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PubMed1996

Changes in protein distribution in normal and protein-deficient rats during an acute-phase 'injury' response.

The present study investigated the effect of the acute-phase 'injury' response, induced by subcutaneous injection of turpentine, on the hydration and protein content of organs and tissues of normally nourished rats receiving a diet containing 200 g protein/kg, and of protein-malnourished rats receiving a diet containing 30 g protein/kg. The measurements were carried out 48 h after turpentine injection, and were compared with both saline-injected animals, and pair-fed control animals. Circulating alpha 2-macroglobulin was also measured as an index of the acute-phase-protein response. In normally nourished rats turpentine injection caused a significant increase in the mean masses of the liver, kidney and lung (7-35% compared with saline-injected animals, and 20-44% compared with pair-fed controls), and a small reduction in the mass of extra-abdominal and extrathoracic tissues ('carcass'). In general the protein content of tissues changed in a similar way (for liver, kidney and lung a 16-33% increase compared with saline-injected animals, and 32-49% compared with pair-fed controls). Protein deficiency produced a significant attenuation in the response to turpentine. The change in the mass and protein content of several tissues was reduced (for lung, liver and kidney, the increase in protein content was only 5-15%), and the effects on anorexia (1 v. 41% reduction in food intake) and the alpha 2-macroglobulin response (1.28 v. 4.28 g/l; P < 0.001) were also reduced. It is concluded that the injury response spares most central thoracic and abdominal organs, but this effect as well as the anorexia and acute-phase-protein response to injury are attenuated by protein deficiency.

Acute-Phase Reaction↗
PubMed1999

Poly(amidoamine)s as potential endosomolytic polymers: evaluation in vitro and body distribution in normal and tumour-bearing animals.

Fusogenic peptides derived from viral coat proteins cause perturbation of the endosomal membrane and are often used to improve the transfection efficiency of non-viral vectors in vitro. However, fusogenic peptides have limited potential for use in vivo due to their inherent immunogenicity. Totally synthetic polymers that are endosomolytic should circumvent this problem and could be useful as components of non-viral delivery systems as long as they do not immediately localise in the liver after intravenous (i.v.) injection. Linear poly(amidoamine) polymers (PAAs) having amido- and tertiary amino-groups along the main polymer undergo pH-dependent conformational change and thus provide an ideal opportunity for design of polymers that display membrane activity at low pH. Here we describe four PAAs, ISA 1 (Mn = 6900 Da) and ISA 23 (Mn = 10,500 Da) and their analogues ISA 4 and ISA 22 (Mn approximately 8000 Da) containing approximately 1 mol% 2-p-hydroxyphenyl ethylamine to allow radioiodination and thus monitoring of their biodistribution. In vitro cytotoxicity was assessed by MTT assay after incubation of PAAs with B16F10 and Mewo cell lines. The IC50 values observed for all PAAs were > 2 mg/mL in comparison with poly(L-lysine) which displayed an IC50 in the range 0.01-0.1 mg/mL. At pH 7.4 none of the PAAs studied was haemolytic at 1 h at concentrations below 3 mg/mL. PAAs were subsequently incubated with rat red blood cells for 24 h (1 mg/mL) at different pHs. In contrast to poly(L-lysine) which was haemolytic at pH 7.4, 6.5 and 5.5, none of the PAAs was lytic at pH 7.4, but they became membrane active at lower pH (approximately 45% for ISA 4, 50% for ISA 22 and 90% for ISA 23). These observations were substantiated by SEM and confirm the pH-dependence of membrane activity. After i.v. injection to rats 125I-labelled ISA 4 was immediately taken up by the liver (> 80% recovered dose at 1 h) whereas 125I-labelled ISA 22 was not (liver uptake was < 10% recovered dose at 5 h). Furthermore, biodistribution studies in mice bearing subcutaneous B16F10 melanoma showed that 125I-labelled ISA 22 was still accumulating in tumour tissue after 5 h (2.5% dose/g). PAAs have potential as endosomolytic agents and quantitation of the endosome to cytoplasm transfer is warranted after i.v. administration.

Animals↗
PubMed1995

Dental health indicator based on a questionnaire.

