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Biomedical subjects

A Eisenberg

Publications and source records attributed to A Eisenberg.

At least 19 recordsLinked to original sources
PubMed2003

Control of amphiphilic block copolymer morphologies using solution conditions.

It is well known that the morphology of block copolymer aggregates depends on polymer properties such as the molecular weight, the relative block length, and the chemical nature of the repeat unit. Recently, we have shown that if aggregates are allowed to self-assemble in solution, then in addition to the above factors, a high degree of control over the aggregate architecture can be achieved by adjusting the solution conditions. Factors such as the water content in the solvent mixture, the solvent nature and composition, the presence of additives (ions, surfactants, and homopolymer) and the polymer concentration were successfully employed to control the aggregate shape and size. In this paper, we review a series of studies performed in our group to show how solution properties can control the architecture of aggregates prepared from a given copolymer. The control mechanism is explained in terms of the effect of each property on the forces that govern the formation of any given morphology, namely the core-chain stretching, corona-chain repulsion and interfacial tension.

Journal Article↗
PubMed2001

Block copolymers modify the internalization of micelle-incorporated probes into neural cells.

An important therapeutic concern is rate and extent of internalization of drugs into cells. Hydrophilic agents often internalize poorly and slowly, and highly lipophilic ones too rapidly. The incorporation of drugs into micelles allows regulation of their internalization parameters, and newly-described block copolymers can be selectively tailored to suit specific drugs. This report compares internalization of Cell Tracker CM-DiI (DiI), a highly lipophilic non-cytotoxic fluorescent probe in common use in biology, from the freely-presented (non-micelle-incorporated) and micelle-incorporated states. DiI was effectively incorporated (>60%) into 25-50 nm diameter spherical micelles made from polycaprolactone-b-polyethylene oxide block copolymer. Confocal microscopy was used to evaluate the internalization of DiI into mixed neuron-glia cultures (2-14 days in vitro, 2DIV-14DIV). Incorporation of DiI into micelles strikingly reduced the rate and extent of its internalization in both 2DIV and 14DIV cultures. Both the age of the cultures and the block copolymer employed to construct the micelles significantly influence the internalization of micelle-incorporated probe.

Analysis of Variance↗
PubMed2000

Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone.

Block copolymer micelles formed from copolymers of poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) were investigated as a drug delivery vehicle for dihydrotestosterone (DHT). The physical parameters of the PCL-b-PEO micelle-incorporated DHT were measured, including the loading capacity of the micelles for DHT, the apparent partition coefficient of DHT between the micelles and the external medium and the kinetics of the release of DHT from the micelle solution. The MTT survival assay was used to assess the in vitro biocompatibility of PCL-b-PEO micelles in HeLa cell cultures. The biological activity of the micelle-incorporated DHT was evaluated in HeLa cells which had been co-transfected with the expression vectors for the androgen receptor and the MMTV-LUC reporter gene. The PCL-b-PEO micelles were found to have a high loading capacity for DHT and the release profile of the drug from the micelle solution was found to be a slow steady release which continued over a 1-month period. The biological activity of the micelle-incorporated DHT was found to be fully retained.

Dihydrotestosterone↗
PubMed2000

Rigid piston approximation for computing the transfer function and angular response of a fiber-optic hydrophone.

The transfer function of a fiber-optic hydrophone (FOH) is computed for various fiber core radii. The hydrophone is modeled as a rigid disk, with plane waves impinging at normal or oblique incidence. The total sound field is written as the sum of the incident field and the field diffracted from the hydrophone. The diffracted field is approximated by the field generated by a vibrating planar piston in an infinite rigid baffle. For normal incidence and a pointlike fiber core, an analytical solution is presented. For finite fiber core radii, and for oblique incidence, the transfer functions are computed numerically. The calculated transfer functions exhibit an oscillatory frequency dependency that is most pronounced for small fiber cores. The solution for a core radius of 2.5 microm can be very well approximated by the analytical solution for a pointlike core at frequencies of up to 30 MHz. The results for normal incidence can be directly employed to deconvolute ultrasonic pressure signals measured with an FOH. From the transfer functions for oblique incidence, the angular response of the hydrophone is calculated. The angular response obtained here differs significantly from the model commonly used for piezoelectric hydrophones. The effective hydrophone radius derived from the angular response shows a strong frequency dependency. For low frequencies, it is found to be larger than the outer fiber radius, whereas it generally lies between the outer radius and the fiber core radius for frequencies above 10 MHz.

