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At least 19 recordsLinked to original sources
PubMed2002

Systolic heterogeneity of transmural myocardial function in normal subjects: physiological functional heterogeneity.

Because of the lack of a clinical method for assessing the transmural myocardial function, few studies on the heterogeneity during the myocardial contraction/relaxation sequence inside the human ventricular wall have been reported, despite the fact that the importance of the pathophysiology in the transmural heterogeneity has been stressed in previous experimental studies. We studied the transmyocardial functional heterogeneity of the basal anteroseptal segment in normal subjects (n = 8, 40.0 +/- 12.8 year, male), adopting the novel high resolution Doppler measurement "Phased Tracking Method". Each transmural layer of 0.75 mm thickness showed functional heterogeneity (physiological transmural functional heterogeneity), namely larger thickening occurred in the left ventricular endocardial side (right side 1/3: 26.1 +/- 5.2% of the total wall thickness, middle 1/3: 31.9 +/- 2.7%, left side 1/3: 42.1 +/- 6.4%) and the peak thickening shifted smoothly in time from the middle layers to the left subendocardial side during the contraction period. We concluded that transmural functional heterogeneity does exist in normal subjects as well as in the experimental animals of previous reports. Smooth and coordinate myocardial layer contraction across the ventricular wall (physiological transmural functional heterogeneity) is fundamental to maintain the normal ventricular function.

Adult↗
PubMedDate not supplied

Comparison of calculated and measured heterogeneity correction factors for 125I, 137Cs, and 192Ir brachytherapy sources near localized heterogeneities.

The influence of tissue and applicator heterogeneities on brachytherapy dose distributions is not well understood, despite widespread use of shielded applicators in intracavitary therapy. Heterogeneity correction factors (HCF) have been measured using a silicon diode detector arising from bounded heterogeneities consisting of lead, steel, titanium, silver, aluminum, and air cylinders near brachytherapy sources of 125I, 137Cs, and 192Ir. In addition, transverse-axis dose distributions for the three sources in homogeneous water were measured for distances of 0.2 to 16.0 cm. For each point of measurement, relative diode readings were simulated by a Monte Carlo photon transport code utilizing accurate models of the source internal structure, the experimental measure geometry and the source-strength calibration geometry. Comparison of measured and calculated HCF's reveals excellent agreement (1%-3% average) over a wide range of materials, diameters, and thicknesses. In addition, Monte Carlo simulation not only accurately reproduced the relative transverse-axis dose distributions in homogeneous medium, but was able to predict the variation of diode response with photon energy with an accuracy of 3% over the range of 30-662 keV. Our measurements demonstrate that HCF's vary by as much as 60%-100% with distance and heterogeneity diameter for a fixed thickness. Finally, silicon diode measurements of HCF (denied as reading with heterogeneity/reading in homogeneous medium) is shown to lead to errors of 5%-30% for 137Cs and 192Ir sources in the presence of high-atomic number shielding materials. This paper concludes, that Monte Carlo simulation is a powerful, convenient and accurate tool for investigating the long-neglected area of brachytherapy heterogeneity corrections.

Biometry↗
PubMed1986

Detecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data.

Interest in searching for genetic linkage between diseases and marker loci has been greatly increased by the recent introduction of DNA polymorphisms. However, even for the most well-behaved Mendelian disorders, those with clear-cut mode of inheritance, complete penetrance, and no phenocopies, genetic heterogeneity may exist; that is, in the population there may be more than one locus that can determine the disease, and these loci may not be linked. In such cases, two questions arise: (1) What sample size is necessary to detect linkage for a genetically heterogeneous disease? (2) What sample size is necessary to detect heterogeneity given linkage between a disease and a marker locus? We have answered these questions for the most important types of matings under specified conditions: linkage phase known or unknown, number of alleles involved in the cross at the marker locus, and different numbers of affected and unaffected children. In general, the presence of heterogeneity increases the recombination value at which lod scores peak, by an amount that increases with the degree of heterogeneity. There is a corresponding increase in the number of families necessary to establish linkage. For the specific case of backcrosses between disease and marker loci with two alleles, linkage can be detected at recombination fractions up to 20% with reasonable numbers of families, even if only half the families carry the disease locus linked to the marker. The task is easier if more than two informative children are available or if phase is known. For recessive diseases, highly polymorphic markers with four different alleles in the parents greatly reduce the number of families required.

