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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↗
PubMed2003

Is it homogeneous or heterogeneous catalysis? Identification of bulk ruthenium metal as the true catalyst in benzene hydrogenations starting with the monometallic precursor, Ru(II)(eta 6-C6Me6)(OAc)2, plus kinetic characterization of the heterogeneous nucleation, then autocatalytic surface-growth mechanism of metal film formation.

A reinvestigation of the true catalyst in a benzene hydrogenation system beginning with Ru(II)(eta(6)-C(6)Me(6))(OAc)(2) as the precatalyst is reported. The key observations leading to the conclusion that the true catalyst is bulk ruthenium metal particles, and not a homogeneous metal complex or a soluble nanocluster, are as follows: (i) the catalytic benzene hydrogenation reaction follows the nucleation (A --> B) and then autocatalytic surface-growth (A + B --> 2B) sigmoidal kinetics and mechanism recently elucidated for metal(0) formation from homogeneous precatalysts; (ii) bulk ruthenium metal forms during the hydrogenation; (iii) the bulk ruthenium metal is shown to have sufficient activity to account for all the observed activity; (iv) the filtrate from the product solution is inactive until further bulk metal is formed; (v) the addition of Hg(0), a known heterogeneous catalyst poison, completely inhibits further catalysis; and (vi) transmission electron microscopy fails to detect nanoclusters under conditions where they are otherwise routinely detected. Overall, the studies presented herein call into question any claim of homogeneous benzene hydrogenation with a Ru(arene) precatalyst. An additional, important finding is that the A --> B, then A + B --> 2B kinetic scheme previously elucidated for soluble nanocluster homogeneous nucleation and autocatalytic surface growth (Widegren, J. A.; Aiken, J. D., III; Ozkar, S.; Finke, R. G. Chem. Mater. 2001, 13, 312-324, and ref 8 therein) also quantitatively accounts for the formation of bulk metal via heterogeneous nucleation then autocatalytic surface growth. This is significant for three reasons: (i) quantitative kinetic studies of metal film formation from soluble precursors or chemical vapor deposition are rare; (ii) a clear demonstration of such A --> B, then A + B --> 2B kinetics, in which both the induction period and the autocatalysis are continuously monitored and then quantitatively accounted for, has not been previously demonstrated for metal thin-film formation; yet (iii) all the mechanistic insights from the soluble nanocluster system (op. cit.) should be applicable to metal thin-film formations which exhibit sigmoidal kinetics and, hence, the A --> B, then A + B --> 2B mechanism.

Journal Article↗
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↗
PubMed1991

Correlation of phenotypic and genetic heterogeneity in cystic fibrosis: variability in sweat electrolyte levels contributes to heterogeneity and is increased with the XV-2c/KM19 B haplotype.

We have reinvestigated a classification of clinical heterogeneity among cystic fibrosis (CF) patients that we previously reported and investigated the possible relationship of the identified CF subgroups to haplotypes around the CF gene and to HLA-DR haplotypes. Age-corrected values for sweat electrolytes, rate of progression of lung disease as assessed by Brasfield chest x-ray scores, and severity of pancreatic insufficiency as assessed by daily supplemented enzyme dosage were obtained for 55, 59, and 59 patients, respectively. XV-2c and KM19 RFLPs were determined by hybridization to TaqI and PstI digests of human genomic DNA, respectively, and analysis of mutations by PCR amplification followed by allele-specific oligo-deoxynucleotide hybridization was performed for 29 patients. HLA-DR restriction fragment length polymorphisms (RFLPs) were determined by hybridization of cDNA beta 1 and genomic DQ alpha probes to TaqI digests of human genomic DNA. The results show that the previous subdivision on the basis of age-corrected levels of sweat electrolytes, as well as measures of severity of lung disease and pancreatic disease, is valid. In addition, the C and D haplotypes are associated with lower age-corrected sweat sodium level. No significant relationship between CF haplotypes and the other two disease variables or between HLA-DR haplotypes and any of the clinical variables was found.

Child↗
PubMed1984

Functional heterogeneity of the descending limbs of Henle's loop. I. Internephron heterogeneity in the hamster kidney.