Dentistry has lacked an effective indicator of the impact of dental problems on a person's daily life. Subjective factors in dental health need to be included in order to improve current indicators. The purpose of this research was to develop a new type of indicator recorded from a questionnaire which takes account of subjective factors in dental health. The indicator we constructed has the following advantages. 1. Calculation process is simple in practice. 2. The indicator values range from 0 to 100, with values closer to 100 indicating a more favorable condition for the individual. 3. The distribution of indicator values is similar to the normal distribution. 4. The score of each item is reflected on the indicator, suggesting the individual's characteristics in terms of dental health. 5. Although it is principally an indicator for individuals, it can also be applied to groups. This study will also provide a model for the preparation of a dental health indicator.

Adult↗
PubMed1999

Sample size-based indication of normality in lognormally distributed populations.

Occupational and environmental hygiene sampling strategies are usually dictated by factors that limit sample sizes to relatively small numbers. Often, parameters estimated from small sample sizes are then used to make further estimates of the occurrence of extreme events, which are governed by the underlying exposure distribution. We investigated the limitations superimposed by the number of samples in distinguishing an asymmetric (Lognormal) distribution through the rejection of a hypothesized symmetric (Normal) distribution. Sets of 5 to 250 synthetic samples from underlying Lognormal distributions with unit median were generated for 24 separate geometric standard deviations (GSDs), ranging from 1.25 to 7.00. Each simulated combination was repeated in blocks of 200 and each block was repeated tenfold. The synthetic samples were then tested for goodness of fit for Normality by using the Shapiro and Wilk's W Test. Results indicated that the number of samples required to distinguish between Normal and Lognormal distributions was inversely related to GSD. When GSD = 1.25, 169 samples were required for 90 percent distinction at alpha = 0.05. The criteria for success for GSD of 2.00 and 4.00 were 25 and 15 samples, respectively. These results led to the conclusion that the general inability to distinguish an underlying distribution may impose serious difficulties in the estimation of extreme events associated with occupational and environmental hygiene-related sampling.

Environmental Monitoring↗
PubMed2001

A brief history of numbers and statistics with cytometric applications.

A brief history of numbers and statistics traces the development of numbers from prehistory to completion of our current system of numeration with the introduction of the decimal fraction by Viete, Stevin, Burgi, and Galileo at the turn of the 16th century. This was followed by the development of what we now know as probability theory by Pascal, Fermat, and Huygens in the mid-17th century which arose in connection with questions in gambling with dice and can be regarded as the origin of statistics. The three main probability distributions on which statistics depend were introduced and/or formalized between the mid-17th and early 19th centuries: the binomial distribution by Pascal; the normal distribution by de Moivre, Gauss, and Laplace, and the Poisson distribution by Poisson. The formal discipline of statistics commenced with the works of Pearson, Yule, and Gosset at the turn of the 19th century when the first statistical tests were introduced. Elementary descriptions of the statistical tests most likely to be used in conjunction with cytometric data are given and it is shown how these can be applied to the analysis of difficult immunofluorescence distributions when there is overlap between the labeled and unlabeled cell populations.

Cell Count↗
PubMed2001

FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration.

Subcortical motor nuclei show differential expression of FosB immediate early gene products and specifically deltaFosB after short (8, 19, or 21 days) chronic exposure to typical and atypical neuroleptics represented by haloperidol and clozapine, respectively. We quantitatively examined whether there are light microscopic regional variations in area density of FosB or the truncated deltaFosB in several motor-related nuclei of adult rats receiving vehicle or long chronic (6 months) administration of either depot haloperidol or clozapine in their drinking water. In control animals the dorsomedial and ventromedial caudate-putamen nucleus (CPN) had a significantly higher density of FosB-immunoreactive cells than the dorsolateral and ventrolateral regions. The nucleus accumbens (NAc) core also serving motor functions had a higher basal expression than the limbic shell region in control animals. The mediolateral gradient in area density of FosB-labeled cells was maintained in animals receiving either haloperidol or clozapine. In animals receiving haloperidol, but not clozapine, however, there was a regionally selective increase in the area density of only FosB-immunoreactive neurons in the dorsolateral and ventrolateral CPN and in both the core and shell of the NAc. Only the animals receiving chronic haloperidol showed vacuous chewing movements, the animal equivalent of tardive dyskinesia in humans. Our results suggest that, whereas the medial striatal neurons are activated under basal conditions, long chronic haloperidol induced FosB expression more exclusively in the lateral CPN and NAc core, implicating these regions specifically in the motor side effects of this drug.

