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Biomedical subjects

D W Nelson

Publications and source records attributed to D W Nelson.

At least 19 recordsLinked to original sources
PubMed2001

Alpha-(trifluoromethyl)amine derivatives via nucleophilic trifluoromethylation of nitrones.

(Trifluoromethyl)trimethylsilane (TMSCF(3)) reacts with nitrones to afford alpha-(trifluoromethyl)hydroxylamines protected as O-trimethylsilyl ethers. Potassium t-butoxide initiates the nucleophilic trifluoromethylation. The reaction works best with alpha,N-diaryl nitrones, and the conditions are compatible with a range of substituents on the aryl groups. Acidic deprotection of the nitrone/TMSCF(3) adducts generates alpha-(trifluoromethyl)hydroxylamines. Catalytic hydrogenation of the adducts produces alpha-(trifluoromethyl)amines. Nitrone/TMSCF(3) adducts with strong electron-withdrawing groups on the alpha-aryl ring or heterocyclic alpha-aryl groups undergo an elimination/addition sequence to generate alpha,alpha-bis(trifluoromethyl)amines. Nitrones with alkyl groups bound directly to the 1,3-dipolar moiety fail to react with TMSCF(3), but trifluoromethylation of beta,gamma-unsaturated nitrones followed by reduction of the double bond can circumvent this limitation.

Journal Article↗
PubMed1998

5'-flanking sequences required for efficient transcription in vitro of 5S RNA genes, in the related nematodes Caenorhabditis elegans and Caenorhabditis briggsae.

In the nematode C. elegans, we had previously observed apparent species specificity in 5S RNA transcription. We have now undertaken a further study of 5S RNA gene transcription in this organism and in the related nematode, C. briggsae; the latter was chosen because it might show evolutionarily conserved, functionally important features. Deletion mutagenesis and transcription in vitro, followed by more precise replacements of short blocks of 5' sequence, show that a short, TATA-like sequence at -25 is essential for efficient transcription in vitro of the 1.0-kb C. elegans 5S DNA repeat, and of both C. briggsae 0.7- and 1.0-kb 5S DNA repeats. Internal sequences within the 5S RNA gene appear to be required and can compete for limiting transcription components, whereas 5' flanking sequences do not. These observations suggest that the process of 5S RNA transcription is similar in these nematodes and other higher eukaryotes.

Animals↗
PubMed1997

L-type calcium channels regulate gastrin release from human antral G cells.

In mRNA samples isolated from a gastrin (G) cell-enriched human antral cell preparation, reverse transcription-polymerase chain reaction identified products encoding part of the alpha 1-subunit of class C and D L-type voltage-dependent Ca2+ channels (VDCCs). Analysis of the polymerase chain reaction products demonstrated a 100% homology with the known human gene sequences. An antibody to the class D alpha 1-subunit immunostained 30-40% of the cultured cells; of these 90% were gastrin immunoreactive. Gastrin release stimulated by terbutaline (beta 2-agonist) and forskolin was abolished by blockade of L-type VDCCs; the effect of 3.6 mM extracellular Ca2+ was only partially reversed. In G cells the rise in intracellular Ca2+ observed in response to increasing extracellular Ca2+ from 0.5 to 3.6 mM was reduced by nitrendipine. These results indicated that human antral cells expressed class C and D L-type VDCCs. Activation of G cells with beta-adrenergic agonists required an influx of extracellular Ca2+ through these channels to stimulate gastrin release. However, activation of L-type channels was not the only mechanism underlying Ca(2+)-stimulated gastrin release.

Adrenergic beta-Agonists↗
PubMed1993

Transvaginal ultrasonographic findings in surgically verified ectopic pregnancy.

