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PubMed1978

Growth related changes in the content of heparin and 5-hydroxytryptamine of mast cells.

Heparin and 5-hydroxytryptamine (5-HT) were quantitated cytofluorometrically in individual mast cells from rats of various ages and body weights. Mast cells were studied in animals 35-200 days of age (150-575 g) representing a period of major body growth and about a quarter of the life span of the rat. Mast cell numbers as well as the content of both heparin and 5-HT in the mast cells was found to be strongly related to body weight and age of the animals. The number of mast cells increased about 3.5 times, the content of heparin in mast cells was doubled and the content of 5-HT increased at least three times during the growth period studied. There were great variations in the content of heparin and 5-HT within the cell populations of both young and old animals. The heparin content in the mast cell populations appeared to be either approximately normally distributed or slightly positively skewed. The skewness was not as marked as in a log-normal distribution. The 5-HT distribution profiles, on the other hand, were more strongly positively skewed. Except in the youngest age group, the 5-HT content appeared to be log-normally distributed within the mast cell population. A strong positive correlation was found between the median values of 5-HT and heparin content in the mast cell populations of growing rats.

Aging↗

PubMed1999

Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy.

OBJECTIVE: To test the hypothesis that changes in the normal regional distribution of potassium and calcium currents contribute to the different regional changes in action potential duration in isoprenaline-induced hypertrophy in rats. METHODS: Hypertrophy was elicited in rats by seven daily injections of isoprenaline. Left ventricular myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial tissue. Membrane currents were measured using the whole-cell patch-clamp technique at 35 +/- 1 degrees C. RESULTS: Cell membrane capacitance was similar in all three groups and was increased by 17% in hypertrophy (P < 0.001, t-test). Changes in the calcium-independent transient outward current (Ito1) density in hypertrophy were different in the three regions (P < 0.05, ANOVA). Ito1 was reduced in sub-epicardial (control, 23.4 +/- 2.0 pA pF-1; hypertrophy, 15.8 +/- 1.5 pA pF-1, P < 0.01 ANOVA) and in mid-myocardial myocytes (control, 24.0 +/- 2.8 pA pF-1; hypertrophy, 13.8 +/- 1.3 pA pF-1, P < 0.01 ANOVA) and was not significantly altered in sub-endocardial myocytes (control, 8.5 +/- 0.7 pA pF-1; hypertrophy, 7.4 +/- 1.8 pA pF-1). Steady-state background current density was reduced in hypertrophy (P < 0.05, ANOVA). The regional difference in steady-state background current in control hearts (P < 0.05, ANOVA) was altered in hypertrophy. Calcium current (ICa) density was similar in the three regions studied in both control and hypertrophied hearts. ICa was reduced in hypertrophy (P < 0.05, ANOVA). CONCLUSION: The normal regional differences in Ito1 are reduced, in steady-state background current are altered and in ICa are unchanged in catecholamine-induced hypertrophy in the rat left ventricle. These data may in part explain the reduction in the normal regional differences in APD observed in hypertrophy.

Action Potentials↗

PubMed2000

Normal and abnormal day-to-day variability of urinary albumin excretion in control and diabetic subjects.

Urinary albumin excretion (UAE) is very variable from day to day. This variability, more or less potent, might by itself have a patho-physiological significance. We analyzed day-to-day UAE in 207 elderly (60-75 years) inpatients (134 with and 73 without diabetes mellitus) attending the department of internal medicine of the Angers University hospital. Twenty-four-hour urine was collected 3 times during a 5-10 day hospitalization period. One-hundred-fifty-one patients (73%) displayed normoalbuminuria (UAE<30 mg/24 h in 2 or 3 measures) while 56 patients (27%) had microalbuminuria (UAE within 30-300 mg/24 h in 2 or 3 measures). As the raw data of UAE was not normally distributed, we transformed UAE into the variable z=log (log (k + UAE)) where k is an integer and looked for a k value for which z might be normally distributed. We found that z was actually normally distributed for k=2. Mean value and coefficient of variation of z in the 3 measurements were used to define the level and the temporal intra-individual variability of UAE. Expressed in term of z, the day-to-day intra-individual variability of UAE showed a potent change (from large variability to small variability) at the particular level z=1.25, corresponding to UAE=30.8 mg/24 h. This value is precisely the level currently used to define microalbuminuria in diabetic subjects. It is remarkable that the day-to-day variability of UAE collapses when UAE crosses the level which has been used to define microalbuminuria.

