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Biomedical subjects

E Berman

Publications and source records attributed to E Berman.

At least 37 records · Page 2Linked to original sources

In vivo cyclic AMP responses in rat brain are not modified by chronic electroconvulsive shock.

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on the cyclic AMP (cAMP) responses to noradrenaline (NA) and to forskolin in the cortex of freely-moving conscious rats. Microdialysis probes were inserted on the final day of ECS administration, and cAMP responses measured the following day. Chronic ECS did not modify the responses to either NA or forskolin. These results differ markedly from those previously obtained with incubated slices of rat brain. It is concluded that care is needed in interpreting results obtained by either ex vivo or in vitro methods.

Adrenergic alpha-Agonists↗

Parathyroid hormone gene expression in Hyp mice fed a low-phosphate diet.

BACKGROUND: The murine analogue of X-linked hypophosphataemia is the Hyp mouse; it has chronic phosphate depletion from an inherited defect of renal tubular reabsorption. Phosphate directly regulates the parathyroid (PT) in normal rats and it is of interest whether this regulation is intact in Hyp mice. METHODS: Hyp mice were fed either a low-phosphate diet or control diet and PTH mRNA levels were measured. In addition changes in NMR-visible kidney and muscle intracellular phosphate potentials in normal and Hyp mice were determined. Mice were maintained on a low-phosphate (0.02%) or normal-phosphate (0.6%) diet for 24 and 72 h. RESULTS: On the normal diet, Hyp mice had hypophosphataemia, normocalcaemia, and normal PTH mRNA levels. Phosphate deprivation for 72 h led to a profound fall in plasma phosphate, a slight but significant rise in plasma calcium, and a dramatic decrease in PTH mRNA, similar to that of normal mice fed this diet. Changes in kidney and muscle intracellular phosphate measured by NMR spectroscopy were not affected by diet or genotype. CONCLUSION: Dietary phosphate deprivation decreased Hyp mice PTH mRNA levels and caused no change in intracellular phosphate potentials. Therefore Hyp mice parathyroids' adapt appropriately to phosphate deprivation albeit at a lower threshold compared to normal mice.

Animals↗

Recent advances in the treatment of acute leukemia.

This review briefly summarizes literature considered noteworthy in the field of adult acute leukemia published during 1996. Does intensity remains a controversial issue in both acute myelogenous and lymphoblastic leukemia. The most convincing data showing efficacy of high dose fractionated chemotherapy was presented in patients with Burkitt's lymphoma/leukemia; the remainder of clinical studies failed to show a definitive advantage to high-dose therapy. Numerous studies addressed the role of the multidrug resistant phenotype and, at least in adult disease, demonstrated that the presence of this particular phenotype was a poor prognostic indicator. In the pediatric population, the significance of multidrug resistance expression appeared less clear. Discrepancies between protein expression and function were also evaluated in clinical samples and outcomes reported in large clinical series. Among the most interesting scientific investigations were those focused on the molecular mechanisms involved in the specific translocations t(15;17) and t(8;21) in acute myelogenous leukemia and t(12;21) in acute lymphoblastic leukemia. The genes PML and AML1, and ETO were examined in normal hematopoietic progenitors and their fusions proteins, PML/RAR alpha and AML1/ETO, measured in patients in clinical remission, and important data were presented concerning these proteins and measurement of minimal residual disease. Provocative data were also presented suggesting that retinoic acid may induce synthesis of a protein that selectively degrades PML/RAR alpha, and that interferons may regulate PML/RAR alpha expression.

Acute Disease↗

Relational psychoanalysis: a historical background.

The author hopes Relational Psychoanalysis, as a broad emphasis on Self and Other, will not develop into another constraining and dogmatic school. In studying its sources I wish to maintain a dialectical view, and avoid ancestor worship. For me, its roots can be found both in the inner contradictions of theorists, such as Freud and Klein, and in the intense and generative dyads they created, particularly Freud-Ferenczi and Klein-Winnicott, where the defiance of the older colleague's authority led the younger one toward better understanding of relational dynamics. While both Fairbairn and Sullivan failed to draw full clinical conclusions from their innovative theoretical models, their work-as well as the contributions of Balint, Guntrip, Racker, Kohut and others, and the growing dissatisfaction with the traditional drive-defense model-helped Greenberg and Mitchell formulate in the 1980s their new relational integration. These ideas are most fully expressed in the Relational Track of NYU's postdoctoral psychoanalytic program, and in the journal Psychoanalytic Dialogues. Among major issues debated by relational theorists are motivation (wish/need/drive), knowledge and truth in relationships (social constructivism), relational developmental models, the nature of intersubjectivity, the significance of feminism and postmodernism for psychoanalysis, and the implications of a relational approach for technique and for training.

