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Biomedical subjects

D C Jones

Publications and source records attributed to D C Jones.

At least 19 recordsLinked to original sources

Effects of sampling standardization on estimates of Phanerozoic marine diversification.

Global diversity curves reflect more than just the number of taxa that have existed through time: they also mirror variation in the nature of the fossil record and the way the record is reported. These sampling effects are best quantified by assembling and analyzing large numbers of locality-specific biotic inventories. Here, we introduce a new database of this kind for the Phanerozoic fossil record of marine invertebrates. We apply four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories. Variation introduced by the use of two dramatically different counting protocols also is explored. We present sampling-standardized diversity estimates for two long intervals that sum to 300 Myr (Middle Ordovician-Carboniferous; Late Jurassic-Paleogene). Our new curves differ considerably from traditional, synoptic curves. For example, some of them imply unexpectedly low late Cretaceous and early Tertiary diversity levels. However, such factors as the current emphasis in the database on North America and Europe still obscure our view of the global history of marine biodiversity. These limitations will be addressed as the database and methods are refined.

Animals↗

Serotonergic neurotoxicity of 3,4-(+/-)-methylenedioxyamphetamine and 3,4-(+/-)-methylendioxymethamphetamine (ecstasy) is potentiated by inhibition of gamma-glutamyl transpeptidase.

Reactive metabolites play an important role in 3,4-(+/-)-methylenedioxyamphetamine (MDA) and 3,4-(+/-)-methylenedioxymethamphetamine (MDMA; ecstasy)-mediated serotonergic neurotoxicity, although the specific identity of such metabolites remains unclear. 5-(Glutathion-S-yl)-alpha-methyldopamine (5-GSyl-alpha-MeDA) is a serotonergic neurotoxicant found in the bile of MDA-treated rats. The brain uptake of 5-GSyl-alpha-MeDA is decreased by glutathione (GSH), but sharply increases in animals pretreated with acivicin, an inhibitor of gamma-glutamyl transpeptidase (gamma-GT) suggesting competition between intact 5-GSyl-alpha-MeDA and GSH for the putative GSH transporter. gamma-GT is enriched in blood-brain barrier endothelial cells and is the only enzyme known to cleave the gamma-glutamyl bond of GSH. We now show that pretreatment of rats with acivicin (18 mg/kg, ip) inhibits brain microvessel endothelial gamma-GT activity by 60%, and potentiates MDA- and MDMA-mediated depletions in serotonin (5-HT) and 5-hydroxylindole acidic acid (5-HIAA) concentrations in brain regions enriched in 5-HT nerve terminal axons (striatum, cortex, hippocampus, and hypothalamus). In addition, glial fibrillary acidic protein (GFAP) expression increases in the striatum of acivicin and MDA (10 mg/kg) treated rats, but remains unchanged in animals treated with just MDA (10 mg/kg). Inhibition of endothelial cell gamma-GT at the blood-brain barrier likely enhances the uptake into brain of thioether metabolites of MDA and MDMA, such as 5-(glutathion-S-yl)-alpha-MeDA and 2,5-bis-(glutathion-S-yl)-alpha-MeDA, by increasing the pool of thioether conjugates available for uptake via the intact GSH transporter. The data indicate that thioether metabolites of MDA and MDMA contribute to the serotonergic neurotoxicity observed following peripheral administration of these drugs.

3,4-Methylenedioxyamphetamine↗

CD1 genotyping of patients with Mycobacterium malmoense pulmonary disease.

