Showing papers by "Case Western Reserve University published in 1983"

Current status of transition-state theory

Abstract: We present an overview of the current status of transition-state theory and its generalizations. We emphasize (i) recent improvements in available methodology for calculations on complex systems, including the interface with electronic structure theory, (ii) progress in the theory and application of transition-state theory to condensed-phase reactions, and (iii) insight into the relation of transition-state theory to accurate quantum dynamics and tests of its accuracy via comparisons with both experimental and other theoretical dynamical approximations.

Salmonella mutagenicity test results for 250 chemicals

Abstract: This publication is a presentation of Salmonella testing results on 250 coded chemicals, encompassing 370 tests. The majority of these results were previously summarized in issues of the National Toxicology Program Technical Bulletin. However, some interpretations were changed since publication in the NTP Bulletin, based upon a reevaluation of the data. The presentation here is designed both to summarize the results in the text and to present the data so that the reader has the opportunity of performing an independent evaluation of the data. The chemicals tested, their source, and purity (where known) are listed and their structures are given in Appendix 1.

Mutagenicity and genotoxicity of nitroarenes: All nitro-containing chemicals were not created equal

Abstract: The nitrated polycyclic aromatic hydrocarbons constitute a group of chemicals of environmental concern which display a broad spectrum of mutagenic, genotoxic and carcinogenic properties. Some members of the group are the most potent direct-acting bacterial mutagens while others exhibit low levels of potencies which require metabolic activation mixtures. Bacterial mutagenicity is dependent upon reduction of the nitro function. In mammalian cell systems the genetic and genotoxic effects of these nitrated chemicals include the induction of unscheduled DNA synthesis, sister-chromatid exchanges, chromosomal aberrations, gene mutations and cell transformation. The qualitative as well as quantitative expression of these effects is dependent upon the species and tissue of origin as well as culture history of the cell which in turn determine their enzymic capabilities and the conversion of these nitroarenes to ultimate mutagens and genotoxicants. In eukaryotic cells the following bioactivation pathways have been recognized: (a) reduction of the nitro moiety, (b) ring oxidation (the nature of which is influenced by the nitro function) followed by reduction of the nitro group, and (c) ring oxidation without concomitant reduction of the nitro moiety.

Impaired Cell-Mediated Immunity in Patients with Classic Hemophilia

Abstract: THREE cases of Pneumocystis carinii pneumonia, two of which were fatal, have recently been observed in patients with severe classic hemophilia who had been treated with lyophilized preparations of ...

Pyogenic and fungal vertebral osteomyelitis with paralysis.

Abstract: A retrospective review of the cases of sixty-one patients with vertebral osteomyelitis revealed that the associated diseases of diabetes mellitus and rheumatoid arthritis as well as increased age and a more cephalad level of infection predisposed to paralysis. For patients with paralysis and a long-term follow-up, the prognosis for isolated nerve-root deficits is good with or without surgery. For patients with spinal cord compression, the results generally are better with anterior decompression and stabilization than with laminectomy. Early treatment should be directed at prevention of intrinsic spinal-cord damage, which is irreversible.

The Effect of Stimulus Parameters on the Recruitment Characteristics of Direct Nerve Stimulation

Abstract: The effect of stimulus parameters on the recruitment characteristics of motor nerve was studied for regulated current monophasic and balanced charge biphasic stimuli. Results of a nerve model investigation indicated that the threshold difference between different diameter nerve fibers would be dependent on pulse width, the choice between monophasic and biphasic stimuli, and the delay between the primary cathodic and secondary anodic pulses. Threshold difference increased with decreasing pulse width, the greatest effects evident for pulses less than 100 ?s. Biphasic stimulation with no delay between pulses provided greater threshold separation than monophasic stimulation or biphasic stimulation with delay. Animal experiments, in which recruitment in a nerve trunk composed of mixed diameter nerve fibers was examined, showed a decrease in recruitment slope with a decrease in pulse width and with the use of a biphasic, zero delay pulse. These results were examined through muscle force measurements using both a metal loop electrode encircling the nerve trunk and a nerve cuff electrode, i. e., a loop electrode in an insulating tube.

