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Y Burstein

Publications and source records attributed to Y Burstein.

At least 19 recordsLinked to original sources
PubMed1992

Identification of cleavage sites involved in proteolytic processing of Pseudomonas aeruginosa preproelastase.

The extracellular elastase (33 kDa) of Pseudomonas aeruginosa is synthesized as a 53.6 kDa preproenzyme containing a long, N-terminal propeptide. The free propeptide and the elastase precursor generated upon propeptide removal were isolated from P. aeruginosa cells and subjected to N-terminal amino acid sequence analysis. The results identified Ala-174 and Ala+1 as the amino terminal residues of the propeptide and the elastase precursor, respectively, indicating that: (1) the signal peptide consists of 23 amino acid residues and its molecular weight is 2.4 kDa, (2) the propeptide contains 174 amino acid residues and is of 18.1 kDa molecular weight, and (3) no additional N-terminal proteolytic cleavage is required for elastase maturation.

Amino Acid Sequence↗
PubMed1992

Alterations in human fetal hematopoiesis are associated with maternal HIV infection.

In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1992

A unique ascorbate peroxidase active component in the cyanobacterium Synechococcus PCC 7942 (R2).

Ascorbate peroxidase active component (APAC) was purified and characterized in Synechococcus PCC 9742 (R2) cells. APAC was isolated from freshly harvested cells, by ion exchange chromatography on DEAE cellulose, ultrafiltration through a 3000 dalton cut off filter and high pressure liquid chromatography through a reversed phase C-18 column. APAC was found to be extremely stable to harsh treatments of boiling water for 30 min, acidification to pH 2.0 and proteolytic digestion. A close correlation between activity and iron content of APAC was observed throughout the purification steps. E.S.R. spectrum of APAC showed a resonance line at g = 4.3 in the oxidized from. Peroxide reduction by ascorbate decreased the E.S.R. signal, which reappeared upon reoxidation by H2O2. The affinities of APAC to H2O2 and ascorbate were high (0.38 mM and 0.2 mM, respectively). Amino acid composition analysis of APAC revealed the presence of glutamic acid:glycine:cysteine residues at 2:1:1 ratio.

Ascorbate Peroxidases↗
PubMed1992

Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth.

Thymus humoral factor-gamma 2 (THF gamma 2), an octapeptide important for T-lymphocyte regulation, was assessed for its effect on the in vitro growth of human hematopoietic progenitor cells. This was achieved using a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)-stimulated myeloid cell colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) assay as well as a recombinant erythropoietin (rEpo)-stimulated erythroid burst formation (erythroid burst-forming units, BFU-E) assay. Cells were obtained from bone marrow (BM) and peripheral blood (PB) of normal healthy donors and from patients with suppressed bone marrows. The latter group included aplastic anemia, leukemia, and lymphoma patients and patients with solid tumors who responded to intensive chemotherapy with significant pancytopenia. THF gamma 2 significantly enhanced normal BM and PB GM-CFC and PB BFU-E by 2- to 2.5-fold. This effect was totally dependent on the presence of the respective growth factors, that is, rGM-CSF or rEpo, and was specifically reversed by an anti-THF gamma 2 antiserum. Furthermore, although THF gamma 2-induced enhancement of GM-CFC colony formation was not affected by lymphocyte or monocyte depletion, the augmenting effect of the peptide on BFU-E was completely abrogated in the absence of lymphocytes. THF gamma 2-induced augmented growth of progenitor cells derived from severely suppressed marrows was minimal. However, cells from moderately neutropenic patients with leukemia in remission or with lymphoma under chemotherapy responded to the peptide similarly to cells from normal donors. These results suggest a stimulatory role for THF gamma 2 on human myeloid and erythroid hematopoietic progenitor cells. They also suggest the lymphocyte dependence of BFU-E enhancement and lymphocyte independence of GM-CFC stimulation by THF gamma 2. In the former case the thymus-derived peptide may act through the induction of certain erythroid-enhancing lymphokines.

Adjuvants, Immunologic↗
PubMed1991

Thymic function.

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Hematopoiesis↗
PubMed1991

Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase (EC 3.4.24.11).

A search for the natural substrates for neutral endopeptidase (NEP; EC 3.4.24.11) in the immune system led to investigation of the enzyme's action on thymic humoral factor gamma 2 (THF). The ectoenzyme rapidly and efficiently hydrolyses the Lys6-Phe7 bond of the octapeptide. The site of cleavage was confirmed by h.p.l.c. analysis, amino acid analysis and sequence determination of the products. Phosphoramidon (3.6 microM), a potent inhibitor of the enzyme, prevents this cleavage even during prolonged incubation. The high efficiency of hydrolysis of THF by NEP is similar to that reported for [Leu5]enkephalin, and the dipeptide Phe-Leu is the C-terminal product in the hydrolysis of both peptides. The presence of NEP, reportedly identified as the common acute lymphoblastic leukaemia antigen (CALLA), in bone-marrow cells and other cells of the immune system raises the possibility that it may play a role in modulating the activity of peptides such as THF.

