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Biomedical subjects

E Katz

Publications and source records attributed to E Katz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Syntheses and antimalarial activities of 10-substituted deoxoartemisinins.

Two series of 10-substituted deoxoartemisinin derivatives have been synthesized. The first employed the reaction of dihydroartemisinin acetate with several silyl enol ethers in the presence of titanium tetrachloride. The second utilized the reaction of 10-(2-oxoethyl)deoxoartemisinin with several Grignard reagents. The in vitro antimalarial activities of both series were determined against two drug-resistant clones of P. falciparum. The activities of 13 beta and 15 beta were 5-7 times greater than that of artemisinin.

Animals↗
PubMed2000

[Changes in medications acting on the cardiovascular system during hospitalization].

The present study was conducted to assess the extent to which the treatment of patients who take one or more cardiovascular drugs regularly is changed during hospitalisation and over the course of the subsequent two months after release from hospital. In order to elucidate the question more exactly, data was collected on 107 patient after a hospital stay on the internal medicine ward of a university hospital and on 107 patients who had been hospitalised in two non-university hospitals. The average number of changes in medication in patients in the university setting was 2.7 and in patients in the non-university setting it was 2.2. The treatment of patients who were hospitalised for cardiovascular complications was switched more often than that of patients whose circulation was stable at admission. Over the course of the subsequent two months after release, the attending general practitioners (GP) switched the medication at a much lower frequency than the hospitals had done. Within one specific drug class there was no more frequent changes in medication during the hospital stay as afterwards. A drug was discontinued in 107 patients in the university setting and in 124 cases in the two non-university hospitals. The same drug was prescribed again by the treating GP in 30 and 40 patients, respectively, after release. The results of the study show that treatment with drugs that have an effect on the patient's understanding of his illness with regard to its severity may be likely to cause doubts about the effectiveness of the drug and whether the therapeutic decisions that were made by the doctors for medical or other reasons were correct. Therefore, it makes more sense to avoid unnecessary changes in medication whenever possible and only then in unavoidable cases with a clear medical indication.

Adult↗
PubMed2000

Sensing of acetylcholine by a tricomponent-enzyme layered electrode using faradaic impedance spectroscopy, cyclic voltammetry, and microgravimetric quartz crystal microbalance transduction methods.

A three-enzyme layered assembly on Au electrodes or Au-quartz crystals, consisting of horseradish peroxidase, HRP, choline oxidase, ChO, and acetylcholine esterase, AChE, is used to sense acetylcholine by the HRP-mediated oxidation of 3,3',5,5'-tetramethylbenzidine, TMB (1), by H2O2, and the formation of the insoluble product (2) on the respective transducers. The analyte-substrate, acetylcholine, is hydrolyzed by AChE to choline that is oxidized by ChO and O2 to yield the respective betaine and H2O2. The amounts of generated H2O2 and the resulting insoluble product on the transducers correlate with the concentration of acetylcholine in the samples. The formation of the insoluble product (2) on electrode supports is followed by faradaic impedance spectroscopy that probes the increased interfacial electron-transfer resistance upon the formation of 2, and by cyclic voltammetry that reflects electron-transfer barriers upon the formation of the precipitate. The frequency of the Au-quartz crystal decreases as a result of the accumulation of the insoluble precipitate. The amount of insoluble product formed on the transducers is controlled by the concentration of acetylcholine and by the time interval of biocatalyzed precipitation. The generation of the insoluble product provides a means to amplify the sensing processes. Acetylcholine concentrations corresponding to 1 x 10(-5) M are easily sensed by the different transducers.

Acetylcholine↗
PubMed2000

From homoleptic to heteroleptic double stranded Copper(I) helicates: the role of self-recognition in self-assembly processes

