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An immunohistochemical technique was used to localize the major constitutive cytochrome P450 isozyme, P450 LM2, and the major beta-naphthoflavone-inducible isozyme, P450 LM4b, in the livers of untreated and aflatoxin B1 (AFB1)-initiated, tumor-bearing rainbow trout. In hepatic tissue sections from untreated trout, no regular anatomical pattern within the hepatic parenchymal cells could be discerned for either isozyme. Immunostaining was observed for P450 LM2 along the sinusoidal border of some of the parenchymal cells, there was moderate staining within the cytoplasm of most cells, and there were focal areas of increased staining. There was intense, uniform immunostaining for P450 LM2 within the cytoplasm of the bile duct cells, in the endothelial lining of arterioles, and along the epithelial surface of the gall bladder. Staining for P450 LM4b in livers from untreated trout was barely detectable. In liver tissue sections from AFB1-treated tumor-bearing fish, P450 LM2 appeared to be reduced and P450 LM4b was absent in the hepatocellular carcinoma nodules. An apparent increase in immunostaining for P450 LM4b was observed in nonneoplastic cells juxtaposed next to neoplastic cells as well as in areas distant to the tumors. These results may indicate that the pattern of P450 isozymes is altered in nonneoplastic cells of tumor-bearing trout livers.
The isolation and characterization of monoclonal antibodies reacting with cell surface antigenic determinants of normal and leukemic avian hematopoietic cells is described. The antibodies were produced by immunizing mice with normal macrophages, as well as with myeloid cells transformed with the avian acute leukemia viruses MC29, AMV and E26. Eleven antibodies were characterized for their reactivity with a variety of normal and leukemic cells of the myeloid, B- and T-lymphoid and of the erythroid cell lineage. Using several methods, they could be subdivided into five distinct types: I. Four antibodies were specific for the myeloid lineage, predominantly reacting with immature myeloid cells. II. One antibody reacted with mature and immature myeloid cells as well as with T-lymphoid cells. III. Four antibodies reacted with myeloid, erythroid and T-lymphoid cells. IV. One antibody reacted with myeloid as well as with T- and B-lymphoid cells. V. One antibody reacted with all kinds of chicken hematopoietic cells except erythrocytes. The first type of antibodies detected glycoproteins with MWs of 170 and 130 kD. The pattern of antigens precipitated varied with the different monoclonal antibodies of this group. The antibody of the fourth type precipitated a 30 kD polypeptide from extracts of myeloid and lymphoid cells. None of the other antibodies precipitated any detectable proteins.
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A cell cycle model developed by Smith and Martin is generalized to allow for the possibility that the duration of the B phase is not fixed. The B phase is the equivalent of the traditional S, G2, and M phases of the cell cycle. The duration of the B phase is represented by a Gaussian probability distribution; the duration of the resting or A state which replaces the traditional G1 phase is represented by a decaying exponential distribution. A doubling time distribution, termed the CEG distribution, is obtained by convolution of the A state and B phase distributions. Like the reciprocal normal, rate normal, and log normal distributions, it is a rounded unimodal peak that is skewed to the right. None of the three former distributions is associated with a cell cycle model that includes a resting state. However the CEG distribution, which is so associated, bears little resemblance to the delayed exponential distribution which results when the duration of the B phase is fixed and the duration of the A state is random. Consequently, it would be difficult to use the doubling time distribution to determine whether or not a resting state exists in a particular cell population.
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The numbers of normal copies of each of the chromosomes in representative karyotypes from 165 malignant tumors of the bladder, breast, cervix, colorectum, and testis studied in this laboratory or described in the literature were assessed to determine whether particular chromosomes were over- or underrepresented. For each chromosome, the mean number of copies was expressed as a percentage of the number expected on the basis of the total number of chromosomes in the karyotypes. The most highly represented autosomes in the tumors as a whole were, in descending order of frequency, numbers 7, 20, 12, 19, 21, and 3, while those most underrepresented were numbers 10, 1, 4, 5, 14, 17, 11, and 18. In tumors of males, the Y tended to be underrepresented. The X was highly represented in the testicular tumors (there were usually two or more copies) and in colorectal tumors of males, but not in the other tumor categories studied. For the tumors as a whole, statistically significant differences could be demonstrated between pairs of autosomes that were at opposite ends of the frequency range. Differences between tumors at the different sites studied were not demonstrable. It is suggested that the determination of the number of normal copies of chromosomes, i.e., whether there are more or fewer than expected, may usefully complement observations on structural changes by reflecting the presence of oncogenes and tumor-suppressor genes, respectively. It may also point to chromosomes that are involved in significant genic changes in which cytogenetic observations on structural changes are equivocal.