Aged↗

PubMed1982

In vitro modulation of the distribution of normal human plasma high density lipoprotein subfractions through the lecithin: cholesterol acyltransferase reaction.

The effect of the lecithin: cholesterol acyltransferase reaction on the chemical composition, morphology and distribution of normal human plasma high density lipoprotein (HDL) subclasses was studied in vitro. Incubation of plasma in the presence of polyenephosphatidylcholine (PPC) resulted in a 45 +/- 11% (n = 6) decrease in unesterified cholesterol after 20 h. This effect was abolished by prior heating of the plasma at 56 degrees C or by the addition of diisopropyl fluorophosphate (DIFP). Plasma triacylglycerol levels were constant. Analysis of the plasma lipoproteins by zonal ultracentrifugation and isopycnic equilibrium banding revealed a bimodal distribution of the HDL of native plasma and both heat-inactivated or DIFP-treated samples with peak maxima at d = 1.084 g/ml and d = 1.110 g/ml. Following the lecithin:cholesterol acyltransferase reaction essentially all of the HDL material had flotation characteristics typical of HDL2. The peak maximum was d = 1.086 g/ml. There were no apparent changes in the distribution of the lipoproteins of d less than 1.063 g/ml. The newly formed HDL were poor in PC and unesterified cholesterol but rich in cholesteryl ester, sphingomyelin and lyso-PC. The HDL apolipoprotein pattern was unaltered. HDL morphology was not affected by the lecithin:cholesterol acyltransferase reaction. Similar results were obtained in the absence of PPC. However, under these conditions the total phospholipid content of the HDL was reduced and lyso-PC was not demonstrable as a product of the lecithin:cholesterol acyltransferase reaction after 20 h. The results are interpreted to indicate that lecithin:cholesterol acyltransferase is involved in the transformation of HDL3 into HDL2.

Female↗

PubMed1976

An approach to numerical identification of bacterial species.

The distribution of matching coefficients (M values) for strains of a species to their own 'hypothetical mean organism' (HMO) or to HMO patterns of other organisms was studied in 754 strains of 19 mycobacterial species, testing for 91 discriminating characters. The M values of strains of a species to the HMO of other species usually showed a normal distribution, and M values to their own HMO showed either a normal distribution of a binomial distribution, depending on the mean of M values. If the number of test characters was large, the binomial distribution usually resembled the normal distribution. After preparation of the HMO for every species and estimation of the mean of the M values (M) and the standard deviation (s), numerical identification could be carried out: if a test strain had an M value to the HMO of species chi that only fell within the range (M +/2s) for species chi, the strain would be identified as a member of that species.

Bacteria↗

PubMed2004

Parametric methods for estimating covariate-dependent reference limits.

Age-specific reference limits are required for many clinical laboratory measurements. Statistical assessment of calculated intervals must be performed to obtain reliable reference limits. When parametric, covariate-dependent limits are derived, normal distribution theory usually is applied due to its mathematical simplicity and relative ease of fitting. However, it is not always possible to transform data and achieve a normal distribution. Therefore, models other than those based on normal distribution theory are needed. Generalized linear model theory offers one such alternative. Regardless of the statistical model used, the assumptions behind the model should always be examined.

Humans↗

PubMed1986

Relation between signs and symptoms in Paget's disease of bone.

