Biomedical subjects

M D Morris

Publications and source records attributed to M D Morris.

At least 37 records · Page 2Linked to original sources

PubMed1999

Dynamic changes in plasma proinsulin/insulin ratio during insulin secretion influence correlation between radioimmunoassay (RIA) and IMX measurements of insulin.

Because proinsulin and insulin have different circulatory half-lives, the ratio of proinsulin to insulin in plasma depends on the dynamics of insulin secretion. This variation can potentially influence comparison of IMX assays and radioimmunoassays (RIAs) for [insulin], given that the antibody used in the IMX assay has negligible cross-reactivity with proinsulin compared to the 40% cross-reactivity with proinsulin of the antibody used in the RIA. Simulation of a simple mass balance model for insulin and proinsulin concentrations during an oral glucose tolerance test predicts that the ratio (R) of RIA to IMX insulin measurements of [insulin] should transiently decrease, pass through a minimum, increase past the initial value, pass through a maximum and eventually return to the initial value. Using time course specimens from patients, this pattern of variation in R was observed in the majority (12/16) of cases studied. The variation in R for time course specimens (CV = 26%) was significantly greater than for other specimens (fasting, random or undesignated; P < 0.05). Thus, when comparing IMX and RIA measurements of [insulin], variation in R for samples from differing states of dynamic insulin secretion contains a component that is attributable to dynamic changes in the ratio of [proinsulin]/[insulin] in plasma.

Glucose Tolerance Test↗

PubMed1999

Sphingomyelinase activity of livers from control and NCTR-BALB/c mice.

NCTR-BALB/c mice have an autosomal recessive disorder involving storage of sphingomyelin and unesterified cholesterol in their tissues and reduced tissue sphingomyelinase activity. With [N-methyl-14C]sphingomyelin as substrate, Vmax for the enzyme in livers from control and mutant mice were, respectively, 29.6 and 11.6 nmol of substrate hydrolyzed h(-1) mg(-1) protein, and the corresponding Km values were 94.6 and 132.3 microM. The control and mutant enzymes showed similar pH profiles and temperature sensitivities. When the control and mutant liver homogenates were mixed in various proportions, the resulting activities were 70-80% of the theoretical values. Cross and straight addition of total lipid extracts of control and mutant livers had minimal effect on their enzyme activities. The results suggest that the reduced sphingomyelinase activity of mutant liver is not due to the presence of inhibitors or absence of activators in this tissue.

Animals↗

PubMed1998

Isotachophoretic separations on a microchip. Normal Raman spectroscopy detection.

Isotachophoretic separations of the herbicides paraquat and diquat are performed in a glass microchip etched channel and monitored on-chip by normal Raman spectroscopy. The 40-micron-wide and 75-micron-deep separation channels are chemically etched in a serpentine design to 21-cm total length. A 120-micron-thick glass cover slip is used to seal the channels. Separation field strengths up to 380 V/cm are used. The microchip is directly coupled to a Raman microprobe. No interfacing is required. Raman spectra are generated with a 2-W, 532-nm NdY-VO4 laser and collected at 8-cm-1 resolution with a holographic transmissive spectrograph and a cryogenically cooled CCD. Data acquisition is at 2-5 spectra/s. Raman isotachopherograms of the pesticides at starting concentrations as low as 2.3 x 10(-7) M (60 ppb paraquat/80 ppb diquat) are presented.

Diquat↗

PubMed1998

Capillary isotachophoresis with fiber-optic Raman spectroscopic detection. Performance and application to ribonucleotides.

A fiber-optic Raman probe fitted with a microscope objective was used to obtain on-line normal Raman spectra of adenosine 5'-monophosphate, cytidine 5'-monophosphate, guanosine 5'-monophosphate and uridine 5'-monophosphate separated by capillary isotachophoresis. With multimode optical fiber, the system interrograted a 40-micron length of capillary. Fiber-optic coupling facilitated use of an unmodified spectrograph and conventional capillary mounting systems. Raman spectra were excited with a 2W 532 nm NdYVO4, laser as the excitation source, with collection of 1 spectrum per second. Even at 2.10(-5) M initial concentration, Raman spectra were obtained at a good signal-to-noise ratio.

Electrophoresis↗

PubMed1998

High-speed separation of linear and supercoiled DNA by capillary electrophoresis. Buffer, entangling polymer, and electric field effects.