Mycobacterium malmoense is an opportunistic mycobacterium that occasionally causes disease in non-immunosuppressed individuals. As only a few individuals exposed to these organisms actually develop clinical disease, it is possible there is a genetic component to susceptibility. CD1 molecules are capable of presenting antigens from more virulent mycobacteria to T cells; therefore, we were interested in discovering whether recently described polymorphisms in CD1 molecules modulated susceptibility to M. malmoense pulmonary disease. The CD1 system comprises five genes (CD1A, -B, -C, -D, and -E) located on chromosome 1 (1q22-23). CD1 molecules are structurally and functionally related to major histocompatibility complex (MHC) class I molecules and are expressed on dedicated antigen-presenting cells. The primary function of CD1 molecules is to present lipid and glycolipid antigens to T cells. We have developed an allele-specific polymerase chain reaction-sequence-specific primer (PCR-SSP) method of CD1 genotyping. Using this method, we compared the allele and haplotype frequencies of CD1 in 49 HIV-negative patients with M. malmoense pulmonary disease with those in 342 normal controls. The CD1A and CD1E alleles were nominally identified as CD1A*01, CD1A*02, CD1E*01 and CD1E*02, and the control gene frequencies were found to be 5%, 95%, 67% and 33%, respectively. No significant difference was observed between the patient and control cohorts. Positive linkage disequilibrium values of 0.73 were observed between CD1A*02 and CD1E*01 (P<0.0001; chi2 test), and 0.94 between CD1A*01 and CD1E*02 (P<0.0001; chi2 test). Typing was also performed for two previously described CD1D alleles (CD1D*01 and CD1D*02), although only CD1D*01 was detected.

Antigens, CD1↗

Monoamniotic twins in a triplet gestation with favorable outcome.

BACKGROUND: Monoamniotic twins in a triplet gestation is a rare combination. Each condition is separately associated with significant perinatal morbidity and mortality. There are no data about the outcome and management of such gestations. CASE: We report a case of monoamniotic twins in a spontaneous dichorionic triplet gestation with a favorable outcome. Transvaginal ultrasound examination at nine weeks confirmed the diagnosis. Close follow-up was established that included continuous fetal monitoring after 30 weeks. At 35 weeks and after confirming fetal lung maturity, elective cesarean delivery was performed resulting in three liveborn female infants. CONCLUSION: Favorable outcome of such a rare coexistence of monoamniotic twins in a triplet gestation is possible. Vigilant fetal monitoring and timed delivery remain the mainstays of management.

Adult↗

Intraplacental smooth muscle tumor. A case report.

BACKGROUND: Chorioangioma is the leading diagnosis for circumscribed placental lesion noted on ultrasound. Other rare intraplacental tumors may have a significant clinical impact on the mother and fetus. CASE: An intraplacental, hypoechoic area consistent with chorioangioma was noted on ultrasound examination at 17 weeks' gestation. The lesion remained stable in size throughout gestation, with no evidence of fetal hydrops or polyhydramnios. At term, a live-born male infant was delivered vaginally, followed by spontaneous expulsion of the placenta. Histologic examination of the placenta revealed an intraplacental, potentially malignant smooth muscle tumor. Six weeks postpartum, total abdominal hysterectomy and pelvic node sampling were performed. No residual disease was found on the final histologic examination. CONCLUSION: Although ultrasound differentiation is difficult, rare nontrophoblastic tumors should be considered in the differential diagnosis of placental masses. To our knowledge, this is the first report of such a lesion in the placenta.

Adult↗

Experimental evidence of host specificity of Bartonella infection in rodents.

A large number of Bartonella species and genetic variants were compared for their ability to cause bacteremia in different rodent species: the cotton rat (Sigmodon hispidus), white-footed mouse (Peromyscus leucopus), BALB/c mouse and Wistar rat. Experimental data supported field observations that host specificity can occur among certain Bartonella species and rodent species. Bacteremia could only be readily produced in cotton rats or white-footed mice if the strains used for inoculation were originally obtained from the same species or from a phylogenetically close species. A few Bartonella colonies could be observed in the blood of some BALB/c mice by 7 days after inoculation, but no evidence of the persistence of the infection was found. Host specificity suggests the possibility of a long co-speciation of Bartonella species with their rodent hosts. Host-parasite relationships measured by the duration and level of bacteremia and the minimal infectious dose may serve as additional criteria for classification of Bartonella isolates obtained from natural environments.

