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Biomedical subjects

E Berman

Publications and source records attributed to E Berman.

At least 127 records · Page 7Linked to original sources

The effect of ciprofloxacin on methicillin-resistant Staphylococcus aureus.

Ciprofloxacin exhibited good in-vitro activity for methicillin-resistant Staphylococcus aureus with a MIC90 of 0.5 mg/l. The postantibiotic effect was 2.16 h. When ciprofloxacin was evaluated in combination studies with an aminoglycoside, none of the strains met the criterion of synergy as defined by FIC or FBC interaction indices of less than or equal to 0.25. However, killing kinetic experiments indicated that the combination of ciprofloxacin was synergistic for two of 12 strains with gentamicin and three of 12 strains with amikacin. Although the inoculum size had no effect on the rate of killing by ciprofloxacin, an increase in turbidity was noted when a high inoculum was tested. This increase in turbidity was due to the swelling of the staphylococci to several times their normal size and the formation of clusters of multicellular, incompletely divided staphylococci. If a high inoculum is used for susceptibility testing, this increase in turbidity could be misinterpreted as bacterial growth and could result in a false report of an elevated MIC.

Anti-Bacterial Agents↗

Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity.

Fludarabine phosphate (9-beta-D-arabinofuranosyl-2-fluoroadenine), a novel purine nucleoside, has demonstrated excellent preclinical antitumor activity and little toxicity in phase I clinical trials. We evaluated the clinical use of fludarabine given as a continuous intravenous (IV) infusion for remission induction in patients with relapsed or refractory leukemia. Thirty infusions were administered to 25 patients. At doses less than or equal to 125 mg/m2/d for five days, only three of 17 patients cleared their bone marrow of leukemic cells, and none achieved complete remission (CR). Nine patients received doses of 150 mg/m2/d for five days or 125 mg/m2/d for seven days. Four of these patients achieved CR (three patients with acute nonlymphoblastic leukemia (ANLL), one patient with acute lymphoblastic leukemia (ALL]. However, severe CNS toxicity was encountered in five patients at the two highest dose levels. Initial symptoms of neurotoxicity were delayed from 21 to 43 days after starting treatment and consisted of optic neuritis, cortical blindness, altered mental status, and generalized seizure. Only one patient regained visual and neurologic function; four other patients experienced progressive neurologic deterioration and died. Clinicopathologic evaluation suggested widespread, severe demyelination as the etiology of these reactions. We conclude that fludarabine is an effective drug for remission induction in acute leukemia. However, doses required to achieve CR are associated with unacceptable CNS toxicity. In view of its potent antileukemic activity, further evaluation of fludarabine at lower doses (less than or equal to 75 mg/m2/d for five days) may be warranted in combination with other chemotherapeutic agents for the treatment of patients with acute leukemia.

Acute Disease↗

Gamma interferon induces colony-forming cells of the human monoblast cell line U937 to respond to inhibition by lactoferrin, transferrin, and acidic isoferritins.

