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Biomedical subjects

E Berman

Publications and source records attributed to E Berman.

At least 91 records · Page 5Linked to original sources
PubMed1990

One- and two-dimensional NMR studies of the N-terminal portion of glycophorin A at 11.7 Tesla.

One- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy (at 11.7 Tesla) was used to gain some structural and spectral information about glycophorin AM, glycophorin AM tryptic glycopeptide, a related pentapeptide, and two related monoglycosylated pentapeptides. The protein spectral information suggests that the highly glycosylated N-terminus of glycophorin does not seem to possess a unique tertiary structure. Furthermore, the spectral information provided by the carbohydrate residues also indicates that there is no strong carbohydrate-protein interaction resulting in a unique tertiary structure. This result does not preclude any unique protein-carbohydrate interactions. For the small monoglycosylated pentapeptide containing alpha-D-GalNAc attached to Thr, a unique NOESY cross-peak was observed between the anomeric proton and the beta-proton of Thr. A cross-peak between the beta-proton of Ser and the anomeric proton was not observed for a related monoglycosylated pentapeptide containing alpha-D-GalNAc O-linked to Ser.

Animals↗
PubMed1989

4-demethoxydaunorubicin (idarubicin) in combination with 1-beta-D-arabinofuranosylcytosine in the treatment of relapsed or refractory acute leukemia.

We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.

Adolescent↗
PubMed1989

Lack of effects from 2000-Hz magnetic fields on mammary adenocarcinoma and reproductive hormones in rats.

Female rats were implanted with mammary adenocarcinoma tissue and 25 days later exposed to 2,000-Hz magnetic fields 1 h a day for 9 days. Analysis showed that tumor weights and the levels of several reproductive hormones were not significantly different between treated and control animals. Other studies with a similar design have also reported no significant effects from magnetic field exposure. However, vaginal smear data from all animals revealed that handling and restraint stress may have confounded the detection of subtle magnetic field effects.

Adenocarcinoma↗
PubMed1989

Toxicity of complex waste mixtures: a comparison of observed and predicted lethality.

The ability to predict the biological effect of complex waste mixtures from chemical characterization data was examined by comparing observed mortality to that predicted by a mathematical additivity model with literature LD50 values for the chemicals identified in the mixtures. Male F344 rats were exposed by gavage to 1 of 10 samples of complex industrial waste. Seven of the 10 waste samples caused death within 24 h of administration at dosages ranging from 1 to 5 ml/kg body weight. Two of the 7 lethal waste samples produced 100% mortality at a dosage of 2.5 ml/kg; another 2 waste samples produced 100% mortality at 5 ml/kg. The partial chemical analysis, although providing more extensive information on chemical composition than might normally be available for most complex waste mixtures, was not sufficient to distinguish lethal from nonlethal waste samples or to indicate lethal potency. Possible explanations for the apparent inability to predict readily lethality from the chemical characterization data include the possible inappropriateness of an additivity model due to the presence of interactions, such as synergism or antagonism; the kinetics of chemical absorption, distribution, and elimination, which may be affected by administration of the chemical in a complex matrix; and the presence of unidentified chemicals in the mixture that may have contributed to the observed toxicity.

Animals↗
PubMed1989

The solution conformation of the antibiotic anticancer chromomycin A3 by two-dimensional NMR spectroscopy.

The solution conformations of chromomycin A3 (CRA) and dechromose-A chromomycin A3 (CRA-B) in dichloromethane and methanol were studied by two-dimensional (2D) NMR techniques. In dichloromethane, the drugs are found in a compact wedged-like conformation, with the phenolic hydroxyls at the tip and the side chains folded back to one side of the aglycon plane, oriented parallel to each other. The overall structure is stabilised by intramolecular hydrogen bonds and by the formation of a hydrophobic pocket, enclosed by the three side chains. In methanol, the drugs have the expected open conformation with extended side chains. Like its parent drug, CRA-B binds to d(ATGCAT)2 duplex with a major groove orientation, a 2:1 drug/duplex ratio and a two-fold symmetry of the resultant complex. The drug molecule is suggested to reside diagonally across the two strands of the duplex and to span 3 base pairs, while all three side chains of the drug are folded away from the major groove of the DNA. The observed nonequivalent positions of CRA and CRA-B within the major groove of the duplex results from the different conformation adopted by the sugar side-chains in the two complexes.

Chromomycin A3↗
PubMed1989

Toxicology screening in urban trauma patients: drug prevalence and its relationship to trauma severity and management.

