A suspicion that the incidence of cancer is rising in a residential or workplace community is often a cause of alarm among members of that community. The seemingly excessive number of diagnoses encountered may he due to: (i) a known explanatory variable, such as ageing of the community members; (ii) random occurrence of an event which is rare under stable conditions; (iii) exposure to an undefined carcinogenic agent. An exploratory analysis is suggested in order to consider the support indicated by the data with respect to each of the two last possibilities while controlling the first. The analysis involves several procedures which differ with respect to the targeted temporal pattern of the diagnoses. These procedures are mainly based on the a priori probability that a diagnosis is made within the time interval observed between consecutive diagnoses. When the number of diagnoses is found to be excessively large, the temporal pattern of the diagnoses may indicate whether the event is likely to be an incidental occurrence or due to the effect of a carcinogen.

Bias↗

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Determination of therapeutic doses of bisquaternary oximes in large animals.

This report presents a non-lethal method for estimating a range of therapeutic doses of bisquaternary oximes that serve as antidotes against organophosphorus poisoning. We have estimated therapeutic oxime doses that are equivalent in their relative toxicity rather than selecting arbitrary fractions of their LD(50). Thus, toxic signs of the oximes HI-6, HLö-7, Toxogonin, AB-8 and AB-13 were monitored quantitatively in baboon monkeys and beagle dogs. Using Toxogonin as a reference oxime, a calculated unit of equivalent dose (CED) was defined as the oxime dose equal to the ratio between its minimal toxic dose (MTD) and the therapeutic ratio (TR) of Toxogonin i.e. CED = MTD/TR. Assuming that the tails of dose-response curves of toxicity for bisquaternary oximes are shallow and similar to one another, one could substitute the ED(10) for the MTD. The ED(10) values for bisquaternary oximes were estimated using the log-log model following experimental observations and quantitative scoring of toxic signs in dogs and monkeys. The MTD values then were calculated using the ED(10) values and the experimental therapeutic dose of the reference oxime Toxogonin. The following CED values were obtained for AB-8, AB-13, Toxogonin, HI-6 and HLö-7 in dogs (d) and monkeys (m): 98.7, 74.2, 30.0, 14.5 and 12.1 (d) and 281.9, 232.1, 41.7, 192.9 and 92.9 (m) micromol kg(-1), respectively. The antidotal efficacy of these oximes against poisoning by the nerve agent tabun was determined in dogs and monkeys. These dose-dependent efficacy data were obtained at 0.3 x CED, 1 x CED and 3 x CED of oximes in combination with atropine. These data provide comparative therapeutic values using oxime doses based on their relative toxicity. The highest antidotal efficacy against tabun in dogs was obtained for toxogonin, whereas HLö-7 and AB-13 were most efficacious in monkeys.

Animals↗

PubMedDate not supplied

A study of three techniques for time-space clustering in Hodgkin's disease.

Three techniques for disease time-space clustering analysis, those of Knox, Mantel and Ederer-Myers-Mantel, were applied to simulated data so as to study their sensitivities. The simulated data corresponded to three alternative non-null models for the distribution, transmission and development of Hodgkin's disease (HD) which were formulated in accordance with the results of published studies. The results indicate that the three techniques may not be sufficiently sensitive to the clustering in a real data set of HD cases. Therefore, the inconclusive results obtained to date with regard to clustering of HD may be related to the low power of the statistical techniques employed.

Hodgkin Disease↗

PubMedDate not supplied

Comparison of two statistical techniques for the surveillance of birth defects through a Monte Carlo simulation.

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Biometry↗

PubMedDate not supplied

Promotion of hexagonal phase formation and lipid mixing by fatty acids with varying degrees of unsaturation.

A series of C18 and C22 fatty acids, with varying degrees of unsaturation, were tested for their ability to alter the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. Lowering the pH from 7.4 to 6.4 greatly decreased the bilayer to hexagonal phase transition temperature of fatty acid-phosphatidylethanolamine mixtures. At pH 7.4, increasing unsaturation of the fatty acid generally increased their hexagonal phase-forming ability. However, oleic acid had somewhat greater hexagonal phase-forming capacity and docosahexaenoic acid somewhat less than would be expected for their degree of unsaturation. At pH 6.4 the difference among fatty acids was small and except for stearic acid, all had similar hexagonal phase forming tendencies. The fatty acids cause acid-induced fusion. There is little effect of fatty acid structure on membrane fusion.

Fatty Acids, Unsaturated↗

PubMedDate not supplied

Motor and associative deficits in D2 dopamine receptor knockout mice.

Behavioral abnormalities produced by D2 dopamine receptor gene deletion in mice have been attributed either to resulting Parkinson-like features (i.e. response slowing and response initiation difficulties) or to behavioral deficits contributed by alleles of the originating 129Sv strain. Three strategies were used to address these conflicting hypotheses: (1) we used mice congenic at n10 backcross into the C57BL/6 line to minimize the 129Sv contribution; (2) we compared mice that were wild-type (+/+), heterozygous (+/-), or homozygous (-/-) for the D2 gene with the two most relevant inbred lines (129Sv and C57BL/6) and (3) we used both conventional and novel behavioral assessment methods. Behavioral attributes were expressed in terms of locomotor activity, wall rearing, rotarod performance, operant response acquisition, operant response performance, lick dynamics (force, rhythm), grip strength, and tremor in response to harmaline challenge. Results showed that, compared to controls, the -/- mice exhibited longer duration wall rears, retarded operant response acquisition, increased latencies to move from the operandum to the reward well, and exaggerated response to harmaline. Age was investigated as a variable (10-11 weeks versus 41-44 weeks of age) in the locomotor activity and wall rear assessments. A gene dosage effect (deficits in the +/- mice) on these two variables became apparent in the older mice. Taken together, the results showed that mice without the D2 gene exhibited Parkinson-like behavioral features that were not easily attributed to alleles contributed by the 129Sv strain, but were consistent with basal ganglia dysfunction.