Amino Acid Sequence↗
PubMed1991

Therapeutic effectiveness against MOPC-315 plasmacytoma of low or high doses of the synthetic thymic hormone THF-gamma 2 in combination with an "immunomodulating" or a "non-immunomodulating" drug.

We reported previously that treatment of mice bearing MOPC-315 plasmacytoma with the drugs L-PAM (phenylalanine mustard) or 5-FU (5-fluorouracil), in combination with low doses of THF-gamma 2, was more effective in increasing their survival time than treatment with the drug alone. We show here that in the combined treatment using a single injection of 5-FU followed by multiple (8-15) injections of THF-gamma 2, the megadoses were more effective than the low doses in increasing the survival time of MOPC-315 tumor-bearing mice. On the other hand, in combination with L-PAM, both low and high doses of THF-gamma 2 were equally effective. The need for high doses of THF-gamma 2, when used in combination with 5-FU, could be due to the fact that 5-FU acts as a "non-immunomodulating" drug and has to be used at a high, immunosuppressive dose.

Animals↗
PubMed1991

Bone marrow cell populations mimicking common acute lymphoblastic leukemia in infants with stage IV-S neuroblastoma.

Immunophenotyping of bone marrow mononuclear cells of 2 infants with stage IV-S neuroblastoma revealed the presence of many lymphoblasts and immature lymphocytes. Immunophenotyping showed that a high percentage of bone marrow cells were positive for the HLA-DR, CD19, CD20 and CD10 phenotype, similar to common acute lymphoblastic leukemia cells. Within 6 months of follow-up, without any treatment, complete regression of the tumors was observed. The coexistence of these two unusual populations will be discussed.

Bone Marrow↗
PubMed1991

Human recombinant CuZn-superoxide dismutase. Amino acid sequence and location of the disulfide bond.

The complete amino acid sequence of recombinant human Cu-Zn superoxide dismutase (CuZnSOD) is presented. The S-carboxymethylated protein was cleaved at lysine residues (with Achromobacter protease I) to provide a set of nine non-overlapping fragments accounting for 90% of the sequence. These fragments were then overlapped and aligned, and the sequence was completed by using peptides generated by cleavage at glutamic acid residues (with S. aureus V8 protease) and at arginine (with clostripain). The recombinant protein contains a single disulfide bond between cysteine residues 57 and 146. The primary sequence of recombinant human CuZnSOD is identical to that predicted by its cDNA sequence.

Alcaligenes↗
PubMed1990

A synthetic thymic hormone, THF-gamma 2, repairs immunodeficiency of mice cured of plasmacytoma by melphalan.

BALB/c mice cured of large MOPC-315 plasmacytomas by melphalan remain deficient in their spleen T-cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T-cells including their subsets CD4 and CD8. IL-2 production and specific cytotoxicity against MOPC-315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in-vivo administration of THF-gamma 2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T-cell subpopulations to normal and an enhanced IL-2 production above normal levels. The potential use of THF-gamma 2 as supportive therapy in cancer treatment is suggested.

Animals↗
PubMed1990

[Israel national childhood acute lymphoblastic leukemia study].

A national childhood acute lymphoblastic leukemia (ALL) study was initiated in Israel in 1984 with the aim of improving results in difficult aspects of treatment including: high-risk groups, the problems of late relapses, and the effect of cranial irradiation for CNS prophylaxis in leading to late neuropsychiatric sequelae and secondary tumors. Induction of chemotherapy with a combination of 6 drugs (vincristine, cyclophosphamide, cytosine arabinoside, adriamycin, prednisone and L-asparaginase), followed by intensification with methotrexate and L-asparaginase, was introduced in both the usual and the high-risk groups. In a selected group with better prognostic factors, therapy was reduced. In an attempt to minimize the sequelae of CNS prophylactic therapy, cranial irradiation was omitted in half the patients and intrathecal (IT) triple therapy was given instead. Following 2 years of unsatisfactory preliminary results in a very high-risk group (VHR; non-T- and T-cell leukemia with WBC counts of greater than 100,000 and greater than 20,000, respectively), treatment was modified and intensified. Between Nov. 1984 and Feb. 1989, 143 patients were enrolled from 10 hospitals. During follow-up of a median of 2.5 years, there were 32 failures (2 failed remissions, 27 relapsed and 3 died of bleeding and sepsis). 107 patients are alive in first remission and an additional 8 in second and third remissions. By Kaplan-Meier life table analysis, the rates of leukemia-free interval (LFI) and event-free interval (EFI) for 4 years were 60% and 57%, respectively. Improved LFI results of 71% for 4 years were achieved in a group with non-T-cell ALL with WBC less than 100,000 (the largest group, 65% of the patients). In the small "good risk" group (10% of patients), and the T-cell group with WBC less than 100,000, LFI for 4 years were 56% and 54%, respectively. In the VHR group, modification seemed to have improved results: LFI of 41% for 3 years. CNS prophylaxis with IT triple therapy was as effective as cranial irradiation in the standard risk group. In 1 out of 33 children on this protocol a single CNS relapse occurred, as compared to 2 out of 35 matched controls with cranial irradiation. These results warrant extension of IT triple therapy to higher risk groups of childhood ALL. As for systemic treatment, increased up-front high-dose intensive therapy is recommended for all groups with ALL, but with reduction of cumulative dose to minimize late effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