Alleles↗
PubMed1985

An antibody binding to human neutrophils demonstrates antigenic heterogeneity detected early in myeloid maturation which correlates with functional heterogeneity of mature neutrophils.

An IgG1 mouse monoclonal antibody (31D8) labels a subpopulation of human peripheral neutrophils. Heterogeneous binding to granulocyte precursors is seen in the bone marrow as early as the myelocyte stage of maturation. 31D8 binding is not affected by the in vitro stimulation or incubation of neutrophils. We demonstrate that the cells which bind 31D8 strongly (31D8-bright) are the same cells which depolarize, reduce nitroblue tetrazolium, and migrate chemotactically when stimulated with the chemoattractant N-formylmethionylleucylphenylalanine. Treatment with cytochalasin B modulates functional activity so that all cells depolarize or reduce nitroblue tetrazolium in response to this chemoattractant, but the heterogeneous binding of 31D8 does not change. The stable binding of 31D8 at 37 degrees C and during activation permitted characterization of the functional capacity of the two populations. These results demonstrate neutrophil heterogeneity early in myeloid maturation and correlate antigenic with functional heterogeneity. 31D8 will make it possible to study the significance of neutrophil heterogeneity in a variety of clinical situations.

Antibody Specificity↗
PubMed2001

A non-parametric approach to translating gene region heterogeneity associated with phenotype into location heterogeneity.

MOTIVATION: The analysis of genetic data poses statistical problems in the form of high dimensionality with small sample sizes. The construction of a composite gene region (sequence pair) heterogeneity measure is one technique for reducing the dimensionality of the problem. This approach however is not without cost, since the contribution of locations to observed gene region differences between groups becomes entangled in this summary measure. This is problematic since it is of scientific interest to identify locations that together depict phenotype. RESULTS: A method is proposed for relating observed gene region heterogeneity back to the location level. In the spirit of a factor analysis-type setting, the approach focuses on identifying a latent variable structure among locations to explain within and between group genetic differences associated with phenotype. The method is flexible for identifying either the additive contribution from individual locations or the additive contribution from a group of locations, to observed gene region heterogeneity, depending upon the weighting scheme used in constructing a gene region heterogeneity measure. The approach is illustrated with clinical trial data, where the problem of altered HIV drug susceptibility is examined through characterizing location contributions to HIV protease gene region differences associated with a phenotypic treatment response. AVAILABILITY: The Splus (MathSoft, Inc. S-Plus 2000, Seattle, WA, 1999) developed menu-driven functions for obtaining results, GENE_ S (J.Kowalski, Harvard School of Public Health, Boston, MA 2001), is available from the author upon request.

Clinical Trials, Phase II as Topic↗
PubMed1978

Heterogeneity in diabetes mellitus--update, 1978. Evidence for further genetic heterogeneity within juvenile-onset insulin-dependent diabetes mellitus.

The concept that idiopathic diabetes mellitus is a genetically heterogeneous group of disorders has been established by twin and HLA studied that have permitted the separation of juvenile-onset and maturity-onset diabetes. The extent of the heterogeneity within the juvenile-onset and maturity-onset types is still in question. On the basis of recent immunologic and metabolic studies we believe that further heterogeneity can be demonstrated within the juvenile-onset diabetic group. We wish to hypothesize that there are at least two distinct forms of juvenile-onset diabetes, one associated with HLA B8 and the other with BW15. The B8 type is characterized by autoimmunity, microangiopathy, and a stronger association with the HLA D locus. The BW15 type is characterized by antibody response to exogenous insulin and a stronger association with the HLA C locus. Greater understanding of the pathogenesis, natural history, and genetics of diabetes mellitus will result as the full extent of genetic heterogeneity is elucidated.

