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Biomedical subjects

J Shultz

Publications and source records attributed to J Shultz.

At least 19 recordsLinked to original sources

An updated 'Essex' by 'Forrest' linkage map and first composite interval map of QTL underlying six soybean traits.

DNA marker maps based on single populations are the basis for gene, loci and genomic analyses. Individual maps can be integrated to produce composite maps with higher marker densities if shared marker orders are consistent. However, estimates of marker order in composite maps must include sets of markers that were not polymorphic in multiple populations. Often some of the pooled markers were not codominant, or were not correctly scored. The soybean composite map was composed of data from five separate populations based on northern US germplasm but does not yet include 'Essex' by 'Forrest' recombinant inbred line (RIL) population (E x F) or any southern US soybean cultivars. The objectives were, to update the E x F map with codominant markers, to compare marker orders among this map, the Forrest physical map and the composite soybean map and to compare QTL identified by composite interval maps to the earlier interval maps. Two hundred and thirty seven markers were used to construct the core of the E x F map. The majority of marker orders were consistent between the maps. However, 19 putative marker inversions were detected on 12 of 20 linkage groups (LG). Eleven marker distance compressions were also found. The number of inverted markers ranged from 1 to 2 per LG. Thus, marker order inversions may be common in southern compared to northern US germplasm. A total of 61 QTL among 37 measures of six traits were detected by composite interval maps, interval maps and single point analysis. Seventeen of the QTL found in composite intervals had previously been detected among the 29 QTL found in simple interval maps. The genomic locations of the known QTL were more closely delimited. A genome sequencing project to compare Southern and Northern US soybean cultivars would catalog and delimit inverted regions and the associated QTL. Gene introgression in cultivar development programs would be accelerated.

Chromosome Mapping↗

An improved method for production of silica from rice hull ash.

Rice hull ash (RHA) contains over 60% silica and can be an economically viable raw material for the production of silica based products. A previously published method for producing silica xerogel involved dissolving RHA silica with alkali solution to form sodium silicate solution and subsequently forming silica aquagel by adding hydrochloric acid to lower the pH from 11.8 to 7.0, followed by washing and drying aquagel to form xerogel. The silica xerogel had over 4% sodium as a contaminant. An improved method to produce silica xerogel with lower sodium is described in this study. The improved method involved production of silica aquagel by adding silicate solution to pH 1.5 hydrochloric, citric, or oxalic acid solutions until the pH 4.0 was reached. The aquagel was washed and dried to form silica xerogel. For comparison silica xerogels were also produced at pH 7.0 by the published method. X-ray photoelectron spectroscopy was used to determine the elemental content of silica xerogels. The silica, sodium, carbon and oxygen content of silica xerogels varied depending on the pH and the type of acid used for the production of these xerogels. Silica xerogels produced by the improved method using citric and oxalic acid had sodium content of 0.52% and 0.22%, respectively.

Acids↗

A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer.

BACKGROUND: Trimetrexate (TMTX) biochemically modulates 5-fluorouracil (5-FU) and leucovorin (LCV). Two phase II trials demonstrated promising activity for TMTX/5-FU/LCV in patients with untreated advanced colorectal cancer (ACC). This trial was designed to demonstrate the safety and efficacy of TMTX/5-FU/LCV as first-line treatment in ACC. PATIENTS AND METHODS: Eligible patients with ACC were randomized in double-blind fashion to receive placebo or TMTX (110 mg/m2) intravenously (i.v.) followed 24 h later by i.v. LCV 200 mg/m2, and 5-FU 500 mg/m2 plus oral LCV rescue. Both schedules were given weekly for 6 weeks every 8 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS), tumor response, quality of life (QoL) and toxicity. RESULTS: A total of 382 eligible patients were randomized. Significant toxicities were noted more frequently with TMTX/5-FU/LCV. Diarrhea was the most common grade 3 or 4 side-effect (41% and 28% on the TMTX and placebo arms, respectively). QoL scores and response rates did not differ between treatment arms. PFS was 5.3 months and 4.4 months in the TMTX and placebo arms, respectively (P = 0.77; Wilcoxon). OS was 15.8 months and 16.8 months, respectively (P = 0.73; Wilcoxon). CONCLUSIONS: The addition of TMTX to a weekly regimen of 5-FU/LCV worsened grade 3 or 4 diarrhea. The inclusion of TMTX did not yield any significant improvements in response rate, PFS or OS.

