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Biomedical subjects

D R Nelson

Publications and source records attributed to D R Nelson.

270 records · Page 15Linked to original sources
PubMedDate not supplied

MR imaging of Hippel-Lindau disease: value of gadopentetate dimeglumine.

Hippel-Lindau disease is an autosomal dominant disorder characterized by tumors of the central nervous system and abdominal viscera. Frequent multisystem radiologic evaluation of persons at risk is desirable. Twenty-seven patients with Hippel-Lindau disease or a family history of the disease were examined with both unenhanced and gadopentetate dimeglumine-enhanced magnetic resonance (MR) imaging to study the usefulness of the contrast medium in the evaluation of these patients. The MR studies were correlated with computed tomographic (CT) scans in seven patients and cerebral angiograms in five. Twelve patients had hemangioblastomas in the brain, and eight of these patients also had spinal cord lesions (most were multiple), well demonstrated with gadopentetate dimeglumine. Contrast-enhanced MR imaging enabled detection of more central nervous system lesions and provided better delineation than unenhanced MR imaging, CT, or angiography. In addition, four patients with multiple renal cysts seen on CT scans and unenhanced MR images had enhancing lesions that were later proved to be renal cell carcinoma at angiography and/or surgery. Four patients had cystic lesions in the pancreas that did not enhance and were later proved to be pancreatic cysts. The authors conclude that gadopentetate dimeglumine-enhanced MR imaging appears to be a useful method for evaluating and following up patients with Hippel-Lindau disease.

Adolescent↗
PubMedDate not supplied

An antibiotic resistant experimental model of Pseudomonas osteomyelitis.

We report a model of chronic Pseudomonas aeruginosa osteomyelitis in the rat that was reproducible, simple and inexpensive. No promoting agent was required to cause infection. Infected animals yielded consistent pseudomonal colony counts (log): 4.98 +/- 0.32 (SD)/g cortical tibia (n = 16). The 95% confidence interval of the mean was 4.83-5.14. The inoculum required to infect 50% of challenged rats (ID50) was log 4.0; the ID 100 was log 6.4. Ceftazidime (50 mg/kg/8 h, subcutaneously), alone and in combination with tobramycin (40 mg/kg/12 h, subcutaneously), produced no significant change in quantitative bacterial count or gross bone pathology when used to treat established disease.

Animals↗
PubMedDate not supplied

Genetic approaches to cell biology and metabolism of spirochetes.

Genetic analysis and methodology have only comparatively recently been applied to the study of spirochetes. Although genetic transfer procedures for spirochetes are not widely available, there are several examples of progress in genetic analysis of spirochetes by other approaches. Some examples of these approaches are the following. 1) Genes for synthetic pathways in Treponema and Leptospira have been cloned by complementation of Escherichia coli serving as plasmid hosts. 2) The OspA protein of Borrelia burgdorferi has been overexpressed in E. coli without the signal peptide; the recombinant product has been suitable for circular dichroism as well as other biochemical analyses. 3) The heat shock proteins of B. burgdorferi are homologous to heat shock proteins of E. coli. 4) Enzyme activity profiles of B. burgdorferi and other spirochetes show strain heterogeneity and also indicate which biosynthetic and enzymatic activities are conserved within different spirochetes. 5) The gene organization of rRNA genes have revealed differences between spirochetes and other types of bacteria.

Bacterial Outer Membrane Proteins↗
PubMedDate not supplied

The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci.

In this update we provide a list of the 71 P450 genes and the four P450 pseudogenes that have been characterized as of September 30, 1988. The chromosomal locations of many of these genes are also summarized. A modest revision of the initially proposed nomenclature of the P450 superfamily (Nebert et al., DNA 6, 1-11, 1987) is described specifically for the human and mouse chromosomal loci. The motivation for this revision is to conform to the rules of nomenclature for human and mouse genes. Recommendations for the naming of chromosomal loci include the root symbol "CYP" for human ("Cyp" for mouse), denoting "cytochrome P450." We recommend that this root also be used for other organisms. For a chromosomal locus, the root symbol is followed by an Arabic numeral designating the P450 family, a letter indicating the subfamily, and an Arabic numeral representing the individual gene within the family or subfamily. Numbers of the individual genes usually will be assigned in the order the genes are identified. This system is consistent with our earlier proposed nomenclature for P450 families and gene products from all eukaryotes and prokaryotes.

Animals↗
PubMedDate not supplied

The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature.