Animals↗

Determination of sulfonamides by packed column supercritical fluid chromatography with atmospheric pressure chemical ionisation mass spectrometric detection.

Sulfonamide antibiotics are widely used to prevent bacterial infections in livestock, and residues are commonly found in milk and meat. Packed column supercritical fluid chromatography (pSFC) with detection using ultra violet (UV) and atmospheric pressure chemical ionisation (APCI) mass spectrometry (MS) provides a versatile method for the detection and quantification of six major sulfonamides. The APCI mass spectra for all the sulfonamides consisted of protonated molecules at low cone voltages. Increasing the cone voltage led to informative fragmentation patterns, which provided structural information for identification purposes. The pSFC-APCI-MS technique was shown to be linear (r2 > or = 0.999) over the concentration range 0.1-50 micrograms ml-1 using total ion current. The precision and the accuracy of the system and validation of sample preparation are acceptable, with RSD < 2% and relative error 8%. Selected ion monitoring gave detection limits as follows: sulfadiazine 41, sulfamethoxazole 45, sulfamerazine 47, sulfamethizole 59, sulfamethazine 181 and sulfadimethoxine 96 micrograms l-1, which are lower than the amounts permitted in milk products. The APCI pSFC-MS system was shown to have a high degree of reproducibility. The technique was then applied to determine the above sulfonamides in milk. The results obtained show that there are no matrix effects from the milk and that the detection limits remained as stated for the standard solutions.

Animals↗

Determination of pesticides in soil samples by supercritical fluid chromatography-atmospheric pressure chemical ionisation mass spectrometric detection.

This paper presents an analytical technique for the determination of pesticides in soil by packed-column supercritical fluid chromatography interfaced with atmospheric pressure chemical ionisation mass spectrometry (pSFC-APCI-MS). The technique provides a versatile method for the detection and quantification of pesticides belonging to three different commonly used classes, triazines (ametryne, atrazine), carbamates (carbofuran) and sulfonylureas (chlorsulfuron, metsulfuron methyl and benzsulfuron methyl). The APCI mass spectra for all the pesticides studied consisted of protonated molecule ions as the most abundant ion at low cone voltages, except for metsulfuron methyl and benzsulfuron methyl, which gave a fragment ion as the most abundant ion with the protonated molecule ion at low intensity. Increasing the cone voltage provided informative fragmentation patterns for all species. The technique shows good linearity over the concentration range of 0.1-50 micrograms ml-1, with r2 values as follows: atrazine 0.997, ametryne 0.995, carbofuran 0.999, benzsulfuron methyl 0.999, chlorsulfuron 0.995 and metsulfuron methyl 0.997. The detection limits in the selected ion mode were atrazine 201, ametryne 144 and carbofuran 385 pg, which were calculated by using the standard solution, and benzsulfuron methyl 2.045, chlorsulfuron 1.435 and metsulfuron methyl 2.414 ng, which were determined by using spiked soil samples. The pSFC-MS system was shown to have a high degree of reproducibility. The technique was then applied to the determination of the above pesticides in soil samples. The results obtained show that there is no matrix effect from the soil and that the detection limits for all pesticides in soil were similar to those found for the standard solutions.

Chromatography, Ion Exchange↗

Dopamine-induced apoptosis is mediated by oxidative stress and Is enhanced by cyanide in differentiated PC12 cells.