Adolescent↗

Analysis of the factor V Leiden mutation using the READIT Assay.

BACKGROUND: A variety of methods exist for the detection of single-nucleotide polymorphisms (SNPs) present in amplified segments of genomic DNA. We show the application of a novel SNP scoring tool for analysis of the factor V Leiden mutation. METHODS AND RESULTS: We have developed a novel method for analyzing SNPs. The luciferase-based technique, known as the READIT Technology (Promega Corp, Madison, WI), was used to analyze 510 residual human samples sent for factor V Leiden testing from three independent testing laboratories. A blinded retrospective analysis of the factor V Leiden mutation was used to determine the accuracy and throughput capabilities of the technology. One hundred percent concordance was observed between the READIT Assay and genotype assignments made in the testing laboratories. In addition, greater than 6 SDs of separation were observed between the means of wild-type and heterozygote sample populations. Repetitive sample measurements with representative wild-type, heterozygote, and mutant samples showed that greater than 9 SDs separated the means of heterozygote and homozygote sample populations. Confidence intervals based on the means of wild-type, heterozygote, and mutant sample populations were determined. CONCLUSION: Perfect concordance using the READIT Assay showed its effectiveness as a SNP scoring tool. The design of the factor V READIT Assay was straightforward, requiring the design of two unmodified oligonucleotides that differ at the 3' penultimate position to form perfect hybrids with the wild-type or Leiden form of the factor V sequence. The use of previously published amplification primers and conditions minimized the time needed to optimize and validate the assay. The READIT Calculator supplied with the assay allowed automated genotype assignments and statistical analysis from the READIT Assay data. Confidence-interval analysis validated the ability to distinguish between wild-type, heterozygote, and mutant samples using the READIT Assay.

DNA↗

Development of a human DNA quantitation system.

The AluQuant Human DNA Quantitation System has been developed for human-specific quantitation of forensic samples. This system uses probes specific to repetitive genetic elements allowing quantitation without target amplification. Target immobilization is unnecessary with employment of solution hybridization. The AluQuant Human DNA Quantitation System uses a series of enzymatic reactions to produce a luminescent signal proportional to the quantity of human DNA present. This report demonstrates a range of quantitation from 0.1-50 ng of human DNA. Signal from non-human DNAs tested was insignificant and addition of non-human DNAs into a human sample did not alter quantitation. Lastly, the system was unaffected by degradation of sample through sonication. The AluQuant Human DNA Quantitation System is a simple and sensitive method for quantitating the concentration of human DNA in forensic samples.

DNA↗

Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection.