OBJECTIVE: Our purpose was to evaluate transvaginal ultrasonographic findings in ectopic pregnancies for positive ultrasonographic sign(s). STUDY DESIGN: Eighty-nine patients admitted with an ectopic pregnancy from September 1987 through September 1989 were retrospectively reviewed. Sixty-nine had undergone transvaginal ultrasonography within 10 days before surgery. The ultrasonographic examinations were reviewed by four radiologists. RESULTS: Ultrasonography revealed adnexal masses in 54 patients (78%). Thirty-six masses had an appearance consistent with an adnexal ring. Twenty-four adnexal rings demonstrated a thin sonolucent area surrounding the ring, a "halo sign" (67%). A control group of 116 intrauterine pregnancies were evaluated by ultrasonography. Forty-one women had adnexal cysts. Twenty-seven of these had an adnexal ring; only two of these had halos. CONCLUSION: The halo sign is presumptive evidence of a living ectopic pregnancy and, when identified, may allow earlier diagnosis and intervention.

Adnexa Uteri↗
PubMed1992

Platelet activating factor alters receptor-coupled function in the isolated perfused rat heart.

Sepsis induces primary myocardial dysfunction. Yet, both hyper- and hypodynamic cardiac states characterize the sepsis syndrome, suggesting a modulatory role of septic mediators. Platelet activating factor (PAF), implicated in the pathogenesis of sepsis, is an endogenous phospholipid with diverse intracellular and extracellular effects. The purpose of this study was to investigate the influence of PAF (1) upon basal mechanical function of the heart, (2) upon receptor-coupled function of the heart, and (3) on basal and stimulated myocardial function at differing concentrations. In order to focus on the relationship between PAF and cardiac mechanical function, rat hearts were isolated and crystalloid perfused using a modified Langendorf preparation. Separate hearts received intracoronary vehicle (5% ethanol, 2.5% BSA) or PAF (20 or 40 microM) as a bolus, followed 10 min later by 0.25 microM isoproterenol (beta-receptor agonist) infusion over 3 min. Both 20 and 40 microM PAF produced a rapid decrease in rate pressure product (RPP = HR X LVDPmax) relative to control (P < 0.05). The depressive effect of PAF upon basal myocardial function did not persist and by 10 min RPP was not different (P > 0.05) among the groups. Isoproterenol infusion increased (P < 0.05) RPP in all groups. However, hearts pretreated with 20 microM PAF demonstrated a greater (P < 0.05) response to beta-adrenergic stimulation relative to vehicle-pretreated controls. This amplified response to isoproterenol was not observed with pretreatment at a higher concentration of PAF (40 microM, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Primed neutrophils injure rat lung through a platelet-activating factor-dependent mechanism.

Bacterial lipopolysaccharide (LPS) promotes transient lung neutrophil sequestration. These LPS-primed neutrophils, when stimulated by an N-formyl peptide (FNLP), promote lung injury. We hypothesized that LPS-primed, FNLP-stimulated neutrophils promote lung injury through a platelet-activating factor (PAF)-dependent mechanism. Rats were pretreated with either saline or WEB2170, a PAF receptor antagonist (10 mg/kg po). One hour after pretreatment, rats were administered intraperitoneal LPS (salmonella typhimurium lipopolysaccharide, 500 micrograms/kg) followed 6 hr later by intravenous FNLP (250 micrograms/kg infused over 30 min). Two hours after the initiation of FNLP infusion, rats were sacrificed and assays were performed to measure: (1) lung neutrophil sequestration with myeloperoxidase (MPO) activity; (2) circulating neutrophil activation with nitroblue tetrazolium (NBT) staining, and (3) lung microvascular leak with 125I-albumin flux. We found that lung myeloperoxidase, circulating neutrophil NBT staining, and lung 125I-albumin flux were increased (P less than 0.05) in saline-pretreated LPS/FNLP rats, relative to control. While lung MPO remained increased (P less than 0.05) in WEB2170-pretreated LPS/FNLP rats, circulating neutrophil NBT and lung 125I-albumin flux were decreased (P less than 0.05) relative to those in saline-pretreated rats. We conclude that PAF mediates LPS/FNLP-induced neutrophil activation and lung injury, but is independent from lung neutrophil sequestration. Thus, lung neutrophil sequestration does not inevitably produce lung injury. Rather, neutrophils can accumulate in the lung without causing lung injury if neutrophil activation can be blocked.