The relation between signs and symptoms of Paget's disease of bone was studied in 180 patients consecutively submitted for treatment. In these patients 826 lesions were identified by scintigraphy. The intensity of scintigraphic uptake was correlated with long-term calcium uptake in bone. The frequency distribution of lesions over the patients was compatible with a 65 per cent chance of local disease once the patient had been exposed to an extraneous agent. The spatial distribution within a skeleton was related to the local density of the osteoclast population. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Within lesions, increases in numbers of osteoclasts and osteoblasts were proportional and these too had a log-normal distribution. Increases of alkaline phosphatase levels and hydroxyproline excretion were closely related and reflected anatomical spread on the one hand and local activity on the other. They were also closely correlated with overall calcium fluxes. It was shown that alkaline phosphatase is the more sensitive and hydroxyproline the more accurate of the biochemical signs. Maximum values, corresponding to total skeletal disease, were approximately 25 times the upper limit of normal. Equilibrium between bone formation and resorption was not always maintained. There were, indeed, wide variations of urinary calcium, which were significantly related to the difference between bone formation and resorption, but the extracellular calcium homeostasis was generally maintained. This may explain the frequent occurrence of normocalcaemic and hypercalcaemic hyperparathyroidism. The hypercalciuria constitutes an additional risk for urolithiasis in men. The most frequent complaint was pain (86 per cent). Extent of lesions was important, but a major decisive factor was the specific nature of the bone affected. The findings allowed assessment of the relative importance of the various signs, symptoms and locations as criteria of disease severity and as indications for treatment.

Adult↗

PubMed1988

[Relationship between angiographical manifestations and operative findings in 100 cases of hemifacial spasm].

Relationship between angiographical manifestations and operative findings of hemifacial spasm was studied in 100 cases. Vertebral angiography was performed, and Towne, straight AP, and lateral projections were routinely studied. The anterior inferior cerebellar artery (AICA) directly compressed the facial nerve root exit zone in 54 instances, the posterior inferior cerebellar artery (PICA) in 38, and the vertebral artery (VA) in 11. Compressions by multiple vessels were observed in 3 cases. Anatomical variations of the AICA and the PICA were classified into 3 groups according to their origins and their distributions of blood supply: Type I, normal distribution of AICA and PICA; Type II, common trunk anomaly with dominant AICA (basilar artery origin); and Type III, common trunk anomaly with dominant PICA (vertebral artery origin). In our cases, 35% of them showed normal distribution, 34% dominant AICA, and 35% dominant PICA. Analyses of the angiograms revealed significantly increased numbers of common trunk anomalies when compared with normal angiograms studied by Takahashi. In 60 of the 65 cases with common trunk anomalies, facial nerves were compressed by the main trunk or the branches of the dominant artery. There were 35 cases which belonged to Type I anatomical classification. They were subdivided into 2 groups according to the size of the AICA and PICA: 1. AICA greater than PICA, and, 2. PICA greater than AICA. In the AICA greater than PICA subgroup, the AICA was the offending artery in all but one case. In the PICA greater than AICA subgroup, the PICA was responsible in 9 of 17 cases. In 31 cases, angiograms showed a redundant VA with lateral elongation into the cerebellopontine angle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1968

Some problems in the use of the Coulter counter for erythrocyte total counts and volume distribution.

Normal erythrocytes were subject to swelling and some haemolysis when suspended in a NaCl-formaldehyde-Na(2)EDTA diluent of pH 4.9 for routine blood-cell counting in the Coulter counter. A phosphate-buffered saline of pH 7.4 was substituted and has proven satisfactory for total erythrocyte counts. Polyvinyltoluene latex was unsuitable for volume calibration of the counter, because of aggregation of the particles in saline. Ragweed pollen grains gave a calibration factor that agreed well with that for fresh erythrocytes. Recent batches of Dade's Erythro-Trol (a suspension of fixed erythrocytes) were satisfactory for both total counts and volume calibration.

Buffers↗

PubMed1981

[On the testing of analgetically active substances (author's transl)].