Automatic calibration of conceptual rainfall-runoff models: The question of parameter observability and uniqueness

Abstract: Reasons for the inability to obtain unique and conceptually realistic parameter sets for conceptual rainfall-runoff models are examined in this paper. The problem is first posed in a framework that allows a more consistent and logical analysis of the related aspects. Response surface studies demonstrate that choice of an objective function that better explains some of the stochastic properties of the errors in the output results in a smoother, better shaped response surface; hence the chances of obtaining unique and realistic parameter estimates are improved. However, our analysis indicates that part of the problem is also due to inadequacies in the model structure. The arguments are illustrated using results obtained with the soil moisture accounting model of the National Weather Service's river forecast system.

Cell surface heparan sulfate mediates some adhesive responses to glycosaminoglycan-binding matrices, including fibronectin

Abstract: Proteins with affinities for specific glycosaminoglycans (GAC's) were used as probes for testing the potential of cell surface GAG's to mediate cell adhesive responses to extracellular matrices (ECM). Plasma fibronectin (FN) and proteins that bind hyaluronate (cartilage proteo-glycan core and link proteins) or heparan sulfate (platelet factor 4 [PF4]) were adsorbed to inert substrata to evaluate attachment and spreading of several 3T3 cell lines. Cells failed to attach to hyaluronate-binding substrata. The rates of attachment on PF4 were identical to those on FN; however, PF4 stimulated formation of broad convex lamellae but not tapered cell processes fibers during the spreading response. PF4-mediated responses were blocked by treating the PF4-adsorbed substratum with heparin (but not chondroitin sulfate), or alternatively the cells with Flavobacter heparinum heparinase (but not chondroitinase ABC). Heparinase treatment did not inhibit cell attachment to FN but did inhibit spreading. Cells spread on PF4 or FN contained similar Ca2+-independent cell-substratum adhesions, as revealed by EGTA-mediated retraction of their substratum-bound processes. Microtubular networks reorganized in cells on PF4 but failed to extend into the broadly spread lamellae, where fine microfilament bundles had developed. Stress fibers, common on FN, failed to develop on PF4. These experiments indicate that (a) heparan sulfate proteoglycans are critical mediators of cell adhesion and heparan sulfate-dependent adhesion via PF4 is comparable in some, but not all, ways to FN-mediated adhesion, (b) the uncharacterized and heparan sulfate-independent "cell surface" receptor for FN permits some but not all aspects of adhesion, and (c) physiologically compatible and complete adhesion of fibroblasts requires binding of extracellular matrix FN to both the unidentified "cell surface" receptor and heparan sulfate proteoglycans.

Prophylactic Cholecystectomy or Expectant Management for Silent Gallstones: A Decision Analysis to Assess Survival

Abstract: Decision analysis was done to compare the consequences of prophylactic cholecystectomy with expectant management for silent gallstone disease. Probability values were derived from a study of the natural history of silent gallstone disease, published cholecystectomy mortality rates, and life tables. The two strategies were compared by calculating cumulative numbers of person-years lost for hypothetical cohorts of men and women. Prophylactic cholecystectomy slightly decreases survival. A 30-year-old man choosing prophylactic cholecystectomy instead of expectant management would lose, on average, 4 days of life; a 50-year-old man would lose 18 days. Consideration of monetary costs and discounting further disfavors prophylactic cholecystectomy. Sensitivity analysis shows that differences between the two strategies remain small over a broad range of probability values, both for men and women.

Biopsy needle characteristics assessed in the laboratory.

Abstract: Radiologists are frequently called upon to perform percutaneous biopsy. Selection of the proper needle is becoming more complex as the number of types increases and reports of better results with certain needles proliferate. The authors evaluated a wide variety of needles of different caliber, cutting tip, and bevel. Using a standard biopsy technique for in vitro specimens, the samples were analyzed quantitatively by precise weight measurement and qualitatively by cytopathological means. It was concluded that large-bore needles were superior to "skinny" needles, and small-bore needles having an acute bevel angle were superior to flat-bevel needles of similar gauge in terms of specimen size and preservation.

Apparatus and method for sensing species, substances and substrates using oxidase

Abstract: A sensor apparatus is disclosed for sensing substances, species, substrates, etc. using oxidase. The apparatus includes a pair of potentiostat operating electrode systems. In one embodiment each electrode system includes respective working, counter and reference electrodes, and in another embodiment each electrode system includes a respective working electrode and the counter and reference electrodes are shared by both electrode systems. The oxidase material is immobilized on the working electrode of one of the electrode systems. A method also is disclosed for concentration sensing using oxidases.