Animals↗
PubMed1988

Red cell vacuoles: their size and distribution under normal conditions and after splenectomy.

The frequency of occurrence of vacuoles in red blood cells was studied by transmission electron microscopy. Small vacuoles were found in about 13% of the cell sections, and they had a mean diameter of 130 +/- 72 nm (mean +/- SD). It can be estimated that there were about 20 small vacuoles per erythrocyte. The frequency of vacuoles was similar in density-separated cell fractions. In splenectomized patients, the small vacuoles were 4 times more frequent; there was again no difference in vacuole density between top and bottom fractions of density-separated red blood cells. The bottom fraction of red blood cells from splenectomized patients, however, had a high incidence of large vacuoles (greater than 300 nm in diameter) and clustering of small vacuoles. These large vacuoles were probably the result of aggregation and fusion of small vacuoles, and their size allowed detection by light microscopy. Hence, the well-known "pocked" or "pitted" red blood cells of splenectomized individuals were more frequent in the bottom fraction. We conclude that small vacuoles occur normally in erythrocytes, that they tend to cluster and fuse during cell aging, and that the spleen is capable of removing these structures when they reach a certain size.

Erythrocytes↗
PubMed1985

Cytology and distribution in normal human cerebral cortex of neurons immunoreactive with antisera against neuropeptide Y.

The frontal, parietal, and temporal cortices in normal human brains (Brodmann areas 10, 7a, 7b, and 21) are well endowed with numerous neurons, identifiable by immunoreactivity with antisera against the 36-amino acid brain peptide neuropeptide Y (NPY). These neurons with rare exception are small, intracortical, nonspiny neurons, 12-20 microns in somatic size, with long slender dendrites and exuberant axon plexuses exhibiting finely beaded varicosities. The cells are rarest in layers I and II, are found with frequency in the lower cortical layers (IV-VI) and in significant numbers in the subcortical white matter. Within the cortex the axonal plexuses of these peptide neurons rise straight up into the upper cortical layers or descend deep into the white matter. In layers I and II, numerous other lengthy axons, some possibly of extracortical afferent origin, run along the pial surface at right angles to the axial ones running perpendicular to the cortex. This endowment of peptide neurons and their processes forms a rich network in the cerebral cortex, relating with one another in complex fashion within palisades of terminals as well as with the other cortical neurons not labeled by these methods. It remains to be shown what functions these NPY neurons have individually and in their remarkable networks, and how they are altered in neurological disease.

Aged↗
PubMed1975

Five types of lymphocytes (Ig-theta-, Ig-theta+weak, Ig-theta+strong, Ig+theta- and Ig+theta+) characterized by double immunofluorescence and electrophoretic mobility. Organ distribution in normal and nude mice.

The simultaneous detection of Ig and theta on the surface of mouse lymphocytes permits the detection of four cell types (Ig-theta-, Ig-theta+, Ig+theta-, and Ig+theta+) which also have distinct electrophoretic profiles. All types are present in variable proportions in all lymphoid organs studied. Results obtained in congenitally athymic nude mice and in T-deprived mice define a new type of lymphocyte, the Ig-theta+weak. This cell is non-recirculating, Ig-, with a low density of theta and a slow electrophoretic mobility. It is a candidate for a T-committed prethymic cell.

Animals↗
PubMed1992

Errors in sizing bands of hypervariable DNA profiles on autoradiograms: are they Gaussian?

The accuracy of procedures for sizing hypervariable restriction fragments by Southern blot analysis (SBA) has been tested under three different experimental conditions: (i) intrablot serial analyses: three heterozygous DNA profiles were tested 14 times each in the same gel electrophoresis; (ii) intralaboratory analyses: we replicated three profiles (six autoradiographic bands) in over 100 SBA experiments; (iii) interlaboratory analyses: 15 serial measurements produced in a recent collaborative study (Forensic Sci. Int. 1991, 49, 1-15) were taken into account. In these three cases, a typical U-shaped correlation curve between molecular size and coefficient of variation was found. We explain decrease of accuracy at both extremities of the gels in terms of: (i) enlarged shapes of bands and mean electrophoretic resolution at the cathode; (ii) diffusion and blurring of bands at the anodal edge. The three populations of data were subjected to a chi 2 test and to the Kolmogorov-Smirnov test in order to verify their compliance with normal distribution. Twenty-three out of 27 tests indicated no significant deviation from the assumption of Gaussian distribution. We recommend the adoption of tests for normality to validate the use of symmetric confidence intervals for calculating gene frequencies and asserting a match between adjacent bands.