To study patterns of iron deposition in the putamen in aging, we reviewed brain magnetic resonance imaging (MRI) scans of 56 normal subjects. We developed the Signal Hypointensity in the Putamen (SHIP) Scale, a semiquantitative measure, to evaluate putamen nuclei for extent of iron deposition relative to the globus pallidus. The SHIP score was highly reliable (kappa = 0.76) and significantly correlated with age (P < 0.0001). We found that age-related iron deposition in putamen nuclei follows a characteristic pattern along a posterolateral-to-anteromedial gradient. This gradient may be related to the microvasculature of the putamen. Other studies are needed to replicate our findings in patients with affective and other neuropsychiatric disorders and to clarify the pathophysiological mechanisms that govern these changes.
Mathematical models describing the growth kinetic parameters (lag phase duration and growth rate) of Bacillus cereus as a function of temperature, pH, sodium lactate and sodium chloride concentrations were obtained in this study. In order to get a residual distribution closer to a normal distribution, the natural logarithm of the growth kinetic parameters were used in modeling. For reasons of parsimony, the polynomial models were reduced to contain only the coefficients significant at a level of p<or=0.05. Using the reduced polynomial models (R2 of 95.2% and 93.9% for ln LAG and ln GR models, respectively), three-dimensional graphs were drawn illustrating the effects of the independent variables on the growth parameters. Predicted data were compared with the predictions from Pathogen Modeling Program (PMP-US Department of Agriculture-Agricultural Research Service) and validated against data extracted from the literature. The mean absolute relative error (MARE) and the median relative error (MRE) of the predicted generation times with the derived model were 25.6% and -16.7%, respectively, showing that the growth rate model accurately and safely predicted the growth kinetics of B. cereus. Results of the modeling study indicated that all of the studied factors had a significant effect on the growth of B. cereus in the experimental range studied.
The influence of sampling variables on the concentration of the dopamine metabolites 3-methoxytyramine (3MT), dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) was examined in equine urine. A logarithmic transformation of the data for all horses gave distribution which approximated the normal distributions for each metabolite. The mean urinary concentration of 3 MT in horses was 214 ng/mL and the application of a threshold with a probability of 1 in 10,000 gave an actionable level of 4 microg/mL. Environmental variables were not forensically significant in determining the population distribution. HVA was not found to be a reliable indicator of dopamine or levodopa administration.
A method for the assay of total serum thyroxine on reusable Sephadex G-25 fine columns, obtained from the Ames Tetralute kit, and competitive protein binding with TBG is described. The columns are regenerated with diluted plasma and may be used for at least 3 months. The procedure is rapid and simple and requires no extraction, centrifugation or evaporation. Recovery of added thyroxine from serum is essentially complete. The between-assay and within-assay coefficients of variation are about 5.5%. Correlation with values obtained using the Tetralute kit was good (r = 0.988). Values in 75 euthyroid subjects were normally distributed and therefore the normal range was taken as the mean +/- 2 SD or 4.6-10.4 mug/100 ml.
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It has been reported that the degree of particle agglomeration in fluidized bed coating is greatly affected by the spray mist size of coating solution. However, the mist size has generally been measured in open air, and few reports have described the measurement of the mist size in a chamber of the fluidized bed, in which actual coating is carried out. Therefore, using hydroxypropylmethyl cellulose (HPMC) aqueous solution as a coating solution, the spray mist size of the coating solution in a chamber of the fluidized bed was measured under various coating conditions, such as the distance from the spray nozzle, fluidization air volume, inlet air temperature and addition of sodium chloride (NaCl) into the coating solution. The mist size in the fluidized bed was compared with that in open air at various distances from the spray nozzle. Further, the relationship between the spray mist size and the degree of suppression of agglomeration at various NaCl concentrations during fluidized bed coating was studied. The mist size distribution showed a logarithmic normal distribution in both cases of the fluidized bed and open air. The number-basis median diameter of spray mist (D50) in the fluidized bed was smaller compared with that in open air. D50 increased with the increasing distance from the spray nozzle in both cases. In the fluidized bed, D50 decreased with the increasing fluidization air volume and inlet air temperature. The effect of NaCl concentration on the mist size was hardly observed, but the degree of suppression of agglomeration during coating increased with the increasing NaCl concentration in the coating solution.
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Although lesion-deficit analysis (LDA) has provided extensive information about structure-function associations in the human brain, LDA has suffered from the difficulties inherent to the analysis of spatial data, i.e., there are many more variables than subjects, and data may be difficult to model using standard distributions, such as the normal distribution. We herein describe a Bayesian method for LDA; this method is based on data-mining techniques that employ Bayesian networks to represent structure-function associations. These methods are computationally tractable, and can represent complex, nonlinear structure-function associations. When applied to the evaluation of data obtained from a study of the psychiatric sequelae of traumatic brain injury in children, this method generates a Bayesian network that demonstrates complex, nonlinear associations among lesions in the left caudate, right globus pallidus, right side of the corpus callosum, right caudate, and left thalamus, and subsequent development of attention-deficit hyperactivity disorder, confirming and extending our previous statistical analysis of these data. Furthermore, analysis of simulated data indicates that methods based on Bayesian networks may be more sensitive and specific for detecting associations among categorical variables than methods based on chi-square and Fisher exact statistics.