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J Mordoh

Publications and source records attributed to J Mordoh.

At least 73 records · Page 4Linked to original sources
PubMed1972

A new element in the control of DNA initiation in Escherichia coli.

When a thermosensitive mutant of E. coli affected in DNA initiation is heated to 41 degrees , a protein needed for DNA initiation is irreversibly denatured. When these bacteria are incubated at 30 degrees in the presence of several concentrations of chloramphenicol, DNA synthesis is greatly stimulated at a chloramphenicol, DNA synthesis is greatly stimulated at a chloramphenicol concentration of 2.5 mug/ml, and then sharply decreases. This stimulation of DNA synthesis appears to be caused by an increased frequency of initiation. The existence of an "anti-initiator" protein controlling the frequency of chromosomal initiation is proposed.

Bacterial Proteins↗
PubMed1970

On the process of cellular division in Escherichia coli. V. Incorporation of deoxynucleoside triphosphates by DNA thermosensitive mutants of Escherichia coli also lacking DNA polymerase activity.

Double mutants of Escherichia coli were constructed by combining DNA thermosensitive mutations affecting either DNA initiation (DnaA) or elongation (DnaB) with the Pol A1 mutation, which abolishes DNA polymerase activity. Incorporation of labeled deoxynucleoside triphosphates was studied in these mutants using toluene-treated cells. This incorporation was found to be exactly correlated with the capacity of the mutants to synthesize DNA in vivo.

DNA Nucleotidyltransferases↗
PubMedDate not supplied

Differential lytic and agglutinating activity of the anti-Lewis(x) monoclonal antibody FC-2.15 on human polymorphonuclear neutrophils and MCF-7 breast tumor cells. In vitro and ex vivo studies.

The Lewis(x) (Le(x)) trisaccharide (CD15) linked to proteins and glycolipids is highly expressed on the surface of normal human polymorphonuclear neutrophils (PMN) and several human neoplasias, such as breast and gastrointestinal carcinomas and chronic myeloid leukemias. FC-2.15 is an IgM murine mAb that specifically recognizes Le(x) and has been previously shown to mediate the in vitro lysis of Le(x)(+) cells by human complement. In a phase I clinical trial of FC-2.15, a temporary neutropenia was the main toxicity, and antitumor responses were observed. In order to characterize FC-2.15 further and determine the physiological relevance of Le(x) binding, the reactivity of FC-2.15 on PMN was investigated under several conditions. Flow cytometry revealed a strong reactivity of FC-2.15 with almost 100% of PMN, and Scatchard analysis demonstrated an affinity constant of 5.14 x 10(9) M(-1) and 1.11 x 10(6) antigen sites/cell. In vitro, the binding of Le(x) epitopes by FC-2.15 induced PMN homotypic aggregation, only 28.4 +/- 4.1% remaining as single cells. When PMN and the Le(x)(+) MCF-7 breast cancer cells were co-incubated, FC-2.15 induced heterotypic aggregation. In 51Cr-release assays employing human complement, FC-2.15 lysed 93.4 +/- 7.9% of PMN and 87.8 +/- 10.7% of MCF-7 cells. However, when the effect of FC-2.15 was tested in ex vivo circulating blood, no lytic activity against PMN was detected, whereas MCF-7 cells were still lysed. Blood smears demonstrated that FC-2.15 induced PMN agglutination and heterotypic aggregates when MCF-7 cells were present. A pretreatment of PMN with colchicine impaired PMN agglutination both in vitro (single PMN = 81.15 +/- 4.35%) and in ex vivo circulating blood. In the latter condition, FC-2.15-lytic activity was restored, suggesting that PMN homotypic aggregation by FC-2.15, but not lysis, is dependent on microtubule integrity and that PMN agglutination hinders their lysis. Moreover, when 51Cr-release assays were performed following agglutination, FC-2.15 cytotoxicity was restricted to isolated PMN. It is suggested that crosslinking of Le(x) epitopes by FC-2.15 induces PMN to form homotypic aggregates. It is suggested that the neutropenia observed in FC-2.15-treated patients would be due to PMN agglutination and margination, rather than lysis. In addition, FC-2.15 appears to be able to lyse Le(x)(+) tumor cells in circulation.

Agglutination↗
PubMedDate not supplied

Different efficacy of in vivo herpes simplex virus thymidine kinase gene transduction and ganciclovir treatment on the inhibition of tumor growth of murine and human melanoma cells and rat glioblastoma cells.