Europe↗

Hitchcock's "Vertigo": the collapse of a rescue fantasy.

The author presents an interpretation of Hitchcock's 'Vertigo', focusing on the way in which its protagonist's drama resonates with the analyst's struggle with deep unconscious identifications, with the impossibility of maintaining detached objectivity or guaranteeing one's role as a reparative good object and with the dangers of grandiosity, omniscience and illusory control. The protagonist's 'countertransference love' crystallises around a rescue fantasy in which he is Orpheus striving to bring Eurydice back from Hades, or a Knight determined to behead an obscure Dragon endangering Beauty. Initially these key roles are sharply differentiated, through splitting and disavowal, which deprive the participants of their conflictual three-dimensionality. Eventually, however, the valiant Knight turns out to be as helpless and lonely as his Beauty, and in the final scene as ruthless and lethal as the Dragon. This interpretation is compared to numerous other views of the film offered in the literature. The survey and comparison of the various views leads to fundamental issues in the psychoanalytic study of art. Interpretations can be seen as unavoidably coloured by the (counter)transference of viewers. It is suggested that a film has no hidden true meaning, and a new individual significance emerges in the transitional space opened up by each viewer's encounter with the emotional universe of the film. A defensive emphasis on the pathology of artists and their work may alienate us from art, and blind us to ways in which we could learn from it personally and professionally.

Drama↗

A 31P NMR study of preconditioned isolated perfused rat heart exposed to intermittent ischemia.

Exposure to a short ischemic period (ischemic preconditioning, IP) will protect the heart from damage following a subsequent longer ischemic episode. The aim of the study was to test whether IP is cardioprotective in the setting of repeated ischemia-reperfusion cycles. Thus, Langendorff-perfused hearts, exposed to IP, were subjected to three consecutive ischemia-reperfusion (10/15 min) cycles. Myocardial energetics, manifested by 31P NMR spectroscopy, was correlated with hemodynamics. ATP recovery was significantly higher for the IP group compared with control (P < 0.02) during reperfusions. However, there was no significant difference in ATP recovery during the three ischemic intervals. The supernormal recovery of phosphocreatine recorded during reperfusion was lower for the IP group (approximately 120%) compared with control (approximately 135%, P < 0.065). Better recovery of the left ventricular-developed pressure was noted during reperfusions for the IP group and became significant only during the last reperfusion (86% versus 68%, P < 0.025). In conclusion, the above results support prolonged IP cardioprotection.

Adenosine Triphosphate↗

Acute renal failure associated with the retinoic acid syndrome in acute promyelocytic leukemia.

All-trans-retinoic acid is an effective agent to induce remission in patients with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this drug exerts its effect by inducing differentiation of immature leukemic cells. A distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight gain, and organ failure (the "retinoic acid syndrome") can occur during treatment with this drug. Postmortem studies have shown extensive organ infiltration by leukemic cells, and the early administration of corticosteroids can result in prompt resolution of symptoms. We describe a patient with APL in whom acute renal failure developed during treatment with all-trans-retinoic acid. Transient renal enlargement during a period of leukocytosis and a beneficial response to treatment with dexamethasone suggest that renal failure in this patient was probably related to the retinoic acid syndrome.

Acute Kidney Injury↗

Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone.

PURPOSE: To evaluate the efficacy and safety of a new induction regimen for adult acute lymphoblastic leukemia (ALL) that does not contain vincristine or corticosteroids. PATIENTS AND METHODS: Thirty-seven adult patients with newly diagnosed ALL and lymphoblastic lymphoma were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission (CR) in an attempt to increase long-term disease-free survival. The induction regimen was cytarabine (Ara-C) 3 g/m2/d for 5 days and mitoxantrone 80 mg/m2 as a single dose on day 3. Granulocyte colony-stimulating factor (G-CSF) 200 micrograms/ m2/d beginning on day 7 was used to promote early myeloid recovery. RESULTS: There were 31 CRs (84%). Median time to CR was 34 days, median hospital stay was 28 days, and the median number of days with a neutrophil count less than 500/microL was 18. There were three patients with resistant disease who experienced treatment failure and three early deaths from sepsis. Four patients with Philadelphia chromosome-positive (Ph+) ALL achieved hematologic and cytogenetic CRs. CONCLUSION: This dose-intense induction regimen produced a high incidence of CRs with acceptable toxicity without the use of vincristine or corticosteroids. Comparisons with our prior vincristine/prednisone-based induction regimen (the L-20 protocol) suggest that patients treated on the current study were more likely to achieve a CR and that they achieved this remission earlier than patients treated with a traditional four-drug (vincristine, prednisone, doxorubicin, and cyclophosphamide) induction regimen.