Capillary electrophoresis in dilute and semidilute (slightly entangled) hydroxyethyl cellulose (HEC) is shown to separate linear double-stranded DNA (ds-DNA) and supercoiled plasmid DNA in the size range 1-16 thousand base pairs in 3 min. The mobilities of linear ds-DNA fragments are stronger functions of electric field strength and buffer concentration than the mobilities of supercoiled plasmids. The effects of HEC concentration and molecular weight are similar for both forms of DNA. The behavioral differences, which are attributed to the greater stiffness of the plasmids, can be used to define conditions that maximize resolution of supercoiled and linear ds-DNA of the same or similar number of base pairs.

Buffers↗

PubMed1998

Atherosclerotic risks from chemicals: part II. A RASH analysis of in vitro and in vivo bioassay data to evaluate 45 potentially hazardous compounds.

As reviewed in the Part I companion manuscript by Basavaraju and Jones (Arch Environ Contam Toxicol), atherosclerosis and carcinogenesis may share some common mechanisms of toxicological action. On that hypothesis, standardized test data taken from the Registry of Toxic Effects of Chemical Substances (RTECS) were used to compute relative potency factors for chemical compounds associated with increased risk of atherosclerosis to humans. Potencies of the different compounds were computed relative to each of six reference compounds comprised of benzo(a)pyrene, nicotine, cisplatin, adriamycin, estrogen, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Reference-specific potencies were all converted to a common numerical scale adjusted to unit potency for B(a)P. Because the list of compounds contained several antibiotics, amino acids, hormones, chemotherapeutic agents, polynuclear aromatics, alkaloids, metals, and vitamins, the standardized estimates of potency varied significantly depending on which of the six reference compounds are considered as standards of comparison. For the n - 1 other substances. Estimates of relative potency, risk coefficients, and generalized risk equations are estimated for cigarette smoke condensate, dietary cholesterol, ethanol, and carbon disulfide. From data on atherosclerosis as a result of cigarette smoking, a tentative risk was estimated as Increased Relative Risk = S (mg/kg-day)-1 x dose (mg/kg-day) x RP, where the dose is chronic intake per kilogram of body weight per day, RP is the potency of the compound of interest relative to that of benzo(a)pyrene, and S is 0.83, 0.25, 0.20, or 13 depending on whether cigarette smoke, cholesterol, ethanol, or carbon disulfide epidemiological data were used as a standard of comparison.

Animals↗

PubMed1998

Depth-resolved Raman microprobe examination of a commercial dental porcelain exposed to a simulated oral environment.

OBJECTIVES: The specific aims were investigation of the chemical transformations into the interior of a commercial dental porcelain upon exposure to a simulated oral environment and identification of structural alterations that contribute to the strengthening of the porcelain. METHODS: Samples of a commercial dental porcelain, Duceram LFC, were exposed to refluxing dilute acetic acid for 0, 1, 5, 10, and 72 h to simulate exposure to the oral environment. The control and refluxed samples were examined using a depth-resolved Raman microprobe system covering the low (0-2550 cm-1) and high (2000-4000 cm-1) frequency ranges. Spectra were processed using exploratory factor analysis. Significant factors were retained, accounting for 99.999% of the variance. RESULTS: The porcelain was found to be significantly depolymerized prior to acid-refluxing. Exposure to water and to acid resulted in the formation of a better-ordered region near the surface. In that region, three intermingled zones of chainlike metaborate and pyroborate, of boroxol rings, and of a mixture of borate and silicate tetrahedra were identified. The borate/silicate factor was dependent on refluxing time. Hydroxyl groups were detected in all of the samples, but no changes to the hydroxyl environment were noted until after 10 or more hours of refluxing. Then, molecular water and isolated hydroxyls/SiOH were detected. After 72 h, an additional unassigned factor around 2800-2950 cm-1 was noted. SIGNIFICANCE: Acid refluxing causes generation of ordered boron-containing species near the surface of the porcelain.

Boron Compounds↗

PubMed1998

Band broadening during dc and field inversion capillary electrophoresis of lambda DNA in dilute hydroxyethylcellulose solutions.