Initial studies have demonstrated the therapeutic efficacy for cancer treatment of in vivo transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir (GCV) treatment. However, recent studies have questioned the validity of this approach. Using retroviral vector-producing cells (VPC) as a source for in vivo gene transfer, we evaluated the efficacy of in vivo transduction of malignant cells using three different tumor cell models: B16 murine and IIB-MEL-LES human melanomas and a C6 rat glioblastoma. In vitro studies showed a bystander effect only in C6 cells. In vivo studies showed an inhibition of tumor growth in the two melanoma models when tumor cells were coinjected with VPC-producing retroviral vectors carrying the herpes simplex virus thymidine kinase gene, followed by GCV treatment; however, 100% of mice developed tumors in both models. Under similar experimental conditions, 70% (7 of 10) of syngeneic rats completely rejected stereotactically transferred C6 tumor cells; most of them (5 of 10) showed a prolonged survival. Treating established C6 tumors with VPC-producing retroviral vectors carrying the herpes simplex virus thymidine kinase gene and GCV led to the cure of 33% (4 of 12) of the animals. Rats that rejected tumor growth developed an antitumor immune memory, leading to a rejection of a stereotactic contralateral challenge with parental cells. The immune infiltrate, which showed the presence of T lymphocytes, macrophages, and polymorphonuclear cells at the site of the first injection and mainly T lymphocytes and macrophages at the site of tumor challenge, strengthened the importance of the immune system in achieving complete tumor rejection.

Animals↗
PubMedDate not supplied

Characterization of IIB-MEL-J: a new and highly heterogenous human melanoma cell line.

A highly heterogeneous cell line, IIB-MEL-J, was established from a human metastatic melanoma. This cell line contains small cells, dendritic cells, and megacells with multiple nuclei. IIB-MEL-J expresses S 100, cytokeratin intermediate filaments and the gangliosides GD2 and GD3. It requires growth factors (insulin, EGF, and transferrin) and antioxidants for optimal growth. When plated under optimal conditions, IIB-MEL-J grows with a doubling time of 70-80 hours. The cells may be fractionated by Percoll gradient centrifugation into several subpopulations (A, B, and C) with different characteristics. Subpopulation A is the slowest growing, and most of the DNA-synthesizing cells are concentrated in fractions B and C. Every subpopulation expresses S 100 and cytokeratin intermediate filaments, whereas only subpopulation B and C express GD2 and GD3. Pigmented cells are concentrated mainly in subpopulation C. Cytogenetic analysis of IIB-MEL-J revealed extensive chromosomal alterations, including a highly heterogeneous chromosome number and chromosomal rearrangements, gains, losses, isochromosomes, and double minutes. This highly heterogeneous cell line may be helpful to study cellular differentiation and interaction between different subpopulations in human melanoma.

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Description of a new monoclonal antibody, FC-2.15, reactive with human breast cancer and other human neoplasias.

FC-2.15 is an IgM monoclonal antibody (MAb) obtained by immunizing Balb/c mice with tumor epithelial cells from a human undifferentiated primary breast carcinoma. FC-2.15 reacts with 93.9% (31/33) of human breast primary tumors, independently of their histology and hormone receptor content. Moreover, FC-2.15 reacts with 79.6 +/- 13.8% (mean +/- SD) of total breast malignant tumor cells and with 88.7 +/- 9.9% of proliferating tumor cells. It recognizes other neoplasia such as colon cancer, squamous carcinoma and melanoma. Among the normal tissues examined, strong cross-reactivity was found with kidney proximal convolute tubules, bone marrow myeloid progeny, peripheral granulocytes and large bowel epithelium. Through Western blots, FC-2.15 recognizes three major bands of Mr 160 kDa, 130 kDa and 115 kDa in membrane extracts of MCF-7 cells grown in nude mice and of human breast carcinoma and three major bands of 250 kDa, 185 kDa and 105 kDa in membrane extracts of peripheral granulocytes. This MAb mediates complement- cytotoxicity against malignant cells, reducing the clonogenic capacity of breast primary tumor cells and MCF-7 cells to 35.6 +/- 41.2% and 11.7 +/- 4.8% of control values respectively, whereas that of normal bone marrow cells is not affected (104.7 +/- 17.4%).

Animals↗