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S T Bennett

Publications and source records attributed to S T Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1996

Molecular analysis of the structure of the maize B-chromosome.

The overall composition of the maize B is similar to that of the standard chromosome complement (A-chromosomes). This has been demonstrated by the use of several methods including: (a) genomic in situ hybridization (GISH), (b) analysis of highly repetitive sequences by the comparison of restriction digests of 0B and +B DNA and (c) the characterization of middle-repetitive cloned sequences. By the use of the technique of random amplification of polymorphic DNA-polymerase chain reaction, we have identified a B-specific repetitive sequence family. Sequence analysis of the B-specific clone reveals a relationship to the PREM-1 family of maize retroelements, which are preferentially transcribed in pollen. These results suggest an internal origin of the B-chromosome from within the maize genome, but demonstrate also that specific sequences can evolve by rapid processes of genomic turnover. Models for the origin of the maize B are discussed in the context of the present data.

Base Sequence↗
PubMed1996

Calibration verification of the International Normalized Ratio.

The International Normalized Ratio (INR) system for reporting the prothrombin time (PT) is essentially a calibration activity intended to standardize PT reporting across various reagent/instrument systems. However, complete standardization of PT reporting through the INR has been difficult to achieve for a variety of reasons, including inaccurate assignment of thromboplastin International Sensitivity Indexes (ISIs) and specific (local) reagent/instrument effects. Until now, the individual laboratory has not been able to easily verify the accuracy of its INR. Using standard lyophilized plasmas with INR values assigned against IRP RBT/90 rabbit thromboplastin, the authors present a method that allows a laboratory to locally verify its range of accuracy for the INR. The method is illustrated on a single coagulometer with two thromboplastin lots of differing sensitivity (Pacific Hemostasis Thromboplastin-DS and Thromboplastin-D from rabbit sources, with respective International Sensitivity Indexes of 1.20 and 1.97). In this illustration of the method, the accuracy of Thromboplastin-DS was superior to that of Thromboplastin-D. Interpretation of the data and cautions regarding the use of standard plasmas for calibration verification are discussed. Using this method, a reportable range of accuracy at a given error tolerance can be established locally for INR measurements within a laboratory. Laboratories of any size can apply this method to study the accuracy of their INR reagent/instrument systems, thus performing calibration verification. When used in conjunction with assessments of assay precision, this method can help laboratories to select better reagent/instrument systems and thereby produce more accurate and more clinically meaningful INR results.

Animals↗
PubMed1996

Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging.

Tumor angiogenesis is associated with metastasis in several types of solid tumors, including melanoma, breast, prostate, lung, bladder, and oral-cavity tumors. The purpose of this study was to determine whether tumor angiogenesis could predict recurrence following curative surgery for colorectal cancer. Thirty-five patients were studied, including 13 patients with recurrent tumor and 22 without. Representative formalin-fixed, paraffin-embedded sections of invasive colorectal cancers from these patients were sectioned. The endothelial cells of microvessels within the tumors were highlighted by immunohistochemical staining for CD31. The most active areas were identified and the microvessels counted in a x 400 field (0.152 mm2) by two observers in a blinded fashion. Tumor microvessel count (p = 0.0062). Dukes' staging (p = 0.0004), vascular invasion (p = 0.0280), and tumor grade (p = 0.0559) were all significantly associated with tumor recurrence. Tumor microvessel counts > or = 65 per x 400 field were associated with tumor recurrence (p = 0.0035, relative risk [RR] = 11.3). Controlling for Dukes' stage, a multivariate logistic regression model revealed that a tumor microvessel count > or = 65 is an important predictor of tumor recurrence (p = 0.0783, RR = 6.0). A backwards elimination proportional hazards model revealed that a microvessel count > or = 65 shows a trend toward independent prediction of time to tumor recurrence (p = 0.1203, RR = 2.967) when controlled for Dukes' staging (p = 0.0029, RR = 9.089). Despite the small number of patients studied, these results suggest that the number of microvessels in sections of invasive colorectal adenocarcinoma immunohistochemically stained with CD31 may be an important independent predictor of tumor recurrence and time to recurrence.