Capillary electrophoresis of lambda double-stranded (ds) DNA (48.5 kbp) in dilute hydroxyethylcellulose (HEC) solutions shows band spreading that cannot be explained by diffusion alone. Dispersion and asymmetry factors of lambda ds-DNA bands were measured as functions of capillary length, HEC concentration and field strength. Band spreading and asymmetry can be explained by a recently developed model in which the dominant contribution is assumed to be dispersion in DNA-HEC disentanglement times. Bandwidth reduction using square-wave field inversion was also investigated. It is proposed that correlation of DNA motion is the source of band narrowing during field inversion.

Bacteriophage lambda↗

PubMed1998

Surface enhanced Raman spectroscopic monitor of P. acnes lipid hydrolysis in vitro.

Surface enhanced Raman spectroscopy (SERS) at a silver microelectrode was used to monitor bacterial hydrolysis of triglycerides in lipid mixtures that model sebaceous gland secretions. Mixtures of wax esters, squalene, triolein, and triisostearin were used as model skin secretions. The transformation was followed in vitro as changes in the SERS caused by hydrolysis of triglyceride to fatty acid. The fatty acid was adsorbed as its carboxylate, which is readily identified by the characteristic band at ca. 1395 cm(-1). Co-adsorption of propionate was also observed. The technique can also confirm the presence of bacteria by detection of short chain carboxylic acids released as products of fermentation during the growth of these cells.

Esters↗

PubMed1997

Capillary electrophoresis of supercoiled and linear DNA in dilute hydroxyethyl cellulose solution.

Capillary electrophoresis in dilute hydroxyethyl cellulose is shown to separate supercoiled DNA in the size range 2000-16,000 base pairs. The plasmids migrate more slowly than linear ds-DNA of the same sizes. Plasmid bandwidths are larger than observed for ds-DNA, allowing identification of the type of DNA by bandwidth. The differing dependence of mobility on chain length can be explained by assuming that a plasmid migrates as an elastic rod, while ds-DNA migrates as a wormlike chain.

Cellulose↗

PubMed1997

Neutron RBEs for cytopenia and repopulation of stroma and hematopoietic stem cells: mathematical models of marrow cell kinetics.

The objectives of this study were to (a) extend previous bone-marrow cell kinetics models that have been published for ionizing photons to include neutron radiations, and (b) provide Relative Biological Effectiveness (RBE) values for time-specific cell killing (cytopenia) and compensatory cellular proliferation (repopulation in response to toxic injury) for neutron doses ranging from 0.01 to 4.5 Gy delivered uniformly over one minute, hour, day, week, and month. RBEs for cytopenia of a cell lineage were based on ratios of protocol-specific doses that determined the same cell population nadir, whereas the RBEs for repopulation of a lineage were based on the ratios of protocol-specific doses that corresponded to the same total number of cells killed over the radiation treatments, and which should be replaced for long-term survival of the animal. Time-dependent RBEs were computed for neutron exposures relative to the effect of 60Co gamma rays given as a prompt dose. By the use of these RBE factors, low or variable dose rates, dose fractionations given over long periods of time, and different protocols involving several radiation qualities can be converted realistically, and by standard convention, into an equivalent dose of a reference radiation comprised of x or gamma rays given either as a pulse or at any other reference dose rate for which risk information based on epidemiological or animal dose-response data are available. For stromal tissues irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 4.24 to 0.70 and RBEs for repopulation varied from a high of 6.88 to a low of 2.24. For hematopoietic stem cells irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 5.02 to 0.22 and RBEs for repopulation varied from a high of 5.02 to a low of 1.98. RBEs based on tissue-kerma-free-in-air would be about twofold lower for isotropic cloud or rotational exposure geometries because marrow dose from isotropic neutron fields suffer factor-of-two greater attenuation than the gamma doses from gamma photons. For certain doses and dose rates, the RBE values computed for compensatory cellular proliferation clearly demonstrate the behavior that is commonly referred to as an inverse dose-rate effect, i.e., protraction of exposure may-under certain conditions-increase the magnitude of the dose response. Furthermore, because of non-linear rates for repair and repopulation, the highest RBEs are not necessarily found for the lowest doses nor the lowest RBEs always found at the highest doses.

Animals↗

PubMed1997

MarCell software for modeling bone marrow radiation cell kinetics.