Alleles↗
PubMed1983

The search for heterogeneity in insulin-dependent diabetes mellitus (IDDM): linkage studies, two-locus models, and genetic heterogeneity.

One hundred families with insulin-dependent diabetes mellitus (IDDM) were analyzed for linkage with 27 genetic markers, including HLA, properdin factor B (BF), and glyoxalase 1(GLO) on chromosome 6, and Kidd blood group (Jk) on chromosome 2. The linkage analyses were performed under several different genetic models. An approximate correction for two-locus linkage analysis was developed and applied to four markers. Two different heterogeneity tests were implemented and applied to all the markers. One, the Predivided-Sample Test, utilizes various criteria thought to be relevant to genetic heterogeneity in IDDM. The other, the Admixture Test, looks for heterogeneity without specifying a prior how the sample should be divided. Results continued to support linkage of IDDM with three chromosome 6 markers: HLA, BF, and GLO. The total lod score for Kidd blood group, under the recessive model with 20% penetrance, is 1.63--down 1.2 from the 2.83 reported by us earlier. The only other marker whose lod score exceeded 1.0 under any model was pancreatic amylase (AMY2). The two-locus correction, which involved lowering the penetrance values used in the analysis, affected estimates of theta (recombination fraction) but did not markedly change the lod scores themselves. There was little evidence for heterogeneity within any of the lod scores, under either the Predivided-Sample Test or the Admixture Test.

Adult↗
PubMedDate not supplied

Phenocopies versus genetic heterogeneity: can we use phenocopy frequencies in linkage analysis to compensate for heterogeneity?

In this study we explore whether a phenocopy frequency (defined as a "penetrance' for nondisease genotypes) can approximate or model genetic heterogeneity in a single-locus analysis. We simulated two types of heterogeneity situations: "sporadic models', where there are two forms of a disease, one genetic and linked to a marker and the other purely random, and "genetic heterogeneity models', where the disease is caused by either of two different loci, one linked to the marker and the other unlinked. We analyzed simulated data sets for linkage, assuming a single-locus analysis with varying phenocopy frequency, in analogy with earlier work on epistatic two-locus models. We found that in the presence of purely random sporadics, there was a difference between assuming any nonzero phenocopy frequency and a zero frequency, but that the actual value of the assumed phenocopy frequency had little effect on the maximum lod score. In contrast, when both forms of disease are genetic, and are generated under similar genetic parameters, assuming a positive phenocopy frequency will not, in general, compensate for the presence of the unlinked form. However, when the modes of inheritance of the two forms differ, the assumption of a nonzero phenocopy frequency does have an effect, either to increase or decrease the maximum lod score, depending on the modes of inheritance of the two disease forms. We conclude with practical recommendations for investigators, based on these results.

Gene Frequency↗
PubMed2001

Heterogeneity of Ion-Exchange Membranes: The Effects of Membrane Heterogeneity on Transport Properties.

The heterogeneity of different cation-exchange membranes (Neosepta CMX, Selemion CMV, and HJC heterogeneous membrane) and their effects on transport properties were investigated using chronopotentiometry, membrane conductivity, and current-voltage curves. Modifying the classical Sand equation, a method has been developed to determine the fraction of the conducting region (epsilon) of the ion-exchange membrane. The epsilon values of the CMX, CMV, and HJC membranes were 0.93, 0.95, and 0.75, respectively. Considering the characteristics of each membrane-the CMX and CMV are reinforced homogeneous membranes, while the HJC is a heterogeneous membrane-the epsilon values determined in this study seem to be reasonable. The dependence of membrane conductivities and the limiting current densities on the fraction of conducting region of each membrane have also been studied. Copyright 2001 Academic Press.

Journal Article↗
PubMed2000

Effect of surface heterogeneity on adsorption on solid surfaces. Application of inverse gas chromatography in the studies of energetic heterogeneity of adsorbents.