Cytogenetic and molecular deletion analyses of azoospermic and oligozoospermic males have suggested the existence of AZoospermia Factor(s) (AZF) residing in deletion intervals 5 and 6 of the human Y-chromosome and coinciding with three functional regions associated with spermatogenic failure. Nonpolymorphic microdeletions in AZF are associated with a broad spectrum of testicular phenotypes. Unfortunately, Sequence Tagged Sites (STSs) employed in screening protocols range broadly in number and mapsite and may be polymorphic. To thoroughly analyze the AZF region(s) and any correlations that may be drawn between genotype and phenotype, we describe the design of nine multiplex PCR reactions derived from analysis of 136 loci. Each multiplex contains 4-8 STS primer pairs, amplifying a total of 48 Y-linked STSs. Each multiplex consists of one positive control: either SMCX or MIC2. We screened four populations of males with these STSs. Population I consisted of 278 patients diagnosed as having significant male factor infertility: either azoospermia, severe oligozoospermia associated with hypogonadism and spermatogenic arrest or normal sperm counts associated with abnormal sperm morphology. Population II consisted of 200 unselected infertile patients. Population III consisted of 36 patients who had previously been shown to have aneuploidy, cytological deletions or translocations involving the Y-chromosome or normal karyotypes associated with severe phenotype abnormalities. Population IV consisted of 920 fertile (control) males. The deletion rates in populations I, II and III were 20.5%, 7% and 58.3%, respectively. A total of 92 patients with deletions were detected. The deletion rate in population IV was 0.87% involving 8 fertile individuals and 4 STSs which were avoided in multiplex panel construction. The ability of the nine multiplexes to detect pathology associated microdeletions is equal to or greater than screening protocols used in other studies. Furthermore, the data suggest a fourth AZF region between AZFb and AZFc, which we have termed AZFd. Patients with microdeletions restricted to AZFd may present with mild oligozoospermia or even normal sperm counts associated with abnormal sperm morphology. Though a definitive genotype/phenotype correlation does not exist, large deletions spanning multiple AZF regions or microdeletions restricted to AZFa usually result in patients with Sertoli Cell Only (SCO) or severe oligozoospermia, whereas microdeletions restricted to AZFb or AZFc can result in patients with phenotypes which range from SCO to moderate oligozoospermia. The panel of nine multiplexed reactions, the Y-deletion Detection System (YDDS), provides a fast, efficient and accurate method of assessing the integrity of the Y-chromosome. To date, this study provides the most extensive screening of a proven fertile male population in tandem with 514 infertile males, derived from three different patient selection protocols.

Female↗

Drug use and syphilis. Co-factors for HIV transmission among commercial sex workers in Guyana.

A cross-sectional survey was conducted among 124 street- and brothel-based female commercial sex workers (CSWs) in Georgetown in January and February 1997 to determine the seroprevalence of human immunodeficiency virus (HIV) infection and describe the sexual practices and drug use patterns. Their median age was 30 years (range 17 to 52 years). 119 (88%) reported regular alcohol consumption while looking for clients, 27 (22%) said they smoked cocaine and 51 (42%) reported use of marijuana. Street-based CSWs were significantly more likely to report marijuana use (p = 0.033). 72% reported that they never used condoms with regular sex partners and 35% reported that they never used condoms with clients. Brothel-based women were significantly more likely to report consistent condom use with their clients (p = 0.05). 46% (54/118) tested HIV positive and 28% (33/118) had a positive serological test for syphilis. Factors that were significantly associated with HIV infection included a positive serological test for syphilis (OR = 7.56; 95% CI = 2.7-21.97; p < 0.01) and a history of having received treatment for syphilis (OR = 2.93; 95% CI = 1.12-7.8). Weak associations were also found between HIV infection and a history of cocaine use (OR = 2.57; 95% CI = 0.95-7.11; p = 0.039); having more than four clients per night (OR = 5.14; 95% CI = 1.65-16.74; p = 0.04); and a history of receiving treatment for salpingitis (OR = 2.31; 95% CI = .93-5.75; p = 0.0035). No statistically significant association was found between HIV infection and marijuana use nor any sociodemographic variables (age, place of work, and duration of sex work). There is an urgent need for a community based behavioural intervention programme targetting this high risk population.

Adolescent↗

Social influences: living arrangements of drug using women at risk for HIV infection.

The purpose of this study was to explore the associations among living arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322 drug users participating in the University of Miami CARES (Community AIDS Research and Evaluation Studies) HIV intervention program. Living arrangements may be associated with HIV prevention behaviors; however, these influences can be either protective or destructive and therefore merit further examination. Statistical analyses indicated differences in the living arrangements of women compared with men, and significant associations were noted among women's living arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The data from this study suggest that future HIV prevention research should investigate not only high-risk individuals, but persons with whom they interact often, especially those with whom they live or with whom they have sex. The next phase of HIV and drug interventions should be attentive to the incorporation of social context and social influences, paying particular attention to understudied populations such as high-risk women.

Adult↗

Improving active compression-decompression cardiopulmonary resuscitation with an inspiratory impedance valve.

