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Class II MHC antigens in the rat digestive system. Normal distribution and induced expression after interferon-gamma treatment in vivo.

The normal and interferon-gamma induced expression of class II MHC antigens was investigated immunohistologically in the digestive system of LEW rats. In the normal state class II molecules were present in interstitial dendritic cells, B lymphocytes and epithelial cells. Epithelial class II expression was restricted to enterocytes in certain portions of the small intestine and to some duct epithelia in salivary glands. After continuous intravenous infusion of interferon-gamma (IFN-gamma) for 3 days, class II MHC antigens were induced in large vessel endothelium and in the surface epithelia of the tongue, oesophagus and proventricle. In the gastric glands class II molecules appeared in mucous neck cells and in parietal cells, while adjacent mucous surface cells and chief cells did not acquire class II reactivity. All enterocytes, including the previously negative colonic epithelium, were induced to express class II antigens. In the salivary glands class II antigens appeared in all duct epithelia. Serous acinar cells were induced in the parotids, but in the submandibular glands and in the pancreas the serous gland epithelium stayed negative. Our study thus shows that the effects of IFN-gamma on class II MHC antigen expression in vivo depend on the differentiation pathway of the individual cell. The normal distribution in rats suggest that class II MHC antigens may play a role in peptide transport across specialized epithelia. It remains to be determined whether such a function is enhanced after IFN treatment.

Animals

Logarithmic normal distribution of incubation times for canine diseases (Sartwell's model).

The distribution of incubation periods for most infectious diseases follows a logarithmic normal distribution (Sartwell's model). The same is true for human neoplastic diseases of known cause and for genetic diseases, when the age at onset of the disease was used as a surrogate measure of the incubation period. In this study, a similar distribution was observed when Sartwell's model was applied to canine diseases of known genetic cause, but not to diseases of an environmental cause. The model was also applied to canine diseases of suspected multifactorial causes for the purpose of distinguishing between the relative importance of genetic and environmental factors that act before or after birth. Limitations of this method were discussed.

Animals

Mixed-model analysis of a censored normal distribution with reference to animal breeding.

A mixed-model procedure for analysis of censored data assuming a multivariate normal distribution is described. A Bayesian framework is adopted which allows for estimation of fixed effects and variance components and prediction of random effects when records are left-censored. The procedure can be extended to right- and two-tailed censoring. The model employed is a generalized linear model, and the estimation equations resemble those arising in analysis of multivariate normal or categorical data with threshold models. Estimates of variance components are obtained using expressions similar to those employed in the EM algorithm for restricted maximum likelihood (REML) estimation under normality.

Analysis of Variance

Log normal distribution of ovarian and placental steroid values in early human pregnancy.

Concentrations of estradiol, progesterone, 17OH-progesterone were measured by radioimmunoassay in individual serum samples obtained from a group of 304 women with normal gestations between the 4th and 17th week of pregnancy. Values obtained underwent statistical analysis in order to determine the arithmetic mean and the 95% normal range (+/- two standard deviations). It was noted hereby that the spread of values above the mean was greater than that below the mean, and that very often the mean minus two standard deviations was either close to zero or negative. Therefore, the data for each hormone were analyzed for normality of the distributions by the chi-square test. For each hormone the chi-square test was significantly different (p less than 0.001) from the normal distribution (Gaussian). Subsequently, linear transformation by rankit analysis revealed the log-normal distribution of our data. Furthermore, rankit analysis was used as a graphical method to delineate a useful clinical range, which includes the mean and meaningful 95% confidence limits for estradiol, progesterone, and 17OH-progesterone in early normal pregnancies.

Estradiol

[Learning and prototype formation of artificial categories defined by multidimensional normal distributions].

In order to approximate the variety of natural categories, two kinds of stimuli whose attributes vary according to different multivariate normal distributions are generated on CRT screen. Twenty undergraduate and graduate students served as subjects. Subject's task was to discriminate the stimuli. Results revealed that subject's performance can be explained very well by the parameters of the distributions (Exp.1). Although in previous studies prototypes have been assumed to be the mean value or central tendency of category instances, there is another possibility, especially when two or more concepts are simultaneously learned, that they have attributes which are emphasized. This hypothesis was confirmed in Exp.2, using 30 undergraduates as subjects. It was argued that we must distinguish at least two kinds of prototypes: the one formed by the most frequent instances and the other the most discriminate in contrast with the other concepts.

Adolescent

Estimation of direct formulation effect under log-normal distribution in bioavailability/bioequivalence studies.

This paper considers estimation of a measure of relative bioavailability of a test formulation to a reference formulation, on the original scale, under the assumption of a log-normal distribution for the data from a 2 x 2 crossover bioavailability/bioequivalence study. We propose the minimum variance unbiased estimator which is equal to the maximum likelihood estimator adjusted for bias by a correction factor. We also derive the variance of the minimum variance unbiased estimator and its unbiased estimator. We derive the biases and mean square errors of the maximum likelihood estimator, the ratio of the least square means, and the least squares mean of individual subject ratios, with respect to this measure, and compare them in a simulation study. Both theoretical and empirical results strongly suggest that one always consider the minimum variance unbiased estimator. A numerical example illustrates the proposed estimation procedure.

