Schafer's contribution: comments on its continuity and development.
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Countertransference↗
Biomedical subjects
E Berman
Publications and source records attributed to E Berman.
13C-NMR study of the binding of [1-13C]galactose-labelled N-acetyllactosamine and [1-13C]galactose-enriched hen ovalbumin to soybean agglutinin.
The binding of the tide compounds to soybean agglutinin was investigated using 13C-NMR spectroscopy. The equilibrium constant for the binding of N-acetyllactosamine was found to be smaller than that obtained for the binding of ovalbumin (1.1 X 10(3) vs. 7.4 X 10(3) M-1). Only two binding sites per lectin tetramer were determined for the binding of ovalbumin, which is half the number of binding sites reported for the binding of small ligands to the lectin. Steric interference between the bulky ovalbumin molecules is believed to be the reason for the observed decrease in the apparent number of binding sites on the lectin.
Amino Sugars↗
Conformational analysis and the fine structure of cross peaks in phase-sensitive homonuclear two-dimensional correlated NMR spectra of oligosaccharides.
Useful structural and conformational information was obtained from a detailed analysis of the fine structure of cross peaks that appears in the phase-sensitive homonuclear correlated two-dimensional spectra of complex large glycopeptides. The small chemical shift range observed for the oligosaccharide part results in a variety of cross-peak patterns. A catalogue of cross-peak fine structures and patterns expected for common carbohydrates are presented which can help in making some, all-important and crucial, proton resonance assignments. Analysis of the vicinal coupling constants extracted from the cross peaks corresponding to the hydroxymethyl protons of the inner core carbohydrates of glycopeptides derived from calf fetuin, has yielded information regarding the time-averaged solution conformation of this triantennary structure. It was shown that in solution the Man(alpha 1-6) arm of the core pentasaccharide unit, which carries a single antenna, adopts for an appreciable part of the time a conformation which brings it close to the arm that is attached to the peptide part. A similar conformation for the Man(alpha 1-6) arm was previously observed for the biantennary oligosaccharide chain. Therefore, we concluded that the presence of an additional antenna on the Man(alpha 1-3) arm of the core unit in the triantennary structure does not alter the basic biantennary conformation.
Animals↗
NMR studies of the interaction of chromomycin A3 with small DNA duplexes I.
1H and 31P NMR spectral analysis of a chromomycin/d(ATGCAT)2 complex provides strong evidence for a nonintercalative mode of drug binding. Investigation of the imino proton region of the duplex suggests a protection of one of the two guanine imino protons from fast exchange with the bulk water up to at least 45 degrees C by the drug. Subsequent one-dimensional nuclear Overhauser enhancement experiments place the exchangeable chromomycin chromophoric hydroxyl proton less than 0.45 nm from this guanine imino proton and the chromophore 7-methyl less than 0.45 from the internal thymine 6-proton and/or the guanine 8-proton. 1H two-dimensional NMR reveals that the duplex retains a right-handed B conformation but there are distortions at the TGC region of one chain and large deviations in the chemical shift of protons relative to the uncomplexed duplex in the other chain in the same TGC region. The data suggest that the chromomycin chromophore is oriented such that the hydrophilic side of the ring system is proximal to the helix center in the major groove near the TG region while the aromatic side of the ring is oriented away from the helix but is partially protected from the solvent by the aliphatic chain, which bends back over the two aromatic protons. Changes in the 31P spectrum of the duplex on binding of the drug are different from the effect of either actinomycin or netropsin on nucleic acid fragments.
Base Composition↗
Mutagenicity in salmonella of hazardous wastes and urine from rats fed these wastes.
