.

A patient with Wegener's granulomatosis (WG) diagnosed by ultrasound-guided transthoracic biopsy of a pulmonary nodule is reported. The case is atypical because of marked eosinophilia in the peripheral blood and the pleural effusion. The granulomatous infiltrate of the lung showed the classic picture of WG without eosinophils. The patient responded dramatically to treatment with steroids and cyclophosphamide. This variant form of WG poses problems in its distinction from Churg-Strauss syndrome, and the differential diagnosis between these two entities is discussed.

Adult↗
PubMed1992

Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2.

Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI-AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down-regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Multiphase process involved in radiation induced murine AML.

Exposure of 3 month old SJL/J mice to a single dose of 300 r yielded 15-30% acute myelomonocytic leukemia (AML) development at a mean latency of 1 year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence to 50%. All tumors were characterized by a partial deletion of one allele of chromosome 2 and the same deletion was detected in bone marrow and spleen cells of most irradiated mice, irrespective of the development of the disease. The presence of potential leukemic cells (PLC) in mice 4 months after the leukemogenic treatment was confirmed by transplantation studies. In these experiments PLC transition into overt AML seemed to be dependent on their transfer into irradiated recipients. Thus, exposure to 300 r results in the initiation of potential leukemic cells. Experiments were conducted in order to explore the possible role of radiation, cytokines and different hemopoietic growth factors on PLC promotion to overt leukemia. Exposure to 300 r, beside PLC initiation, was found to trigger the production of IL-6 and CSF-1; the additional administration of dexamethasone further increased CSF-1 levels. In vivo administration of CSF-1 into mice carrying radiation-induced PLC was most effective in PLC promotion to overt AML development.

Animals↗