Animals↗

PubMedDate not supplied

Low grip strength, impaired tongue force and hyperactivity induced by overexpression of neurotrophin-3 in mouse skeletal muscle.

Transgenic mice overexpressing neurotrophin-3 (NT-3) in skeletal muscle (mlc/NT-3 mice) develop abnormal muscle spindles in skeletal muscle and display abnormal motor function in the form of gait and locomotive disturbances. The purpose of this work was to characterize the functional consequences of NT-3 overexpression in skeletal muscle with further behavioral assessments that permitted inferences about muscle weakness in the tongue or forelimbs as well as potential central nervous system (CNS) abnormalities compared to wild-type controls. Wild-type (n=12) and mlc/NT-3 (n=12) male mice were tested in five procedures (in chronological order): lick dynamics, locomotor activity, grid ataxia, go-no-go discrimination procedure, and grip strength. Relative to wild-type mice, the mlc/NT-3 mice exhibited lower tongue force, hyperactivity, slowed limb retrieval in the grid ataxia test, similar discrimination performance, and lower grip strength. Overall, the data suggest that chronically elevated levels of NT-3 in mouse skeletal muscle cause muscle weakness in the mlc/NT-3 mice. Surprisingly, mlc/NT-3 mice also exhibited significant hyperactivity, suggesting that NT-3 overexpression in the periphery may have caused abnormalities in the CNS that are related to the cortical processing of proprioceptive afferent information.

Afferent Pathways↗

PubMedDate not supplied

Metabolic consequences of phosphotransferase (PTS) mutation in a phenylalanine-producing recombinant Escherichia coli.

E. coli strain PPA305, which has a wild-type PTS system, and PPA316, which utilizes a proton-galactose symport system for glucose uptake, were used as host strains to harbor a phenylalanine overproduction plasmid pSY130-14 and to study the effects of using different glucose uptake systems on phenylalanine production. The non-PTS strain (PPA316/pSY130-14) produced much less phenylalanine, ranging from 0 to 67% of that produced by the PTS strain (PPA305/pSY130-14) depending on cultivation conditions used. The non-PTS strain PPA316/pSY130-14 had an intracellular PEP concentration only one-sixth that of the PTS strain, PPA305/pSY130-14. Additionally, PPA316/pSY130-14 had a substantially lower energy state in terms of the size of the pool of high-energy phosphate compounds and the magnitude of the pH difference across the cytoplasmic membrane. The non-PTS strain consumed oxygen at a higher rate, attained lower biomass concentration, and produced no acetate and phenylalanine during fermentation, suggesting more carbon was oxidized to CO2, most likely through the TCA cycle. Analysis of intracellular fluxes through the central carbon pathways was performed for each strain utilizing exponential phase data on extracellular components and assuming quasi-steady state for intermediate metabolites. The non-PTS strain had a higher flux through pyruvate kinase (PYK) and TCA cycle which, in agreement with the observed higher oxygen uptake rate, suggests that more carbon was oxidized to CO2 through the TCA cycle. Further analysis using rate expression data for PYK and NMR data for the intracellular metabolites identified the regulatory properties of PYK as the probable cause for lower intracellular PEP levels in PPA316/pSY130-14.

Adenosine Triphosphate↗

PubMedDate not supplied

Ferumoxide-enhanced MRI of sideronecrosis superimposed on genetic hemochromatosis.

Genetic hemochromatosis is an autosomal recessive disorder characterized by excessive iron absorption from the gut, resulting in increased total body iron stores, multisystem organ dysfunction, and an increased risk of hepatocellular carcinoma. The magnetic susceptibility effects of excess hepatocellular iron generally cause diffuse hepatic signal loss on T2- or T2*-weighted MR images. Although hepatic iron deposition is usually diffuse, focal areas of iron sparing can occur, and, when present, superimposed neoplasm is a consideration. We describe a patient with cirrhosis, hemochromatosis, and multiple small benign relatively hyperintense iron-poor foci consisting of piecemeal sideronecrosis.

Contrast Media↗

PubMedDate not supplied

Organization of heterogeneous scientific data using the EAV/CR representation.

Entity-attribute-value (EAV) representation is a means of organizing highly heterogeneous data using a relatively simple physical database schema. EAV representation is widely used in the medical domain, most notably in the storage of data related to clinical patient records. Its potential strengths suggest its use in other biomedical areas, in particular research databases whose schemas are complex as well as constantly changing to reflect evolving knowledge in rapidly advancing scientific domains. When deployed for such purposes, the basic EAV representation needs to be augmented significantly to handle the modeling of complex objects (classes) as well as to manage interobject relationships. The authors refer to their modification of the basic EAV paradigm as EAV/CR (EAV with classes and relationships). They describe EAV/CR representation with examples from two biomedical databases that use it.

Database Management Systems↗