15 hazardous industrial waste samples were evaluated for mutagenicity in the Salmonella plate-incorporation assay using strains TA98 and TA100 in the presence and absence of Aroclor 1254-induced rat liver S9. Dichloromethane/methanol extracts of the crude wastes were also evaluated. 7 of the crude wastes were mutagenic, but only 2 of the extracts of these 7 wastes were mutagenic; extracts of 2 additional wastes also were mutagenic. In addition, 10 of the crude wastes were administered by gavage to F-344 rats, and 24-h urine samples were collected. Of the 10 raw urines evaluated, 3 were mutagenic in strain TA98 in the presence of S9 and beta-glucuronidase. The 3 crude wastes that produced these 3 mutagenic urines were, themselves, mutagenic. Adequate volumes of 6 of the 10 raw urines were available for extraction/concentration. These 6 urines were incubated with beta-glucuronidase and eluted through Sep-Pak C18 columns; the methanol eluates of 3 of the urines were mutagenic, and these were the same 3 whose raw urines also were mutagenic. In general, the C18/methanol extraction procedure reduced the cytotoxicity and increased the mutagenic potency of the urines. To our knowledge, this is the first report of the mutagenicity of urine from rodents exposed to hazardous wastes. Based on the present results, the use of only strain TA98 in the presence of S9 might be adequate for general screening of hazardous wastes or waste extracts for genotoxicity. The urinary mutagenesis assay does not appear to be a useful adjunct to the Salmonella assay for screening hazardous wastes. The problems associated with chemically fractionating diverse types of hazardous wastes for bioassay are also discussed.
Animals↗
Intractable manic-depressive psychosis with rapid cycling in an 18-year-old woman successfully treated with electroconvulsive therapy.
An adolescent patient with a history of progressively more severe seasonal depression subsequently developed a refractory manic-depressive psychosis with rapid cycling after the initiation of treatment with trimipramine. A complete remission was obtained after a course of six electroconvulsive therapy (ECT) treatments. This unusual case and its outcome are discussed in terms of apparent drug-induced rapid cycling and the treatment of this condition. It is suggested that ECT can be successfully used as an alternative therapeutic option for patients with intractable rapid-cycling manic-depressive disorder.
Adolescent↗
Feasibility study of batteryless temperature transponders using miniature microwave cavity resonators.
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Animals↗
NE-19550: a novel, orally active anti-inflammatory analgesic.
NE-19550, N-(3-methoxy-4-hydroxybenzyl)oleamide, is a capsaicin analogue that has been shown to possess oral activity in the 55 degrees C rat hot-plate and mouse phenylquinone abdominal constriction analgesia tests. The compound also displayed anti-inflammatory activity orally in the carrageenan-inflamed rat-paw test and topically in the croton oil-inflamed mouse-ear test. NE-19550 activity in the thermal analgesia assay was not blocked by the opioid antagonist naloxone, and no inhibition of prostanoid synthesis in rat platelets or tissues was seen following a high analgesic and anti-inflammatory oral dose (300 mg/kg). A wide variety of known neuronal antagonists (adrenergic, serotonergic, dopaminergic, cholinergic, GABA-ergic, histaminergic) were found not to inhibit NE-19550 analgesia, further indicating a lack of involvement of known drug receptors mediating analgesic responses. Analgesic doses of NE-19550 were also found to lack the acute toxicity and thermoregulatory desensitization characteristics of the parent natural product capsaicin. It appears to represent a new class of potent-acting, non-narcotic, anti-inflammatory analgesic agents.
Administration, Oral↗
Timolol induces HSV-1 ocular shedding in the latently infected rabbit.