Adenocarcinoma↗
PubMed1996

Human type 1 diabetes and the insulin gene: principles of mapping polygenes.

We review the strategy used to identify a susceptibility locus (IDDM2) for type 1 (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the paradigm for dissecting multifactorial disease genetics, the approach described provides important general guidelines for positional cloning of human disease polygenes. Main topics include: (a) historical conspectus of the mapping and identification of IDDM2--a critical survey of the work leading up to the conclusion that IDDM2 most likely corresponds to allelic variation at the insulin gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence) variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d) mechanism of action of the INS VNTR in type 1 diabetes--insulin gene expression, parent-of-origin effects (genomic imprinting); and (e) summary and future prospects--alleles of the insulin VNTR that are protective for type 1 diabetes appear to encode susceptibility to type 2 diabetes.

Alleles↗
PubMed1996

Informatics applications in blood banking.

The dynamic nature of blood banking presents significant challenges in information acquisition, processing, and management. Blood banks have turned increasingly to computer technology for assistance with information handling. Novel applications of computer-based technology in blood banking and transfusion medicine have been developed and reported in the medical literature. This article reviews computer-based donor interviewing, expert system determination of donor eligibility based on viral marker testing results, inventory management through computer simulation analysis, prospective screening of blood orders by experts systems, and computer-based blood compatibility assessment.

Blood Banks↗
PubMed1995

Chromosome identification and mapping in the grass Zingeria biebersteiniana (2n = 4) using fluorochromes.

The grass Zingeria biebersteiniana is one of five angiosperms known with 2n = 2x = 4. Its chromosomes were studied using fluorochrome banding and fluorescence in situ hybridization (FISH). The large pericentromeric region fluoresced much more brightly on chromosome 2 than on chromosome 1, using two different fluorochrome banding methods. These offer rapid and reliable means for identifying chromosomes and work throughout mitosis. FISH located the major site of 18S-26S rDNA sequences at the secondary constriction, which is proximal to two minor sites, all on the short arm of chromosome 1. Two 5S sites were also detected, the most distinct on the short arm of chromosome 2 and the other apparently co-localized with part of the major 18S-26S rDNA cluster on chromosome 1. These results constitute the first steps in constructing a physical gene map for Z. biebersteiniana. Such information may facilitate future studies of the organization and reorganization of grass genomes, including research into the spatial arrangement of the genome in Zingeria nuclei and much wider comparisons of synteny and genome evolution in grasses.

Centromere↗
PubMed1995

Evidence for somatic translocation during potato dihaploid induction.

Potato dihaploid PDH55 (Solanum tuberosum) is exclusively euploid (2n = 24) but apparently contains and expresses DNA from dihaploid inducer IVP48 (S. phureja). Genomic in situ hybridization (GISH) suggested IVP48 DNA incorporated stably into PDH55 by somatic translocation. This finding has two important implications. Firstly, the long-held implicit assumption that euploid dihaploids produced by dihaploid inducers are pure S. tuberosum seems incorrect. This may complicate meiotic, genetical and molecular studies involving potato dihaploids. Secondly, if such translocations are not rare, the phenomenon may offer a novel way to introduce useful traits directly from wild dihaploid-inducing species into S. tuberosum.

Base Sequence↗
PubMed1995

Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus.

The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5. By 'cross-match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself. Other polymorphisms were systematically excluded as primary disease determinants. Transmission of IDDM2 may be influenced by parent-of-origin phenomena. Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR. Allelic variation at VNTRs may play an important general role in human disease.

Adult↗
PubMed1995

Insulin gene region-encoded susceptibility to IDDM maps upstream of the insulin gene.

The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at -23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the -23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2.

Chromosome Mapping↗
PubMed1995

Two-locus maximum lod score analysis of a multifactorial trait: joint consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes.