BACKGROUND: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) has recently been demonstrated to provide significantly more blood flow to vital organs during cardiac arrest. To further enhance the effectiveness of this technique, we tested the hypothesis that intermittent impedance to inspiratory gas exchange during the decompression phase of ACD CPR enhances vital organ blood flow. METHODS AND RESULTS: ACD CPR was performed with a pneumatically driven automated compression-decompression device in a porcine model of ventricular fibrillation (VF). Nine pigs were randomized to receive ACD CPR alone, while 8 pigs received ACD CPR plus intermittent impedance to inspiratory gas exchange with a threshold valve set to 40 cm H2O. Results comparing 2 minutes of ACD CPR alone versus ACD CPR with the inspiratory impedance threshold valve (ITV) revealed significantly higher mean (+/- SEM) coronary perfusion pressures (diastolic aortic minus diastolic right atrial pressures) in the ITV (31.0 +/- 2.3 mm Hg) group versus with ACD CPR alone (21 +/- 3.6 mm Hg) (P < .05). Total left ventricular and cerebral blood flows, determined by radiolabeled microspheres, were 0.77 +/- 0.095 and 0.47 +/- 0.06 mL/min per gram, respectively, with ACD CPR plus the ITV versus 0.45 +/- 0.1 and 0.32 +/- 0.016 mL/min per gram, respectively, with ACD CPR alone (P < .05). Similar improvements in the ITV group were observed after 7 minutes of ACD CPR. After 16 minutes of VF and 13 minutes of ACD CPR, 6 of 8 pigs in the ITV group were successfully resuscitated with less than three successive 150-J shocks, whereas only 2 of 9 pigs with ACD CPR alone were resuscitated with equivalent energy levels (P < .02). With up to three additional and successive 200-J shocks, all pigs in the ITV group and 7 of 9 pigs with ACD CPR alone were resuscitated (P = .18). CONCLUSIONS: Intermittent impedance to inspiratory flow of respiratory gases during ACD CPR significantly improves coronary perfusion pressures and vital organ blood flow and lowers defibrillation energy requirements in a porcine model of VF.

Animals↗

Axial kinematics and muscle activity during terrestrial locomotion of the centipede Scolopendra heros

For centipedes moving steadily on a treadmill at speeds of 0.5, 1.0 and 1.5 L s-1, where L is body length, we obtained video tapes of movement that were synchronized with electromyograms (EMGs) from lateral flexor muscles at six standardized longitudinal positions. Field-by-field analysis of video tapes revealed posteriorly propagated waves of bending at all speeds. Muscle activity was also propagated posteriorly at the same speed as the kinematic wave, and EMGs of the lateral flexors were generally unilateral and alternating (between the left and right sides). The timing of EMG activity relative to lateral bending was consistent with electrical activity during the shortening of muscle fibers; therefore, activity of the axial musculature appears to cause lateral bending. Analysis of variance revealed widespread effects of speed on both kinematic and electromyographic variables, whereas longitudinal position within the centipede (between body segments 8 and 18) generally did not have significant effects on the same variables. For example, as speed increased from 0.5 to 1.5 L s-1, the amplitude of lateral displacement approximately doubled and the amplitude of lateral bending increased approximately threefold. Lag times (in seconds) indicating the propagation of kinematic and EMG events along the length of the centipede decreased significantly with speed. Phase lags among longitudinal sites decreased significantly with increased speed, indicating that the kinematic and EMG wavelengths increased with increased speed. EMG duration approximated 50 % of cycle duration and was unaffected by speed, and the phase of the EMG activity relative to lateral bending was also unaffected by locomotor speed. Hence, all results from all speeds are consistent with active bending of the axial segments during centipede locomotion, conflicting with the widely accepted hypothesis that lateral bending is imposed on the body by the metachronal stepping pattern of the legs and that bending is resisted by axial muscles.

Journal Article↗

Active compression-decompression CPR improves vital organ perfusion in a dog model of ventricular fibrillation.