Timolol iontophoresis into the eye can induce herpes simplex virus type 1 (HSV-1) shedding in rabbits latently infected with HSV-1 strain McKrae. Anodal iontophoresis of 0.01% timolol was done at 0.8 mAmp for 8 min once a day for 3 consecutive days. Viral shedding was determined by the presence of HSV-1 in the preocular tear film obtained by eye swabs. In two experiments, iontophoresis of 0.01% timolol resulted in all eyes (18/18) shedding HSV-1 for an average duration of 4.3 days. When 5.0% timolol was applied topically to rabbit eyes supersensitized by iontophoresis of 6-hydroxydopamine (6-HD), all eyes (10/10) shed virus for an average duration of 2.9 days. All eyes (12/12) receiving iontophoresis of 6-HD, pre- and posttreatment with topical application of 5.0% timolol, and posttreatment with topical application of 1.0% epinephrine shed virus for an average duration of 3.6 days. Eyes treated with topical application of 5.0% timolol alone showed no difference in HSV-1 ocular shedding, compared with untreated eyes. We concluded that both iontophoresis of 0.01% timolol and topical application of 5.0% timolol to adrenergically supersensitized eyes induced HSV-1 shedding reliably and with a high frequency, and that topically applied timolol does not block the HSV-1 ocular shedding induced by epinephrine in adrenergically supersensitized eyes.
Administration, Topical↗
Diagnosis and monitoring in patients with hairy cell leukemia using the monoclonal antibody anti-HC2.
Immunofluorescent staining of peripheral blood mononuclear cells with the monoclonal antibody anti-HC2 combined with phase microscopic examination identified leukemic hairy cells in nine of 13 patients (69%) evaluated at Memorial Hospital prior to treatment with recombinant alpha-interferon (rIFN-alpha A). The remaining four patients required further studies of bone marrow or peripheral blood cytospin samples for diagnosis. In some cases a low percentage of cells staining with anti-HC2 could be significantly increased by depleting T cells from the sample using sheep red blood cell rosetting. These 13 patients represent a subgroup of patients treated on a phase II rIFN-alpha A study at Memorial Hospital. Ten patients (77%) achieved a partial response in a median of 128 days (range, 64-234). One patient achieved a minor response and two patients failed treatment. Nonhematologic toxicity, consisting of fever and malaise, was transient in all patients. Serial determinations of HC2-positive cells in the peripheral blood closely paralleled disease activity in the bone marrow in one patient treated for 4 years with various therapeutic modalities. The antibody anti-HC2 may play a significant role in the diagnosis and monitoring of hairy cell leukemia using peripheral blood sampling.
Adult↗
Binding of [1-13C]galactose-enriched hen ovalbumin to Erythrina cristagalli agglutinin as studied by 13C-NMR spectroscopy.
A study of the equilibrium binding of glycoproteins to lectins was undertaken using the titled compounds as a model system for such interactions. The binding of hen ovalbumin, enriched in galactose specifically 13C-labelled at C1, to Erythrina cristagalli agglutinin was studied by 13C-NMR spectroscopy. The lectin was shown to be bivalent for ovalbumin with an apparent estimated association constant, at infinite dilution, of about 10(4) M-1. The observed association is similar to that found for the corresponding disaccharide, Gal(beta 1-4)GlcNAc. The results strongly suggest that only the N-acetyllactosamine moiety in the carbohydrate side chain of galactose-enriched ovalbumin participates in the binding to the lectin with little, if any, interactions from other parts of either the side chain or the polypeptide backbone of ovalbumin.
Binding Sites↗
Reinvestigation of the carbohydrate chains of calf fetuin using 13C-n.m.r. spectroscopy.
The triantennary structure of the N-linked oligosaccharide side-chain of fetuin, elucidated by a combination of 13C-n.m.r. spectroscopy and enzymic degradations, accords with that reported earlier with respect to the branching pattern, but the ratio of the N-acetylneuraminic acid linkages to the galactose residues [alpha-(2----3) vs. alpha-(2----6)] was found to be 1:1, indicating structural heterogeneity of the side chains. Also, one out of nine galactosyl residues is linked to 2-acetamido-2-deoxy-beta-D-glucose by a (1----3) rather than a (1----4) linkage. The chemical shifts reported are in excellent agreement with those for the intact glycoprotein. Unusual chemical shift effects lead to the conclusion that the alpha-NeuAc-(2----6) residues interact with other parts of the oligosaccharide side-chain. The action of beta-D-galactosidase from Aspergillus niger on desialylated fetuin removed approximately 85% of the beta-Gal residues (1----4)-linked to GlcNAc and 65% of the beta-Gal residues (1----3)-linked to GalNAc, but none of the beta-Gal residues (1----3)-linked to GlcNAc.