Human gamma interferon (HuIFN gamma) was assessed for its capacities to induce MHC class-II antigens on U937 cells and to induce responsiveness of U937 colony-forming cells (CFC) to the suppressive influences of lactoferrin (LF), transferrin (TF), and acidic isoferritins (AIF). U937 cells grown in suspension culture for many years demonstrated variable percentages of MHC class-II antigen+ cells (6%-42%) as determined by analysis with monoclonal anti-MHC class-II and the FACS IV when checked at different times. The percentage of U937 cells positive for MHC class-II antigens, as well as the density distribution of MHC class-II antigens on these cells, was increased by preincubating the cells for 72 h in the presence of 10(-6) M indomethacin and increasing concentrations of natural HuIFN gamma up to 20-40 U/ml. Colony formation by cells preincubated in control medium plus indomethacin for 72 h was not decreased by treating cells with monoclonal anti-MHC class-II plus complement (C'), high specific activity tritiated thymidine (3HTdr), LF, TF, or AIF. After preincubation of U937 cells with natural HuIFN gamma plus indomethacin in suspension culture for 72 h, colony formation in semisolid medium was reduced 40%-50% by treating the cells with anti-MHC class-II plus C', 3HTdr, LF, TF, or AIF. Colony formation was not reduced further by LF, TF, or AIF, after cells were pretreated with anti-MHC class-II (1:200 dilution) plus C' or 3HTdr. Increasing concentrations of HuIFN gamma up to 20 U/ml increased the percentage of MHC class-II antigen+ U937 CFC as well as the sensitivity of U937 CFC to suppression by LF, TF, and AIF. The inducing activities of natural HuIFN gamma were due to the IFN gamma itself since the inducing activity of natural HuIFN gamma was inactivated by pretreatment with a monoclonal antibody against natural HuIFN gamma. Also the inducing effects were mimicked by recombinant HuIFN gamma. The suppressive effects of LF, TF, and AIF on colony formation were blocked by treating the cells with monoclonal anti-MHC class-II (1:50 dilution, but not 1:200 dilution) in the absence of C'. The suppressive effect of TF only was blocked by pretreating cells with a monoclonal antibody against the TF receptor. U937 cells can be used as a model to study the regulatory mechanisms of action of HuIFN gamma, LF, TF, and AIF.

Cell Line↗

Regulation of the proliferation of the established human monoblast cell line, U937, at the single cell level.

U937 cells, an established monoblast or early monocyte cell line, were assessed as a model in vitro for the regulation of cell growth at the single cell level. Colony formation by 500 U937 cells, preinduced to a state of responsiveness to lactoferrin (LF) by incubation with human gamma interferon was suppressed by LF. LF-suppressed colony formation was restored by partially purified growth activity derived from U937 cells. The release of growth factor(s) into conditioned medium required concentrations of greater than 500 U937 cells/ml and this release was dependent on the length of time that the cells conditioned the culture medium. This release was suppressed by LF. U937 cells were induced to a state of responsiveness to LF by incubation with human gamma interferon, washed, and plated as a single cell per well. Individual cells formed colonies with a cloning efficiency of approximately 50% which equalled the cloning efficiency detected when 500 U937 cells/ml were plated, suggesting that U937 colony forming cells might contain endogenous growth activity. Detection of these endogenous growth activities required the use of LF. The cloning efficiency of individually isolated U937 cells was suppressed by approximately 50% with LF, similar to the LF suppression of colony formation when 500 cells/ml were plated. That the LF-suppressed U937 colony forming cells required growth activity was suggested as the cloning efficiency of LF-suppressed individually isolated U937 colony forming cells was restored by partially purified U937 growth activity. Partially purified U937 growth activity did not stimulate, enhance, or inhibit colony formation by normal human bone marrow granulocyte-macrophage progenitors. U937 cells can thus serve as a useful model for the study of growth regulation at the level of a single cell.

Cell Cycle↗

Slower B16 melanoma growth but greater pulmonary colonization in calorie-restricted mice.

Recently, it has been demonstrated that the immune function is preserved longer and spontaneous tumors occur less frequently in calorie-restricted (but not malnourished) mice. In the present report the effect of similar dietary manipulation on tumor growth, metastases, and survival was studied. C57BL/6 mice were fed regular laboratory diets, either restricted in calories or not restricted, and later inoculated with B16 melanoma sc, iv, or ip. Local tumor growth was found to be slower; however, survival after ip injection was no different, and the number of pulmonary metastatic colonies after iv injection was greater for the underfed mice. In this weakly immunogenic tumor model, factors in addition to immunity influenced tumor growth and were altered by calorie restriction.

Animals↗

Activities derived from established human myeloid cell lines reverse the suppression of cell line colony formation by lactoferrin and transferrin.