Dopamine (DA) oxidation and the generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons underlying various neurological conditions. The present study demonstrates that DA-induced cytotoxicity in differentiated PC12 cells is mediated by ROS and mitochondrial inhibition. Because cyanide induces parkinson-like symptoms and is an inhibitor of the antioxidant system and mitochondrial function, cells were treated with KCN to study DA toxicity in an impaired neuronal system. Differentiated PC12 cells were exposed to DA, KCN, or a combination of the two for 12-36 h. Lactate dehydrogenase (LDH) assays indicated that both DA (100-500 microM) and KCN (100-500 microM) induced a concentration- and time-dependent cell death and that their combination produced an increase in cytotoxicity. Apoptotic death, measured by Hoechst dye and TUNEL (terminal deoxynucleotidyltransferase dUTP nick end-labeling) staining, was also concentration- and time-dependent for DA and KCN. DA plus KCN produced an increase in apoptosis, indicating that KCN, and thus an impaired system, enhances DA-induced apoptosis. To study the mechanism(s) of DA toxicity, cells were pretreated with a series of compounds and incubated with DA (300 microM) and/or KCN (100 microM) for 24 h. Nomifensine, a DA reuptake inhibitor, rescued nearly 60-70% of the cells from DA- and DA plus KCN-induced apoptosis, suggesting that DA toxicity is in part mediated intracellularly. Pretreatment with antioxidants attenuated DA- and KCN-induced apoptosis, indicating the involvement of oxidative species. Furthermore, buthionine sulfoximine, an inhibitor of glutathione synthesis, increased the apoptotic response, which was reversed when cells were pretreated with antioxidants. DA and DA plus KCN produced a significant increase in intracellular oxidant generation, supporting the involvement of oxidative stress in DA-induced apoptosis. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester and the peroxynitrite scavenger uric acid blocked apoptosis and oxidant production, indicating involvement of nitric oxide. These results suggest that DA neurotoxicity is enhanced under the conditions induced by cyanide and involves both ROS and nitric oxide-mediated oxidative stress as an initiator of apoptosis.

Animals↗

Pattern-evoked potential latencies from central and peripheral visual fields.

Median P100 and N70 latencies for peripheral field (>8 degrees) TV-generated pattern visual-evoked potentials were 6 and 8 milliseconds less than for central field patterns in subjects with normal pattern visual-evoked potentials. These differences held for patient subgroups with P100 latency maxima from 140 to 100 milliseconds, and for left and right eye data separately compiled. Latencies for central field stimulation exceeded those for peripheral field stimulation in 233 (85%) of 274 eyes for the N70 potential and in 210 (77%) of 274 eyes for the P100 potential. Such data suggest that the faster conducting peripheral visual system, conveying location and motion information, prepares the occipital cortex for the later arriving central data conveying more intricate details.

Electrophysiology↗

Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes.

Nuclear lamins A and C are encoded by LMNA and are present in terminally differentiated cells. Lamins participate in DNA replication, chromatin organization, arrangement of nuclear pores, nuclear growth, and anchorage of nuclear membranes. In several Canadian probands with partial lipodystrophy, since found to have a common ancestor, we identified a rare novel LMNA mutation, R482Q, that completely cosegregated with the partial lipodystrophy phenotype. We evaluated the relationship between quantitative metabolic phenotypes in both diabetic and nondiabetic carriers of LMNA R482Q and family controls, who were LMNA R482/R482 homozygotes. We found that when compared with LMNA R482/R482 homozygotes: (1) diabetic LMNA Q482/R482 heterozygotes had significantly higher glucose, glycosylated hemoglobin, triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol; and (2) nondiabetic LMNA Q482/R482 heterozygotes had significantly higher triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol. We also found that diabetic LMNA Q482/R482 heterozygotes were older and more likely to take antihypertensive medications. Thus, LMNA R482Q was associated with lipodystrophy, hyperinsulinemia, dyslipidemia, diabetes, and hypertension. The results indicate that perturbations in plasma lipids precede the plasma glucose abnormalities in LMNA Q482-associated hyperinsulinemia. Thus, rare mutations in a nuclear structural protein can be associated with markedly abnormal qualitative and quantitative metabolic phenotypes

Adolescent↗

Carcinomatous transformation of a sublingual dermoid cyst. A case report.

Sublingual dermoid cysts are rare lesions. Typically they present as slow-growing masses that may cause elevation of the tongue, interference with speech or the appearance of a double chin. We report the first case of malignant transformation to squamous cell carcinoma of a long-standing sublingual dermoid cyst.

