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A variety of biological materials are suitable for the analysis of bovine DNA. The objective of this study was to evaluate the ease of collection, storage, and cost as well as quality and quantity of DNA samples obtained from Bos taurus (European cattle) and Bos grunniens (yak) using 2 different sample types: whole blood sampling and nasal swabs. Hair follicle DNA samples from yaks were also analyzed. Deoxyribonucleic acid samples were collected from 1 herd of Black Angus yearling bulls (n = 166) and 1 herd of yaks (n = 24). A NanoDrop Bioanalyzer ND1000 was used to quantify DNA. To assess DNA purity, absorbance ratios were determined at wavelengths of 260 nm relative to 280 nm and 260 nm relative to 230 nm. Single nucleotide polymorphism genotyping was performed using a competitive allele-specific PCR (KASP) genotyping system and the call rates to 3 specific SNP were compared. Using a commercially available nonautomated ethanol DNA extraction technique, nasal swabs yielded a greater quantity of DNA than blood (P < 0.0001) and a greater quality DNA sample than blood (P < 0.0001). Blood and nasal swab performance in SNP genotyping assays were similar (P = 0.5). The greater expense of nasal swabs was offset by their ease of use: less time, skill, and equipment was needed to obtain a sample and the storage of samples was more convenient (room temperature). In yaks, accessing the coccygeal vein, which is relatively straightforward in cattle, was difficult. Nasal swabbing and hair follicle sampling in yaks was performed relatively easily. Yak hair follicles were a poor source of DNA. In conclusion, DNA collection using nasal swabs was more convenient and provided a greater quantity of DNA and better quality sample than blood collection in both Angus and yak. Notably, yak hair was a poor source of DNA, and yak blood was difficult to obtain.

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PURPOSE: To determine outflow resistance of the Baerveldt glaucoma implant using different tube configurations. METHODS: Outflow resistance of 6 tube configurations (C1- C6) of Baerveldt implants was measured under conditions of constant pressure perfusion. Pressures ranged from 2 to 55 mm Hg. Venting slits were created using a 7-0 Vicryl, spatulated suture-needle. Seton tubes were occluded by threading a retrograde suture approximately 1.5 cm into the lumen. RESULTS: At pressures between 2 and 55 mm Hg, mean outflow resistance of the normally configured seton (ie, open tube; C1) was 0.41 (+/- 0.6) mm Hg/microL/min. Resistance was unchanged (mean 0.41 (+/- 0.4) mm Hg/microL/min) by the addition of 4 venting slits (C2) to the seton tube. Occlusion of the open seton tube with a 3-0 Supramid suture (C3) significantly increased (P < 0.001) mean outflow resistance to 14.99 (+/- 0.6) mm Hg/microL/min. Occlusion of the tube with a 4-0 Supramid suture (C4) significantly increased (P < 0.001) mean outflow resistance to 1.09 (+/- 0.5) mm Hg/microL/min. In implants where tubes were occluded with a 3-0 Supramid suture, the addition of venting slits (C5) significantly decreased (P = 0.038) mean outflow resistance to 8.98 (+/- 0.4) mm Hg/microL/min. In tubes occluded with a 4-0 Supramid suture, the addition of venting slits (C6) decreased mean outflow resistance to 0.98 (+/- 0.6) mm Hg/microL/min. CONCLUSIONS: Although these results cannot be directly correlated to the clinical setting, they do show that outflow resistance can be modified at the time of surgery by changing tube configuration of the Baerveldt glaucoma implant. Configuration C5 (3-0 Supramid with venting slits) closely approximates the outflow rate in the normal intraocular pressure range.