The ligands 2,9-bis[(6-methyl-2, 2'-bipyridin-6'-yl)methyleneoxymethylenyl]-1,10-phenanthroline (6), 6' ',6' "-bis[(6-methyl-2, 2'-bipyridin-6'-yl)methyleneoxymethylenyl)]-2' ',2' "-bipyridine (2), 5,5'-bis[(6-methyl-2,2'-bipyridin-6'yl)methyleneoxymethylenyl]-2, 2'-bithiophene (7), and 6,6'-bis[(6-methyl-2, 2'-bipyridin-6'-yl)methyleneoxymethylenyl]-2,2'-biphenyl (8) and their respective homo- and heteroleptic double-stranded copper(I) complexes were prepared and characterized in order to estimate the importance of self-recognition in the self-assembly processes of double-stranded copper complexes. The homoleptic double-stranded copper complexes of 2, 6, 7, and 8 were characterized by NMR, FAB-MS, and electrochemistry. It was found that 6 and 2 each form a single double-stranded helicate having the structure of [(L)(2)Cu(3)](3+) (L = 2 or 6), 7 forms two double-stranded [(7)(2)Cu(3)](3+) complexes, and 8 results in a mixture of at least two [(8)(2)Cu(2)](2+) complexes. The potential shift, DeltaE degrees (,) of the Cu(+)/Cu(2+) redox process of these complexes reflects the binding affinity of the different binding sites to the copper cation. The electrochemical data show that the central units have a higher affinity to Cu(+) as compared to the off-center binding sites. NMR was used to determine the actual complex composition obtained from different mixtures of 2, 6, or 7 with Cu(+). Interestingly, we have found that, although 6, 2, and 7 each form homoleptic double-stranded complexes, no heteroleptic double-stranded copper complexes were formed from the mixtures of 7 with either 6 or 2. However, when mixtures of 6 and 2 are used, helicate distributions seem to follow simple statistics. These results are discussed in terms of the relative importance of self-recognition in the self-assembly of double-stranded helicates.

Journal Article↗
PubMed2000

The brief abstinence test: voucher-based reinforcement of cocaine abstinence.

This study assessed the effectiveness of a brief abstinence reinforcement procedure for initiating cocaine abstinence in methadone maintenance patients. On Monday of the test week, 72 cocaine-abusing methadone patients were offered a $100 voucher if urine samples collected on Wednesday indicated that they had abstained from cocaine across that 2-day period. A patient was considered abstinent and the voucher delivered if the urine benzoylecgonine concentration decreased by 50% from Monday to Wednesday (quantitative criterion) or if the concentration of Wednesday's urine sample was < or = 300 ng/ml. Overall, 79% of study patients showed urinalysis evidence of abstention from cocaine between Monday and Wednesday of the test week. In a subsample with complete data (n = 50), significantly more patients abstained from cocaine from Monday to Wednesday of the test week (84%) than from Monday to Wednesday of the week before (36%) or after (32%) the test week. Furthermore, while almost all patients (94%) decreased their benzoylecgonine concentration from Monday to Wednesday of the test week, significantly fewer patients' benzoylecgonine concentrations decreased from Monday to Wednesday of the week before (56%) or after (48%) the test week. This highly efficacious procedure may have clinical application where reliable abstinence initiation is desired, either on a temporary basis (e.g. sobriety sampling) or at the start of longer-term interventions. It may also be possible to use the brief abstinence test as an experimental model to assess the effects of other therapeutic interventions on abstinence initiation in treatment settings.

Adult↗
PubMed2000

Bile acids in xenogeneic ex-vivo liver perfusion: function of xenoperfused livers and compatibility with human bile salts and porcine livers.

BACKGROUND: In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). METHODS: Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM,1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3alpha-hydroxy-6-oxo-5beta-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. RESULTS: The mean duration of perfusions was 4.1+/-1.5 hr. The mean total bile acid clearance from serum (243+/-44 micromol/h) was similar to the total bile acid biliary excretion (286+/-84 micromol/hr, P = 0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. CONCLUSIONS: Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.

Animals↗
PubMed2000

Integration of Layered Redox Proteins and Conductive Supports for Bioelectronic Applications.