Adult↗

The analysis of beta-agonists by packed-column supercritical fluid chromatography with ultra-violet and atmospheric pressure chemical ionisation mass spectrometric detection.

Packed-column supercritical fluid chromatography (pSFC) using ultra-violet (UV) and atmospheric pressure chemical ionisation (APCI) mass spectrometry (MS) provides a versatile method for the identification and quantification of beta-agonists. We have achieved good separation of clenbuterol, salbutamol, terbutaline and fenoterol with good resolution and reasonable retention times using a high concentration of methanol modifier in the supercritical CO2, together with small amounts of both acidic (trifluoroacetic acid, TFAA) and basic (triethylamine, TEA, or diethylamine, DEA) additives. APCI-MS gave unambiguous identification of the 4 analytes, and increasing cone voltage provided informative fragmentation patterns. The pSFC-MS technique was shown to be linear (R2 > or = 0.996) over the concentration range 1-50 micrograms ml-1. Single ion monitoring (SIM) gave detection limits (on-column) of 2.5 ng (clenbuterol), 0.83 ng (terbutaline), 7.6 ng (salbutamol) and 2.7 ng (fenoterol). The pSFC-MS system was shown to be reproducible within a day, between days, and between restrictors. Analysis of milk samples 'spiked' with beta-agonists showed that the matrix caused no interference, with detection limits of approximately 500 micrograms l-1 of beta-agonists. More dilute solutions could be analysed by pre-concentration before the SFC stage.

Adrenergic beta-Agonists↗

Elevated amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in intra-amniotic infection.

OBJECTIVE: The study's objective was to determine and correlate amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 in patients with and without intra-amniotic infection. STUDY DESIGN: Amniocentesis was performed on 41 pregnant women with preterm contractions, labor, or premature rupture of membranes. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture result. Amniotic fluid tests for Gram stain, glucose, leukocyte counts, creatinine level, pH, and specific gravity were performed. Amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were measured by an enzyme-linked immunoassay. Unlike in previous reports, cytokines were normalized by amniotic fluid creatinine levels. RESULTS: Fifteen patients had intra-amniotic infection and 26 did not. Amniotic fluid median levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were significantly higher in pregnant women with intra-amniotic infection than in those without intra-amniotic infection (leukemia inhibitory factor median 3912 pg/mg creatinine, range 0.0-199314, vs 56 pg/mg creatinine, range 0. 0-12148, P =.01; interleukin 6 median 2005 ng/mg creatinine, range 27-4071, vs 990 ng/mg creatinine, range 7.5-3409, P =.005; interleukin 8: median 4933 ng/mg creatinine, range 0.0-55058, vs 61 ng/mg creatinine, range 0.0-2399, P =.005). Amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 were positively correlated. CONCLUSIONS: The data indicate that leukemia inhibitory factor plays an important role in the pathogenesis of intra-amniotic infection. In addition, significant elevations of and correlations among amniotic fluid levels of leukemia inhibitory factor, interleukin 6, and interleukin 8 suggest that measurements of these cytokines in amniotic fluid may be of diagnostic and prognostic importance.

Adolescent↗

Successful ex utero intrapartum treatment (EXIT) procedure for congenital high airway obstruction syndrome (CHAOS) owing to laryngeal atresia.

Congenital high airway obstruction syndrome (CHAOS) caused by laryngeal atresia was diagnosed by prenatal ultrasound in a male fetus at 18-weeks-gestation. Findings included enlarged lungs, inverted diaphragms, dilated trachea distal to the obstruction, and ascites. At 35 weeks' gestation, a planned ex utero intrapartum treatment (EXIT) procedure was performed, allowing bronchoscopic evaluation of the airway and placement of a tracheostomy. The postnatal course was marked by gradual recovery of diaphragmatic function with corresponding weaning from conventional ventilation to positive airway pressure. The sustained improvement in diaphragmatic and pulmonary function after the EXIT procedure for laryngeal atresia is one of the first reported for this entity and provides encouragement for future attempts.

Adult↗