Bias

Microglia in tadpoles of Xenopus laevis: normal distribution and the response to optic nerve injury.

We have studied the distribution of microglia in normal Xenopus tadpoles and after an optic nerve lesion, using a monoclonal antibody (5F4) raised against Xenopus retinas of which the optic nerves had been cut 10 days previously. The antibody 5F4 selectively recognizes macrophages and microglia in Xenopus. In normal animals microglia are sparsely but widely distributed throughout the retina, optic nerve, diencephalon and mesencephalon (other regions were not examined). After crush or cut of an optic nerve, or eye removal, there occurs an extensive microglial response along the affected optic pathway. Within 18 h an increase in the number of microglial cells in the optic tract and tectum can be detected. This response increases to peak at around 5 days after the lesion. At this time the nerve distal to the lesion contains many microglial cells; the entire optic tract is outlined by microglia, extended along the degenerating fibres; and the affected tectum shows a heavy concentration of microglia. This microglial response thereafter decreases and has mostly gone by 34 days. We conclude that the microglial response to optic nerve injury in Xenopus tadpoles starts early, peaks just before the regenerating optic nerve axons enter the brain, and is much diminished by the time the retinotectal projection is re-established. The timing is such that the microglial response could play a major role in facilitating regeneration.

Animals

Evaluation of two assumptions: single straight line, and single normal distribution.

Using graphical and statistical approaches, Laszlo Endrenyi and Mayank Patel describe methods that answer two frequently asked questions: 'Can the data be characterized by a single straight line, or should a more complex model be invoked?' and 'Do the observations follow a single normal distribution, or is there evidence for deviations from this assumption, including the possibility of bimodality?" These methods complement those addressed in a recent Principles article by Dick Barlow.

Research Design

Amino acids in parenteral feeding. I. The normal distribution of serum amino acids in healthy subjects.

Questions as to the utilisation of intravenously supplied amino-acids are answerable by determining nitrogen balances and by ascertaining the pattern of amino-acids in the serum of plasma. In a first study, the normal distribution was established for the individual serum amino-acids in 150 fasting test persons with a healthy metabolism. Sex-specific differences in concentration became clearly evident for the majority of amino-acids present in the serum.

Adolescent

Axial forces and normal distributed loads in twining stems of morning glory.

In analysing the mechanics of twining, we hypothesize that contact forces are important in maintaining the twining habit of viny stems. This hypothesis is formalized with a description of the force balance in the natural coordinate system associated with the Frenet vectors attached to the 'generative helix' of the vine. The force balance indicates that, if shear forces are neglected, an axial force within the stem is balanced by a normal load distributed along the line of contact between the supporting pole and the stem. Two kinds of empirical studies were conducted to verify the importance of the putative normal load. Firstly, vine geometry was measured on and off the supporting pole. When removed from the pole, the helical stem forms a coil of smaller radius, smaller wavelength and larger torsion. Next, forces were estimated from observations of the pressure exerted by a stem twining around a water-filled balloon. Twining around a dowel 0.95 cm in diameter, a typical stem of morning glory (Pharbitis nil) sustains a tension of 100 g balanced by a normal distributed load of -30 g cm-1. Thus the twining stem puts itself into tension and uses a helical geometry to generate contact forces which are large relative to the stem weight of 40 mg cm-1.

Elasticity

Substance P-containing sensory nerves in the rat iris. Normal distribution, ontogeny and innervation of intraocular iris grafts.

Trigeminal, substance P-containing nerves have been studied in the stretch-prepared rat iris with immunohistochemical techniques. The normal iris exhibited a slightly irregular plexus of individual fibres in the dilator, intermingled with thin, meandering axon bundles. The sphincter contained more circumferentially oriented fibres. Occasional free nerve endings were present in all parts of the iris; no obvious association with blood vessels was detected. All substance P-positive nerves in the iris disappeared after lesioning the trigeminal nerve. Irides of neonates showed scattered, smooth fibres in a sparse plexus, without visible axon bundles. Over the first two postnatal weeks, the density of innervation developed rapidly, reaching a transiently supranormal level and fluorescence intensity, compared to adulthood. From 3 weeks on, the pattern and density of substance P-containing fibres approached the normal adult appearance. In irides grafted to the anterior eye chamber, the intrinsic substance P nerves degenerated, disappearing completely after 5 days. Reinnervation from the host irides transpired over the next few weeks, approximating normal density after 3 weeks, and organotypic density and distribution from 4 weeks on. No obvious hyperinnervation was encountered after longer postoperative times (3 months). In the host iris, many substance P fibres disappear or exhibit low fluorescence intensity during the first postoperative week, recovering fully during the next 2 weeks. Over longer postoperative periods irregular, moderate hyperinnervation developed with increased numbers of axons in bundles. In conclusion, we show normal distribution and plasticity during ontogeny and maturity of substance P-containing iris nerves in the rat, with a sensitive immunohistochemical technique in iris whole mounts.

Animals

Use of overlapping normal distributions in genetic counselling.