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The heart develops from a linear tubular precursor, which loops to the right and undergoes terminal differentiation to form the multichambered heart. Heart looping is the earliest manifestation of left-right asymmetry and determines the eventual heart situs. The signalling processes that impart laterality to the unlooped heart tube and thus allow the developing organ to interpret the left-right axis of the embryo are poorly understood. Recent experiments in zebrafish led to the suggestion that bone morphogenetic protein 4 (BMP4) may impart laterality to the developing heart tube. Here we show that in Xenopus, as in zebrafish, BMP4 is expressed predominantly on the left of the linear heart tube. Furthermore we demonstrate that ectopic expression of Xenopus nodal-related protein 1 (Xnr1) RNA affects BMP4 expression in the heart, linking asymmetric BMP4 expression to the left-right axis. We show that transgenic embryos overexpressing BMP4 bilaterally in the heart tube tend towards a randomisation of heart situs in an otherwise intact left-right axis. Additionally, inhibition of BMP signalling by expressing noggin or a truncated, dominant negative BMP receptor prevents heart looping but allows the initial events of chamber specification and anteroposterior morphogenesis to occur. Thus in Xenopus asymmetric BMP4 expression links heart development to the left-right axis, by being both controlled by Xnr1 expression and necessary for heart looping morphogenesis.

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Structure-activity relationships in analogues of the irritant natural product capsaicin have previously been rationalized by subdivision of the molecule into three structural regions (A,B, and C). The hypothesis that resiniferatoxin (RTX), which is a high-potency ligand for the same receptor and which has superficial structural similarities with capsaicin, could be analogously subdivided has been investigated. The effects of making parallel changes in the two structural series have been studied in a cellular functional assay which is predictive of analgesic activity. Parallel structural changes in the two series lead to markedly different consequences on biological activity; the 3- and 4-position aryl substituents (corresponding to the capsaicin 'A-region') which are strictly required for activity in capsaicin analogues are not important in RTX analogues. The homovanillyl C-20 ester group in RTX (corresponding to the capsaicin 'B-region') is more potent than the corresponding amide, in contrast to the capsaicin analogues. Structural variations to the diterpene moiety suggest that the functionalized 5-membered diterpene ring of RTX is an important structural determinant for high potency. Modeling studies indicate that the 3D position of the alpha-hydroxy ketone moiety in the 5-membered ring is markedly different in the phorbol (inactive) analogues and RTX (active) series. This difference appears to be due to the influence of the strained ortho ester group in RTX, which acts as a local conformational constraint. The reduced activity of an analogue substituted in this region and the inactivity of a simplified analogue in which this unit is entirely removed support this conclusion.

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This paper reports on a process for selecting a suite of indicators that, in combination, can be useful in assessing the ecological conditions of rangelands. Conceptual models that depict the structural and functional properties of ecological processes were used to show the linkages between ecological components and their importance in assessing the status and trends of ecological resources on a regional scale. Selection criteria were developed so that relationships could be assessed at different spatial scales using ground and aerial measurements. Parameters including responsiveness and sensitivity to change, quality assurance and control, temporal and spatial variability, cost-effectiveness and statistical design played an important role in determining how indicators were selected. A total of ten indicator categories were selected by a committee of scientists for evaluation in the program. A subset that included soil properties, vegetation composition and abundance, and spectral properties was selected for evaluation in a pilot test conducted in 1992 in the Colorado Plateau region of the southwestern United States. This work is part of a major effort being undertaken by the U.S. Environmental Protection Agency and its collaborators to assess the condition of rangelands (primarily comprised of arid, semi-arid and dry subhumid ecosystems) along with seven other ecosystem groups (forests, agricultural lands, wetlands, surface waters, landscapes, estuaries and Great Lakes) as part of a national Environmental Monitoring and Assessment Program (EMAP). The indicator selection process reported upon was developed to support EMAP's goal of providing long-term, policy-relevant research focusing on evaluating the ecological condition (or health) of regional and national resources.