Integration of redox enzymes with an electrode support and formation of an electrical contact between the biocatalysts and the electrode is the fundamental subject of bioelectronics and optobioelectronics. This review addresses the recent advances and the scientific progress in electrically contacted, layered enzyme electrodes, and discusses the future applications of the systems in various bioelectronic devices, for example, amperometric biosensors, sensoric arrays, logic gates, and optical memories. This review presents the methods for the immobilization of redox enzymes on electrodes and discusses the covalent linkage of proteins, the use of supramolecular affinity complexes, and the reconstitution of apo-redox enzymes for the nanoengineering of electrodes with protein monolayers of electrodes with protein monolayers and multilayers. Electrical contact in the layered enzyme electrode is achieved by the application of diffusional electron mediators, such as ferrocene derivatives, ferricyanide, quinones, and bipyridinium salts. Covalent tethering of electron relay units to layered enzyme electrodes, the cross-linking of affinity complexes formed between redox proteins and electrodes functionalized with relay-cofactor units, or surface reconstitution of apo-enzymes on relay-cofactor-functionalized electrodes yield bioelectrocatalytic electrodes. The application of the functionalized electrodes as biosensor devices is addressed and further application of electrically "wired" enzymes as catalytic interfaces in biofuel cells is discussed. The organization of sensor arrays, self-calibrated biosensors, or gated bioelectronic devices requires the microstructuring of biomaterials on solid supports in the form of ordered micro-patterns. For example, light-sensitive layers composed of azides, benzophenone, or diazine derivatives associated with solid supports can be irradiated through masks to enable the patterned covalent linkage of biomaterials to surfaces. Alternatively, patterning of biomaterials can be accomplished by noncovalent interactions (such as in affinity complexes between avidin and a photolabeled biotin, or between an antibody and a photoisomerizable antigen layer) to provide a means of organizing protein microstructures on surfaces. The organization of patterned hydrophilic/hydrophobic domains on surfaces, by using photolithography, stamping, or micromachining methods, allows the selective patterning of surfaces by hydrophobic, noncovalent interactions. Photoactivated layered enzyme electrodes act as light-switchable optobioelectronic systems for the amperometric transduction of recorded photonic information. These systems can act as optical memories, biomolecular amplifiers, or logic gates. The photoswitchable enzyme electrodes are generated by the tethering of photoisomerizable groups to the protein, the reconstitution of apo-enzymes with semisynthetic photoisomerizable cofactor units, or the coupling of photoisomerizable electron relay units.

Journal Article↗
PubMed2000

Block of the alpha9 nicotinic receptor by ototoxic aminoglycosides.

In the present study, we report that the alpha9 nicotinic acetylcholine receptor (nAChR) expressed in Xenopus laevis oocytes is reversibly blocked by aminoglycoside antibiotics. The aminoglycosides tested blocked the alpha9 nAChR in a concentration-dependent manner with the following rank order of potency: neomycin>gentamicin>streptomycin>amikacin>kanamycin. The antagonistic effect of gentamicin was not overcome by increasing the concentration of acetylcholine (ACh), indicative of a non-competitive type of block. Blockage of ACh-evoked currents by gentamicin was found to be voltage-dependent, being more potent at hyperpolarized than at depolarized holding potentials. Furthermore, gentamicin blockage was dependent upon the extracellular Ca(2+) concentration, shown by the fact that increments in extracellular Ca(2+) significantly reduced the potency of this aminoglycoside to block the alpha9 nAChR. Possible mechanisms of blockage by the aminoglycosides are discussed. The present results suggest that the initial reversible actions of aminoglycosides at the organ of Corti, such as the elimination of the olivocochlear efferent function, are due in part to the interaction with the native alpha9-containing cholinergic receptor of the outer hair cells.

Animals↗
PubMed2000

Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor.

The rat alpha9 nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus laevis oocytes and tested for its sensitivity to a wide variety of cholinergic compounds. Acetylcholine (ACh), carbachol, choline and methylcarbachol elicited agonist-evoked currents, giving maximal or near maximal responses. Both the nicotinic agonist suberyldicholine as well as the muscarinic agonists McN-A-343 and methylfurtrethonium behaved as weak partial agonists of the receptor. Most classical cholinergic compounds tested, being either nicotinic (nicotine, epibatidine, cytisine, methyllycaconitine, mecamylamine, dihydro-beta-erythroidine), or muscarinic (muscarine, atropine, gallamine, pilocarpine, bethanechol) agonists and antagonists, blocked the recombinant alpha9 receptor. Block by nicotine, epibatidine, cytisine, methyllycaconitine and atropine was overcome at high ACh concentrations, suggesting a competitive type of block. The present results indicate that alpha9 displays mixed nicotinic-muscarinic features that resemble the ones described for the cholinergic receptor of cochlear outer hair cells (OHCs). We suggest that alpha9 contains the structural determinants responsible for the pharmacological properties of the native receptor.

Animals↗
PubMed2000

The antiviral activity exerted by vaccinia virus on the growth of herpes simplex virus in BS-C-1 cells.