Sequence-specific interaction of R17 coat protein with its ribonucleic acid binding site

Abstract: The interaction between phage R17 coat protein and its RNA binding site for translational repression was studied as an example of a sequence-specific RNA--protein interaction. Nuclease protection and selection experiments define the binding site to about 20 contiguous nucleotides which form a hairpin. A nitrocellulose filter retention assay is used to show that the binding between the coat protein and a synthetic 21-nucleotide RNA fragment conforms to a simple bimolecular reaction. Unit stoichiometry and a Kd of about 1 nM are obtained at 2 degrees C in buffer containing 0.19 M salt. The interaction is highly sequence specific since a variety of RNAs failed to compete with the 21-nucleotide fragment for coat protein binding.

Postnatally induced formation of the corpus callosum in acallosal mice on glia-coated cellulose bridges

Abstract: Developing axons of the corpus callosum of mice are guided across the cerebral midline by a slinglike glial structure that forms transiently between the hemispheres. If the "sling" is cut at precallosal stages, the would-be callosal fibers whirl into paired neuromas adjacent to the longitudinal cerebral fissure. In experiments on such surgically acallosal animals, the aberrant commissural axons maintained a potential to regrow across the hemispheres at prenatal and early postnatal stages if they were presented with a properly aligned, glia-covered scaffold spanning the hemispheres.

Poly(ADP-ribose) Polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis.

Abstract: Inhibitors of poly(ADP-ribose) polymerase stimulated the level of DNA, RNA, and protein synthesis in DNA-damaged L1210 cells but had negligible effects in undamaged L1210 cells. The poly(ADP-ribose) polymerase inhibitors stimulated DNA repair synthesis after cells were exposed to high concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (68 and 136 microM) but not after exposure to low concentrations (13.6 and 34 microM). When the L1210 cells were exposed to 136 microM N-methyl-N'-nitro-N-nitrosoguanidine, the activation of poly(ADP-ribose) polymerase resulted in the rapid depletion of oxidized nicotinamide adenine dinucleotide (NAD+) levels and subsequent depletion of adenosine 5'-triphosphate (ATP) pools. After low doses of N-methyl-N'-nitro-N-nitrosoguanidine (13.6 microM), there were only small decreases in NAD+ and ATP. Poly(ADP-ribose) polymerase inhibitors prevented the rapid fall in NAD+ and ATP pools. This preservation of the ATP pool has a permissive effect on energy-dependent functions and accounts for the apparent stimulation of DNA, RNA, and protein synthesis. Thus, the mechanism by which poly(ADP-ribose) polymerase inhibitors stimulate DNA, RNA, and protein synthesis in DNA-damaged cells appears to be mediated by their ability to prevent the drastic depletion of NAD+ pools that occurs in heavily damaged cells, thereby preserving the cells' ability to generate ATP and maintain energy-dependent processes.

In vivo biocompatibility studies. I. The cage implant system and a biodegradable hydrogel

Abstract: A cage implant system has been utilized to examine the in vivo biocompatibility of a biodegradable hydrogel, poly(2-hydroxy-ethyl-L-glutamine) (PHEG). This system permits the quantitative determination of the components of the inflammatory exudate which surrounds the implanted polymer within the cage system. This system permits the serial examination of exudate components without sacrificing the animal. In addition, this system allows the subsequent removal of the polymer for surface and mechanical studies. Following implantation of the biodegradable hydrogel, quantitative and differential white cell counts of the exudates were determined over a 21-day period. In addition, concomitant extracellular enzyme analyses for alkaline phosphatase, acid phosphatase, prostatic acid phosphatase, leucine amino-peptidase, and Cathepsin B1 were determined. Corresponding control samples from exudates of the cage implant without the polymer were also determined. The two-tailed Student's t-test for unpaired samples was used to statistically compare the control and implanted polymer values for these respective analyses at the various time periods. A comparison of the cellular response for the control system and the PHEG system did not show statistically significant differences during the first 7 days following implantation. The acute inflammatory response, polymorphonuclear leukocyte predominant, was followed by a mild chronic inflammatory response, macrophage and lymphocyte predominant, and during this time period, 8-14 days, macrophages were present in significantly larger numbers for the PHEG system when compared to the control values. Enzymic analysis of the exudates revealed statistically significant differences between control and PHEG values at time intervals where no differences were noted in cell density or population. These results are discussed in terms of cell-polymer interactions leading to cellular activation and enhanced enzyme exocytosis by the inflammatory cells. Stress-strain measurements on implanted PHEG samples showed that significant in vivo degradation had occurred during the acute inflammatory phase of the response, i.e., the first 7 days.