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The improvement of land management practices on lands susceptible to desertification requires information on the status and condition of the existing resources as well as any change occurring in the resource condition over time. The Environmental Monitoring and Assessment Program (EMAP) of the U.S. Environmental Protection Agency has developed a statistical survey design for monitoring the condition of ecological resources on large spatial scales. EMAP-Rangelands used a uniformity sampling study in 1993 to evaluate response plot designs for three categories of indicators (soils, vegetation, and spectral reflectance) to be used for monitoring ecological condition of a site. The response plot design study was developed to integrate on-site measurements for the three indicator categories. The study was conducted on the Colorado Plateau in southern Utah in three rangeland resource classes (grassland, desertscrub, and conifer woodland) of differing productivity levels in an attempt to develop a common plot design for all three resource classes. Basic measurement units were developed to facilitate integration of data collection. Preliminary spatial analysis of the sampling study found considerable differences in variation patterns among the study sites and measurement categories for the indicator classes used by EMAP-Rangelands. Evidence of substantial trends in the indicator measurements on monitoring sites relative to regional trends leads to the conclusion that nonstationary spatial models for biological processes on a monitoring site may be needed to fulfill the requirements for developing plot designs and indicator criteria.

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Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions--the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.

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This paper provides a review and justification of the minimum data needed to characterize soils for hazardous waste site assessments and to comply with the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Scientists and managers within the regulatory agency and the liable party need to know what are the important soil characteristics needed to make decisions about risk assessment, what areas need remediation and what remediation options are available. If all parties involved in characterizing a hazardous waste site can agree on the required soils data set prior to starting a site investigation, data can be collected in a more efficient and less costly manner. Having the proper data will aid in reaching decisions on how to address concerns at, and close-out, hazardous waste sites.This paper was prepared to address two specific concerns related to soil characterization for CERCLA remedial response. The first concern is the applicability of traditional soil classification methods to CERCLA soil characterization. The second is the identification of soil characterization data type required for CERCLA risk assessment and analysis of remedial alternatives. These concerns are related, in that the Data Quality Objective (DQO) process addresses both. The DQO process was developed in part to assist CERCLA decision-makers in identifying the data types, data quality, and data quantity required to support decisions that must be made during the remedial investigation/feasibility study (RI/FS) process. Data Quality Objectives for Remedial Response Activities: Development Process (US EPA, 1987a) is a guidebook on developing DQOs. This process as it relates to CERCLA soil characterization is discussed in the Data Quality Objective Section of this paper.

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Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance assignments for the 49-residue protein echistatin from the viper Echis carinatus. The protein in solution contains only a small amount of regular secondary structure with four very short beta-strands. These beta-strands form two short segments of antiparallel beta-sheet, as evidenced by the observed cross-strand NOE. The first two strands are connected with a tight reverse turn, whereas the remaining two strands are linked together by an 11-residue loop forming a so-called hairpin. The tripeptide unit Arg-Gly-Asp, responsible for the binding of echistatin to the fibrinogen receptor glycoprotein GPIIb/IIIa, is located at the tip of this very hydrophilic loop.

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The review takes examples, mostly from the recent literature, to illustrate how an understanding of physico-chemical properties and an appreciation of the molecular shape and electronic properties can lead to a better insight into molecular recognition processes. The techniques used to generate 3-dimensional structures of molecules and the influence this information has had on the drug design cycle, are briefly discussed.

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Performance in a driving simulator was evaluated as a function of locus of control, perceived alcohol ingestion (no alcohol versus a no-alcohol placebo), and sex. Using a pretest-posttest design, an analysis of covariance was performed using the pretest performance on a driving simulator as the covariate. There were 10 men and 10 women in each of four groups. As predicted, the external-scoring placebo subjects made more posttest errors than did the internal-scoring placebo group or either of the no-alcohol control groups. This indicated that the external-scoring placebo subjects were more affected by what they expected to happen than their actual physiological state warranted. A difference was also found in which external-scoring women made more errors than did any other group. This was an unexpected finding which, being inconsistent with previous findings involving sex, warrants further research.