The paper presents a literature review of the chromatographic methods used for investigations of the heterogeneity of solid surfaces. Special attention is paid to inverse gas chromatography (IGC). Quantitative characteristics of heterogeneity of real solid surfaces including extreme models on adsorption centre topography of the "patch-wise" and "random" types are described. Analytical and numerical methods used for calculating the adsorption energy distribution function as a quantitative measure of surface heterogeneity are presented. Special attention is paid to the condensation approximation as well as to other approximations based on this assumption. IGC is presented as a quick, precise and effective method to characterise physicochemical properties of different kinds of adsorbents. Advantages of IGC over traditional methods of gas and vapour adsorption are shown.

Adsorption↗
PubMed1977

Heterogeneous nuclear RNA secondary structure: oligo (U) sequences base-paired with poly (A) and their possible role as binding sites for heterogeneous nuclear RNA-specific proteins.

HeLa cell heterogeneous nuclear RNA derived from high-molecular-weight nuclear ribonucleoprotein (RNP) particles contains oligo(U) sequences of 15-50 nucleotides base-paired with poly(A). These duplexes are resistant to pancreatic RNase at 0.5 M NaCl in native RNP, remain so after chemical deproteinization of the RNP digests, and then copurify with poly(A) on oligo(dT)-cellulose chromatography. Oligo(dT)-cellulose binding capacity of the oligo(U)-poly(A) duplexes is abolished by prior titration of the nonduplex poly(A) regions with excess poly(U). The oligo(dT)-purified fraction is 97.5 mole % A + U and the [3H]uridine-labeled component is resistant to redigestion by pancreatic RNase at 0.5 M NaCl but not at 0.01 M NaCl. After thermal denaturation, the [3H]uridine-labeled chains become RNase-sensitive at 0.5 M NaCl. Electrophoresis of [3H]adenosine- or [3H]uridine-labeled material in polyacrylamide gels containing 99% formamide confirms that the oligo(U) sequences are not covalently linked to poly(A). Controls establish that the A-U duplexes are not formed artifactually during isolation of heterogeneous nuclear RNP or subsequent fractionation. The oligo(U)-poly(A) duplexes appear to be associated with protein in native heterogeneous nuclear RNP, as reflected by the differential pancreatic RNase sensitivity of the duplexed oligo(U) in RNP (resistant) and RNA (sensitive), measured at physiological ionic strength.

Base Sequence↗
PubMed1991

The heterogeneity of human chorionic gonadotropin (hCG). I. Characterization of peptide heterogeneity in 13 individual preparations of hCG.

Peptide variations in the alpha-subunit (molecules starting at alpha 3 and alpha 4) and beta-subunit (missing linkages at beta 44-45 and beta 47-48) of hCG have been reported by several investigators. Studies, however, have been limited to standard hCG preparations (purified from large pools of urine) and other hCG samples from mixed urines. In this study we used chromatographic procedures to purify the total hCG content of 13 individual urines, 6 from patients with pregnancy and 7 from those with trophoblast disease (no hCG-containing fractions were excluded). Then, we examined for the first time the peptide variability among individual samples of hCG. We report 1) that individual hCG preparations have nicks (missing linkages) in the beta-subunit, primarily between residue 47-48 (11 of 13 samples) and, less commonly, at the linkage 44-45 or 46-47 (3 of 13 samples); 2) the extent of nicking varies greatly between individual preparations (range, 0-100% of molecules); 3) varying alpha-subunit N-terminal heterogeneity (N-terminus starting at alpha 3 or alpha 4) was also present (range, 0-28% of molecules), but was confined to preparations from individuals with trophoblast disease (6 of 7 samples from trophoblast disease urine, 0 of 6 from pregnancy urine); 4) hCG missing the beta-subunit C-terminal region was also detected (2 of 13 hCG preparations); and 5) 1 of 13 preparations was nicked on the hCG alpha-subunit, between residues 70 and 71. Thus, 12 of 13 individual hCG samples demonstrated at least 1 of 4 different forms of peptide heterogeneity. We conclude that individual hCG samples vary widely in the type and extent of peptide heterogeneity, an observation that is not appreciated when pools of hCG are studied.