Adolescent↗

Assessing the efficacy of three dentifrices in the treatment of dentinal hypersensitivity.

A multicenter clinical trial conducted by the authors compared the desensitizing efficacy of a new 5 percent potassium nitrate: 0.243 percent sodium fluoride dentifrice along with two clinically proven, commercially available desensitizing dentifrices to a placebo dentifrice. Sensitivity to cold air and tactile stimulation, along with patients' subjective assessments, were evaluated to assess the dentinal desensitizing efficacy of the test dentifrices. Results demonstrated that after four weeks, participants who used the new dentifrice formulation experienced significant decreases in dentinal sensitivity compared to the placebo group for all measured indexes.

Adult↗

Granulocyte colony-stimulating factor following chemotherapy in elderly patients with newly diagnosed acute myelogenous leukemia.

Given the high treatment-related mortality in elderly patients with acute myelogenous leukemia (AML), we undertook a study using granulocyte colony-stimulating factor (G-CSF) following chemotherapy in an effort to ameliorate toxicity. Patients ( > 60 years) received induction with idarubicin 12 mg/m2/day x 3 and cytosine arabinoside (Ara-C) 200 mg/m2/day x 5. A second course of chemotherapy consisting of mitoxantrone 12mg/m2/day x 3, etoposide (VP-16) 150 mg/m2/day x 3 and Ara-C 200 mg/m2/day x 4 was given approximately 1 month after achieving a complete remission (CR) or immediately if patients failed the first induction. Twenty-four hours following completion of the chemotherapy, G-CSF (10 micrograms/kg/day continuous i.v. infusion) was started. A historical control group of 28 patients treated without G-CSF was used for comparison. Twenty-six patients were evaluable for response. Following induction, the recovery of neutrophils to greater than 500/microliters and 1000/microliters was more raped in the responders who received G-CSF compared to historical controls (median 13 vs 17 days, P = 0.008; 14 vs 19 days, P = 0.005). The toxic death rate of 8% in the study group was significantly lower than the 32% mortality observed in the historical controls (P = 0.04). There was no difference in supportive care requirements or infectious complications. The complete remission (CR) rate was 58% in the entire study group with 71% of de novo AML patients achieving CR. Disease-free survival and overall survival were comparable between the study and historical control groups. These results indicate that G-CSF benefits elderly patients after intensive chemotherapy for AML by decreasing the duration of neutropenia. The reduced neutropenic period may have contributed to the small number of early toxic deaths.

Aged↗

c-kit ligand stimulates tyrosine phosphorylation of a similar pattern of phosphotyrosyl proteins in primary primitive normal hematopoietic progenitors that are constitutively phosphorylated in comparable primitive progenitors in chronic phase chronic myelogenous leukemia.

