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Biomedical subjects

D Paul

Publications and source records attributed to D Paul.

At least 55 records · Page 3Linked to original sources
PubMed1999

Investigation of plasma protein adsorption on functionalized nanoparticles for application in apheresis.

Particles with specific ligands for the adsorption of plasma proteins can be used in therapeutic or preparative apheresis. The development of these particles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functionalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and with tryptophan and histidine spaced with diamines of different length. Suitable protocols were developed for the washing of particles and the subsequent desorption of proteins adsorbed from human plasma. The adsorption pattern, as well as the quantification of the overall adsorption of proteins on these modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound human serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple correlations although in general more hydrophobic ligands bound higher quantities of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorption of fibrinogen expressed a different pattern. In this case, particular nanoparticles functionalized with aliphatic diamines bound significantly higher amounts of fibrinogen than all other ligands.

Adsorption↗
PubMed1999

Multidrug resistance.

Explore the source record for details and available documents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Weibull models of fracture strengths and fatigue behavior of dental resins in flexure and shear.

In estimating lifetimes of dental restorative materials, it is useful to have available data on the fatigue behavior of these materials. Current efforts at estimation include several untested assumptions related to the equivalence of flaw distributions sampled by shear, tensile, and compressive stresses. Environmental influences on material properties are not accounted for, and it is unclear if fatigue limits exist. In this study, the shear and flexural strengths of three resins used as matrices in dental restorative composite materials were characterized by Weibull parameters. It was found that shear strengths were lower than flexural strengths, liquid sorption had a profound effect on characteristic strengths, and the Weibull shape parameter obtained from shear data differed for some materials from that obtained in flexure. In shear and flexural fatigue, a power law relationship applied for up to 250,000 cycles; no fatigue limits were found, and the data thus imply only one flaw population is responsible for failure. Again, liquid sorption adversely affected strength levels in most materials (decreasing shear strengths and flexural strengths by factors of 2-3) and to a greater extent than did the degree of cure or material chemistry.

Composite Resins↗
PubMed1998

Long-term expression of differentiated functions in hepatocytes cultured in three-dimensional collagen matrix.

Hepatocytes entrapped in collagen gel and cultured in serum-free conditions survived longer than cells cultured on plastic (5 days vs. 3 weeks), showed fewer signs of early cell senescence (no increase in c-fos oncoprotein expression), and maintained the expression of differentiated hepatic metabolic functions over a longer period of time. Cells cultured in collagen gels retained their ability to respond to hormones. The insulin-stimulated glycogen synthesis rate remained fairly constant during 18 days in culture (between 5.4 +/- 0.37 and 9 +/- 2.7 nmol glucose/h/microg DNA). Collagen-cultured hepatocytes recovered glycogen stores to levels similar to those found in liver, or in hepatocytes isolated from fed rats. Urea synthesis from ammonia remained stable for more than 2 weeks (average value, 23 +/- 4 nmol urea/h/microg DNA). The rate of albumin synthesis in collagen-entrapped cells was maintained above the day-1 level during 18 days in culture. Cells showed high levels of glutathione (GSH) (1,278 +/- 152 pmol/microg DNA). Biotransformation activities CYP4501A1, CYP4502A2, CYP4502B1, and CYP4503A1 remained fairly stable in collagen-cultured hepatocytes. CYP4502E1 and CYP4502C11 decreased but were still measurable after 18 days. After 4 days in culture, GST activity returned to levels observed in isolated hepatocytes. In contrast with plastic cultures, cells responded to CYP450 inducers (methylcholanthrene for CYP4501A1, CYP4501A2, and glutathione-transferase, and ethanol for CYP4502E1) for more than 2 weeks. CYP4501A1, CYP4501A2, and glutathione-transferase A2 (GST A2) induction was preceded by an increase in specific mRNA, while the effects on CYP4502E1 seemed to be at a posttranslational level. Analysis of the expression of relevant hepatic genes by reverse Northern and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that culturing hepatocytes in collagen gels results in a sustained higher expression of key liver transcription factor genes DBP, C/EBP-alpha and -beta, and HNF-1 and -4, as well as specific liver enzyme genes (phosphoenol pyryvate carboxykinase, and carbamoylphosphate-synthetase I).

Animals↗
PubMed1998

Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16.

KET is a member of the newly discovered family of proteins that is related to the tumor suppressor p53. Here we describe the molecular cloning of a human cDNA of 4846 bp encoding a protein of 680 amino acids. The human KET protein shares 98% identity with the previously characterized rat homolog. The remarkably high degree of conservation lends support to the notion that KET proteins have important basic functions in development and differentiation. Using the GeneBridge 4 radiation hybrid panel, we have mapped KET to human Chromosome (Chr) 3q27. KET is located between the somatostatin gene SST (proximal) and the apolipoprotein D gene APOD (distal) in a region of conserved synteny to mouse Chr 16. This chromosomal region is deleted in early stages of tumorigenesis of mouse islet cell carcinomas and contains the hitherto unidentified Loh2 gene, a putative suppressor of angiogenesis. The murine homolog Ket was mapped in an interspecific backcross panel and falls into this region of loss of heterozygosity. From our mapping data we infer that KET might act as a tumor suppressor and is considered as a candidate for Loh2.