To investigate the genetic component of multifactorial diseases such as type 1 (insulin-dependent) diabetes mellitus (IDDM), models involving the joint action of several disease loci are important. These models can give increased power to detect an effect and a greater understanding of etiological mechanisms. Here, we present an extension of the maximum lod score method of N. Risch, which allows the simultaneous detection and modeling of two unlinked disease loci. Genetic constraints on the identical-by-descent sharing probabilities, analogous to the "triangle" restrictions in the single-locus method, are derived, and the size and power of the test statistics are investigated. The method is applied to affected-sib-pair data, and the joint effects of IDDM1 (HLA) and IDDM2 (the INS VNTR) and of IDDM1 and IDDM4 (FGF3-linked) are assessed with relation to the development of IDDM. In the presence of genetic heterogeneity, there is seen to be a significant advantage in analyzing more than one locus simultaneously. Analysis of these families indicates that the effects at IDDM1 and IDDM2 are well described by a multiplicative genetic model, while those at IDDM1 and IDDM4 follow a heterogeneity model.

Diabetes Mellitus, Type 1↗
PubMed1994

A genome-wide search for human type 1 diabetes susceptibility genes.

We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromosome regions showed some positive evidence of linkage to disease. Linkages to chromosomes 11q (IDDM4) and 6q (IDDM5) were confirmed by replication, and chromosome 18 may encode a fifth disease locus. There are probably no genes with large effects aside from IDDM1. Therefore polygenic inheritance is indicated, with a major locus at the major histocompatibility complex.

Adolescent↗
PubMed1994

Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping.

To facilitate large-scale genetic mapping of the human genome, we have developed chromosome-specific sets of microsatellite marker loci suitable for use with a fluorescence-based automated DNA fragment analyser. We present 254 dinucleotide repeat marker loci (80% from the Généthon genetic linkage map) arranged into 39 sets, covering all 22 autosomes and the X chromosome. The average distance between adjacent markers is 13 centiMorgans, and less than 4% of the genome lies more than 20 cM from the nearest marker. Each set of microsatellites consists of up to nine marker loci, with allele size ranges that do not overlap. We selected marker loci on the basis of their reliability in the polymerase chain reaction, polymorphism content, map position and the accuracy with which alleles can be scored automatically by the Genotyper program.

Automation↗
PubMed1994

The international normalized ratio and uncertainty. Validation of a probabilistic model.

The motivation behind the creation of the International Normalized Ratio (INR) was to improve interlaboratory comparison for patients on anticoagulation therapy. In principle, a laboratory that reports the prothrombin time (PT) as an INR can standardize its PT measurements to an international reference thromboplastin. Using probability theory, the authors derived the equation for the probability distribution of the INR based on the PT, the International Sensitivity Index (ISI), and the geometric mean PT of the reference population. With Monte Carlo and numeric integration techniques, the model is validated on data from three different laboratories. The model allows computation of confidence intervals for the INR as a function of PT, ISI, and reference mean. The probabilistic model illustrates that confidence in INR measurements degrades for higher INR values. This occurs primarily as a result of amplification of between-run measurement errors in the PT, which is inherent in the mathematical transformation from the PT to the INR. The probabilistic model can be used by any laboratory to study the reliability of its own INR for any measured PT. This framework provides better insight into the problems of monitoring oral anticoagulation.

Evaluation Studies as Topic↗
PubMed1994

The influence of the reference mean prothrombin time on the international normalized ratio.