Animals↗
PubMed1991

Characterizing osteochondral lesions by magnetic resonance imaging.

In a double-blind prospective study, 12 patients with osteochondral lesions of either the knee or talus were studied using magnetic resonance imaging (MRI) prior to arthroscopic treatment. MRI correctly staged 11 of the 12 lesions. We developed a new staging system for osteochondral lesions, which accurately correlates MRI with arthroscopic findings.

Adult↗
PubMed1991

CT-guided fixation of sacral fractures and sacroiliac joint disruptions.

Open reduction and internal fixation (ORIF), the currently preferred method for treatment of unstable posterior pelvic and sacral fractures, has two significant disadvantages: the need for blind placement of the fixation screws and the occurrence of high complication rates. Advantages of computed tomographic (CT)-guided sacral fixation include direct visualization of the course of the screws and absence of significant complications. Eight patients with unstable but reducible sacral fractures or sacroiliac joint (SIJ) disruptions (seven unilateral and one bilateral) underwent CT-guided sacral fixation with use of the standard orthopedic A-O, 7.0-mm-diameter cannulated screw system. The guide pin was positioned across the fracture or SIJ by using depth and angulation measurements derived from the scout CT scans. After confirmation of the position of the pin with CT, the screw tract was drilled, and the cannulated screw was placed into position. Radiographic and clinical follow-up (5-9 months) showed healing with no significant complications in all eight patients. CT-guided sacral fixation is a safe alternative to ORIF in patients with reducible unstable pelvic fractures.

Adolescent↗
PubMed1991

Pretreatment with a nontoxic derivative of endotoxin induces functional protection against cardiac ischemia/reperfusion injury.

We hypothesized that low-dose pretreatment of an intact animal with a nontoxic derivative of endotoxin, monophosphoryl lipid A (MPL), would induce protection against cardiac ischemia/reperfusion (I/R) injury. The purposes of this study were to investigate whether MPL pretreatment would induce functional protection against cardiac I/R injury, to delineate the temporal induction of protection, and to examine antioxidant enzyme induction as a mechanism of protection. Rats were administered a 5 mg/kg dose of MPL at 2 hours and 24 hours before a 25-minute, global, 37 degrees C ischemic insult followed by reperfusion (modified Langendorff). At 40 minutes of reperfusion, ventricular function was assessed (ventricular balloon; developed pressure, rate of contraction, rate of relaxation). Hearts from rats pretreated with MPL 24 hours before isolation exhibited preservation of ventricular function (p less than 0.05). After I/R, hearts from rats pretreated with MPL 24 hours before isolation had increased (p less than 0.05) catalase activity compared to saline pretreated controls and rats pretreated with MPL 2 hours before isolation. We conclude that (1) pretreatment with MPL induces functional protection against cardiac I/R injury, (2) protection (not evident at 2 hours) is maximal at 24 hours, suggesting enzyme induction, and (3) increased catalase activity correlates with the functional protection.

Analysis of Variance↗
PubMed1989

Two highly conserved transcribed regions in the 5S DNA repeats of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae.

The 5S RNA genes of Caenorhabditis briggsae consist of approximately 65 copies of a 1 kb repeat unit and 20 copies of a related 0.7 kb repeat unit, organized in separate tandem clusters. DNA sequence comparisons with the 1kb 5S DNA repeat from the closely related nematode C. elegans show that the 5S RNA coding region is perfectly conserved. Both C. briggsae 1 kb and 0.7 kb repeats are also efficiently transcribed in vitro,suggesting that both represent functional 5S RNA genes. Surprisingly, a second block of 118 bp is also perfectly conserved between the 1 kb repeats,and is less well conserved in the 0.7 kb repeat. In C. elegans, this DNA is transcribed to produce and abundant 100 nt transcript (SL RNA) which participates in a trans-splicing process (Krause and Hirsh, Cell 49:753, 1987). This SL RNA region of the C. briggsae 1 kb 5S DNA repeat also appears to be transcribed in vivo, while the corresponding region of the 0.7 kb repeat is not.