Myeloid cell lines were evaluated for the release of substances needed for colony formation by their own colony-forming cells (CFC) and by other myeloid cell lines. Dialyzed U937 conditioned medium (CM) had no effect on the cloning efficiency of U937 cells, whether or not U937 CFC had been induced for MHC class-II antigens by preincubation of these cells for 72 h with indomethacin and human gamma interferon (HuIFN gamma). Dialyzed U937 CM, however, restored colony formation of HuIFN gamma-induced U937 cells suppressed by lactoferrin (LF) or transferrin (TF). Dialyzed U937 CM did not restore colony formation of U937 cells suppressed by acidic isoferritins (AIF) or prostaglandin E2 (PGE2). Detection of the growth-restoring effects of U937 CM required that U937 CM be prepared in the presence of indomethacin or that the CM be dialyzed to remove inhibitors of U937 colony formation. Dialyzed U937 CM did not inactivate LF. Dialyzed U937 CM did not stimulate or enhance colony formation of normal human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), or multipotential (CFU-GEMM) progenitor cells, but did contain potent inhibitory activity against these progenitor cells. HL-60, EM2, EM3, and K562 cells were also evaluated. HL-60-, EM3-, and K562-CFC that were not preincubated with HuIFN gamma did not express MHC class-II antigens, and colony formation by these cells was not influenced by LF, TF, or AIF. Noninduced EM2-CFC constitutively expressed MHC class-II antigens, and colony formation by these cells was suppressed by LF, TF, and AIF. After induction of MHC class-II antigens on HL-60- and EM3-CFC by HuIFN gamma, colony formation by these cells was suppressed by LF, TF, and AIF. Colony formation by HuIFN gamma-induced EM2 cells was more responsive to inhibition by LF, TF, and AIF than was colony formation by noninduced EM2 cells. K562 cells were not induced into a responsive state to LF, TF, or AIF by HuIFN gamma. Dialyzed CM from HL-60, EM2, and EM3 cells contained activities that restored colony formation by their own LF-suppressed CFC. The activities present in dialyzed CM from U937, HL-60, EM2, and EM3 cells may be similar since they could each restore LF-suppressed colony formation of U937, HL-60, EM2, or EM3 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Line↗

Hairy cell leukemia: a model for studying the B cell family of diseases.

Nineteen patients with hairy cell leukemia (HCL) were treated with recombinant interferon alpha-2a/Roche (Roferon) given by daily intramuscular injection of 3 X 10(6) for 6 months followed by three injections per week. Pretreatment and follow-up marker studies were performed on 14 of 16 evaluable patients. Peripheral blood and bone marrow mononuclear cells were analyzed by flow cytometry for reactivity with monoclonal antibodies to B cell associated surface antigens (B1, B2, B4, BL1, BL3, and BL7) and two hairy cell (HC) antibodies, anti-HCL1 and HCL3. B cell monoclonality was determined by clonal excess calculation of immunoglobulin light chains. Right angle scatter analysis showed that HCs are scattered between lymphocytes and monocytes. Nine of the 14 patients achieved a partial remission, three patients achieved a minimal response, and two patients failed therapy. Phenotypically, ten patients had kappa clonal excess and four had lambda clonal excess. These cases expressed a mature B cell phenotype, ie, BL1-, BL7+, BL3+, B1+, B2-, B4+, HCL1+, HCL3+. All 12 responders became nonreactive with monoclonal antibodies 4 to 8 weeks after therapy; in five of these cases, reactivity with monoclonal antibodies was again detected at the time of maximum clinical response (2 to 8 months), without affecting clinical response status. In four of 12 responders, clonal excess disappeared 4 to 8 weeks after therapy; in three more patients, clonal excess disappeared at the time of maximum clinical response (2 to 4 months); in three patients, clonal excess disappeared from the peripheral blood, but not from the bone marrow at the time of maximum clinical response (3 to 5 months); two patients had persistent clonal excess. In the two failures, there was persistence of clonal excess and reactivity with monoclonal antibodies. This study shows that phenotypic analysis is a sensitive and objective method of assessing response of HCL to alpha interferon. This system could be used as a model for the study of other B cell neoplasms.

Adult↗

NMR studies of chromomycin A3 interaction with DNA.