We provide here a list of 154 P450 genes and seven putative pseudogenes that have been characterized as of October 20, 1990. These genes have been described in a total of 23 eukaryotes (including nine mammalian and one plant species) and six prokaryotes. Of 27 gene families so far described, 10 exist in all mammals. These 10 families comprise 18 subfamilies, of which 16 and 14 have been mapped in the human and mouse genomes, respectively; to date, each subfamily appears to represent a cluster of tightly linked genes. We propose here a modest revision of the initially proposed (Nebert et al., DNA 6, 1-11, 1987) and updated (Nebert et al., DNA 8, 1-13, 1989) nomenclature system based on evolution of the superfamily. For the gene we recommend that the italicized root symbol CYP for human (Cyp for mouse), representing cytochrome P450, be followed by an Arabic number denoting the family, a letter designating the subfamily (when two or more exist), and an Arabic numeral representing the individual gene within the subfamily. A hyphen should precede the final number in mouse genes. We suggest that the human nomenclature system be used for other species. This system is consistent with our earlier proposed nomenclature for P450 of all eukaryotes and prokaryotes, except that we are discouraging the future use of cumbersome Roman numerals.

Animals↗
PubMedDate not supplied

The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature.

We provide here a list of 221 P450 genes and 12 putative pseudogenes that have been characterized as of December 14, 1992. These genes have been described in 31 eukaryotes (including 11 mammalian and 3 plant species) and 11 prokaryotes. Of 36 gene families so far described, 12 families exist in all mammals examined to date. These 12 families comprise 22 mammalian subfamilies, of which 17 and 15 have been mapped in the human and mouse genome, respectively. To date, each subfamily appears to represent a cluster of tightly linked genes. This revision supersedes the previous updates [Nebert et al., DNA 6, 1-11, 1987; Nebert et al., DNA 8, 1-13, 1989; Nebert et al., DNA Cell Biol. 10, 1-14 (1991)] in which a nomenclature system, based on divergent evolution of the superfamily, has been described. For the gene and cDNA, we recommend that the italicized root symbol "CYP" for human ("Cyp" for mouse), representing "cytochrome P450," be followed by an Arabic number denoting the family, a letter designating the subfamily (when two or more exist), and an Arabic numeral representing the individual gene within the subfamily. A hyphen should precede the final number in mouse genes. "P" ("p" in mouse) after the gene number denotes a pseudogene. If a gene is the sole member of a family, the subfamily letter and gene number need not be included. We suggest that the human nomenclature system be used for all species other than mouse. The mRNA and enzyme in all species (including mouse) should include all capital letters, without italics or hyphens. This nomenclature system is identical to that proposed in our 1991 update. Also included in this update is a listing of available data base accession numbers for P450 DNA and protein sequences. We also discuss the likelihood that this ancient gene superfamily has existed for more than 3.5 billion years, and that the rate of P450 gene evolution appears to be quite nonlinear. Finally, we describe P450 genes that have been detected by expressed sequence tags (ESTs), as well as the relationship between the P450 and the nitric oxide synthase gene superfamilies, as a likely example of convergent evolution.

Alleles↗
PubMedDate not supplied

Traumatic flexor tendon injuries in 27 cattle.

Information for all cattle with a diagnosis of tendon injury entered into the Veterinary Medical Data Base (VMDB) was retrieved and selected medical records reviewed. The proportional morbidity rate for tendon disruption was 0.89 cattle/1,000 cattle admissions and 95 of 99 cattle survived. Female and dairy cattle had a greater risk of tendon disruption than male or beef cattle, respectively. Also, cattle 6 months to 7 years old had a greater risk than cattle younger than 6 months old. Complete medical records were examined for 27 cattle. Affected cattle were 2.5 +/- 1.8 years old and weighed 593.6 +/- 315.6 kg. Injuries were most commonly caused by accidents involving farm machinery (72%). Unilateral superficial digital flexor tendon injury occurred in 8 cattle (30%); multiple tendon injury occurred in the other 19 cattle (70%). A single limb was involved in 25 cattle, a rear limb was involved in 24 cattle, and an open wound was associated with the injury in 26 cattle. Wounds were identified most commonly at the mid (13 cattle) and proximal metatarsus (4 cattle). Treatment of tendon disruption included tenorrhaphy and casting (9 cattle), external coaptation, alone, (14 cattle), stall confinement, alone, (1 cow), and euthanasia or salvage (3 cattle). External coaptation was maintained for 74.4 +/- 34.3 days, and total confinement period was 88.3 +/- 59.5 days. Short-term complications included severe tendon laxity (one cow) and fatal septic peritonitis (one bull). Twenty-two of 24 cattle treated for tendon disruption survived. Follow-up information was available for 16 cattle; 14 cattle (87%) returned to productivity and 11 of 15 cattle with long-term follow-up (73%) were considered productive. Long-term complications included persistent lameness (56%) and persistent hyperextension of the digits (19%).