The basis of the insensitivity of Salmonella typhimurium strain TA98/1,8-DNP6 to the mutagenic action of nitroarenes

Abstract: Salmonella typhimurium tester strain TA98/1,8-DNP6 is resistant to the mutagenicity of 1,8-dinitropyrene because it lacks an esterification enzyme which is needed for the formation of the ultimate mutagen, presumably the corresponding hydroxamic acid ester. This enzyme does not appear to be required for the activation of all nitroarenes and arylamines, as some of these are fully active in TA98/1,8-DNP. It is suggested that these form electrophilic arylnitrenium ions nonenzymatically from nitroso- and N-hydroxylamino-arenes intermediates. The esterification enzyme appears to be a transacetylase. An assay using 2-aminofluorene as the acetyl acceptor is described. Derivatives of S. typhimurium TA100 also lacking this enzyme were obtained by Tn5-mediated mutagenesis.

Surface Roughness Effects in Hydrodynamic Lubrication: The Flow Factor Method

Abstract: Extension et generalisation du modele d'ecoulement moyen de Patir et Cheng pour l'obtention d'une equation de Reynolds moyenne en presence d'une rugosite de surface bidimensionnelle. Calcul des valeurs des facteurs d'ecoulement apparaissant dans le formalisme au moyen d'un developpement de perturbation de la pression dans un film parallele nominal. Accord des resultats de perturbation avec les resultats d'une simulation numerique recente jusqu'a ce que le contact de surface devienne important les deux approches devenant inadequates a ce moment-la. Mise en evidence de la dependance des facteurs d'ecoulement des parametres de rugosite sous une forme explicite simple

Fluid Mechanics in Crystal Growth—The 1982 Freeman Scholar Lecture

Abstract: An attempt is made to unify the current state of knowledge in crystal growth techniques and fluid mechanics. After identifying important fluid dynamic problems for such representative crystal growth processes as closed tube vapor transport, open reactor vapor deposition, and the Czochralski and floating zone melt growth techniques, research results obtained to date are presented. It is noted that the major effort to date has been directed to the description of the nature and extent of bulk transport under realistic conditions, where bulk flow determines the heat and solute transport which strongly influence the temperature and concentration fields in the vicinity of the growth interface. Proper treatment of near field, or interface, problems cannot be given until the far field, or global flow, involved in a given crystal growth technique has been adequately described.

Pressure telemetry implant

Abstract: An implantable intracranial pressure (ICP) telemetry transmitter. Data transmission is accomplished by means of a radio frequency (RF) link coupled to a silicon piezoresistive pressure transducer. Electrostatic bonding of this transducer onto a tubular glass support provides long-term stability, stress isolation and a hermetic package. Because of the large temperature coefficient of the electrostatically bonded pressure transducer (-6 to -9 mm Hg/°C.), a temperature sensor is added to allow temperature compensation to be carried out. Pulse code modulation is employed to assure accurate data transmission. Use of low duty cycle pulse powering techniques lowers the power consumption of the telemeter. The complexity of the electronics is reduced by the use of a custom integrated circuit. Two lithium batteries can provide more than one month of continuous operation and an RF command receiver provides ON/Off control of the telemeter to extend the lifetime of the telemeter.

Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy.

Abstract: Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.

Molecular and cell isoforms during development.

Abstract: Development proceeds by way of a discrete yet overlapping series of biosynthetic and restructuring events that result in the continued molding of tissues and organs into highly restricted and specialized states required for adult function. Individual molecules and cells are replaced by molecular and cellular variants, called isoforms; these arise and function during embryonic development or later life. Isoforms, whether molecular or cellular, have been identified by their structural differences, which allow separation and characterization of each variant. These isoforms play a central and controlling role in the continued and dynamic remodeling that takes place during development. Descriptions of the individual phases of the orderly replacement of one isoform for another provides an experimental context in which the process of development can be better understood.