Acoustics↗
PubMed1999

Cellular internalization of PCL(20)-b-PEO(44) block copolymer micelles.

The cellular internalization of polycaprolactone-b-poly(ethylene oxide) (PCL(20)-b-PEO(44)) copolymer micelles were investigated in PC12 cells cultures. The micelles were found to be internalized into PC12 cells when followed over the 4-h incubation period. Also, the internalization process was found to fulfill the basic criteria for endocytotic uptake in that it was time, temperature, pH and energy dependent. In addition, the use of other pharmacological manipulations (hypertonic treatment, Brefeldin A) provide further evidence that the mode of cellular internalization is in fact endocytotic.

Animals↗
PubMed1999

5-Cyanovaleramide production using immobilized Pseudomonas chlororaphis B23.

A biocatalytic process for the hydration of adiponitrile to 5-cyanovaleramide has been developed which can be run to higher conversion, produces more product per weight of catalyst, and generates significantly less waste products than alternate chemical processes. The biocatalyst consists of Pseudomonas chlororaphis B23 microbial cells immobilized in calcium alginate beads. The cells contain a nitrile hydratase (EC 4.2.1.84) which catalyzes the hydration of adiponitrile to 5-cyanovaleramide with high regioselectivity, and with less than 5% selectivity to byproduct adipamide. Fifty-eight consecutive batch reactions with biocatalyst recycle were run to convert a total of 12.7 metric tons of adiponitrile to 5-cyanovaleramide. At 97% adiponitrile conversion, the yield of 5-cyanovaleramide was 13.6 metric tons (93% yield, 96% selectivity), and the total weight of 5-cyanovaleramide produced per weight of catalyst was 3150 kg/kg (dry cell weight).

Amides↗
PubMed1997

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D2 receptor Taq A1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with SAB was similarly found.

Adult↗
PubMed1997

Fluorescence imaging in human identity testing.

We have investigated the use of fluorescence detection and the FluorImager S1 System (Molecular Dynamics) for analyzing a comprehensive set of human DNA typing tests. We used an alkaline phosphatase-conjugated YNH24 oligonucleotide probe to the repeat-containing D2S44 locus to detect both alleles in 50 ng of human genomic DNA (0.025 amol) by Southern hybridization using a chemifluorescent substrate. We used a similar approach to quantify human DNA using an enzyme-conjugated oligonucleotide probe to the D17Z1 locus. Both fluorescent nucleic acid gel staining and direct fluorescent labeling methods were tested to detect PCR-based D1S80 and short tandem repeat (STR) multiplex allele profiles. The fluorescent staining method sensitively detected these allelic profiles in both denaturing and non-denaturing acrylamide gels using a simple, 10-min procedure. Fluorescent primers eliminate the doublet band patterns often seen with staining methods, which label both strands of the amplified products. This complicates interpretation of STR typing tests. Only one primer for each locus is labeled, so only one strand of the DNA product is detected. Fluorescein end-labeled primers were used in multiplex PCR to amplify, detect and type STRs.

Benzothiazoles↗
PubMed1996

Ion-Induced Morphological Changes in "Crew-Cut" Aggregates of Amphiphilic Block Copolymers

The addition of ions in micromolar (CaCl2 or HCl) or millimolar (NaCl) concentrations can change the morphology of "crew-cut" aggregates of amphiphilic block copolymers in dilute solutions. In addition to spherical, rodlike, and univesicular or lamellar aggregates, an unusual large compound vesicle morphology can be obtained from a single block copolymer. Some features of the spontaneously formed large compound vesicles may make them especially useful as vehicles for delivering drugs and as models of biological cells. Gelation of a dilute spherical micelle solution can also be induced by ions as the result of the formation of a cross-linked "pearl necklace" morphology.

Journal Article↗
PubMed1996

Using multiplex PCR amplification and typing kits for the analysis of DNA evidence in a serial killer case.