Characteristic of Philadelphia (Ph)+ chronic myelogenous leukemia (CML) is the presence of the chimeric BCR/ABL (p210) protein possessing elevated protein tyrosine kinase activity relative to the normal c-abl tyrosine kinase. Our previous studies demonstrated subtle differences in the growth, phenotypic and morphologic characteristics of the most primitive subpopulations of primary lin-Ph+ chronic phase CML blasts and comparable primary lin- normal blasts. Recently, in comparing proteins phosphorylated on tyrosine in these cell populations, we reported a prominent 62 kDa phosphotyrosyl (P-tyr) protein constitutively present in primary primitive lin- CML chronic phase blasts which was virtually undetectable in primary primitive lin- normal blasts. In the present studies, we demonstrate that this P-tyr p62 from primary primitive lin- chronic phase CML blasts co-immunoprecipitates with ras-GAP. Furthermore, in addition to the p210 protein, we show in whole cell lysates the presence of other clearly consistent but less prominent P-tyr proteins with molecular weights of approximately 155, 140, 110, 55 and 45 kDa as well as more minor P-tyr proteins of approximately 190, 85, 52, 42 and 39 kDa constitutively present in primary primitive lin- chronic phase CML blasts. In analyzing proteins tyrosine phosphorylated in primary primitive lin- normal blasts in response to various hematopoietic growth factors, we found a striking similarity in the phosphorylation of four major (approximately 140, 110, 62 and 56 kDa) and three minor (approximately 51, 45 and 42 kDa) P-tyr proteins after stimulation with c-kit ligand and the P-tyr proteins constitutively phosphorylated in primary primitive lin- chronic phase CML blasts. Other growth factors tested (ie GM-CSF, G-CSF, IL-3, FLT3 ligand and EPO) were much less active or stimulated phosphorylation of other proteins. It is provocative that at least seven proteins rapidly and transiently phosphorylated on tyrosine in the c-kit ligand signal transduction pathway in lin- normal blasts may be constitutive substrates for the p210 activated tyrosine kinase in comparable lin- chronic phase CML blasts. In addition, it is intriguing that some of the biological effects on hematopoietic progenitors attributed to the c-kit ligand may be similar to some of the observed biological consequences of the p210 protein, including survival and expansion of a more mature stem cell population, probably at the time of lineage commitment rather than at the level of the earliest self-renewing stem cell.

Cell Lineage↗

An early transient increase of intracellular Na+ may be one of the first components of the mitogenic signal. Direct detection by 23Na-NMR spectroscopy in quiescent 3T3 mouse fibroblasts stimulated by growth factors.

23Na-NMR spectroscopy was designed to allow for continuous recording of intracellular Na+ in 3T3 fibroblasts stimulated by serum growth-factors in the presence of ion transport inhibitors. The metabolic state of cells at rest and following stimulation was monitored by 31P-NMR spectra of ATP and related high-energy phosphates. The study demonstrates that early activation of ion transporters by addition of serum is marked by the appearance of transient increase of the intracellular Na+, beginning 3 min after addition of serum to quiescent culture and lasting approx. 20 min. The initial rise in cellular Na+ results from an increased activity of the bumetanide-sensitive Na+/K+/Cl- cotransport and of the amiloride-sensitive Na+/H+ antiport. It is suppressed by any one of these inhibitors. Subsequent activation of the ouabain-sensitive Na+/K(+)-ATPase results in an increased Na+ efflux, leading to a return of intracellular Na+ to its initial baseline. Previous work had shown that the early activation of bumetanide-sensitive and amiloride sensitive ion-transporters by growth-factors was essential for induction of cell division, at least in some cell types. Preventing ion activation by adding ion-transport inhibitors lead to the inhibition of DNA synthesis 18 h later. This process was reversible upon elimination of these inhibitors. Even though alternative non-specific effects of these inhibitors cannot be ruled out, the observed transient peak in intracellular Na+ may be one of the earliest components of the mitogenic signal. On the basis of previous works, its effect seems to be related to the activation of Ca(2+)-dependent and cyclic AMP second messenger pathways. The different mechanisms whereby the activated Na+/K+/Cl- cotransport and the Na+/H+ antiport contribute to this signal need to be further investigated.

3T3 Cells↗

Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations.

Although dihydrofolate reductase (DHFR) gene amplification is a common mechanism of resistance to methotrexate (MTX) in tumor cell lines, with the exception of a few case reports, the incidence of this phenomenon as a mechanism of MTX resistance in the clinic has not been reported. We studied 38 untreated patients and 29 patients in relapse with acute lymphoblastic leukemia (ALL) for gene amplification and p53 gene mutations. Three patients were studied both at diagnosis and at each of two relapses after treatment with MTX. Nine of 29 relapsed patients (31%) had low-level DHFR gene amplification (two to four gene copies) associated with increased levels of DHFR mRNA and enzyme activity. Of significance was a correlation of gene amplification with p53 mutations in seven of nine relapsed patients (P < .001). Low-level DHFR gene amplification may be an important cause of MTX resistance in ALL and strengthens the concept that mutations in the p53 gene may lead to gene amplification as a consequence of defective cell cycle control.

Adolescent↗

Assessment of proton magnetic resonance spectroscopy of blood serum as a diagnostic tool in bone marrow transplantation.

