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Biomedical subjects

J W Morris

Publications and source records attributed to J W Morris.

At least 19 recordsLinked to original sources

A comparison of linear and exponential models for drug expiry estimation.

While a large portion of pharmaceutical stability data is known to follow an exponential model decay, linear modeling of this data for expiry estimation is the norm. Expiry predictions based on linear and exponential fits to stability data were made to estimate the bias due to the linear fitting. It was found that within the usual expiry limits on drug potency, the difference between the model fits is relatively trivial. In cases of loss of potency greater than 15%, small assay variability, or great disparity between the length of the study and the time of expiry prediction, however, there is a nontrivial difference in the predictions and the exponential model is preferable.

Drug Compounding

KVP meter errors induced by plastic wrap.

The purpose of this study was to determine whether erroneous kVp meter readings, induced by plastic wrap, affected the actual kVp (output) of a dental X-ray machine. To evaluate the effect of plastic wrap on dental X-ray machine kVp meters, a radiation output device was used to measure output in mR/ma.s. An intraoral dental X-ray unit (S.S. White Model #90W) was used to make the exposures. First, the kVp meter was not covered with plastic wrap and output readings were recorded at various kVp settings with the milliamperage and time held constant. Secondly, the same kVp settings were selected before the plastic wrap was placed. Milliamperage and time were again held to the same constant. The X-ray console was then covered with plastic wrap prior to measuring the output for each kVp. The wrap possessed a static charge. This charge induced erroneous kVp meter readings. Out-put readings at the various induced kVp settings were then recorded. A kVp of 50 with no wrap present resulted in the same output as a kVp of 50 induced to read 40 or 60 kVp by the presence of wrap. Similar results were obtained at other kVp settings. This indicates that the plastic wrap influences only the kVp meter needle and not the actual kilovoltage of the X-ray machine. Dental X-ray machine operators should select kVp meter readings prior to placing plastic wrap and should not adjust initial settings if the meter is deflected later by the presence of wrap. The use of such a procedure will result in proper exposures, fewer retakes, and less patient radiation. If plastic wrap leads to consistent exposure errors, clinicians may wish to use a 0.5% sodium hypochlorite disinfectant as an alternative to the barrier technique.

Communicable Disease Control

Identification of an Agrobacterium tumefaciens virulence gene inducer from the pinaceous gymnosperm Pseudotsuga menziesii.

Inducible T-strand mobilization from the Ti plasmid of Agrobacterium tumefaciens to the genome of a plant host is mediated by the activation of a cascade of bacterial virulence genes. It is initiated when the bacterium senses the presence of a low molecular weight inducer secreted by the plant. Although many hydroxyphenylpropanoid and phenolic compounds can activate the virulence cascade, the only native inducers that have been identified to date are acetosyringone and hydroxyacetosyringone. A new inducer, the phenylpropanoid glucoside coniferin, has now been isolated from Pseudotsuga menziesii (Douglas-fir). Agrobacterium strains that were more tumorigenic on gymnosperms were more effectively induced by coniferin.

Cinnamates

The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas.

The expression of fos protein was examined in 30 cases of human osteosarcoma as formalin-fixed and paraffin-embedded tissue sections using two monoclonal antibodies and, for five cases, as frozen sections using 3 polyclonal antibodies. Nuclear antibody labeling intensities were determined either by visual scoring (3 pathologists) or by microdensitometry and included over 700 tumor, 350 normal and 150 benign tissue observations. Visual scores were shown to be linear with optical density with a correlation coefficient of 0.97. Analysis of the osteosarcoma cases at one antibody concentration revealed two groups: a minority (39%) with a low average visual score of 2 +/- 0.2 which was very similar to benign and normal tissues, and a majority (61%) with an average score of 3.1 +/- 0.3. The difference is highly significant (t-test), P less than or equal to 0.01. The results were supported by an analysis of partial immunotitration curves using a curve-fitting procedure which yielded estimates of FOSo (maximum relative fos protein concentration) which were ca. 150% increased for the majority tumor group compared to the minority group or benign or normal tissues. In previous studies of v-sis transformed cells, which exhibit ca. 300% over-expression of c-fos protein as observed here, antisense techniques were used to show that over-expression leads to increased growth and loss of contact inhibition. Thus the combined results suggest that steady state c-fos protein is significantly elevated in, and may contribute to, the aggressive growth properties of a majority of human osteosarcomas.

Antibodies, Monoclonal

Atmosphere contamination following repainting of a human hyperbaric chamber complex.

The Naval Medical Research Institute currently conducts hyperbaric research in a Man-Rated Chamber Complex (MRCC) originally installed in 1977. Significant engineering alterations to the MRCC and rusting of some of its interior sections necessitated repainting, which was completed in 1988. Great care was taken in selecting an appropriate paint (polyamide epoxy) and in ensuring correct application and curing procedures. Only very low levels of hydrocarbons were found in the MRCC atmosphere before initial pressurization after painting and curing. After pressurization, however, significant chemical contamination was found. The primary contaminants were aromatic hydrocarbons: xylenes (which were a major component of both the primer and topcoat paint) and ethyl benzene. The role that pressure played in stimulating off-gassing from the paint is not clear; the off-gassing rate was observed to be similar over a large range in chamber pressures from 1.6 to 31.0 atm abs. Scrubbing the chamber atmosphere with the chemical absorbent Purafil was effective in removing the contaminants. Contamination has been observed to slowly decline with chamber use and is expected to continue to improve with time. However, this contamination experience emphasizes the need for a high precision gas analysis program at any diving facility to ensure the safety of the breathing gas and chamber atmosphere.