Analysis of DNA evidence in a serial killer case was performed using the AmpliType HLA-DQ alpha-, AmpliType PM-, and the GenePrint STR Multiplex System PCR Amplification Kits. In addition, a sex typing procedure using the X-Y homologous gene amelogenin was carried out. DNA profiles from a single hair with attached sheath material, recovered from underneath the seat cover of the suspect's car seat were compared with DNA profiles derived from reference head hairs from a homicide victim. From the evidentiary sample only 9 ng of human DNA could be recovered. In a sample, where the quantity of DNA becomes a critical issue a powerful route is the simultaneous amplification of several loci (multiplex PCR). This is the first report where commercially available multiplex PCR amplification and typing kits have been introduced for the analysis of DNA evidence in a serial killer case and the analysis has been admitted in court.

Adult↗
PubMed1990

Increased migration rate observed in DNA from evidentiary material precludes the use of sample mixing to resolve forensic cases of identity.

The analysis of restriction fragment length polymorphisms in forensic DNA samples can be used to determine whether any two or more samples have the same biological origin. However, sometimes DNA recovered from evidentiary material, such as blood or semen stains, migrates at a different rate than an exemplar sample. This difference in migration, while maintaining the same overall pattern, produces a shift in the position of the bands. To verify that a shift in migration has occurred between evidence and exemplar samples, we have utilized two DNA probes that recognize DNA fragments that do not vary in size between individuals (monomorphic). The results obtained with this type of internal control show that differences in migration rate between exemplar and evidentiary samples can be recognized and accounted for and do not affect the ability to decide whether two patterns match. A common practice in many analytical tests, to show identity between two samples, is to test the properties of the samples individually and mixed. However, this approach is not applicable to all forensic DNA identity tests. In many cases, DNA from forensic samples may be irreversibly modified and this can alter the migration rate of the DNA samples. Thus, in a mixture of DNA from exemplar and evidence, the same polymorphic DNA fragments may not comigrate and produce a composite pattern which could lead to false exclusions.

DNA↗
PubMed1989

Comparison of phenotyping and genotyping of lymphoid neoplasms.

Comparison of phenotyping (PT) and genotyping (GT) of lymphoid neoplasms was performed on 51 specimens including lymph nodes, bone marrows, and body fluids. PT was performed with a flow cytometer using a large monoclonal antibody panel. GT included the testing for gene rearrangements of heavy chain, kappa and lambda light chains, and T-cell receptor beta-chain genes with DNA probes. The results obtained from these two techniques were generally compatible in terms of clonality and cell lineage. Only one case of B-cell lymphoma was not diagnosed by PT but showed gene rearrangement. For T-cell lymphoma, GT offers a more definitive diagnosis than does PT. Biclonality was demonstrated in one case of hairy cell leukemia by GT only. The rearranged band also offers a definitive clonal identification based on electrophoretic mobility. GT can detect a monoclonal population as small as 5% and can be performed on old or fresh specimens. PT requires 20% abnormal cells and a fresh specimen. It is concluded that GT is superior to PT for lymphoid tumor diagnosis, but it should be reserved as a supplementary test at this stage because of its technical complexity.

Antibodies, Monoclonal↗
PubMed1988

Clonal immunoglobulin gene rearrangements in chronic lymphocytic leukemia: a correlative study.

Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for immunoglobulin gene and T-cell receptor gene rearrangements. Immunoglobulin heavy chain gene rearrangements were demonstrable in 41 cases. One rearrangement of the T-cell receptor beta chain gene was detected. Quantification of the relative intensities of germline and rearranged DNA bands suggests that a significant component of the lymphocytosis may be due to cell populations other than the malignant clonal population, particularly in earlier stages of the disease. A direct relationship was found between severity of disease and the relative amount of clonal immunoglobulin heavy chain gene rearrangement. Preliminary data for 12 patients followed sequentially indicated that clinical deteriorations or improvements are reflected in an increase or decrease, respectively, in the proportion of cells with rearranged immunoglobulin genes. Change in the relative proportion of cells with germline versus rearranged genes may provide an additional useful criterion for staging CLL, for more precisely defining the abnormal lymphocyte population, and for monitoring progression of the disease and efficacy of treatment.

Adult↗