OBJECTIVES: This study was designed to assess whether a new method of cardiopulmonary resuscitation (CPR), termed active compression-decompression CPR, or ACD-CPR, improves organ perfusion when compared with standard (S) CPR in a dog model of ventricular fibrillation. BACKGROUND: ACD-CPR has recently been shown to improve hemodynamic and respiratory parameters during cardiac arrest when compared with standard CPR. However, to our knowledge, the effects of ACD-CPR on tissue perfusion have not been investigated. METHODS: Ventricular fibrillation was induced in eight anesthetized, intubated animals. ACD-CPR and standard CPR were each performed twice in alternating order. All interventions were preceded by 1 min of ventricular fibrillation, in which no CPR was performed, and consisted of 6 min of CPR with either technique during which tissue perfusion was measured. Compressions were performed at 80/min with a 50 percent duty cycle and 175 to 200 N downward force applied to the chest wall for both techniques. Epinephrine was administered at the beginning of each 6-min CPR interval. Hemodynamic monitoring of aortic and right atrial pressure was performed continuously and myocardial, cerebral, and renal blood flows were measured using the radiolabeled microsphere technique at baseline and during all interventions. RESULTS: Baseline organ perfusion and hemodynamics were similar for all dogs. Baseline left ventricular, brain, and renal blood flows were 62.0 +/- 5.5, 14.1 +/- 2.1, and 476.3 +/- 55.5 ml/min/100 g, respectively (mean +/- SEM). Compared with standard CPR, ACD-CPR resulted in higher global left ventricular (22.5 +/- 6.2 vs 14.1 +/- 4.0 ml/min/100 g, p < 0.01), cerebral (12.0 +/- 2.4 vs 8.5 +/- 2.3 ml/min/100 g, p < 0.01), and renal cortical (27.8 +/- 5.0 vs 17.5 +/- 5.0 ml/min/100 g, p < 0.05) blood flows. Regional flows to the epicardium, endocardium, and midmyocardium as well as to the frontal, parietal, and occipital lobes of the brain were all significantly improved by ACD-CPR. Aortic systolic (61.7 +/- 4.1 vs 49.5 +/- 3.1 mm Hg, p < 0.01), aortic mean (31.6 +/- 2.8 vs 27.2 +/- 2.2 mm Hg, p = 0.001), and myocardial perfusion pressure (12.9 +/- 3.4 vs 10.4 +/- 3.4 mm Hg, ACD-CPR vs standard CPR, p < 0.01) were all higher during ACD-CPR than during standard CPR. CONCLUSIONS: We conclude that ACD-CPR improves tissue perfusion and systemic hemodynamics compared with standard CPR.

Animals↗

Atrioventricular nodal reentrant tachycardia initiated by catecholamine-induced ventricular tachycardia. A case report.

The authors describe a patient who experienced recurrent wide-complex and narrow-complex tachycardias during exercise. Electrophysiologic testing in the resting state revealed dual atrioventricular (AV) nodal pathways. AV nodal reentrant tachycardia was inducible by ventricular premature stimulation but was always nonsustained, terminating with block in the anterograde slow pathway. During isoproterenol infusion, runs of ventricular tachycardia occurred frequently, and spontaneously initiated sustained AV nodal reentrant tachycardia. Exercise testing also provoked ventricular tachycardia and sustained AV nodal reentrant tachycardia. The patient was effectively treated with a combination of atenolol and verapamil. This case is an unusual example of a catecholamine-induced arrhythmia, possibly due to triggered activity (exercise-induced ventricular tachycardia), initiating an arrhythmia due to reentry (AV nodal reentrant tachycardia).

Catecholamines↗

The nucleotide sequence of the aroF gene of Escherichia coli and the amino acid sequence of the encoded protein, the tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase.

The translated sequence of aroF, the first structural gene of the tyrosine operon of Escherichia coli, has been determined. The 1068 nucleotides encode the 356 amino acids that form the subunit of the dimeric tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase. The primary structure of this enzyme has been confirmed by automated Edman degradation of peptide fragments produced by cleavage with cyanogen bromide, limited trypsin digestion, Staphylococcus aureus strain V8 protease, or mild acid hydrolysis. The amino acid sequence of this enzyme is compared with the sequence of the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, deduced from the aroG DNA sequence (Davies, W. D., and Davidson, B. E. (1982) Nucleic Acids Res. 10, 4045-4058).

3-Deoxy-7-Phosphoheptulonate Synthase↗