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E Berman

Publications and source records attributed to E Berman.

At least 19 recordsLinked to original sources

Levels of phospholipid metabolites in breast cancer cells treated with antimitotic drugs: a 31P-magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy (MRS) methods have provided valuable information on cancer cell metabolism. In this study, we characterized the 31P-MR spectra of breast cancer cell lines exhibiting differences in hormonal response, estrogen receptors (positive/negative), and metastatic potential. A correlation was made between the cytotoxic effect of antimitotic drugs and changes in cell metabolism pattern. Because most anticancer drugs are more effective on proliferating cells, our study attempted to elucidate the metabolic profile and specific metabolic changes associated with the effect of anticancer drugs on proliferating breast cancer cell lines. Accordingly, for the 31P-MRS experiments, cells were embedded in Matrigel to preserve their proliferation profile and ability to absorb drugs. The MRS studies of untreated cells indicated that the levels of phosphodiesters and uridine diphosphosugar metabolites were significantly higher in estrogen receptor-positive and low metastatic potential cell lines. 31P-MRS observations revealed a correlation between the mode of action of anticancer drugs and the observed changes in cell metabolic profiles. When cells were treated with antimicrotubule drugs (paclitaxel, vincristine, colchicine, nocodazole), but not with methotrexate and doxorubicin, a profound elevation of intracellular glycerophosphorylcholine (GPC) was recorded that was not associated with changes in phospholipid composition of cell membrane. Remarkably, the rate of elevation of intracellular GPC was much faster in cell population synchronized at G2-M compared with the unsynchronized cells. The steady-state level of GPC for paclitaxel-treated cells was reached after approximately 4 h for synchronized cells and after approximately 24 h (approximate duration of one cell cycle) for the unsynchronized ones. These observations may indicate a correlation between microtubule status and cellular phospholipid metabolism. This study demonstrates that 31P-MRS may have diagnostic value for treatment decisions of breast cancer and reveals new aspects of the mechanism of action of antimicrotubule drugs.

Antineoplastic Agents↗

Characterization of two novel sublines established from a human megakaryoblastic leukemia cell line transfected with p210(BCR-ABL).

Disease progression in chronic myelogenous leukemia (CML) is usually accompanied by chromosomal abnormalities such as an additional Ph chromosome, trisomies of chromosome 8 or 19, or i(17) in addition to the standard translocation t(9;22) (q34;q11). However, detailed studies of the various steps involved during this evolution are difficult to perform, thereby making the study of cell lines that contain the transposed genes BCR-ABL, especially those of human origin, an important focus. In this analysis we investigated the human megakaryoblastic cell line MO7e and its subline transfected with BCR-ABL, MO7e/p210. Initial studies demonstrated that the phenotype of the MO7e line was consistent with a megakaryocytic lineage as originally described and was growth factor dependent in liquid culture. The MO7e/p210 subline, however, was growth factor independent and could be further separated into two distinct sublines based on expression of glycophorin A using the monoclonal antibody R10. The subline R10 negative (R10-) was similar to the parent line MO7e but R10 positive (R10+) cells had a distinct erythroid phenotype. In addition, the R10- and R10+ sublines demonstrated strikingly different colony morphology when cultured in semisolid medium. Furthermore, R10+ cells had additional chromosomal abnormalities not detected in the R10- population. These results demonstrate that the insertion of the BCR-ABL in this human leukemia cell line resulted in two distinct subpopulations of cells, each now growth factor independent, but one with a phenotype and karyotype identical to the parent cell line and the other with a different phenotype and additional chromosomal abnormalities. These two subpopulations derived from the MO7e/p210 transfected cell line may prove useful in further understanding the multistep events that occur in the progression of this disease.

Chromosome Aberrations↗

Recent advances in the treatment of acute leukemia: 1999.