Although toxicology screening is often used when treating trauma patients, its utility and significance remain controversial. Data from 623 toxicology screens performed in urban trauma center patients with mental status alterations are reported. The study patients were predominantly black and male, with a mean age of 32 (+/- 22) years. Overall, 86% of screens were positive. Substances of abuse, including ethanol, were noted in 525 (84%) of urine toxicology screens. Ethanol, cannabinoids, and cocaine were the drugs most commonly found in urine, with positivity noted in 53%, 37%, and 34% of screens. Serum analysis was 44% positive, with ethanol noted in 41% of patients. In blacks, the odds ratio of illicit drug use before trauma ranged from 1.9 to 4.2 (p less than 0.005), and in those aged 17 to 40 years, the odds ratio for illicit urine drugs ranged from 4.7 to 16.8 (p less than 0.001). In patients older than 40 years, the odds of a positive serum ethanol level were 1.7 times greater than in younger patients, and a level above 300 mg% was 3.8 times more likely in this age group (p less than 0.001). When serum ethanol was detected, the odds ratio of a head injury was 1.4 relative to patients without serum ethanol (p less than 0.06), and the odds ratio for abdominal injury was 1.6 for patients with serum ethanol (p less than 0.03). The odds of a TS less than 12 were 1.8 (p less than 0.05), and the odds of a GCS less than 12 were 3.3 (p less than 0.001) with ethanol levels greater than 100 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells.

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU-E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti-HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.

Bone Marrow↗
PubMed1989

Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol.

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.

Age Factors↗
PubMed1988

Solution conformation of the antitumor antibiotic chromomycin A3 determined by two-dimensional NMR spectroscopy.

A conformational analysis and a complete assignment of the nonexchangeable proton resonances of chromomycin A3, dechromose-A chromomycin A3, and deacetylchromose-B chromomycin A3 were carried out in organic solvents. The resulting conformation in methanol has the three side chains of chromomycin A3 fully extended, away from one another and from the aglycon. In dichloromethane on the other hand, the drug was shown to adopt a highly compact conformation in which most of the 26 oxygen atoms in the molecule point out toward the solvent. The two carbohydrate side chains extend parallel to each other on the same side of the aglycon. Two intramolecular nuclear Overhauser enhancement contacts have been observed between different sugar units on these side chains, indicating close proximity for these moieties. In addition, the aliphatic side chain is folded toward the aglycon, parallel to the two oligosaccharide side chains. The overall conformation has a wedge-like shape with the two phenoxy groups exposed at the pointed edge. The presence of some exchange cross-peaks in the NOESY spectra suggests the presence of intramolecular hydrogen bonds that probably help to maintain the compact conformation. The derivatives of chromomycin A3 have qualitatively similar conformations, though their respective conformations are not as compact as the parent drug. The significance of these results is discussed in terms of a model of chromomycin A3 binding to DNA in the major groove.

Chromomycin A3↗
PubMed1988

A two-dimensional 1H-n.m.r. (500 MHz) and 13C-n.m.r. (125 MHz) study of N-linked glycopeptides derived from calf fetuin.

The oligosaccharide part of an N-linked triantennary glycopeptide from calf fetuin with fourteen carbohydrate residues and its smaller derivatives obtained by successive enzymic cleavage of the terminal residues were investigated using 2D 1H-n.m.r. (500 MHz) and 13C-n.m.r. (125 MHz) spectroscopy. Assignments have been made of the resonances of almost all the protons of the constituent carbohydrate residues in these glycopeptides. A comparison of the 1H chemical shifts and coupling constants, as determined from the cross-peaks, has shown the dependence of these parameters on the interactions of spatially related neighbouring carbohydrates. Small conformational changes take place upon elongation of the oligosaccharide side-chains.

Carbohydrate Conformation↗
PubMed1988

Lethality and hepatotoxicity of complex waste mixtures.

Male F344 rats were exposed by gavage to samples of complex mixtures and evaluated 24 hr later. Seven of the 10 samples caused death at doses ranging from 1 to 5 ml/kg body wt. Eight of the 10 samples were hepatotoxic based on histopathologic evaluation; 6 were centrilobular and 2 were periportal hepatotoxicants. The waste samples exerted toxicity through different mechanisms, as indicated by differences in the severity and lobular location of the tissue damage. Nine of the 10 samples caused an increase in the ratio of liver weight to body weight (relative liver weight). With histopathological evaluation as the criterion, relative liver weight was the single best indicator of hepatotoxicity. Exposure to several of the waste samples increased serum total bilirubin and serum enzyme activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and ornithine carbamyl transferase. As a battery, but not individually, the serum indicators separated the 8 hepatotoxic samples from the 2 nonhepatotoxic samples. In general, the hepatotoxicity of the waste samples did not appear to be readily predicted from (partial) chemical characterization data. An approach that includes both chemical characterization and biological testing should provide valuable information regarding the hazardous nature of complex wastes.

Animals↗