Four standard analgetics were tested using the tail-flick and the hot-plate method, and by means of the Writhing syndrome. The frequency distributions of the data obtained from the control group were recorded first. The skewed distributions of the data yielded by the tail-flick and the hot-plate method were transformed into normal distributions. These normal distributions of data obtained form larger samples of control animals by the tail-flick and the hot-plate method permitted to develop alternative procedures of evaluation which led to dose-effect curves allowing to determine whether or not the effects of any single doses of the substances under study are significantly different. Testing the analgetics by means of the Writhing syndrome also yielded statistically interpretable dose-effect curves which resulted from a comparison with the frequency distributions of the data from control animals, all-or-not solutions being avoided. The evaluation procedures presented in this paper have the advantage that, in any case, the dose-related effects may be statistically interpreted due to the greater slopes of the dose-effect curves. Furthermore, these procedures improve the reproducibility of the dose-effect curves.

Analgesics↗

PubMed1983

[A test for the evaluation of the amplitude distribution of the EEG].

After a critical analysis of the available publications, a new test for the examination of the EEG amplitudes with respect to a normal distribution is presented. By means of autoregressive models, a linear transformation of the EEG to noise signals of a low-degree correlation is carried out, the normal distribution which is studied with respect to obliquenes and excess. In this way, the compromise between the demands for a low scanning frequency, a large extent of random tests and short EEG intervals, which is necessary for the correct application of the adaptation test, is avoided. A total of 82 percent of the tested 40 EEG intervals showed a normal distribution, EEG's with slight general changes being more frequent than alpha-EEG's.

Alpha Rhythm↗

PubMedDate not supplied

Urinary lithium: distribution shape, reference values, and evaluation of exposure by inductively coupled plasma argon-emission spectrometry.

Inductively coupled plasma argon-emission spectrometry (ICPAES) was used to evaluate the lithium content of undiluted urine samples. The method can be performed with 1 mL of urine in a single tube using a routine ICPAES analysis for rapid and convenient assessment of lithium exposure in humans. Urine samples obtained from male workers (n = 86) who had not been exposed to lithium were used for the determination of this element by ICPAES. The obtained concentrations were corrected using a specific gravity of 1.024. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Geometric mean value for urinary lithium in the nonexposed male workers was 23.5 microg/L, and the confidence interval from a log-normal distribution was 11.0 to 50.5 microg/L. Taking into consideration a short biological half-life and the massive urine excretion of lithium, urinary lithium was considered to be a useful index for monitoring of exposure. Calibration curves obtained for lithium standards had good sensitivity and linearity. Good reproducibility was assessed by lithium addition to urine samples. It was concluded that the obtained lithium reference values would be useful for the early diagnosis of lithium intoxication or in the assessment of the degree of exposure to lithium in subjects at risk.

Adult↗

PubMed1995

Assessment of data sets containing a considerable number of values below the detection limits.

Using real examples it is demonstrated that the concentrations of non-essential substances in biological systems always follow a statistical log-normal distribution. This is based on the assumption that in a first-order approximation the rate of excretion of the quantity of unwanted molecules or atoms in the biological system is only dependent on their concentration. Applying a natural logarithmic transformation, the resulting log-normal distribution always has a standard deviation of about 1, as shown by statistical analysis of more than 680 clusters of analytical results. Assuming a log-normal distribution with a standard deviation of 1, it is possible to derive factors for the estimation of percentiles, such as the median, even when this percentile is below the detection limit; quantifiable and higher percentiles only must be multiplied by a specific factor. This new method has the advantage that no arbitrary assumptions must be made about artificial parameters such as the numerical treatment of non-detectable analytical data. The assumptions used for the calculation of the factors are justified by proof with experimental data. The applicability of the new method is demonstrated for various contaminants in various plants and animals.

Animals↗

PubMed1996

N-Acetylated domains in heparan sulfates revealed by a monoclonal antibody against the Escherichia coli K5 capsular polysaccharide. Distribution of the cognate epitope in normal human kidney and transplant kidney with chronic vascular rejection.