Amino Acid Sequence↗
PubMed1998

Functionality of MDCK kidney tubular cells on flat polymer membranes for biohybrid kidney.

The prerequisite for the development of a biohybrid artificial kidney, is a substrate for confluent growth of renal cells forming an epithelial monolayer without any leaks. Conventional cell culture supports cannot be adapted for this purpose, because they lack adequate mechanical properties and thermal stability. From two suitable materials, polysulfone and polyacrylonitrile, two permeable polymeric membranes have been produced that were, according to ISO 10993-5, not cytotoxic. Cloned Madin Darby Canine Kidney (MDCK) cells (an established renal cell line) were cultured on the surface of the plastic materials, and on conventional cell culture supports. With all materials, assays of mitochondrial and lactate dyhydrogenases exhibited similar proliferation and the viability of the MDCK cells. Transmission electron microscopy showed the expression of a normal morphology of kidney tubular cells. Perfect barrier function, consequent on the formation of intercellular junctions in a confluent tight epithelium, was visualized in electron micrographs, and quantified by measurement of the transepithelial resistance. The uniformity of the cells grown was demonstrated in samples by electron microscopy and in the whole epithelium by intravital impedance analysis. It was concluded that polymeric membranes produced from polysulfone or polyacrylonitrile are appropriate substrates in the design of biohybrid kidney devices.

Journal Article↗
PubMed1998

A concept analysis of parent-infant attachment.

A concept analysis, the clarification of a concept, is the first step towards building the foundations of nursing theory, research and practice. As a relevant concept for nurses working with childbearing families, parent-infant attachment is an important part of the body of nursing knowledge. Wilson's method of concept analysis was used to generate antecedents, critical attributes and consequences of parent-infant attachment, highlighting the need to refine measurements of this concept.

Canada↗
PubMed1998

Crack propagation directions in unfilled resins.

Posterior composite restorative materials undergo accelerated wear in the occlusal contact area, primarily through a fatigue mechanism. To facilitate the timely development of new and improved materials, a predictive wear model is desirable. The objective of this study was to develop a finite element model enabling investigators to predict crack propagation directions in resins used as the matrix material in composites, and to verify these predictions by observing cracks formed during the pin-on-disc wear of a 60:40 BISGMA:TEGDMA resin and an EBPADMA resin. Laser confocal scanning microscopy was used to measure crack locations. Finite element studies were done by means of ABAQUS software, modeling a cylinder sliding on a material with pre-existing surface-breaking cracks. Variables included modulus, cylinder/material friction coefficient, crack face friction, and yield behavior. Experimental results were surprising, since most crack directions were opposite previously published observations. The majority of surface cracks, though initially orthogonal to the surface, changed direction to run 20 to 30 degrees from the horizontal in the direction of indenter movement. Finite element modeling established the importance of subsurface shear stresses, since calculations provided evidence that cracks propagate in the direction of maximum K(II)(theta), in the same direction as the motion of the indenter, and at an angle of approximately 20 degrees. These findings provide the foundation for a predictive model of sliding wear in unfilled glassy resins.

Composite Resins↗
PubMed1998

Tactile illusion-produced number perception in blind and sighted persons.

OBJECTIVE: To determine whether tactile receptive communication is possible in both sighted and blind persons through the use of a mechanical device that creates the perception of continuous contact through sequential points of vibration on the skin and whether the ability of these two groups differs. MATERIAL AND METHODS: The cohort consisted of 20 sighted and 20 blind subjects who had no prior exposure to a tactile communication device that produces a tactile illusion. Each subject was presented number sequences created by the tactile illusion in the form of single-digit, three-digit, and four-digit sequences, and the number of trials needed for correct identification was recorded. RESULTS: On average, the sighted subjects tended to identify the digit sequences sooner than did the blind subjects by almost one trial; however, this difference was not statistically significant. Younger subjects and female subjects also tended to identify the digit sequences sooner. Nevertheless, the overall correlation between age and number of trials across all replications was relatively minor. CONCLUSION: Tactile receptive communication is possible through the use of a mechanical device used to create tactile illusions. The tactile illusion of numbers is equally perceived by blind and sighted persons.

Adult↗
PubMed1997

Transgenic mice transcribing the human H1 zero histone gene exhibit a normal phenotype.