This review briefly summarizes literature noteworthy in the field of adult acute leukemia published during 1999. The relationship between specific cytogenetic abnormalities and response to treatment was explored within a clinical framework. In particular, detailed analyses of the abnormalities seen in acute promyelocytic leukemia were examined. Two case reports of special interest were published: one shed light on the role of histone deacetylase inhibitors in combination with all-trans retinoic acid, and the other, on the role of granulocyte colony-stimulating factor in this disease. The clinical activity of arsenic was also reported and its mechanism of action explored. In acute lymphoblastic leukemia, attention was focused on occult translocations, and the importance of minimal residual disease was again emphasized. Lastly, results of early clinical trials using an anti-CD19 antibody were reported, with provocative results.

Acute Disease↗

Psychoanalytic supervision: the intersubjective development.

The author argues that an intersubjective perspective on the analytic process makes the notion of purely didactic supervision, avoiding countertransference issues, untenable and that countertransference is both a clue to the analysand's psychic reality and a factor in its evolution. Supervision is seen as a highly personal learning process for both supervisor and supervisee and its emotional climate as a crucial factor in its evolution into a transitional space, generating new meanings. Supervision is portrayed as the crossroads of a matrix of object relations of three persons, of a complex network of transference/countertransference patterns. The avoidance or denial of the supervisor's subjective role in it, maintaining 'a myth of the supervisory situation', may make supervision stilted or even oppressive and stand in the way of resolving supervisory crises and stalemates. It is argued that several factors contribute to the conflictuality of supervision for all partners (often including the analysand): the continuous process of mutual evaluation, the reciprocal fears of exposing one's weaknesses, the impact of the institute as a setting and the transferences it arouses and the inherent conflicts of loyalty for each participant in the analytic/supervisory triad. The resulting dynamics and relational patterns could become a legitimate and freeing topic in supervisory discourse.

Countertransference↗

Enhancement of 5-fluorouracil anabolism by methotrexate and trimetrexate in two rat solid tumor models, Walker 256 carcinosarcoma and Novikoff hepatoma, as evaluated by 19F-magnetic resonance spectroscopy.

Although 5-fluorouracil (5-FU) is one of the most effective single agents in treating solid tumors, its low effectiveness as a single agent has led to development of a number of modulators intended to enhance its therapeutic effectiveness. Of these, methotrexate (MTX) and trimetrexate (TMTX) have been shown to have synergistic anticancer activity with 5-FU. The effect of these two drugs on the uptake and the intratumoral metabolism of 5-FU was studied in two rat tumor models using 19F-nuclear magnetic resonance spectroscopy: on excised samples of Walker 256 carcinosarcoma and noninvasively (in vivo) in Novikoff hepatoma. In the rats bearing the Walker 256 tumor, a 4-hr pretreatment with MTX showed the maximal increase in the rate of conversion from 5-FU to its fluorinated nucleotides/nucleosides. In the rats bearing the Novikoff hepatoma, both modulators increased the amounts of cyctotoxic anabolites of 5-FU, but at the doses administered, the cumulative amounts of 5-FU anabolites formed after MTX were significantly higher than those formed after TMTX or after saline control. On the other hand, the increase in the levels of the fluorinated nucleotides/nucleosides after TMTX peaked at a later time. The possible significance of these findings is that timing of administration of a modulator is important because it affects both transport and metabolism of 5-FU. The two modulators studied, both antifolates, act differently on transport and on metabolism: MTX affects both, whereas TMTX, at the level studied, appears to affect predominantly the metabolic process. In addition, significant differences exist between tumor models. These data suggest possible mechanisms and processes that should be studied further in humans, using these noninvasive pharmacokinetic imaging methods for monitoring 5-FU targeting and metabolism.

Animals↗

Fibrin microbeads (FMB) as biodegradable carriers for culturing cells and for accelerating wound healing.