Amino Acid Sequence↗
PubMed1997

Heterogeneity of DMIPP uptake and its relationship with heterogeneous myocardial blood flow.

UNLABELLED: To assess its potential role as a new metabolic probe, the relationship between regional uptake of the 15-(p-[125I]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) fatty acid analog and myocardial blood flow was studied. METHODS: In 14 open-chest dogs, the left anterior descending coronary artery was cannulated and extracorporal bypass-perfused at normal (control group; n = 4) and reduced flow (intervention group; n = 10). Myocardial blood flow (MBF) was assessed with 46Sc-labeled microspheres. Forty minutes after intravenous injection of DMIPP, the heart was excised and cut into 120 samples. In each sample, MBF ml x g(-1) x min(-1) and DMIPP uptake (percentage of the injected dose per gram, %ID/g) were assessed. RESULTS: In normal myocardium, MBF and DMIPP uptake were 1.10 +/- 0.18 ml x g(-1) x min(-1) and 1.18 +/- 0.42 x 10(-2) %ID/g, respectively. In the extracorporal bypass area, flow was reduced to 0.49 +/- 0.20 ml x g(-1) x min(-1) (p < 0.0001 compared to normal), and DMIPP uptake was decreased to 0.75 +/- 0.26 x 10(-2) %ID/g (p < 0.0001 compared to normal). DMIPP uptake and MBF positively correlated in normal (DMIPP uptake = 0.77 +/- 0.23 x MBF; r = 0.41; p < 0.0001) and hypoperfused (DMIPP uptake = 0.35 +/- 0.70 x MBF; r = 0.63; p < 0.0001) myocardium. The heterogeneity, indicated by the coefficient of variation, in normal myocardium was 0.23 +/- 0.05 for MBF and was lower (p < 0.0001) for DMIPP uptake: 0.13 +/- 0.05. During flow reduction, heterogeneity increased significantly (p < 0.0001) for both MBF (0.59 +/- 0.22) and DMIPP uptake (0.37 +/- 0.23). Also heterogeneity of the DMIPP uptake to MBF ratio, as an indicator of agreement, increased from 0.23 +/- 0.07 in normal to 0.46 +/- 0.19 in hypoperfused myocardium (p < 0.0001). CONCLUSION: DMIPP detects regionally hypoperfused myocardium, in which agreement between MBF and fatty acid uptake deteriorates. DMIPP uptake shows a different relationship with MBF in hypoperfused compared to normal myocardium. These observations suggest that DMIPP uptake may provide additional, unique information on regional myocardial ischemia.

Animals↗
PubMed1987

The heterogeneity of bovine IgG2--III. The ion-exchange heterogeneity of IgG2a is the result of VH-region variation.

Bovine IgG2a from an animal homozygous at the A-locus could be fractionated on DEAE columns into subpopulations; studies using analytical size columns showed that the number of subpopulations was dependent on the ionic strength of equilibration buffer. Subpopulations of IgG2a could be purified by this method which did not differ in their carbohydrate content but had mean Ips consistent with their elution behavior. The spectrotype of their H-chains but not their L-chains, paralleled the spectrotype of the corresponding intact IgG2a subpopulations. When papain digests of each subpopulation were fractionated by chromatofocusing, their Fc fragments eluted homogeneously with a pI ca 6.0 while their Fabs eluted heterogeneously with pIs ranging from 8 to 5. The distribution of carbohydrate among such fractions corresponded to the distribution of the Fcs. The behavior of the IgG2a Fabs on chromatofocusing paralleled the elution behavior of the parent IgG2a subpopulations from DEAE-Sephadex and the isoelectric behavior of their H-chains. The antibody activity of Fab fragments, separated by chromatofocusing, are consistent with the concept of idiotypic variation. The differential antibody activity of each intact IgG2a subpopulation for seven different antigens suggests that the ion-exchange behavior of IgG2a, in which the influence of allotypes and sub-isotypes has been excluded and for which charge-related L-chain heterogeneity is minimal, must reside in the VH-regions of the different IgG2a subpopulations. Investigators are cautioned against assigning ruminant subclass designations on the basis of subpopulations isolated by ion-exchange chromatography.

