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D Michaeli

Publications and source records attributed to D Michaeli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Anti-gonadotrophin releasing hormone antibodies inhibit the growth of MCF7 human breast cancer xenografts.

The human breast cancer cell line (MCF7) was established as xenografts in intact female nude mice. Xenografts did not require oestrogen supplementation for growth, although oestrogen supplementation caused more rapid tumour growth. GnRH Pharmaccine is an immunogen composed of gonadotrophin releasing hormone (GnRH) linked to diphtheria toxoid. Anti-GnRH antibodies purified from the serum of rabbits immunized with GnRH Pharmaccine, were used to passively immunize nude mice. In mice treated with anti-GnRH antibodies, xenograft growth was significantly inhibited relative to controls (median times of 71 and 29 days respectively taken for tumours to attain a predetermined cross-sectional area of 200 mm2, P < 0.001). The inhibition of tumour growth achieved by anti-GnRH antibodies was not significantly different from that produced by the anti-oestrogen, tamoxifen (59 days). Ovarian/uterine weights were reduced by 61% (P < 0.001) in anti-GnRH antibody-treated animals compared with controls. Histologically there was underdevelopment and atrophy of the reproductive organs. Serum levels of both oestrogen and luteinizing hormone were reduced by treatment with anti-GnRH antibodies (to 24.9% and 53% respectively of levels in controls, both P = 0.04). It is postulated that one of the mechanisms by which anti-GnRH antibody treatment inhibits tumour growth is indirectly, by reducing serum oestrogen levels.

Animals↗
PubMed1999

Mutations in FIE, a WD polycomb group gene, allow endosperm development without fertilization.

A fundamental problem in biology is to understand how fertilization initiates reproductive development. Higher plant reproduction is unique because two fertilization events are required for sexual reproduction. First, a sperm must fuse with the egg to form an embryo. A second sperm must then fuse with the adjacent central cell nucleus that replicates to form an endosperm, which is the support tissue required for embryo and/or seedling development. Here, we report cloning of the Arabidopsis FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) gene. The FIE protein is a homolog of the WD motif-containing Polycomb proteins from Drosophila and mammals. These proteins function as repressors of homeotic genes. A female gametophyte with a loss-of-function allele of fie undergoes replication of the central cell nucleus and initiates endosperm development without fertilization. These results suggest that the FIE Polycomb protein functions to suppress a critical aspect of early plant reproduction, namely, endosperm development, until fertilization occurs.

Alleles↗
PubMed1999

A comparison of the therapeutic effectiveness of gastrin neutralisation in two human gastric cancer models: relation to endocrine and autocrine/paracrine gastrin mediated growth.

BACKGROUND: Gastrin is a growth factor for established tumours. AIMS: To investigate the therapeutic effect of antibodies, raised against the Gastrimmune immunogen, which neutralise the glycine extended and carboxy amidated forms of gastrin 17 in two human gastric cancer models. METHODS: MGLVA1 cells (which have a gastrin autocrine/paracrine phenotype) and ST16 cells (which have an endocrine phenotype) were injected into the peritoneal cavity of SCID mice. Peritoneal tumours, ascites, and cachexia formation occurred, with the monitored endpoint being morbidity. RESULTS: In MGLVA1 cells, intravenous administration of antibodies raised against Gastrimmune increased the 50% median survived by 25% at three different initial cell seeding concentrations (1 x 10(6)-5 x 10(5) per mouse). In ST16 cells, the effect of Gastrimmune induced antibodies on time to morbidity was greatest at the lowest cell seeding concentration (5 x 10(5) cells/mouse) with the 50% median survival increased by 74% and overall survival achieved in 38% of the mice. CONCLUSIONS: Gastrimmune may have potential therapeutic benefit on gastrin sensitive gastric tumours and may interact with both endocrine and autocrine mediated growth pathways.

Animals↗
PubMed1998

Expression of CCKB/gastrin receptor isoforms in gastro-intestinal tumour cells.

Anti-serum raised against the human cholecystokinin B (CCKB)/gastrin receptor was used in Western blotting to differentiate the cellular locations of receptor isoforms expressed by human gastro-intestinal (GI) tumour cell lines. Using anti-serum directed against the amino-terminal extracellular tail of the CCKB/gastrin receptor, 8/9 cell lines were shown to express immunoreactive proteins of either m.w. 70 or 40 kDa, or both. Both isoforms were found to be associated with intracellular, non-nuclear membranes, whereas only the 70 kDa protein was expressed in the plasma membrane. Receptor expression was related to gastrin production and secretion. Both progastrin and glycine-extended gastrin-17 were produced and secreted by the tumour cell lines; however, carboxy amidated gastrin was not detected by radioimmunoassay. A CCKB/gastrin receptor transfectant NIH3T3 cell line did not produce detectable gastrin and showed exclusive expression of the 70 kDa receptor on the plasma membrane. One cell line had <50 pg/ml cell-associated progastrin and no detectable receptor form. Cell lines expressing 50-150 pg/ml had both 40 and 70 kDa receptor forms. Those expressing >150 pg/ml progastrin had only the 40 kDa isoform, which was shown to be exclusively expressed on intracellular, non-nuclear membranes, in one of the cell lines. Of the 4 cell lines exclusively expressing the lower m.w. receptor, 3 had gastrin present within the cell, which was not secreted. Thus, if cell-associated gastrin induces a proliferative effect, it may be by an intracrine pathway. Our study has identified the presence of CCKB/gastrin receptor isoforms in different cellular locations and may help toward understanding the complex autocrine and intracrine pathways mediated by gastrin peptides.