The Escherichia coli K5 capsular polysaccharide has the same (GlcUA-->GlcNAc)n structure as the nonsulfated heparan sulfate/heparin precursor polysaccharide. A monoclonal antibody (mAb 865) against the K5 polysaccharide has been described (Peters, H., Jürs, M., Jann, B., Jann, K., Timmis, K. N., and Bitter-Sauermann, D. (1985) Infect. Immun. 50, 459-466). In this report, we demonstrate the binding of anti-K5 mAb 865 to N-acetylated sequences in heparan sulfates and heparan sulfate proteoglycans but not to heparin. This is shown by direct binding and fluid phase inhibition of mAb 865 in an enzyme-linked immunosorbent assay. In this system we found that the binding of the mAb decreased with increasing sulfate content of the polysaccharide. By testing chemically modified K5 and heparin polysaccharides, we found that each of the modifications that occur during heparan sulfate (HS) synthesis (N-sulfation, C-5 epimerization, and O-sulfation) prevents recognition by mAb 865. Samples of heparan sulfate from human aorta (HS-II) were selectively degraded so as to allow the separate isolation of N-sulfated and N-acetylated block structures. N-Sulfated oligosaccharides (obtained after N-deacetylation by hydrazinolysis followed by nitrous acid deamination at pH 3.9) were not recognized by mAb 865, in contrast to N-acetylated oligosaccharides (obtained after nitrous acid deamination at pH 1.5), although the reactivity was lower than for intact HS-II. Analysis of the latter's pH 1.5 deamination products by gel filtration indicated that a minimal size of 18 saccharide units was necessary for antibody binding. These results lead us to propose bivalent antibody-heparan sulfate interaction, in which both F(ab) domains of the mAb interact with their epitopes, both of which are present in a single large (>/=18 saccharide units) N-acetylated domain and additionally with single epitopes present in two N-acetylated sequences (each <18 saccharide units) bridged by a short N-sulfated domain. Immunohistochemistry with mAb 865 on cryostat sections of normal human kidney tissue, revealed its binding to most but not all renal basement membranes. However, all renal basement membranes contain heparan sulfate, as shown by a mAb against heparitinase-digested heparan sulfate stubs (mAb 3G10). This finding indicates that not all heparan sulfate chains present in basement membranes express the mAb 865 epitopes. Besides the normal distribution, mAb 865 staining was found in fibrotic and sclerotic lesions in vessels, interstitium, and mesangium in transplant kidneys with chronic vascular rejection. Occasionally, a decrease of staining was observed within tubulo-interstitium and glomeruli. These findings show that N-acetylated sequences in heparan sulfates can be demonstrated by anti-K5 mAb 865 in normal and diseased kidneys.

Acetylation↗

PubMed1985

Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH.

A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 micrograms/ml. gamma OH-phenylbutazone had a modal plasma concentration of less than 1 microgram/ml, a mean level of 1.39 micrograms/ml and a range of up to 7.32 micrograms/ml. All plasma concentration frequency distributions were well fitted by log normal distributions. Urinary concentrations of phenylbutazone yielded modal concentrations of less than 1 microgram/ml, a mean urinary concentration of 2.9 micrograms/ml, with a range of up to 30.5 micrograms/ml. This population fitted a log-normal distribution. For oxyphenbutazone the modal concentration was less than 3 micrograms/ml, the mean concentration was 15.26 micrograms/ml, with a range to 81.5 micrograms/ml. The frequency distribution of these samples was apparently bimodal. For gamma OH-phenylbutazone, the modal concentration was less than 4 micrograms/ml, the mean concentration 21.23 micrograms/ml, with a range of up to 122 micrograms/ml. The population frequency distribution for gamma OH-phenylbutazone was indeterminate. Analysis of the pH of these post-race urine samples showed a bimodal frequency distribution. The pH values observed ranged from 4.9 to 8.7, with peaks at about pH 5.25 and 7.25. This bimodal pattern of urinary pH values is consistent with observations made in England and Japan. Urinary pH influenced the concentrations of phenylbutazone, oxyphenbutazone and gamma OH-phenylbutazone found in the urine samples. The concentration of these metabolites found in alkaline urines were from 32 to 225 times greater than those found in acidic urines. Plasma concentrations of phenylbutazone and its metabolites, however, were unaffected by urinary pH. In interlaboratory experiments, horses running at Hollywood Park were dosed with phenylbutazone at about 2 g/1000 lbs 24 and 48 h before racing, and a mean dose of 0.6 g/1000 lbs at 72 h prior to racing. Post-race plasma samples from these horses showed phenylbutazone concentrations ranging from 0.44 to 9.97 micrograms/ml, with a mean concentration of 4.09 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