Animals↗
One- and two-dimensional 90.5-MHz 13C-NMR spectroscopy of the N-linked triantennary oligosaccharide units of calf fetuin.
Complete assignments of all anomeric resonances in the proton and carbon spectra of the N-linked oligosaccharide units of fetuin were made using one- and two-dimensional NMR spectroscopy. We are able to confirm the presence of microheterogeneity in the N-acetylneuraminic acid linkages to the galactose residues and the presence of a unique triantennary structure which carries a side chain: NeuAc alpha(1-3)Gal beta(1-3)GlcNac beta(1-4)-. Anomeric carbon chemical shifts changes resulting from long-range conformational effects were observed.
Animals↗
Treatment of blastic transformation of chronic myelogenous leukemia with mitoxantrone.
Twenty-four patients with blastic-phase chronic myelogenous leukemia (CML) were treated with mitoxantrone. The patients included 19 whose cells were Philadelphia chromosome (Ph1+) and 5 who were either Ph1- or in whom cytogenetics were not available. Six of the 19 whose cells were Ph1+ responded and one of those who were Ph1- responded. The patients were further characterized into lymphoid or nonlymphoid on the basis of terminal deoxynucleotidyl transferase or morphology. Two of the patients with lymphoid transformation and 3 of those with nonlymphoid transformation responded. In 3 patients post-treatment cytogenetic evaluation revealed the presence of Ph1- metaphases. We conclude that mitoxantrone has modest activity in blCML and that the cytogenetic responses suggest the possibility of greater efficacy in chronic-phase CML.
Adult↗
Current status of treatment of acute leukemia in adults: an overview of the Memorial experience and review of literature.
The results of treatment of 629 previously untreated adults with acute leukemia at Memorial Hospital are reviewed. During the past 14 years, 135 adults (greater than 15 years) with acute lymphoblastic leukemia (ALL) have been treated with one of three successive multidrug-intensive treatment protocols (L2, L10/10M, and L17/17M), each calling for 2.5 to 3 years of systemic chemotherapy and prophylactic intrathecal methotrexate without cranial irradiation. The complete remission (CR) rates were L2 (n = 22) = 77%; L10/10M (n = 69) = 86%; L17/17M (n = 44) = 77%. The median durations of survival and remission were, respectively, L2 = 33 and 30 months; L10/10M = 62 months and not reached; and L17/17M = not reached. Almost all relapses occurred within the first 3 years while still continuing treatment, and there were only rate late relapses after stopping treatment. It appears that approximately half of the patients may have been cured with the latest two protocols. During the last 17 years, 494 adults aged 15 to greater than 70 with acute nonlymphoblastic leukemia (ANLL) were treated with one of five successive multiple drug treatment protocols of varying intensity (arabinosylcytosine + 6-thioguanine [n = 36]; L6 [n = 101]; L12 [n = 104]; L14/14M [n = 121]; and L16/16M [n = 132]). Patients with myelodysplastic syndromes generally were not treated until they developed acute leukemia, but were then entered and included in the results. Secondary leukemias following treatment of other neoplastic diseases were not included. The complete remission rates were fairly constant between 47 and 64% and the median durations of remissions were between 9 and 21 months. The intensive treatment L14 and L16 protocols were associated with more early deaths and did not result in a significantly improved remission incidence or duration or survival. With all protocols, the majority of relapses occurred within the first 2 years, but relapses continued to occur at a decreasing rate for 4 years and occasionally even later. Whereas a small fraction (approximately 10 to 15%) of adults with ANLL are now apparently being cured with combination chemotherapy, despite intensive efforts there has been little improvement during the last decade and more selective and effective forms of treatment are urgently needed.
Acute Disease↗
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↗