The growth of herpes simplex virus type 2 (HSV-2) in BS-C-1 cells, was inhibited following super-infection with vaccinia virus. This inhibition was efficiently induced by both the intracellular mature virus (IMV) form of vaccinia virus and the extracellular enveloped virus (EEV), containing an additional external viral membrane. Treatment of vaccinia IMV with the detergents NP-40, Brij-58 or n-octyl-alpha-D-glucopyranoside, abolished its ability to inhibit the growth of HSV-2. Ultraviolet irradiation of vaccinia virus, that completely inactivated the infectivity of the virus, resulted in partial loss of the capability to inhibit the growth of HSV-2: 16-fold more irradiated virus was needed for the inhibition. Electron microscopy showed that the irradiated vaccinia virus adsorbed and penetrated into the HSV-infected cells but remained morphologically intact within the cells for at least 22 h. When the steps in the growth of HSV affected by the irradiated vaccinia virus were followed, it was found that while the synthesis of HSV DNA was partially decreased, the synthesis of HSV proteins was very strongly inhibited and virus particles were not formed.

Animals↗
PubMed2000

High calcium permeability and calcium block of the alpha9 nicotinic acetylcholine receptor.

At the synapse between olivocochlear efferent fibers and outer hair cells (OHCs) of the cochlea, a non-classical ionotropic cholinergic receptor allows Ca(2+) entry into the hair cell, thus activating a Ca(2+)-sensitive K(+) current which hyperpolarizes the cell's membrane. In the mammalian ear, this leads to a reduction in basilar membrane motion, altering auditory nerve fiber activity and reducing the dynamic range of hearing. The alpha9 nicotinic acetylcholine receptor (nAChR) subunit mediates synaptic transmission between cholinergic olivocochlear fibers and OHCs. Given that Ca(2+) is a key player at this inhibitory synapse, we evaluated the permeability to Ca(2+) of the recombinant alpha9 receptor expressed in Xenopus laevis oocytes and the modulation of its activity by extracellular Ca(2+). Our results show that the alpha9 receptor is highly permeable to Ca(2+) and that this cation potently blocks monovalent currents through this channel (IC(50)=100 microM, at -70 mV) in a voltage-dependent manner. At a Ca(2+) concentration similar to that found in the perilymph bathing the base of the OHCs, approximately 90% of the Na(+) current through the alpha9 receptor is blocked, suggesting that one of the main functions of this channel could be to provide a pathway for Ca(2+) influx.

Animals↗
PubMed2000

An integrated NAD+-dependent enzyme-functionalized field-effect transistor (ENFET) system: development of a lactate biosensor.

An integrated NAD+-dependent enzyme field-effect transistor (ENFET) device for the biosensing of lactate is described. The aminosiloxane-functionalized gate interface is modified with pyrroloquinoline quinone (PQQ) that acts as a catalyst for the oxidation of NADH. Synthetic amino-derivative of NAD+ is covalently linked to the PQQ monolayer. An affinity complex formed between the NAD+/PQQ-assembly and the NAD+-cofactor-dependent lactate dehydrogenase (LDH) is crosslinked and yields an integrated biosensor ENFET-device for the analysis of lactate. Biocatalyzed oxidation of lactate generates NADH that is oxidized by PQQ in the presence of Ca2+-ions. The reduced catalyst, PQQH2, is oxidized by O2 in a process that constantly regenerates PQQ at the gate interface. The biocatalyzed formation of NADH and the O2-stimulated regeneration of PQQ yield a steady-state pH gradient between the gate interface and the bulk solution. The changes in the pH of the solution near the gate interface and, consequently, the gate potential are controlled by the substrate (lactate) concentration in the solution. The device reveals the detection limit of 1 x 10(-4) M for lactate and the sensitivity of 24+/-2 mV dec(-1). The response time of the device is as low as 15 s.

Biosensing Techniques↗
PubMed2000

Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin.

A series of N-substituted 11-azaartemisinins were prepared in high yield employing base-catalyzed additions to an amide nitrogen of olefins and terminal acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when the EWG was a nitrile. In vitro antimalarial activities of each compound were determined against two drug-resistant strains of Plasmodium falciparum. Many of the compounds prepared were several times more active than artemisinin.

Animals↗
PubMed2000

Biomaterial engineered electrodes for bioelectronics.