If a numerical variable can be assumed to be normally, but differently, distributed in each of two or more populations, then for an 'unknown' individual whose numerical value is known the relative probability of his belonging to each of the populations can be simply calculated. We briefly review the method and its application in genetic counselling.

Genes

The mucosa-associated microflora of the rat intestine: a study of normal distribution and magnesium sulphate induced diarrhoea.

Specimens of intestinal mucosa of rats were examined closely to determine the distribution of the mucosa-associated microbial flora. Six distinct zones were found along the length of the intestinal tract. The first zone, in the small intestine 50 cm or more from the ileocaecal junction, had no associated flora: however, each of the five other zones had different populations of microorganisms associated with the mucosa. Some of these organisms have not been reposted previously. Treatment of rats with oral doses of the purgative magnesium sulphate resulted in dramatic changes in the distribution of these mucosa-associated microorganisms. The normal flora of ileal and caecal crypts disappeared, while the organisms in colonic crypts were unchanged. Large numbers of mucosa-associated bacteria appeared in the stools of treated animals.

Animals

Normal distribution of complement C3b receptor (CR1) numbers on erythrocytes in blood donors: low levels are associated with HLA-B27.

Blood donors were examined for C3b receptor (CR1) levels on erythrocytes by a microtiter plate enzyme-linked immunosorbent assay and for HLA-A, -B, and -C antigens, C3 phenotypes and blood groups. The CR1 levels among 150 donors varied in the range from 24 to 130% (mean +/- 1 SD = 69.9 +/- 22.9) of an erythrocyte standard, and in accordance with a polygenic model of inheritance the distribution of CR1 was well approximated by a normal curve (chi-square goodness-of-fit test nonsignificant, p = 0.66). Low CR1 levels were associated with HLA-B27 (n = 11, p = 0.05), which was confirmed by investigation of further 20 HLA-B27-positive donors (p = 0.05). The CR1 levels were not associated with a certain C3 phenotype. Possibly, the blood group phenotype M-M + S-s+ is associated with high and the S antigen with low CR1 numbers. The relation between low CR1 numbers and HLA-B27 might be important for the understanding of the association between HLA-B27 and certain inflammatory rheumatological diseases.

Blood Donors

Mapping of the normal distribution of substance P-like immunoreactivity in the spinal trigeminal nucleus of the cat.

Although a recent preliminary report indicated a pattern of substance P-like immunoreactivity within the spinal trigeminal nucleus that is similar to the projection sites for dental afferent fibers, details of this substance P distribution are lacking. Our purpose was to describe in cats the complete normal pattern of this immunoreactivity within each of the spinal trigeminal subnuclei. Special emphasis was given to the distribution of substance P-like immunoreactive axons and terminals located in the rostral subnucleus caudalis and the periobex region of subnucleus interpolaris, as these are regions shown to receive dental afferent fibers. Careful mapping in normal cats showed, within the resolution of the light microscope, a consistent pattern of distribution that included only a portion of the previously identified dental relay sites, but was somewhat broader in certain levels and more restricted in others. The results are compared with those provided by others from regions such as the dorsal horn and subnucleus caudalis of the spinal trigeminal nucleus. The findings also provide an anatomical basis for a recent physiologic report on specific cell types associated with dental nociceptive afferent fibers. This study also provides a baseline control for future investigations of possible changes in substance P-like immunoreactivity that follows various peripheral, including dental and central, lesions.

Animals

c-Ha-ras-1 polymorphism in human breast carcinomas: evidence for a normal distribution of alleles.

Analysis of the c-Ha-ras-1 locus for restriction fragment length polymorphism was determined by Southern blot hybridization in 112 specimens of primary breast carcinoma. Normal cell samples were lymphocytes obtained from 61 of these breast cancer patients and from 62 healthy donors. Our data indicate that the distribution of c-Ha-ras-1 alleles in breast carcinoma patients did not significantly differ from that found in normal individuals. In addition the loss of one allele detected in 5 tumor samples was not correlated to the aggressiveness of breast cancer. Consequently our data imply that hereditary predisposition to breast cancer is not associated with the c-Ha-ras-1 polymorphism as previously reported.

Alleles

Normal distribution of lysozyme- and lactoferrin-secreting cells in the chinchilla tubotympanum.

The distribution of the antibacterial enzyme lysozyme- and lactoferrin-secreting cells in the tubotympanum of normal chinchillas was studied using an immunohistochemical technique. The middle ear mucosa contained lysozyme-secreting cells and lactoferrin-secreting cells. The former were localized primarily in the columnar epithelium area and the latter primarily in the cuboidal epithelium area (that contains serous cells) of the transitional zone. In the eustachian tube, the lysozyme was localized in goblet cells of the mucosal epithelium and mucous cells of the glands, while lactoferrin was localized in serous cells of the glands. Our results indicate that secretory lysozyme and lactoferrin are secreted by different cell types (mucous or serous), supporting the notion of heterogeneity of the secretory cells of the tubotympanum. This finding is consistent with the concept that antibacterial enzyme secretion is an integral part of the normal mucosal defense system in the tubotympanum.

Animals