The binding of chromomycin A3 to calf thymus DNA and poly(dG-dC) has been studied by 13C and 1H NMR with emphasis on the mode of binding, the role of Mg2+, and pH effects. The most prominent changes in the DNA base pair 13C NMR resonances upon complexation with chromomycin were observed for G and C bases, consistent with the G-C preference exhibited by this compound. Comparison of the 13C spectrum of DNA-bound chromomycin A3 with that of DNA-bound actinomycin D, a known intercalator, showed many similarities in the base pair resonances. This suggested the possibility that chromomycin A3 binds via an intercalative mechanism. 1H NMR studies in the imino proton, low-field region of the spectrum provided additional evidence in support of this binding mode. In the low-field spectrum of chromomycin A3 bound to calf thymus DNA, a small shoulder was observed on the upfield side of the G-C imino proton peak. Similarly, in the chromomycin A3 complex with poly(dG-dC), a well-resolved peak was found upfield from the G-C imino proton peak. These results are expected for ligands that bind by intercalation. Furthermore, in both the calf thymus and poly(dG-dC) drug complexes (in the presence of Mg2+) a broad peak was also present downfield (approximately 16 ppm from TSP) from the DNA imino protons. This was attributed to the C-9 phenolic hydroxyl proton on the chromomycin chromophore. Visible absorbance spectra at different pH values showed that the role of Mg2+ in the binding of chromomycin A3 to DNA is more than simple neutralization of the drug's anionic change.

Animals↗

Binding of [1-13C]galactose-labeled N-acetyllactosamine to Erythrina cristagalli agglutinin as studied by 13C-NMR.

The equilibrium binding kinetics of enzymatically prepared N-acetyllactosamine to the lectin from Erythrina cristagalli have been investigated by 13C-NMR spectroscopy. Under the experimental conditions used, NMR signals in the spectrum, corresponding to both the free and bound disaccharide species, were observed for the first time. This has permitted the simultaneous determinations of the equilibrium binding constant and the number of binding sites per lectin molecule. At the relatively high lectin concentrations used (0.3-0.87 mM), the association constants determined at 31 degrees C (approximately 6 X 10(3) M-1) are typically lower then those obtained by other methods employing much lower lectin concentrations. Extrapolation of the experimentally observed values to infinite dilution gave a better fit of the data (Ka approximately 1.4 X 10(4) M-1) with the binding constant determined by other methods (K approximately 1.1 X 10(4) M-1). The sugar residence time on the lectin (approximately 0.2 s) was determined directly from the signal's line-width using total line-shape analysis. Similar NMR experiments may permit an analysis of the interaction of the lectin with glycoproteins and cells labelled with 13C-enriched galactose residues. Moreover, information on lectin-galactose interactions at the binding site may be obtained by using galactose labeled at various carbons.

Amino Sugars↗

Elimination kinetics of blood lead in workers with chronic lead intoxication.

Blood lead elimination half-lives were determined for 65 patients with occupational chronic lead intoxication who were removed from exposure, treated with intravenous EDTA, and followed for periods of up to 2,419 days. The median overall blood lead elimination half-life was 619 days in patients with normal renal function and 1,907 days in patients with renal impairment. Slow-phase elimination half-lives in patients followed for longer than 5 years ranged from 1,658 to 7,189 days. Blood lead concentrations declined during periods of chelation with a mean half-life of 7 days and rebounded to near prechelation concentrations following termination of chelation with a mean doubling time of 27 days. The overall blood lead elimination half-life was positively associated with length of follow-up (p less than 0.001), age (p = 0.04), and duration of exposure (p = 0.02), but was not associated with the initial blood lead concentration following cessation of exposure or the total amount of EDTA received.

Adult↗

Lethality in mice and rats exposed to 2450 MHz circularly polarized microwaves as a function of exposure duration and environmental factors.