Animals↗
PubMedDate not supplied

Oxidative stress in normospermic men undergoing infertility evaluation.

The purpose of this study was to determine whether normospermic infertile men have high seminal oxidative stress, using 3 measures of oxidative stress: reactive oxygen species (ROS), total antioxidant capacity (TAC), and a composite ROS-TAC score. Forty-three normospermic men without leukocytospermia and 19 healthy donors who came to our infertility clinic were included. Patients were categorized into 3 groups: group I, varicocele and no female factor (n = 16); group II, positive female factor (n = 16); and group III, idiopathic infertility (n = 11). In addition, 52 treated male factor patients and 19 donors were included as reference groups. We measured seminal ROS, TAC, and the ROS-TAC score in the patient groups and the controls. Normospermic infertile patients as a group had higher ROS levels (mean log [ROS + 1] 1.76 +/- 0.13) compared with controls (1.39 +/- 0.16; P = .03). Patients in the idiopathic subgroup had significantly higher ROS levels (2.29 +/- 0.25; P = .004) than controls. Normospermic infertile patients as a group not only had reduced TAC levels (970.18 +/- 73.95 Trolox equivalents), but each subgroup also had significantly lower TAC than controls (1650.93 +/- 95.87; P < .003). The ROS-TAC scores in all normospermic infertile patients as a group (35.7 +/- 1.8) as well as in each subgroup was significantly reduced compared with the ROS-TAC levels in the controls (50.0 +/- 2.1; P < .005). We conclude that oxidative stress is associated with male factor infertility. The presence of oxidative stress in infertile normospermic men may explain previously unexplained cases of infertility otherwise attributed to female factors.

Humans↗
PubMedDate not supplied

Quality control of reactive oxygen species measurement by luminol-dependent chemiluminescence assay.

A total of 28 donor semen samples were used to evaluate the characteristics of laboratory variability in measuring reactive oxygen species (ROS). The objectives of this study were to assess the interassay (same sample observed on different days by the same observers) variability; interdonor, intraobserver (replications of the same sample on the same day) variability; and interobserver (multiple observers on the same day with the same sample) variability of the luminol-dependent chemiluminescence assay and to establish an optimal semen age and sperm concentration. Semen samples were collected from 6 healthy donors for 108 measures of ROS. ROS levels were measured by the assay using luminol as the probe. An additional assessment measured the effect of time (age of the sample) on ROS production in 12 donor samples at 60, 120, 180, and 240 minutes after the specimen was produced. Last, to evaluate the effect of sperm concentration on ROS production, ROS levels were measured in 10 donor sample aliquots with sperm concentrations ranging from 1 to 120 x 10(6)/mL. In the controls, the mean ROS level was 0.218 x 10(6) counted photons per minute; the interassay variability standard deviation (SD) was 0.077. The interobserver SD was 0.002 for an interobserver reliability of 97.5% (coefficient of variation [CV] = 0.9%). The intraobserver (between replication) SD was 0.001 for an intraobserver reliability of 98.7% (CV = 0.5%). The interassay SD was 0.005 for an interassay reliability of 93.8% (CV = 2.0%). There was no statistically significant interobserver, intraobserver, or interassay variation (P > .80). ROS levels decreased significantly with time; a dramatic decline in ROS production was seen in the specimens that were more than 60 minutes old (P < .001). ROS values decreased by 31% at 120 minutes and 62% at 180 minutes compared with the 60-minute-old specimens. A linear relationship was seen between the ROS levels and sperm concentration in 8 of the 10 samples analyzed (R2 = .99). Our results demonstrate that the luminol-dependent chemiluminescence assay for ROS measurement is both accurate and reliable when the sperm concentration is greater than 1 x 10(5)/mL and the samples are analyzed within the first hour after specimen collection.

Clinical Laboratory Techniques↗
PubMedDate not supplied

Relationship between seminal white blood cell counts and oxidative stress in men treated at an infertility clinic.