Analysis of Variance↗
PubMed1988

Fatigue properties of acrylic bone cement: S-N, P-N, and P-S-N data.

The determination of the fatigue properties of a material is a fundamental criteria in the engineering design process. The fatigue properties are governed by a number of factors, one of which is the inherent scatter in the data. In order to take into account this scatter in the results, the concept of the probability of failure (P) is introduced and interconnected with the well known stress (S) versus number of cycles to failure (N) data. This report determines the S-N curve, P-N curve, and P-S-N contour for the three leading acrylic bone cements: Surgical Simplex P, Zimmer LVC, and Zimmer Regular. Tensile specimens were fabricated according to ASTM D638 specifications and tested in uniaxial, zero-tension fatigue. The resulting stress versus number of cycles to failure data was subjected to a nonlinear least-squares analysis to determine the mathematical expression of the fatigue curve. Statistical analysis showed excellent fit of the data to the predicted curve for estimation of the endurance limit of each cement. The results indicated that Zimmer LVC had the highest endurance limit while the limit of Simplex-P and Zimmer Regular were significantly lower. No significant difference was noted in the endurance limit between Simplex-P and Zimmer Regular. The probability of failure at each stress level was determined with respect to fatigue distribution functions. Using the normal distribution function and previous S-N data, the P-S-N contour was generated for each cement. The P-S-N contour fully describes the fatigue characteristics of the material.

Acrylates↗
PubMed1995

Conduction velocity distributions compared to fiber size distributions in normal human sural nerve.

Compound action potentials (CAPs) were recorded from the sural nerve of healthy volunteers. A mathematical technique (inverse modeling) was used to compute conduction velocity (CV) histograms from the data. Results were compared to the morphology of age-matched normal sural nerve biopsies. Coefficients of variation (CoVs) revealed the statistical relationship between morphological data (diameter histograms) and electrophysiological data (CV histograms and conventional CAP parameters). No differences were found for the thick fiber group when comparing the CoVs of the diameter histogram parameters with the corresponding CV histogram parameters. Apparently, the same inherent biological interindividual variability is encountered. The CoVs of the CVs of the CAP's main phases are in good agreement with the CoVs of the estimated mean velocity of the thick fiber group. Inverse modeling increases the reliability of the estimation of the number of active fibers as compared to direct CAP amplitude interpretation.

Action Potentials↗
PubMed1986

Desmin-containing stellate cells in rat liver; distribution in normal animals and response to experimental acute liver injury.

Using immunohistochemical methods, we have confirmed that the perisinusoidal cells in rat liver express the intermediate filament protein, desmin, and we have used this marker for identification of the cells on light microscopy. The study has been extended to quantify the response of perisinusoidal cells to acute liver injury induced by carbon tetrachloride. A significant increase in desmin-positive cells was observed in areas of necrosis as early as 48 h following the administration of a single bolus of carbon tetrachloride. This reached a peak at 72 h, with a five-fold increase in desmin-positive cells in areas of necrosis. These observations are consistent with the hypothesis that perisinusoidal cells are involved in the response to acute liver injury. Anti-desmin antibodies are of potential value in further characterizing the functional role of perisinusoidal cells in normal and diseased liver.

Animals↗
PubMed1989

T-cell antigen receptor beta-chain variable region families: a study of their distribution in normal and reactive tissues.

The beta chain of the T-cell antigen receptor is constructed using a variable region gene from one of approximately 20 variable gene families. Antibodies that react with the products of these gene families have been used to demonstrate clonal proliferation of T cells. Here, we describe the expression of two beta-chain variable region families in normal and reactive lymphoid tissues. In all the tissues studied, expression was scattered throughout the T-cell areas, without any clustering of expression.

Antibodies, Monoclonal↗
PubMed1985

Beta-adrenergic regulation of the blood lymphocyte phenotype distribution in normal subjects and splenectomized patients.