[Normal cerebral perfusion of 99mTc-ECD brain SPECT--evaluation by an anatomical standardization technique].

A single photon emitter labeled tracer, 99mTc-ethyl cysteinate dimer (99mTc-ECD), has now been used for rCBF studies with SPECT. However, normal distribution pattern of this agent in the brain still remains unclear. Therefore, the specific purpose of this study was to investigate the normal distribution pattern of 99mTc-ECD SPECT image. Regional cerebral distribution was measured with SPECT and 984 +/- 17 MBq of 99mTc-ECD in ten normal subjects. During the SPECT measurement, subjects were placed comfortably in a supine position with their eyes closed. Each SPECT image was anatomically standardized using a computerized brain atlas system of Roland et al. (HBA: Human Brain Atlas) and X-CT image. Anatomically standardized SPECT images were globally normalized to 100 count/voxel. Then, the mean and SD images of brain SPECT were calculated voxel-by-voxel basis. The highest radioactivity was found in the medial aspect of the occipital lobe. The results indicate that the normal distribution pattern of 99mTc-ECD in the human brain may be not simply reflect the regional cerebral blood flow.

Adult↗

PubMed1978

Thyroid hormone concentrations in a large scale community survey. Effect of age, sex, illness and medication.

Total thyroid hormone concentrations have been measured in the course of a large scale community survey to determine the distribution of these variables in the normal population and to assess the effect of age, sex, previously undectected thyroid disease and medication upon these parameters. 2779 subjects were studied. Serum T4 concentrations were normally distributed. A progressive increase in T4 levels with age was noted in the males, and a smaller increase in females which was concealed by the raised T4 values secondary to oral contraceptive therapy in females under the age of 45. Serum T3 levels were also normally distributed. There was a small reduction in T3 with age in the males but this fall was not seen in the females. T3 values were relatively higher in females under the age of 45 but this increase was not noted after exclusion of subjects taking an oral contraceptive. The changes in thyroid hormone concentrations with age are relatively minor (particularly with respect to T3) in a randomly selected sample from an English town. It is suggested that the changes reported by other authors reflect the process of selection used, and the high frequency of undetected thyroid disease, other illness and medication in hospital-based communities.

Adolescent↗

PubMed1975

Iodoamino acid content and distribution in normal and abnormal human thyroids.

Iodoamino acid content and distribution were measured in adenomas, nodular goiters, thyroiditis and carcinomas and compared to thyroids from patients who died suddenly and normal thyroid tissues originally adjacent to diseased tissue. Tissues were hydrolyzed with Pronase, derivatized and analyzed by gas chromatography as had previously been reported for rat thyroids. Considerable overlap in values was found among adenomas, nodular goiters and papillary and follicular carcinomas as compared to values in normal thyroid tissue, but low values were also found in several diseased tissues. MIT/DIT and T3/T4 ratios were essentially constant in most tissues, even when T4 values were low. MIT/DIT ratios were, however, high and iodothyronines undetectable in all Hurthle cell neoplasms, clearly differentiating them from other thyroid conditions.

Adenoma↗