A series of single-cysteine-containing cytochrome c, Cyt c, heme proteins including the wild-type Cyt c (from Saccharomyces cerevisiae) and the mutants (V33C, Q21C, R18C, G1C, K9C and K4C) exhibit direct electrical contact with Au-electrodes upon covalent attachment to a maleimide monolayer associated with the electrode. With the G1C-Cyt c mutant, which includes the cysteine residue in the polypeptide chain at position 1, the potential-induced switchable control of the interfacial electron transfer was observed. This heme protein includes a positively charged protein periphery that surrounds the attachment site and faces the electrode surface. Biasing of the electrode at a negative potential (-0.3 V vs. SCE) attracts the reduced Fe(II)-Cyt c heme protein to the electrode surface. Upon the application of a double-potential-step chronoamperometric signal onto the electrode, where the electrode potential is switched to +0.3 V and back to -0.3 V, the kinetics of the transient cathodic current, corresponding to the re-reduction of the Fe(III)-Cyt c, is controlled by the time interval between the oxidative and reductive potential steps. While a short time interval results in a rapid interfacial electron-transfer, ket1 = 20 s-1, long time intervals lead to a slow interfacial electron transfer to the Fe(III)-Cyt c, ket2 = 1.5 s-1. The fast interfacial electron-transfer rate-constant is attributed to the reduction of the surface-attracted Fe(III)-Cyt c. The slow interfacial electron-transfer rate constant is attributed to the electrostatic repulsion of the positively charged Cyt c from the electrode surface, resulting in long-range electron transfer exhibiting a lower rate constant. At intermediate time intervals between the oxidative and reductive steps, two populations of Cyt c, consisting of surface-attracted and surface-repelled heme proteins, are observed. Crosslinking of a layered affinity complex between the Cyt c and cytochrome oxidase, COx, on an Au-electrode yields an electrically-contacted, integrated, electrode for the four-electron reduction of O2 to water. Kinetic analysis reveals that the rate-limiting step in the bioelectrocatalytic reduction of O2 by the integrated Cyt c/COx electrode is the primary electron transfer from the electrode support to the Cyt c units.

Biocompatible Materials↗
PubMed2000

Acceptance of an ABO-incompatible mismatched (AB(+) to O(+)) liver allograft with the use of daclizumab and mycophenolate mofetil.

Liver allograft survival rates of 50% to 60% are reported in blood group A, group B, group O (ABO)-incompatible mismatched grafts even when aggressive immunosuppressive protocols, including plasmapheresis, OKT(3), cyclophosphamide, cyclosporine, prostaglandin E(1), and steroids, are used. A 59-year-old woman, blood type O(+), required emergency retransplantation posttransplantation day 2 because of primary nonfunction of the liver allograft. A blood type AB(+) allograft was used. Induction immunosuppressive therapy included tacrolimus, mycophenolate mofetil, OKT(3) (muromonab-CD(3)), steroids, and prostaglandin E(1). In addition, plasmapheresis was performed daily for 9 days. OKT(3) and prostaglandin E(1) were also discontinued postoperative day 9. Biopsy-proven acute cellular rejection was diagnosed postoperative day 12 and was treated with double-dose OKT(3) (10 mg) for another 6 days. On the day OKT(3) was discontinued, daclizumab, 60 mg, was administered intravenously. This dose was repeated every 2 weeks for a total of 5 doses. At 1-year follow-up, the patient is doing very well with normal liver function. We are unaware of previous reports of the use of daclizumab and mycophenolate mofetil as part of an immunosuppressive protocol aimed to induce acceptance of ABO-incompatible mismatched liver allografts. Based on our experience with this case, it seems that mycophenolate mofetil is an adequate replacement for cyclophosphamide. We also believe daclizumab provided adequate protection at a critical time. Further experience with both these drugs is required to establish their role in ABO-incompatible mismatched liver allografts.

Antibodies, Monoclonal↗
PubMed2000

Management of recurrent hepatitis C after liver transplantation: a concise review.

Recurrent hepatitis C infection and subsequent graft failure are increasingly recognized problems after orthotopic liver transplantation. Although many prospective therapeutic, controlled trials in primary hepatitis C disease have been reported, large-scale studies are yet to be performed in patients with posttransplant recurrent hepatitis C after liver transplantation. In this review, we summarize the current literature on the therapeutic approaches for recurrent hepatitis C and discuss the results of published studies on therapy with ribavirin or interferon (IFN) alone and on combination therapy with IFN plus ribavirin. Further, we discuss results of prophylactic approaches to the problem of recurrent hepatitis C after transplant. Finally, we discuss additional aspects of anti-hepatitis C virus therapy after liver transplantation.

Antiviral Agents↗