The beta-adrenergic effect on the release of immunoregulatory cells from the spleen was investigated by physical stress testing (bicycle ergometry up to submaximal work capacity) in 19 normal subjects (15 males, median 21 years) and in 10 male patients splenectomized for trauma (median 29 years). It was repeated in 6 subjects of each group during beta-blockade with 80 mg oxprenolol. Blood samples for leucocyte analysis were taken before and at the end of the test. Leucocyte subpopulations were analyzed in a cytofluorograph after staining of buffy coat cells by direct (B cells) or indirect immunofluorescence with monoclonal antibodies directed against the phenotypes of T- (Leu-1), T helper- (Leu-3a), T suppressor/cytotoxic (Leu-2a) cells and natural killer (OKM1+ lymphocytes) cells. In the controls all leucocyte subsets increased at ergometry, but B-, Leu-2a- and OKM1-cells increased more than Leu-3a cells. During beta-blockade the leucocyte changes reached only 50% of the value without treatment; the B- and Leu-2a cell mobilization was reduced more than the Leu-3a-, OKM1 cell- and monocyte changes. In splenectomized patients the proportional cellular changes were only half of those found in normal subjects, except for the Leu-3a cells which were not released. Beta-blockade during ergometry had no effect on Leu-3a cells, a similar effect on B- and Leu-2a cells as in normal subjects and a stronger effect on granulocytes, monocytes and OKM1 cells than in controls. In conclusion, the B- and Leu-2a cell mobilization from the spleen (50%) was beta-adrenoceptor dependent, while the one from other lymphoid organs was beta-adrenoceptor independent. The strongly spleen dependent Leu-3a cell changes were not beta-adrenoceptor mediated. Granulocyte-, monocyte- and OKM1 cell changes were only partly spleen dependent. The spleen independent changes however were strongly beta-adrenoceptor dependent.

Adolescent↗
PubMed1994

Protein 1 and Clara cell 10-kDa protein distribution in normal and neoplastic tissues with emphasis on the respiratory system.

Thirty-six different normal tissues and 13 different malignant epithelial tumours, were examined immunohistochemically for the presence of protein 1 (P1) and Clara cell 10-kDa protein (CC10). Adenocarcinomas of the lung were also examined for the expression of pulmonary surfactant apoprotein using a monoclonal antibody (PE-10). The staining results of P1 and CC10 were almost identical both in normal tissues and in malignant tumours. In normal lung, Clara cells were strongly positive for both P1 and CC10. In addition, some goblet cells and non-ciliated non-mucus cells in the upper airways were moderately positive for both proteins. In the malignant tumours, some lung cancers were positive for P1 and CC10, both of which were positive in the same tumour cells on sequential sections. In 117 lung cancers, P1 and CC10 were positive in 10.2% of adenocarcinomas, 20.5% of squamous cell carcinomas, and 12.5% of large cell carcinomas. PE-10 stained positively in 65.3% of adenocarcinomas, a frequency significantly higher than that of P1 and CC10 (P < 0.01). These results suggest that P1 and CC10 are nearly identical proteins, that both are useful markers of Clara cells, and that many pulmonary adenocarcinomas express surfactant apoprotein rather than Clara cell proteins.

Adenocarcinoma↗
PubMed1981

The mode of genetic transmission of gouty family with increased phosphoribosylpyrophosphate synthetase activity.

The mode of genetic transmission of gout and increased activity of phosphoribosylphrophosphate synthetase (PRPPS) was studied in one family. Among 15 members of Family F, two male members had gout and had PRPPS activity of erythrocyte lysates three times higher than normal subjects. Five female members had activity 2.5 times higher than normal. The difference between the activities of male and female affected members was statistically significant (P less than 0.05). To examine the genetic trait of this abnormal PRPPS, the incorporation of 3H-adenine into erythrocytes or lymphocytes was studied using autoradiography. The number of grains which show the uptake of labeled adenine into cells revealed a normal distribution pattern in two normal persons and in two male patients, and a mixed pattern of the two cell populations in two female affected members. These results suggested mosaicism in female members and X-linked dominant transmission of this trait. Thermal inactivation of PRPPS of an affected female was intermediate between that from a normal subject and that from the affected males. This result showed the heterogeneity of the PRPPS from the hemolysate of an affected female. The genotype of PRPPS on the X-chromosome was assumed and the lod score between PRPPS and Xg was also estimated. From these findings and electrophoretical study, it was suggested that the abnormal enzyme was a mutant enzyme transmitted in an X-linked dominant trait, and that the mutation occurred on the structural gene of the PRPPS.

Adenine↗