By using the in vitro microperfusion technique, were examined functions of the descending limbs of Henle's loop obtained from either the short-loop nephron (SDL) or the upper portion of the long-loop nephron of hamsters (LDLu). Morphological distinctions between these segments were confirmed by light and electron microscopic observations. Both segments were highly permeable to water. The LDLu was highly permeable to sodium and to chloride: efflux coefficients (10(-7) cm2 x s-1) for 22Na and 36Cl were 41.0 +/- 5.4 and 3.8 +/- 0.6, respectively. The SDL were less permeable to sodium and to chloride: efflux coefficient for 22Na and 36Cl were 2.9 +/- 1.4 and 0.9 +/- 0.2, respectively. In contrast, the SDL was more permeable to urea as compared to the LDL, efflux coefficients for urea being 5.1 +/- 1.4 vs 1.4 +/- 0.3, respectively. When composition of the perfusate was identical to that of the bathing fluid, no transepithelial voltage was demonstrated. The volume flux was very small or undetectable. From these observations, we propose that the internephron heterogeneity must be taken into consideration for constructing a model of countercurrent system in the renal medulla.

Animals↗
PubMed2003

QTL fine-mapping with recombinant-inbred heterogeneous stocks and in vitro heterogeneous stocks.

We compared strategies to fine-map Quantitative Trait Loci (QTL) in mice with heterogeneous stocks (HS). We showed that a panel of about 100 Recombinant Inbred Lines (RIL) derived from an HS, and which we called an RIHS, was ideally suited to fine-map QTL to very high resolution, without the cost of additional genotyping. We also investigated a strategy based on in vitro fertilization of large numbers of F(1) offspring of HS males crossed with an inbred line (IVHS). This method required some additional genotyping but avoided the breeding delays and costs associated with the construction of an RI panel. We showed that QTL detection was higher by using RIHS than with IVHS and that it was independent of the number of RI lines, provided the total number of animals phenotyped was constant. However, fine-mapping accuracy was slightly better with IVHS. We also investigated the effects of varying the number of HS generations and using multiallelic microsatellites instead of SNPs. We found that quite modest generation times of 10-20 generations were optimal. Microsatellites were superior to SNPs only when the generation time was 30 or more and when the markers were widely spaced.

Analysis of Variance↗
PubMed1987

Metabolic consequences of genetic heterogeneity of lipoprotein composition (lipoprotein heterogeneity).

Lipoprotein composition varies among different genetic forms of hyperlipidemia. An increase in hepatic triglyceride (TG) synthesis in subjects with familial hypertriglyceridemia (FHTG) is associated with secretion of large, TG-enriched, very low-density lipoproteins (VLDL), which have an increased affinity for lipoprotein lipase (LPL) in vivo as compared with VLDL from subjects with familial combined hyperlipidemia (FCHL) or from normal subjects. Elevated levels of plasma low-density lipoprotein (LDL) apoprotein B in FCHL are associated with high apoprotein B production rates. The LDL in FCHL is heterogeneous, with a preponderance of an LDL subfraction, which is denser, smaller, and lipid poor as compared with LDL from normal subjects. The more buoyant LDL subfraction in FCHL seems to be catabolized more rapidly than this dense LDL subfraction.

Apolipoproteins B↗
PubMed2005

Dynamic site heterogeneity in amorphous maltose and maltitol from spectral heterogeneity in erythrosin B phosphorescence.

We have used phosphorescence from erythrosin B (tetraiodofluorescein) dispersed in thin films of either maltose or maltitol to investigate the physical properties of these amorphous pure sugar matrixes. Intensity decays collected as a function of emission wavelength over the range from 640 to 720 nm were analyzed using a stretched exponential kinetic model in which the lifetime (tau) and the stretching exponent (beta) were the physically relevant parameters. The lifetimes varied systematically with emission wavelength in both matrixes. Analysis of the temperature dependence of the lifetime at each wavelength provided an estimate of the activation energy for nonradiative quenching of the triplet state; the activation energy also varied with emission wavelength. In addition, time-resolved emission spectra exhibited a blue shift with time following excitation. These data support a photophysical model in which probes are distributed among sites that vary in terms of overall molecular mobility and in which sites with lower rates of dipolar relaxation also have lower rates of collisional quenching of the erythrosin triplet state. The amorphous matrix of both maltose and maltitol in both the glass and the melt state is thus characterized by dynamic site heterogeneity in which different sites vary in terms of their overall molecular mobility.

Erythrosine↗
PubMed2006

Predicting the long-time dynamic heterogeneity in a supercooled liquid on the basis of short-time heterogeneities.