Animals↗
PubMed1974

Genetic variation in a heterogeneous environment. I. Temporal heterogeneity and the absolute dominance model.

The conditions for a stable polymorphism and the equilibrium gene frequency in an infinite population are compared when there is spatial or temporal environmental heterogeneity for the absolute dominance model. For temporal variation the conditions for stability are more restrictive and the equilibrium gene frequency is often at a low gene frequency. In a finite population, temporal environmental heterogeneity for the absolute dominance model was found to be quite ineffective in maintaining genetic variation and is often less effective than no selection at all. For comparison, the maximum maintenance for temporal variation is related to the overdominant model. In general, cyclic environmental variation was found to be more effective at maintaining genetic variation than where the environment varies stochastically. The importance of temporal environmental variation and the maintenance of genetic variation is discussed.

Animals↗
PubMedDate not supplied

Temporal electrical heterogeneity for detecting coronary artery disease: results in a heterogeneous cardiac population.

BACKGROUND: A new 22-lead electrocardiographic test has been advocated as a screening tool for coronary artery disease and has been shown to have accuracy similar to stress electrocardiography in specific patient populations. OBJECTIVE: To determine the accuracy of this test for detecting coronary artery disease in patients undergoing coronary angiography for a variety of cardiac conditions. METHODS: We prospectively determined the temporal electrical heterogeneity (TEH) index at rest in 70 patients who had no angina or Q waves on the resting 12-lead electrocardiogram before they underwent coronary angiography. RESULTS: Twenty-six of the 70 patients had significant coronary artery disease, defined as 70% stenosis or greater in at least one major epicardial coronary artery. A TEH index of 80 or more had a sensitivity of 58%, a specificity of 75%, and a positive predictive value of 58%. The group with significant coronary disease had a mean TEH index of 77.2, and the group without coronary disease had a mean index of 65.5 (P = .02), despite similar clinical characteristics and indications for angiography. CONCLUSION: The TEH index shows promise as a screening tool for coronary artery disease in a heterogeneous cardiac population. However, larger studies are needed before it can be endorsed for widespread clinical use.

Aged↗
PubMed1995

Intratumoral heterogeneity of hst-1 gene amplification in esophageal carcinoma with reference to DNA stem line heterogeneity.

Amplification of the hst-1 gene was examined in 112 neoplastic lesions from 27 patients with esophageal carcinoma. Ninety specimens were separately obtained from two or more sections of each individual primary tumor with DNA stem line heterogeneity and 22 specimens were obtained from metastatic lymph node lesions. The assessment was that hst-1 gene amplification within each individual primary tumor was identical in all 27 cases (100%) and that the intensity of amplification in the primary tumor matched that in the metastatic lesion in 18 of 22 cases (82%). When we examined 33 endoscopic biopsy specimens from esophageal carcinoma in the same manner, the intensity of hst-1 gene amplification in the specimens was similar to that obtained in surgical specimens from 26 of the 33 patients (79%). These results suggest that hst-1 gene amplification might occur in a homogeneous manner as a relatively early genetic event prior to lymph node metastasis, and that therefore, prior to surgical treatment, it can be evaluated from a single biopsy specimen.

Adult↗
PubMed1983

Phenotypic heterogeneity in neural tube defects: a clue to causal heterogeneity.

We report here retrospective data on 991 liveborn and stillborn infants with neural tube defects (NTDs) born to Utah residents from January 1, 1940 to December 31, 1979. Data were obtained from multiple sources including approximately 1.25 million vital statistics records and several hundred physician and hospital charts. Causal heterogeneity among NTD patients is presumed because 6% of our cases have other congenital anomalies not part of the NTD field defect. A significant association of NTDs with oral clefts is noted. Sex ratios and empiric recurrence risks for isolated NTDs and NTDs associated with other major malformations are also calculated.

Abnormalities, Multiple↗