In semen, granulocytes are major producers of reactive oxygen species (ROS), which can damage sperm. The diagnosis of leukocytospermia is usually based on the World Health Organization (WHO) definition of 1 x 10(6) white blood cells per milliliter, but controversy remains over the minimum leukocyte level that impairs fertility. The goals of this study were to clarity the relationship between leukocyte count and oxidative stress and to establish the minimum leukocyte count associated with oxidative stress. To do so, we compared oxidative stress in semen samples with different leukocyte counts (by the Endtz test) after a simple wash-and-resuspend procedure and determined the correlation between leukocyte counts and oxidative stress (expressed as ROS-TAC score, a composite score calculated from ROS levels and total antioxidant capacity (TAC), both measured with chemiluminescence assays). ROS-TAC decreases as oxidative stress rises. We compared specimens from 271 men attending an infertility clinic and 28 healthy controls. About 9% of patients had WHO-defined leukocytospermia and an additional 16% had some leukocytes. Samples with no seminal leukocytes had significantly lower ROS levels and significantly higher ROS-TAC scores than samples with any seminal leukocytes, even very low levels. Oxidative stress was correlated with rising white blood cell (WBC) count (r = .39; P < .001). Receiver operating characteristics curves showed that ROS-TAC score would be fairly accurate at distinguishing between patients with any leukocytes and those with no leukocytes (area under the curve, 75%). In conclusion, oxidative stress occurs even in patients with very low seminal WBC counts (between 0 and 1 x 10(6)/mL) and rises with an increase in WBC count. Therefore, we are unable to determine a safe minimum WBC count; the presence of any WBCs is associated with oxidative stress and may therefore impair fertility. Complete removal of WBCs from semen samples used for assisted reproduction may help reduce oxidative stress.

Area Under Curve↗
PubMedDate not supplied

The formation, disposition, and hepatic metabolism of dimethylnitrosamine in the pig.

The disposition, metabolism, and endogenous formation of N-nitrosodimethylamine (NDMA) from nitrosatable precursors was studied in the intact pig and in animals with cannulated hepatic and portal veins and catheterized bile ducts. Rates of disappearance of NDMA from peripheral venous and arterial blood after iv injections were virtually identical and the compound appeared in bile after a lag time of about 1 hr, with a subsequent decline in biliary concentration at about the same rate as in circulating blood. Measurements of NDMA in portal and hepatic vein blood after oral doses of 10, 1.0 and 0.1 mg/kg, respectively, showed progressively greater hepatic extraction with levels in the hepatic vein approaching the limits of detection after the lowest dose. Both halothane and ethanol virtually abolished the hepatic extraction of NDMA, presumably due to their known inhibitory action on its metabolism in the liver. Endogenous formation of NDMA and N-nitrosomorpholine after oral doses of the amines plus nitrite was demonstrated by their detection and measurement in the portal vein blood. Morpholine was nitrosated more effectively than dimethylamine and inhibited the nitrosation of the latter when the two amines were given together. NDMA was found in the portal blood after sequential oral administration of aminopyrine and nitrite, the concentration being considerably greater after fasting for 24 hr than after a 2-hr fast when much food was present in the stomach.

Aminopyrine↗
PubMedDate not supplied

Maintenance of adequate hemodialysis access. Prevention of neointimal hyperplasia.

The maintenance of adequate hemodialysis vascular access is frequently complicated in the patient with polytetrafluoroethylene (PTFE) A-V hemodialysis grafts by venous anastomotic stenosis. This stenosis is caused by neointimal hyperplasia (NIH), a response to vascular injury. In this study, the authors prospectively analyzed the effect of a short-term regimen consisting of administration of two medications, heparin and low molecular weight dextran, on the development of NIH at the venous anastomosis in 79 patients with PTFE A-V hemodialysis grafts. In addition, they evaluated other parameters' effects on the development of NIH. In comparison with control subjects, heparin had some effect in minimizing the development of NIH in the PTFE grafts when evaluated radiologically at 3 months, although this effect was not statistically significant. Low molecular weight dextran, however, had no trend or statistically significant effect on this venous anastomotic narrowing. Interestingly, patient age, use of calcium channel blockers, and presence of diabetes mellitus (DM) all appeared to affect the development of NIH. Increasing age and use of calcium channel blockers was associated with decreased development of NIH; conversely, DM was associated with worsened NIH. In evaluation of access survival (time to first access failure), degree of venous anastomosis stenosis at 3 months was not predictive. Patient time on dialysis pre graft placement was the only measured parameter related to access failure. The method of dialysis pre graft placement (hemodialysis versus peritoneal dialysis) was not a significant factor in early access failure. Pharmacologic treatment of venous anastomotic narrowing in PTFE hemodialysis grafts due to NIH continues to be difficult. Short-term treatment with the tested medication failed to statistically affect NIH. Patient age, use of calcium channel blockers, and presence of DM were all factors in the development of NIH. Of measured parameters, time on dialysis pre graft placement was the only factor correlated with early access failure. In future treatment regimens, one should consider more prolonged treatment. In addition, noted risk factors should be considered when determining type of renal replacement therapy.

Adult↗