3T3 Cells↗
PubMed1998

Coexpression of gastrin and gastrin receptors (CCK-B and delta CCK-B) in gastrointestinal tumour cell lines.

BACKGROUND: The peptide hormone gastrin is a recognised growth factor for gastrointestinal (GI) tumour cells. Carboxyamidated gastrins bind to the cell surface gastrin/cholecystokinin B (CCK-B) receptor which can be expressed as either a normal or a truncated isoform (delta CCK-B). AIMS: To compare gastrin gene expression with delta CCK-B and total CCK-B (both isoforms) gene expression in both GI and non-GI tract derived human tumour cell lines. METHODS: Total RNA was extracted and gene expression was assayed by the reverse transcription-polymerase chain reaction followed by Southern blotting and hybridisation with specific oligo probes. RESULTS: Gastrin was expressed by 5/5 gastric and 7/8 colorectal cell lines. Coexpression of gastrin CCK-B isoform was found in 80% of gastric and 75% of colorectal cell lines. Non-GI cell lines, with the exception of a lymphoblastic leukaemia cell line, showed no coexpression. The truncated receptor, delta CCK-B, was shown in 3/5 gastric and 5/8 colorectal cell lines and was always coexpressed with gastrin. CONCLUSIONS: The truncated gastrin receptor, delta CCK-B, is coexpressed with gastrin in 8/13 GI tumour cell lines. Gastrin and CCK-B receptor isoforms may be involved in maintaining autocrine/paracrine growth pathways in GI cancer cells.

Blotting, Southern↗
PubMed1996

Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer.

The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced degree of necrosis, with the area of viable tumor in the Gastrimmune-immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.

Amino Acid Sequence↗
PubMed1995

[Ebola disease].

Explore the source record for details and available documents.

Ebolavirus↗
PubMed1995

Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5.

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

3T3 Cells↗
PubMed1995

Israel's National Health Insurance Law: expectations and concerns.

An historical overview of the Israeli health care system is followed by detailed discussion of recent reforms mandated by the government to control rising yearly expenditures. The author examines the advantages and disadvantages of the reforms, concluding that they are only a first step toward long-term success.

Health Care Costs↗
PubMed1993

High levels of photosystem I subunit II (PsaD) mRNA result in the accumulation of the PsaD polypeptide only in the presence of light.

The light-regulated mRNA and polypeptide accumulation of the nuclear encoded subunit II (PsaD) of the photosystem I reaction center was studied during the greening of etiolated spinach seedlings. Upon exposure to continuous white light, the mRNA, detected at low levels in etiolated seedlings, accumulated in a specific pattern. In contrast, the PsaD subunit could not be detected in the etiolated seedlings; the polypeptide could first be detected in thylakoid membranes approximately 4 h after exposure to continuous light. A pulse of red light induced the expression of the PsaD mRNA, but the polypeptide could not be detected unless the seedlings were exposed to light. In the light (but not in the dark), the PsaD mRNA was found associated with the polysomal fraction. Taken together, the data suggest a dual regulatory mechanism in which both the level of mRNA and the presence of light control the accumulation of the PsaD polypeptide.

Gene Expression Regulation↗
PubMed1992

Involvement of a chloroplast HSP70 heat shock protein in the integration of a protein (light-harvesting complex protein precursor) into the thylakoid membrane.

Molecular chaperones, including those belonging to the 70-kDa family of heat shock proteins (HSP70), assist both the translocation of proteins across membranes and their assembly into oligomeric complexes. We purified a chloroplast HSP70 (ct-HSP70) and demonstrated that it plays a major role in the insertion of the precursor of the major light-harvesting complex of photosystem II (pLHCP; an integral membrane protein) into the thylakoids (the inner membranes of the chloroplast). Addition of the purified ct-HSP70 is necessary for efficient insertion of pLHCP into isolated thylakoid membranes. This activity of the purified ct-HSP70 is similar to that previously reported for the total stromal extract. When the chloroplast stromal extract is depleted of HSP70, a correlative reduction in the insertion activity of pLHCP is observed. The interaction between the ct-HSP70 and pLHCP involves physical association. The purified HSP70 acts directly on the membrane protein, presumably prevents its refolding, and thereby helps to maintain its competence for insertion into membranes.

Journal Article↗
PubMed1991

Monomeric and trimeric forms of photosystem I reaction center of Mastigocladus laminosus: crystallization and preliminary characterization.

Photosystem I (PSI) reaction centers (RCs) of the thermophilic cyanobacterium Mastigocladus laminosus were purified and characterized. The PSI RC was obtained in two forms, monomeric and trimeric. The two forms contained the same number of pigments per P700 and displayed similar photochemical activities. The two forms had nearly identical polypeptide subunit compositions; the only observed difference was an additional subunit of about 12 kDa observed in the trimeric form. The purified preparations of both the monomeric and the trimeric forms were used for crystallization and preliminary crystallographic analysis. The trimeric PSI RC preparations produced several three-dimensional crystal forms, one of which, the "hexagonal needle" form (THN), had a hexagonal unit cell with dimensions of 300 x 300 x 160 A, containing four PSI RC trimers. The monomeric preparations also produced single crystals of several forms under various crystallization conditions. One of these crystal forms, the "hexagonal plate" (MHP), diffracted to a resolution of about 5.5 A. It had a hexagonal unit cell with dimensions of 192 x 192 x 163 A, containing six PSI RC monomers. Comparison of the PSI RCs in the crystals with those in the precrystallization preparations demonstrated that neither the monomeric nor the trimeric form of PSI RC was altered by the crystallization process. Both forms retained their original polypeptide subunit composition and their pigment content.

Blotting, Western↗