We report that the local Debye-Waller factor in a simulated 2D glass-forming mixture exhibits significant spatial heterogeneities and that these short-time fluctuations provide an excellent predictor of the spatial distribution of the long-time dynamic propensities. In contrast, the potential energy per particle of the inherent structure does not correlate well with the spatially distributed dynamics.

Journal Article↗
PubMed2005

Tissue regeneration and in loco administration of platelet derivatives: clinical outcome, heterogeneous products, and heterogeneity of the effector mechanisms.

BACKGROUND: In loco administration of platelet (PLT) derivatives is a relatively new auxiliary treatment for tissue regeneration to be hastened. Enthusiastic reports are faced by more critical ones. The more obvious rationale for the in vivo administration of PLT derivatives resides in their growth factor content. STUDY DESIGN AND METHODS: The relevant literature was systematically reviewed. Close scrutiny of the technical details was carried out to find out the procedural differences accounting for conflicting results. RESULTS: An impressively vast heterogeneity of conduct was found in both in vitro and in vivo studies. Major outcome-affecting variables were recognized such as those associated with PLT preparation; growth factor measurement; proliferation test; dose, timing, and administration of the PLT derivatives; study design; and primary endpoints. CONCLUSIONS: So many variables were found making standardization or confrontation of the in vitro and the in vivo studies barely conceivable or manageable. The mechanisms of action are very complex. The attribution of tissue regeneration capacity of PLT derivatives solely to the PLT-derived growth factors is simplistic. The results obtained through in vitro experiments are indicative for general mechanisms. Their simplistic hold to the complex in vivo environment may be misleading.

Animals↗
PubMed2000

Heterogenous vascular effects of AP5A in different rat resistance arteries are due to heterogenous distribution of P2X and P2Y(1) purinoceptors.

In the accompanying article, we showed that AP5A displayed heterogenous vasoactive effects in rat resistance arteries. It induced a stable vasoconstriction in the superior epigastric artery (SEA) and a transient vasoconstriction in the mesenteric resistance artery (MrA). In the phenylephrine-precontracted MrA AP5A induced a marked vasorelaxation. In this study the noncompetitive inhibition of the AP5A-induced vasoconstriction with pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was found to be significantly stronger in MrA than in SEA. The nonselective P2 purinoceptor antagonist suramin inhibited AP5A-induced vasoconstriction in MrA only. The vasoconstriction by the P2X purinoceptor agonist alpha,beta-methylene ATP was inhibited by with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and suramin similarly to that induced by AP5A. Thus, the AP5A-induced vasoconstriction is due to P2X receptor activation, but two different P2X receptors seem to be operational in the two different vessels. The AP5A-induced vasorelaxation of phenylephrine-precontracted MrA was inhibited by the P2Y(1) receptor antagonist ADP3'5'. The vasorelaxation induced by ADPbetaS (P2Y(1) agonist) also was inhibited by ADP3'5'. These findings suggest that AP5A-induced vasorelaxation of MrA is caused by P2Y(1) receptor activation. The P1 (A(2)) receptor antagonist 3, 7-dimethyl-1-propargylxanthine only slightly inhibited AP5A-induced vasorelaxation at high concentrations. Adenosine and the A(2) receptor agonist CGS21680 failed to produce significant vasorelaxation. Therefore, vasorelaxation in MrA does not involve A(2) purinoceptor activation. AP5A-induced vasorelaxation was not inhibited by Ca(2+)- or ATP-dependent K(+) channel blockade with clotrimazole, apamin, or glibenclamide. These data indicate that vasoconstriction in MrA and SEA by AP5A is due to different P2X receptors, and vasorelaxation in precontracted MrA is due to P2Y(1) receptor activation.

Animals↗
PubMedDate not supplied

[Heterogeneity of the cases of chronic B-cell leukemia and the heterogeneity of leukemic cell populations].

In a group of 23 patients with chronic lymphocytic leukaemia in 1-4 clinical stages of the disease according to Rai et al (34) classification, mostly untreated (only 5 treated) considerable heterogeneity was found as evidenced by: variability of the morphological patterns of bone marrow, differences of immunological phenotypes of peripheral blood lymphocytes between individual cases, --coexistence of the features of maturity and immaturity in the populations of peripheral blood lymphocytes in the same case.

Adult↗