Differential equations were used to model cellular injury, repair, and compensatory proliferation in the irradiated bone marrow. Recently, that model was implemented as MarCell, a user-friendly MS-DOS computer program that allows users from a variety of technical disciplines to evaluate complex radiation exposure. The software allows menu selections for different sources of ionizing radiation. Choices for cell lineages include progenitor, stroma, and malignant, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive feature is that any protracted irradiation can be compared with an equivalent prompt dose (EPD) in terms of cell kinetics for either the source used or for a reference such as 250 kVp x rays or 60Co. EPD is used to mean a dose rate for which no meaningful biological recovery occurs during the period of irradiation. For human as species, output from MarCell includes: risk of 30-day mortality; risk of whole-body cancer and leukemia based either on radiation-induced cytopenia or compensatory cell proliferation; cell survival and repopulation plots as functions of time or dose; and 4-week recovery following treatment.

Animals↗

PubMed1996

An aluminum heat sink and radiator for electrophoresis capillaries.

An aluminum heat sink and radiator are used with forced air cooling of an electrophoresis capillary. Theoretical analyses of the operating limits and heat dissipation characteristics are presented. A system designed for power dissipation as high as 5 W is shown to dissipate heat efficiently and to operate without arcing at voltages higher than 30 kV.

Aluminum↗

PubMed1996

Ultrafast high resolution separation of large DNA fragments by pulsed-field capillary electrophoresis.

Pulsed-field capillary electrophoresis (PFCE) in buffers containing ultradilute polymer solutions is used to separate long chain dsDNA in less than 4 min. Separations are shown to work with chain lengths below 10 kbp and greater than 1.5 Mbp. Several pulse protocols have been examined. If running time is to be minimized, a field inversion with higher peak amplitude in the forward direction than in the reverse, but with equal pulse durations, provides the best resolution. Other protocols can provide higher resolution, but only with longer running times.

Cellulose↗

PubMed1996

Fluorescence resonance energy transfer visualization of DNA aggregates formed during electrophoretic separations in ultradilute hydroxyethylcellulose.

Fluorescence resonance energy transfer (FRET) microscopy is used to observe structures of DNA aggregates formed during electrophoresis in ultradilute hydroxyethylcellulose (HEC). FRET gives evidence of aggregates with a tightly packed core and random entanglement of DNA in the outer portions. HEC concentrations also appear to play a role in aggregate formation. DNA aggregates take longer to assemble in higher HEC concentration solutions and assume a less compact form than those formed at lower HEC concentrations.

Cellulose↗

PubMed1996

Modeling marrow damage from response data: evolution from radiation biology to benzene toxicity.

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between 5 and 30 days. Mortality data from 27 experiments with 851 dose-response groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals: 12,827 mice, 2925 rats, 1676 sheep, 829 swine, 479 dogs, and 204 burros. Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is critical to hematopoietic recovery does not resemble stemlike cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in fitting of model coefficients.

Animals↗

PubMed1995

On-line Raman spectroscopy of ribonucleotides preconcentrated by capillary isotachophoresis.

Normal Raman spectroscopy is used as an on-line detector for capillary isotachophoresis (ITP) of adenosine 5'-triphosphate, adenosine 5'-diphosphate, and adenosine 5'-monophosphate in phosphate buffers. Preconcentration is from a 1 x 10(-2) M phosphate buffer (pH 7.5) into a leading electrolyte of 0.1 M KCl or Na2SO4, with a terminating electrolyte of 0.1 M 4-morpholinepropane-sulfonic acid. The ribonucleotides are concentrated to above 10(-2) M at the detection window, allowing measurement of Raman spectra with 1 s integration, from starting concentrations of 5 x 10(-6) M or higher.

Adenosine Diphosphate↗

PubMed1995

Dynamics of DNA during pulsed field electrophoresis in entangled and dilute polymer solutions.

Using fluorescence video microscopy, DNA electrophoretic behavior under field inversion conditions has been investigated in hydroxyethyl cellulose (HEC) solutions both above and below its entanglement limit. DNA conformational fluctuation periods are found to be strongly influenced by the frequency of the applied electric field. DNA maximum extension is found to be dependent on both the frequency and the strength of the applied field. It is proposed that both above and below the HEC entanglement limit, field inversion serves to keep the average DNA conformation in a size-dependent regime intermediate between full extension and random coil. In this time-averaged geometry, efficient long-chain DNA electrophoretic separation is enabled.

DNA, Fungal↗