Animals↗
PubMed1988

Unusual sequences, homologous to 5S RNA, in ribosomal DNA repeats of the nematode Meloidogyne arenaria.

There are sequences homologous to 5S ribosomal RNA in the ribosomal DNA (rDNA) repeats of the plant-parasitic nematode Meloidogyne arenaria. This is surprising, because in all other higher eukaryotes studied to date, the genes for 5S RNA are unlinked to and distinct from a tandem rDNA repeat containing the genes for 18S, 5.8S, and 28S ribosomal RNA. Previously, only prokaryotes and certain "lower eukaryotes" (protozoa and fungi) had been found to have both the larger rRNAs and 5S rRNA represented within a single DNA repeat. This has raised questions on the organization of these repeats in the earliest cell (progenote), and on subsequent evolutionary relationships between pro- and eukaryotes. Evidence is presented for rearrangements and deletions within Meloidogyne rDNA. The unusual life cycles (different levels of ploidy, reproduction by meiotic and mitotic parthenogenesis) of members of this genus might allow rapid fixation of any variants with introduced 5S RNA sequences. The 5S RNA sequences in Meloidogyne rDNA may not be expressed, but their presence raises important questions as to the evolutionary origins and stability of repeat gene families.

Animals↗
PubMed1986

Transcription of class III genes in cell-free extracts from the nematode Caenorhabditis elegans.

Using the nematode Caenorhabditis elegans as a model organism, we have prepared cell-free extracts which accurately transcribe cloned homologous 5S RNA genes in vitro. These extracts also transcribe cloned tRNA genes, and actively process the resulting products. Unlike tRNA genes, transcription of 5S DNA shows some species specificity: C. elegans extracts do not transcribe Xenopus 5S RNA genes, nor does a Xenopus extract efficiently transcribe the heterologous nematode 5S DNA. However, addition of limiting amounts of C. elegans fractions permits Xenopus extracts to transcribe nematode 5S RNA genes. This apparent biochemical "complementation" may provide an assay to purify 5S RNA gene-specific factors from C. elegans.

Animals↗
PubMed1986

Genetic mapping of the 5S rRNA gene cluster of the nematode Caenorhabditis elegans.

We have identified a restriction fragment length difference (RFLD) affecting the genomic sequences immediately flanking the 5S rRNA gene cluster in the Bristol and Bergerac strains of the nematode Caenorhabditis elegans. We have used this RFLD as a molecular marker to follow the segregation of the 5S rRNA gene cluster through a series of two- and three-factor interstrain crosses. Our results show that the 5S rRNA gene cluster maps between unc-76 and dpy-21 on the right arm of linkage group V. This genetic localization provides a linkage group V "landmark" with which to localize other cloned sequences by in situ hybridization.

Animals↗
PubMed1985

Genes coding for 5S ribosomal RNA of the nematode Caenorhabditis elegans.

We have identified a 1-kb genomic sequence that represents the major class of 5S rRNA genes in the nematode Caenorhabditis elegans. This 1-kb sequence is tandemly repeated 110 times in the haploid genome forming a single homogeneous gene family. Other nematode genomic sequences, distinct from the major 1-kb repeat class but homologous to it, may represent dispersed 5S rRNA genes or the ends of a gene cluster. One such fragment shows a restriction fragment length difference between two C. elegans strains. This should allow the genetic analysis of 5S rRNA-coding DNA (5S X rDNA) and its flanking regions in C. elegans.

Animals↗
PubMed1985

A hard lens with extended wear possibilities.

The variety of parameters affecting extended wear lenses makes it obvious that the ability to use a lens under an eye closed in sleep is by no means solely contingent upon the oxygen transmission characteristics of the material. This study shows that a new silicone acrylate lens apparently permits sufficient tear-flow to maintain a viable cornea while the lens is worn overnight. In this preliminary report, over eighty percent of the previously successful hard lens patients fitted with lenses made of this material were able to maintain contact lens wear on an extended basis.

Adult↗