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To investigate the influence of locus of control on a fine motor corrdination task where subjects had ingested or believed that they had ingested alcohol, 60 men who were enrolled in introductory psychology and scored in the upper or lower thirds of the population on Rotter's I-E Scale (30 external and 30 internal scorers) were randomly assigned to one of three treatment conditions: a control group (no alcohol expected/no alcohol received), an alcohol group (alcohol expected/alcohol received), and a placebo group (alcohol expected/no alcohol received). Pretest and posttest measures of performance on the Purdue Pegboard Test were obtained from all subjects. Subjects in the control groups were given three 6-oz. (177.4-ml) glasses of fruit punch over a 35-min. waiting period between pretest and posttest on the Purdue Pegboard. The alcohol groups drank a sufficient number of similar glasses (usually three) to produce a 0.1% measure on a breathalyzer before completing the posttest on the Purdue. Pegboard. The placebo groups were told that they were drinking an alcohol-based drink but were served three glasses of a nonalcoholic, rum-flavored fruit drink. These groups were also told that they measured 0.1% on a breathalyzer. Control groups, both internal and external scorers, showed essentially no change from pre- to posttest on the Purdue Pegboard. The alcohol groups, on the other hand, both internal and external scorers, showed a significant decrement in performance. The internal-placebo group did not differ from the two control groups and showed no decrement in performance.(ABSTRACT TRUNCATED AT 250 WORDS)

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In order to analyze the evolutionary behavior of the cobra venom cytotoxins, their probable tertiary structure was predicted using computer graphics. The 41 amino acid sequences known show that the major evolutionary changes have taken place in two particularly exposed areas of the molecular surface. In each area, neighboring residue positions seem to have evolved interdependently, but there is no obvious interdependence between the two areas. Indeed, the relative evolution of these two areas prompts a subdivision of the sequence set into four groups. According to the known cytotoxin circular dichroism spectra, one of these four groups could be characterized by a difference in molecular secondary structure. Since the two variable areas have functional associations, it is suggested that their evolution may be governed by a target with several similar binding sites.

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The clinical value of magnetic resonance (MR) imaging was prospectively evaluated in 189 patients referred for examination of the brain or spine. Comparison of the attending physician's diagnosis, proposed treatment, and estimated prognosis before and after MR imaging indicated a substantial effect of the additional information provided by this study. A suspected diagnosis was refined or changed in 16% of all patients, and the physician's level of confidence in the diagnosis changed in over half of the cases in which the diagnosis was unchanged. In two-thirds of all cases the physician indicated that the treatment or estimated prognosis was altered.

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Preventive medicine could be the answer to many of the problems facing medicine, the author says. However, to be cost effective, we need to merge this new type of care with the traditional treatment of the sick that has been the foundation of health care for centuries.

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Two term neonates born within four days of each other at a small hospital developed sepsis and meningitis caused by a unique strain of Citrobacter diversus not previously reported to cause meningitis. Eleven (27.5%) of 40 other infants admitted to the nursery during the epidemic period developed rectal or umbilical colonization by C. diversus. Contact soon after birth with either of two nurses was more common among infected or colonized infants than among infants who were not infected or colonized. Hand cultures of both nurses and a rectal culture of one of the nurses yielded the epidemic strain. C. diversus may have been introduced into the nursery by the rectal carrier and spread person to person. Six weeks later continued surveillance identified a second cluster (of four colonized infants) associated with a mother who was a carrier of C. diversus and whose newborn infant became colonized at birth. The outbreak ended after strict control measures were used.

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As hospital restructuring becomes more frequent, therein lies an opportunity for pathologists to establish regional laboratories, either independently or as joint ventures with hospitals. The author discusses some of the pressures to unbundle, and steps that pathologists can take to meet this challenge.

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A previously healthy 49-year-old woman had symptoms of acute hypercalcemia that was not parathyroid-hormone mediated. Despite no clinical signs or symptoms of arthritis, a bone scan showed increased uptake in the juxtaarticular areas of the joints in the upper and lower extremities. The biopsy specimen of skeletal lesions noted on roentgenograms supported a diagnosis of multiple myeloma. Symmetrical lesions on bone scan in a patient with asymptomatic joints and acute hypercalcemia may be the first sign of an underlying hematologic malignant neoplasm.

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In this article, a pathologist with experience under New Jersey's diagnosis-related group system makes some predictions about the practice of pathology under the new reimbursement laws and regulations.

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