The linker histone H1degree accumulates in terminally differentiating cells and replaces other members of the H1 histone family, even in the absence of cell division. To study the role of H1degree in vivo, we have created two lines of transgenic mice with either the human H1degree promoter (HH minigene) or the mouse metallothionein T promoter (MH minigene) upstream of the human H1degree gene. Mice bearing the minigenes HH or MH overexpress human H1degree mRNA at 10-20-fold higher levels than in normal mice in a constitutive or metal-inducible manner. In contrast to this increase in mRNA content, which was studied in liver, kidney and brain, no significant changes in the relative proportions of the H1 protein subtypes, including H1degree were observed. Transgenic mice exhibited normal anatomic phenotypes, growth rates and reproduction rates. Thus, our results suggest a posttranscriptional and/or translational mechanism that compensates the unbalanced linker-histone expression in different tissues.

Animals↗
PubMed1997

The effects of postmortem delay on mu, delta and kappa opioid receptor subtypes in rat brain and guinea pig cerebellum evaluated by radioligand receptor binding.

Studies of human and animal central nervous system receptor degradation and measurement postmortem are important as human tissue can rarely be collected under ideal experimental conditions. Correlating the change in binding of opioid receptor subtypes over time will help define the conditions under which human studies may be valid. The present study was designed to investigate the rate at which opioid receptor subtypes degrade postmortem. Brains from rats or cerebelli from guinea pigs were kept at 22 degrees C or 4 degrees C at times from zero to 24 hours to simulate two common human collection techniques; room temperature and morgue refrigeration. Tissue homogenates from these brains were analysed for mu1, mu2, delta, kappa1 and kappa3 opioid receptor binding using standard radioligand binding techniques. At room temperature mu1, mu2 and delta opioid receptor binding was reduced between 6 and 12 hours, whereas kappa1 and kappa3 binding was reduced after 24 hours. At 4 degrees C mu1, mu2, delta, kappa1 and kappa3 binding remained constant over the 24 hour period.

Animals↗
PubMed1997

Contact activation of plasmatic coagulation on polymeric membranes measured by the activity of kallikrein in heparinized plasma.

Kallikrein is involved in the generation of bradykinin during extracorporal circulation, that is believed to play an important role in cases of anaphylactic shock during hemodialysis. Therefore, a method for the assessment of kallikrein generation was developed, based on the chromogenic substrate S-2302. Comparison of kallikrein-like activity on glass using citrate or heparinized plasma demonstrated enhanced activity in the presence of heparin. The applicability of the assay, and the time course of kallikrein generation was demonstrated with glass and cuprophan. Membranes based on pure polyacrylonitrile, or its copolymers differing in their content of acrylic acid, 2-hydroxyethyl acrylate, and allylsulphonate were investigated with respect to kallikrein-like activity, and physicochemical surface properties. It was found that high content in 2-hydroxyethyl acrylate, and acrylic acid caused a substantial activation of the contact system while low content in allylsulphonate (less than 2 mol%) did not result in enhanced kallikrein-like activity. The activating materials were characterized to be highly wettable, and had the most negative zeta potentials.

Acrylates↗
PubMed1997

Morphological evidence for a different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata.

A polyclonal antibody against the beta 1 subunit of the fibronectin (FN) receptor was used to mimic the early events of integrin receptor functioning to study the initial cellular processes during the organization of FN matrix on biomaterials. Hydrophilic glass and hydrophobic octadecylsilane (ODS) surfaces have been applied as models for different biocompatible materials. By immunofluorescence we could demonstrate that FN receptors organize on the dorsal cell surface of adhering fibroblasts in a specific linear pattern along with actin filaments, but only if the cells were attached to hydrophilic glass. In contrast, FN receptors were not reorganized on hydrophobic octadecylsilane (ODS). In parallel experiments, FN matrix formation after 72 h of incubation on the same substrata has been analyzed microscopically, and quantified by cell ELISA, in order to be further correlated with the integrin receptor functioning in contact with the biomaterials. It was found that FN structuring and the amount of FN matrix have been significantly diminished on ODS that was related to the observed changes in integrin receptor functioning. To learn more about the mechanism of this phenomenon, desorption of 125I-FN from these substrata was studied and found to be significantly decreased on hydrophobic ODS. As a consequence, FN receptor (function) might be arrested on the ventral cell surface, thus the important role of beta 1 integrins in the positional organization of the FN matrix may be disturbed. In light of these facts, antibody-induced clustering of FN receptor can be considered as a useful model for studying the early steps of FN matrix formation on biomaterials.

Adsorption↗
PubMed1997

Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients.

PURPOSE: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes. PATIENTS AND METHODS: Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n = 3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY). RESULTS: Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients (20 mg/m2), and transient clinical and/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail. CONCLUSION: We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Adult↗