The International Normalized Ratio (INR) is a mathematical transformation of the prothrombin time (PT). The transformation requires a laboratory to compute the geometric mean of its own reference population. In this paper, the authors examine how the reference mean PT influences the INR accuracy and precision using a validated probabilistic model. The variance of the geometric mean of reference populations in three laboratory settings was determined. Because the variance of an individual laboratory geometric mean is not directly determinable by simple parametric equations, its variance is estimated using bootstrap analysis. The geometric mean is compared to the computationally simpler arithmetic mean for effects on accuracy and precision of the resulting INR. The study shows mathematically and empirically that using the arithmetic mean biases INR determinations so that patients tend to be over-anticoagulated. However, in the laboratory settings examined, the amount of bias was both statistically and clinically insignificant. An analysis of the effect on the INR of errors in estimating the geometric mean reference PT also is performed. For large biases in estimating the reference mean, the INR can be significantly affected and can trigger inappropriate clinical actions in patients. The authors demonstrate empirically and mathematically that biases in the geometric mean reference PT do not affect the INR coefficient of variation. However, they produce significant differences in confidence intervals for INR determinations. Laboratories must exercise care in determining specific reference means to ensure that biases do not occur in geometric mean reference PT determinations. This can be achieved by circumspection in the selection of normal subjects for the reference population, carefully reviewing the data, and performing the proper calculations on the data.

Female↗
PubMed1994

Examination of International Normalised Ratio (INR) imprecision by comparison of exact and approximate formulas. Intermountain Laboratory Data Project.

AIM: To evaluate the accuracy of the approximate linear formula of International Normalised Ratio (INR) imprecision by formal mathematical analysis. METHODS: Using probability theory, an exact formula for the coefficient of variation (CV) of the INR was derived. The CV from the approximate formula was compared with the CV from the exact formula for INR determinations between 1.0 and 10.0 with International Sensitivity Indices (ISIs) between 1.0 and 3.0 and prothrombin time ratio CVs between 1.0 and 10.0%. RESULTS: When the ISI equals 1.0, the approximate formula and the exact formula are equal. When the ISI is more than 1.0, the approximate formula overestimates the exact CV, but by less than one hundredth of the exact CV in the parameter ranges studied. The approximate formula is most accurate when laboratories achieve excellent prothrombin time measurement precision and use sensitive thromboplastins. CONCLUSIONS: The approximate formula provides a simple means for estimating the imprecision of the INR and is sufficiently accurate to warrant its use in clinical laboratories.

Humans↗
PubMed1992

Quality assurance and standards in hematopoietic progenitor processing.

Bone marrow transplantation is an increasingly important therapeutic procedure. As more laboratories have become involved in the processing of hematopoietic progenitor cells from marrow or blood, it has been recognized that standards are required for hematopoietic progenitor processing, storage, and handling. Quality assurance is the process of monitoring whether laboratory procedures, equipment, and personnel fulfill their expected functions, and the aim of quality assurance is to ensure compliance with standards. Some standards for hematopoietic progenitor processing have recently been issued by professional organizations. Although these standards are not comprehensive, where applicable they should be met or exceeded. In the absence of published standards, principles of good laboratory practice should guide quality assurance programs. This article presents concepts of quality assurance in hematopoietic progenitor processing, based on standard laboratory practice and published standards.

Blood↗
PubMed1992

Certification of cholesterol measurements by the National Reference Method Laboratory Network with routine clinical specimens: effects of network laboratory bias and imprecision.

The National Reference Method Laboratory Network has initiated a program to certify clinical laboratory cholesterol measurement performance by using routine clinical specimens. Clinical laboratory and reference laboratory measurements of split samples are used to assess whether the clinical laboratory is meeting the Laboratory Standardization Panel's goals for accuracy and precision. We used a computer-based Monte Carlo simulation model of split-sample proficiency testing to evaluate the certification program and, in particular, to analyze the effects of reference laboratory bias and imprecision. Results of our simulations indicate that the accuracy of the certification program is strongly influenced by reference laboratory bias and less influenced by reference laboratory imprecision. The certification program is potentially highly accurate, but unless reference laboratory bias is tightly controlled, the number of classification errors may limit its utility. Moreover, the decision limit of the certification program needs to be higher than the Laboratory Standardization Panel's goal (3.5% instead of 3.0%) to ensure that an acceptably high proportion of well-performing clinical laboratories can become certified.

Certification↗