Neuromuscular transmission and correlative morphology in young and old mice

Abstract: 1. Age changes in spontaneous and evoked transmitter release, in receptor number and in ultrastructure at the neuromuscular junction were studied in the CBF-1 mouse strain, which stays physically active and relatively free of organ pathology into advanced age. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) were recorded in the following young (8-12 months) and old (29-33 months) mouse muscles: extensor digitorum longus (e.d.l.), soleus (sol.), gluteus maximus (g.m.), diaphragm (diaph.) and extensor digitorum communis (e.d.c.). 3. M.e.p.p. amplitudes were unchanged with age in four muscle groups despite increases in input resistance (in e.d.l., sol. and g.m.). M.e.p.p. amplitude in old diaph. increased 54% with no change in input resistance. Bimodal distributions of m.e.p.p. amplitudes were observed in 6-23% of muscle fibres but were not more prevalent in old mice. There was little or no change in resting membrane potential with age. 4. Numbers of junctional acetylcholine receptors (measured with 125I-α-bungarotoxin) were the same in all young and old muscles except e.d.l., where a 30% decrease was noted. Extrajunctional receptors and other indicators of denervation (decreases in resting potential, twitch tension or muscle fibre diameter) were absent or minimal. 5. M.e.p.p. frequency decreased in e.d.l., sol. and e.d.c. but not in g.m. or diaph. There was no correlated change in the cholinesterase-positive end-plate area. 6. It is concluded that m.e.p.p. amplitude is maintained in old muscles by a combination of compensatory changes. The decline in m.e.p.p. frequency varies between muscle groups and is independent of the length of the motoneurone axon or level of innervation. 7. Evoked end-plate potentials (e.p.p.s) were recorded in e.d.l., sol. and diaph. from young (11-13 months) and old (29-30 or 34-35 months) male CBF-1 mice in curarized preparations stimulated at 2 or 20 Hz. The amplitude of the initial e.p.p. of the trains was increased by 122% in old e.d.l. and 93% in old sol., and plateau e.p.p. amplitudes were also increased by about 100% (e.d.l.) and 67% (sol.). This, combined with the absence of change in m.e.p.p. amplitude with age, suggests that the number of quanta released per nerve impulse was increased. In diaph. there was no change with age. 8. In all muscle groups, the threshold for initiation of the muscle action potential was unchanged with age. Thus, the relative safety factor of transmission was increased in curarized old e.d.l. and sol. (but not diaph.). 9. Depression of the indirect twitch in solutions with a decreased calcium: magnesium ratio was also used as a relative measure of synaptic efficacy. Old sol. and e.d.l. but not diaph. muscles showed less depression of indirect twitch amplitude than did young muscle under these conditions. 10. In cut-fibre preparations of sol. and diaph. stimulated at 20 Hz, there was no age-dependent difference in e.p.p. amplitude, in directly measured quantal content, or in curare sensitivity. In view of other results, these findings require careful interpretation. 11. Ultrastructural morphometry was carried out in e.d.l. The nerve terminals in old (30 and 34 months) e.d.l. muscles exhibited pronounced loss of synaptic vesicles. In 34-month animals, decreased nerve terminal area and post-synaptic folds devoid of nerve terminals were often observed. Since no evidence of denervation was found by physiological criteria, it is concluded that in 34-month mice, nerve terminals withdraw from some synaptic gutters but do not abandon any junction entirely. The large presynaptic ultrastructural changes contrast with the physiological data showing no deficit and even increases in transmitter release. Therefore, under these conditions, these profound structural changes are either not functionally significant or are well compensated.

Effect of surface texture on the soft tissue response to polymer implants

Abstract: The ion beam etching process produces micro hairlike filaments on PTFE without causing any chemical or physiochemical alterations to the material. Implantation of this textured material subcutaneously, altered the interfacial cells and the kinetics of fibrous capsule development. Interfacial cells associated with textured interfaces (shown to be monocytic phagocytes) display increases in adhesion, vacuolization, filopodia formation, cytoplasmic-to-nuclear ratio, metabolism, acid phosphatase activity, and increased FBGC formation. The fibrous capsule associated with textured implants is reduced in thickness at 8 weeks but is similar to smooth controls at later time periods. The results of this investigation demonstrate that the surface texture of an implant is a critical variable in determining the soft tissue response to a material.

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer.

Abstract: Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while e...