THF-gamma 2, a synthetic thymic hormone, increases effectiveness of combined chemotherapy and immunotherapy against RPC-5 murine plasmacytoma.

The effect of a synthetic thymic hormone, THF-gamma 2, on the anti-tumor activity of spleen cells was studied in mice immunized against the RPC-5 tumor. Following two courses of the THF-gamma 2 treatment, the mean RPC-5 specific cytotoxic response of immune spleen cells was significantly increased when compared to normal cells (P less than 0.001) and to untreated immune spleen cells (P less than 0.04). In addition, THF-gamma 2 treatment improved the competence of immune spleen cells in adoptive immunotherapy (AIT) when performed in combination with chemotherapy by melphalan. Recipients of spleen cells from THF-gamma 2 treated mice showed a 35% increase in survival when compared to AIT with immune cells alone. The results suggest that THF-gamma 2 treatment of donors for AIT might be applicable to cancer therapy in humans.

Animals↗
PubMed1990

Hepatomegaly as a single presenting sign of stage IV-S neuroblastoma.

This article presents the case of an infant who on routine physical examination at the age of 5 months was found to have hepatomegaly. The initial investigation revealed borderline liver function tests, and ultrasonography showed multiple space-occupying lesions. Further workup using different imaging techniques, urinary vanillylmandelic acid, serum catecholamines, and liver biopsy led to the diagnosis of stage IV-S neuroblastoma. No primary site outside of the liver could be demonstrated. The tumor regressed spontaneously.

Hepatomegaly↗
PubMed1990

Therapy of a fatal murine cytomegalovirus infection with thymic humoral factor (THF-gamma 2) treated immune spleen cells.

Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. We performed adoptive transfer experiments to evaluate the prospects for enhancing the anti-viral potential of murine CMV immune spleen cells by THF-gamma 2. Adult BALB/c mice resistant to murine CMV become highly susceptible following immunosuppression by cyclophosphamide. Recipient mice were injected with murine CMV and cyclophosphamide concomitantly, and 24 h later adoptive transfers of syngeneic immune spleen cells were performed. We showed that passive transfers of murine CMV immune spleen cells prevented the development of a fatal disease in 38% of the recipient mice. Daily injections of murine CMV immune donor mice with THF-gamma 2 enhanced considerably (93%) the therapeutic potential of virus-specific immune cells. These experiments provide direct evidence for the antiviral capacity of THF-gamma 2 through its immunomodulatory effect on immune T cells.

Animals↗
PubMed1990

Infantile idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of the patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment.

Child↗
PubMed1990

Immune modulation exerted by thymic humoral factor (THF-gamma 2), on T-cell subsets and IL-2 production of umbilical cord blood lymphocytes.

The effect of a synthetic thymic humoral factor, THF-gamma 2, on the immune competence of T-cells was investigated in vitro on lymphocytes from human cord blood (UCBL). It was found that preincubation of UCBL with THF-gamma 2 caused an increase in the percentage of cells expressing the CD4 or the CD8 differentiation antigens, but did not affect the percentage of CD3 cells. The effect of THF-gamma 2 on PHA-induced IL-2 secretion was also studied and found that a 3hr preincubation with THF-gamma 2, prior to suboptimal PHA stimulation caused an increase in the IL-2 activity of the treated UCBL cultures. This effect was THF-gamma 2 dose dependent with an optimum in the range of 300-600 ng/ml and was not influenced by irradiation of the UCBL. These results indicate that THF-gamma 2, a synthetic octapeptide, modulates the immune state and response of human umbilical cord blood lymphocytes.

Antigens, Differentiation, T-Lymphocyte↗