Adult male CD-1 mice and CD rats were used to determine LD50/24 h lethality rates from exposure to 2450-MHz circularly polarized microwaves. Groups of 16 mice or six rats were exposed in each of 32 combinations of nominal power density (10, 25, 50 or 75 mW cm-2), exposure duration (1 or 4 h), and environmental temperature (20 or 30 degrees C) and relative humidity (35 or 80%). An analysis of variance probit model was used to determine the influence each variable had on the probability of death. Significant factors in lethality were nominal power density, exposure duration and environmental temperature, but not environmental relative humidity. The estimated power density (mW cm-2) required to kill 50% of the animals in 24 h is halved when the environmental temperature is increased from 20 to 30 degrees C. Similarly, only 20-25% of the power density is required when the exposure duration is increased from 1 to 4 h. The use of nominal power density as a predictor of the probability of death was more efficient than specific absorption rate estimated experimentally by twin-well calorimetry. The exposure of one mouse at a time, instead of 16, did not alter the predicted death rate.

Animals↗

13-cis-Retinoic acid does not increase the true remission rate and the duration of true remission (induced by cytotoxic chemotherapy) in patients with chronic phase chronic myelogenous leukemia.

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Adolescent↗

Description and implications for analysis of brain growth in suckling mice.

The growth pattern of the brains of normal CD-1 mice was studied from day 1 through day 21 after birth. The main purpose of the study was to decide on suitable methods of statistical analysis of these kinds of data including whether to analyze brain weight or the brain-to-body weight ratio. A secondary purpose, which aided the main purpose, was to find functions that describe the relationships between growth parameters. Linear-linear segmented polynomials were found to describe well the relationships between brain weight and body weight, brain weight and age, brain-to-body weight ratio and body weight and brain-to-body weight ratio and age. The analyses indicated that brain weight alone is the preferred variable to analyze. Regression analysis of brain weight with sex and up to the first three powers of body weight and age as independent variables would be a suitable method of analysis. Litter size per se had no effect on brain weight.

Aging↗

Structural and conformational analysis of sialyloligosaccharides using carbon-13 nuclear magnetic resonance spectroscopy.

The analysis of the carbon-13 chemical shift data of NeuAc alpha (2----3)Gal beta (1----4)Glc and NeuAc alpha (2----3)Gla beta-(1----4)GlcNAc and their respective NeuAc alpha (2----6) isomers established distinct and different conformations of the sialic acid residue, depending on the type of anomeric linkage [alpha-(2----3) vs. alpha (2----6)]. Interactions between the NeuAc residue and the Glc or GlcNAc residue are particularly strong in the case of the alpha (2----6) isomers. Similar effects are observed for the larger oligosaccharides [II3(NeuAc)2Lac and IV6NeuAcLcOse4] and even in intact glycoproteins and polysaccharides. It is proposed that the NeuAc alpha (2----3) isomers assume an extended conformation with the sialic residue at the end (terminal) of the oligosaccharide chain or branch. The NeuAc alpha (2----6) isomers are assumed to be folded back toward the inner core sugar residues.

Animals↗

Bone lesions in hairy cell leukemia. A case report and response of bone pains to steroids.

An unusual case of hairy cell leukemia is reported. The patient experienced severe bone pains at the sites of the bone lesions caused by infiltration by hairy cells documented histologically. The pains were resistant to various analgesics. Administration of corticosteroids resulted in prompt, full, and sustained response despite the persistence of bone lesions radiographically.

Biopsy↗

Growth and development of mice offspring after irradiation in utero with 2,450-MHz microwaves.

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm2 (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, 5, 10, 12, 15, and 17 of age. The tests used to determine differences in developmental age in the two treatment groups were body weight, urine concentrating ability, brain weight, tolerance to ouabain, and bone lengths. Fifteen sham-irradiated and 26 RF-irradiated litters, normalized to eight pups/litter, were used in this study. Mean body weight of the microwave-irradiated offspring were significantly (p = .0003) decreased only on day 1 of age. Brain weight on days 10, 12, and 17 were significantly lower in microwave-irradiated pups (p = .01). There were no significant differences in the two groups in urine concentrating ability on day 5, ouabain tolerance on day 15, or bone length on days 5, 10, 12, and 17. It is concluded that there is a persistent delay in postnatal development of the brain after RF irradiation with 16.5 W/kg during gestation.

Animals↗