We have developed biodegradable fibrin-derived microbeads as potent cell carriers. The fibrin-derived microbeads, 50-200 microm in diameter, were tested for their attachment to a wide range of cell types. Fibrin-derived microbeads were shown to be greatly haptotactic to cells (such as endothelial cells, smooth muscle cells and fibroblasts), which respond to fibrinogen in contrast to keratinocytes and different cell lines derived from leukocytic lineage. The cells on fibrin-derived microbeads could be maintained for more than 10 d and achieved a high density. 31P-nuclear magnetic resonance was employed to monitor phosphate metabolism in cells, with densities on the order of 100 million cells per g of fibrin-derived microbeads. The 31P-nuclear magnetic resonance adenosine triphosphate and phosphocreatine signals, equivalent to the signal obtained with perfused normal skin, indicated that metabolism of cells on fibrin-derived microbeads was responsive to oxygenation and nutrients. Light, fluorescent, and confocal laser microscopy revealed that the porous fibrin-derived microbeads accommodate up to 200-300 cells due to their high surface area which minimized contact inhibition. Cells could degrade the fibrin-derived microbeads and be transferred to seed culture flasks without trypsinization. In a pig skin wound healing model, fibrin-derived microbeads + fibroblasts were transplanted into full thickness punch wounds. This procedure was compared with other treatment modalities, such as the addition of human platelet-derived growth factor BB or fibrin-derived microbeads alone. By the third day after wounding, only the wounds in which fibroblasts on fibrin-derived microbeads were added showed significant formation of granulation tissue. Based on the above, we project many uses of our novel fibrin-derived microbead technology for cell culturing, wound healing and tissue engineering.

Animals↗

Diffusion and perfusion magnetic resonance imaging following closed head injury in rats.

Diffusion-, perfusion-, T1-, and T2-weighted magnetic resonance imaging (MRI) were performed at 1-2 h, 24 h, and 1 week following closed head injury (CHI) in rats, and data was compared with hematoxylin and eosin histology. At 1-2 h, large areas of low perfusion in the damaged hemisphere overestimate the histological damage. In the first 2 h, the histological damage seems to be a superposition of abnormalities in the T1- and diffusion-weighted images. In areas with more than 10% reduction in the apparent diffusion coefficients (ADCs), reduced regional cerebral blood volume (r-CBV) was also observed. The decrease in ADCs and rCBV correlated with r = 0.78. Changes in the MRI parameters revealed the following: (a) Further reduction in ADC occurred from 83+/-15% at 1-2 h after trauma to 69+/-9% at 24 h, and 1 week later a marked elevation in the ADC values is observed. (b) Blood perfusion measurements performed 1-2 h posttrauma revealed a pronounced reduction in r-CBV (53+/-18%) in the damaged hemisphere in all rats. At 24 h postimpact, areas of hyper- and hypoperfusion were observed. One week later, similar perfusion was found in both hemispheres of all rats. (c) T2 hyperintensity at 24 h overestimated the histological damage found at 1 week. At one week following the trauma, the T2 hyperintensity underestimated the histological damage. It is concluded that CHI, which is a heterogeneous insult, should be studied by a combination of MRI techniques. The superposition of the abnormalities seen on T1 and on the diffusion-weighted MR images at early time point represents best the histological damage. Both T2 and rCBV images are less informative in terms of actual histological damage.

Animals↗

Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to generate long-term visual associations.

When monkeys perform a delayed match-to-sample task, some neurons in the anterior inferotemporal cortex show sustained activity following the presentation of specific visual stimuli, typically only those that are shown repeatedly. When sample stimuli are shown in a fixed temporal order, the few images that evoke delay activity in a given neuron are often neighboring stimuli in the sequence, suggesting that this delay activity may be the neural correlate of associative long-term memory. Here we report that stimulus-selective sustained activity is also evident following the presentation of the test stimulus in the same task. We use a neural network model to demonstrate that persistent stimulus-selective activity across the intertrial interval can lead to similar mnemonic representations (distributions of delay activity across the neural population) for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural machinery for generating long-term stimulus-stimulus associations.

Animals↗

Comparative effects of added sodium chloride, ammonium chloride, or potassium bicarbonate in the drinking water of broilers, and feed restriction, on the development of the ascites syndrome.