Air Pollutants

Biostatistical evaluation of evidence from continuous allele frequency distribution deoxyribonucleic acid (DNA) probes in reference to disputed paternity and identity.

We present a development and discussion of the biostatistical evaluation of deoxyribonucleic acid (DNA) probe evidence in forensic science cases of disputed paternity and identity. We restrict ourselves to single-locus codominant systems (highly analogous to more conventional systems) which have the apparently novel complication of an experimentally continuous allele frequency distribution. This complication necessitates reformulations of standard biostatistical summaries of the evidence (the paternity index (PI) and the phenotype frequency, respectively). These reformulations, rather than representing a unique case, have applicability to the evaluation of evidence obtained in standard genetic systems now in widespread use.

DNA

PGM1 and Gc subtype gene frequencies in a California Hispanic population.

The gene frequencies of the subtypes of the Gc (group-specific component) protein and PGM1 (phosphoglucomutase) enzyme systems have been determined by means of isoelectric focusing for a California Hispanic population (no. = 404). The Gc subtyping, done by immunofixation on a polyacrylamide gel, gave the following results: 1s = 0.491; 1f = 0.288; 2 = 0.218; variant = 0.0025. The PGM subtyping, done on agarose gel, gave results as follows: 1+ = 0.502; 1- = 0.266; 2+ = 0.128; 2- = 0.104. Because the gene frequencies for Hispanics in both these systems are relatively evenly balanced, the systems are of great value in Hispanic paternity investigations. The average power of exclusion is calculated to be 34.4% (Gc subtyping) and 39.8% (PGM1 subtyping).

Alpha-Globulins

Effects of ethanol, acetaldehyde and acetate on insulin release from perifused pancreatic islets.

It has been postulated that ethanol-induced changes in carbohydrate hemeostasis are mediated in part by alterations in pancreatic endocrine function. In this study ethanol (40, 120 and 240 mg/dl) produced dose-related suppression of immunoreactive insulin (IRI) release from isolated rat islets perifused with glucose and theophylline. Acetaldehyde inhibited IRI release at a concentration (39 mg/dl) much higher than can be achieved in vivo. A high concentration (29 mg/dl) of acetate did not influence IRI release. These results suggest that the ability of ethanol to inhibit IRI release resides principally in the parent compound and not its metabolites.

Acetaldehyde

Effect of ethanol on basal and arginine-stimulated plasma levels of glucose, insulin and glucagon in fasted unanesthetized rabbits.

Plasma glucose, insulin (IRI) and glucagon (IRG) levels were determined in fasting unanesthetized rabbits following pretreatment of either saline or ethanol (1.5 g/kg p.o.) and i.v. infusion of either saline or arginine (10 mg/kg/min for 30 min). Ethanol lowered plasma glucose and IRI levels but raised IRG levels in rabbits infused with saline. Arginine-induced hyperglycemia and hyperinsulinemia were markedly suppressed by ethanol so that any further increase expected by the infusion of arginine was minimized. Thus, ethanol not only alters basal levels of IRI, IRG and glucose but also suppresses arginine-stimulated levels as well.

Animals

Triacetylated insulin: biologic activity and resistance to degradation.

Tritiated N-hydroxysuccinimide acetate was prepared with specific activities up to 5 Ci/mmole and utilized to prepare tritiated triacetyl insulin. Binding of triacetyl insulin to liver plasma membranes was measured by its capacity to displace 125I-monoiodoinsulin. At low concentrations, less than 10 ng/ml triacetyl insulin appears to be as effective as native insulin in reducing the binding of 125I-monoiodoinsulin to plasma membranes. At concentrations of 20 ng/ml and higher, triacetyl insulin is significantly less effective than native insulin in displacing binding of 125I-monoiodoinsulin to plasma membranes. The properties of triacetyl insulin in this system are not ascribable to deacetylation and conversion of the substituted product to native insulin. Biologic activity of triacetylated insulin was studied in two other in vitro systmes. A comparison was made of the capacity of native beef insulin and its triacetyl derivative to stimulate glucose oxidation by epididymal fat pads. At all three concentrations tested (2, 6, and 18 ng/ml), triacetyl insulin exerted considerable activity, although its potency was significantly less than that of native insulin. Similar effects were observed when biologic activity was measured by induction of tyrosine-alpha-ketoglutarate transaminase in a cultured liver cell system where significant activity of triacetyl insulin was found at concentrations of 10(-9)-10(-7) M. In all systems tested, the activity of triacetylated insulin could not be accounted for by deacetylation and conversion to native insulin. In all systems studied, triacetyl insulin was more resistant to degradation than was monoiodoinsulin.

Adipose Tissue