The use of proton high-resolution magnetic resonance spectroscopy (MRS) allows the rapid detection and quantitation of modification in the blood serum metabolic profiles in haematooncological patients. This study examines the feasibility of using proton MRS as a diagnostic tool in predicting the outcome of bone marrow transplantation (BMT) at the earliest possible date. Proton spectra of serum samples from 18 BMT patients (11 autologous-BMT and seven allogeneic-BMT), six hematooncological patients that did not undergo BMT and six normal individuals were recorded at 400 MHz. A longitudinal MRS study was carried for these groups and the data were evaluated for statistical significance. It was determined that the MRS results, taken at different time points before and after the BMT treatment, are statistically significant. However, no significant difference was observed in the MRS parameters between the transplanted patients and the control patients. We could not obtain significant correlation between the MRS results and the immunoglobulin level, engraftment parameters or the age, sex, stage of basic disease, conditioning protocols, transplant type, post transplant complications (including death) and outcome.

Adolescent↗

A multidisciplinary approach to toxicological screening: I. Systemic toxicity.

The toxicity of 10 chemicals, including pesticides (carbaryl, chlordane, heptachlor, and triadimefon), solvents (carbon tetrachloride, dichloromethane, tetrachloroethylene, and trichloroethylene), and industrial chemicals [diethylhexylphthalate (DEHP) and phenol] was examined in the liver, kidneys, spleen, thymus, and adrenals of female F344 rats after 1 or 14 d of oral dosing. For each chemical, 4 doses were based on fractions of the acute LD50, which was estimated using an abbreviated (up-and-down) method. A multivariate analysis (MANOVA) was conducted for each organ using selected measures of toxicity. A post hoc contrast analysis was also conducted for significant MANOVA results in order to determine effective and ineffective doses. A single dose of heptachlor resulted in necrotic lymphocytes in the spleen and thymus at doses > or = 23 mg/kg. Triadimefon altered liver and spleen weights; this effect has not been described previously. Dichloromethane (> or = 337 mg/kg/d for 14 d) increased the incidence of necrosis of individual centrilobular hepatocytes. Trichloroethylene-induced hepatotoxicity was obtained at doses an order of magnitude lower than those reported in the literature. Acute DEHP (150 mg/kg) increased mitotic figures in hepatocytes, which were replaced by hepatocellular cytomegaly after 14 d of dosing at the same level. Following phenol exposure, there was an increased incidence in hepatocellular necrosis at 1 d, and an increased incidence of kidney lesions at 1 and 14 d; these findings were considered to be the result of vascular stasis. Overall, the algorithm used to select doses was effective for both 1- or 14-d dosing regimens. For all chemicals except carbon tetrachloride, the lowest effective dose for systemic toxicity was within the range of 3-56% of the LD50 for acute dosing, and 1-30% of the LD50 for repeated administration.

Administration, Oral↗

A multidisciplinary approach to toxicological screening: IV. Comparison of results.

Toxicity data collected under standardized test conditions may be of the utmost importance in health risk assessment, in which human exposure limits are often derived from laboratory experiments. A standardized approach to data collection is also important for evaluating the sensitivity and specificity of test methods used to determine toxic potential. Several experiments were undertaken to determine the effects of chemical exposures using a multidisciplinary screening battery, which included tests for systemic, neurological and developmental toxicity. The effects of 1- and 14-d exposures to 10 chemicals on systemic and neurological indices of toxicity were determined in female F344 rats using standardized test batteries. Parallel experiments determined chemical effects on prenatal and postnatal development following exposure of the dams for 14 d. The chemicals included four pesticides (carbaryl, triadimefon, chlordane, and heptachlor), four solvents (trichloroethylene, tetrachloroethylene, carbon tetrachloride, and dichloromethane), and two industrial compounds (phenol and diethylhexyl phthalate). The results showed that the chemicals produced markedly different qualitative patterns of effect on systemic, neurological, and developmental indices of toxicity. Differences in the pattern of systemic and neurological effects were also obtained that depended on dosing duration. Quantitative analyses indicated that the highest ineffective dose as well as the lowest effective dose could vary by as much as two orders of magnitude across the different indices of toxicity. These results clearly show that a test battery focused on a single endpoint of toxicity cannot be used to accurately predict either qualitatively or quantitatively a chemical's systemic, neurological, and developmental toxicity profile.

Analysis of Variance↗