A hypothesis that the ionic composition of drinking water might affect development of the ascites syndrome in broilers was investigated in two trials. The first trial comprised four groups of 650 male chicks. A control treatment was normal tap water and the other three treatments comprised the addition to the tap water of 1,000 mg/L sodium as NaCl, 5,000 mg/L NH4Cl, or 5,000 mg/L KHCO3, supplied from age 2 to 47 d. At Day 28, equally sized subsets of these groups were moved to individual cages, where they received a severe exposure to ambient cold. The development of the ascites syndrome was monitored by measurements of hematocrit and arterial blood oxygen saturation (PaO2) by oximetry, body weight, and examination of dead birds for cause of death. Mortality from ascites in cold-exposed birds from Days 28 to 47 was 28, 48, 40, and 16% in the tap water, NaCl, NH4Cl, and KHCO3 groups, respectively; only the NaCl mortality was significantly different from the tap water mortality. The KHCO3 treatment increased PaO2 (compared with tap water treatment) at Day 28 by 5.5% and at Day 35 by 10.5%, but not at Day 42. The KHCO3 caused a reduction in body weight, which was 13% less than the tap water group at Day 42, probably due to a chronic toxicity. The second trial specifically examined the same parameters with lower water levels of KHCO3 (3,000 and 1,000 mg/L), in comparison to a 10% feed restriction protocol, in order to clarify whether the increased PaO2 was due to a specific effect of the KHCO3 or was a metabolic manifestation of a reduced growth rate. The 3,000 mg/L KHCO3 treatment had no effect on PaO2, but the 1,000 mg/L treatment augmented PaO2 by 5.3% at Day 35 (but not at Days 28 or 42), without reducing the final body weight. The feed restriction group showed an elevated PaO2 of 5.4% at Day 35 (but not at Days 28 or 42), with no reduction in the final body weight. The inclusion of 1,000 mg/L of KHCO3 into the drinking water of broilers or a temporary 10% feed restriction may be means to augment PaO2.

Ammonium Chloride↗

Homosexuality.

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Female↗

Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia.

BACKGROUND: Most clinical trials for acute leukemia have reported results after 2-3 years of follow-up. Comparisons between the original data and longer-term follow-up data may be of interest, particularly with regard to promising new therapies. METHODS: In 1996, survival data were updated from three prospective, randomized comparisons of idarubicin and daunorubicin that began in 1984 and 1985. These were trials of the Memorial Sloan-Kettering Cancer Center (MSKCC), the U.S. Multicenter Study Group, and the Southeastern Cancer Study Group (SEG). The original results of these trials were reported in 1991 and 1992. RESULTS: The original results of the SEG trial demonstrated no significant difference between idarubicin and daunorubicin. The updated survival analysis showed similar results. The MSKCC trial revealed a significant advantage of idarubicin compared with daunorubicin in both the original and the updated analyses. The U.S. Multicenter trial found a significant difference favoring idarubicin in the original analysis, but the difference was not significant in the updated analysis. CONCLUSIONS: It is essential that the median length of follow-up be clearly stated in any clinical trial. When the results obtained with a particularly promising new drug or procedure are presented early in the course of study (within 1-2 years), the investigators should strongly consider a repeat evaluation after an additional 3-5 years of follow-up.

Acute Disease↗

Diffusion- and T2-weighted MRI of closed-head injury in rats: a time course study and correlation with histology.

Diffusion- and T2-weighted MRI were used to evaluate changes in brain water characteristics following closed-head injury in rats. Images were collected within the first 2 h and at 24 h and 7 days following the traumatic event and then compared with histology. The ratios between the apparent diffusion coefficients (ADCs) of the traumatized tissues and normal brain tissues were significantly different from unity and were found to be 0.79 +/- 0.25 (p < 0.01), 0.49 +/- 0.33 (p < 0.0002), and 3.47 +/- 1.36 (p < 10(-6)) at 1-2 h, 24 h, and 1 week after the trauma, respectively. In severe trauma, areas of hyperintensity which were not apparent on the T2-weighted images could be detected on the diffusion-weighted images within 1-2 h after the trauma. At 24 h following the traumatic event, large areas of hyperintensity are observed in both types of images. One week following the trauma, the ADCs of the traumatized tissues (1.84 +/- 0.69 x 10(-5) cm2/s) are much larger than those of normal brain (0.57 +/- 0.19 x 10(-5) cm2/s) and approach the value of free water. At 7 days, the areas of hyperintensity in the T2-weighted images seem to underestimate the injured areas found by histology. At this time point a good correlation is obtained between the areas of hypointensity observed on the diffusion-weighted images and the infarct areas obtained by histology (r = 0.88).

Animals↗