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Biomedical subjects

N Carter

Publications and source records attributed to N Carter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Androgen-linked control of carbonic anhydrase III expression occurs in rat perivenous hepatocytes; an immunocytochemical study.

Carbonic anhydrase (CA) isozymes CAII and CAIII were assayed by a radioimmunosorbent technique in liver cytosolic fractions and in isolated hepatocytes of adult male and female rats. Male livers contained 0.16 mg of CAII and 57 mg of CAIII per g cytosolic protein. Corresponding values for female livers were 0.34 mg CAII and 4 mg CAIII. Similar values and differences between CAII and III were found in isolated hepatocytes. Neonatal and adult castration of males reduced the CAIII levels to those of the females. Treatment with testosterone for three weeks restored the copulatory behaviour in the males castrated at adult age, but restored only partially the levels of CAIII. No significant effects of the endocrine manipulations were seen on CAII. Oophorectomy, with or without testosterone substitution, had no significant effect on CAII and CAIII levels in female rats. Immunohistochemistry and histochemistry showed that the regulation of CAIII is confined to perivenous hepatocytes. CAIII can therefore serve as a useful marker in the separation of these cells. CAIII appears to belong to the proteins and enzymes of the rat liver, known to be regulated via the hypothalamo-pituitary-liver axis. It may be used as a model of gene regulation in perivenous hepatocytes.

Androgens↗
PubMed2000

Deaths associated with MBDB misuse.

The use of phenethylamines in the dance scene is now well established. Apart from amphetamine, the commonest phenethylamine encountered in clinical and forensic settings is 3,4-methylenedioxymethamphetamine (MDMA) commonly known as ecstasy. Other phenethylamines, which have similar effects are encountered, such as 3,4-methylenedioxyethylamphetamine (MDEA) and their use has resulted in death. We report two deaths associated with another less commonly encountered member of the group, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), also known as Methyl-J and Eden.

3,4-Methylenedioxyamphetamine↗
PubMed2000

QT interval in twins.

QT interval has been determined in 103 monozygotic (MZ) and 198 dizygotic (DZ) female twins. Mean values of corrected QT (QTc) were almost identical for both groups at 413 ms (MZ) and 412 ms (DZ). There was a significant age and environmental effect on QT interval. Heritability explained about 25% of the variation in QT. Further research will show whether any of the genes known to cause Long QT syndrome have any effect on QT interval at the sub-clinical level. Journal of Human Hypertension (2000) 14, 389-390

Adolescent↗
PubMed2000

Adverse health effects among women living with heavy snorers.

Women living with heavy snorers were more frequently affected by symptoms of insomnia, morning headache, daytime sleepiness, and fatigue than women living with non-snorers. Questionnaire data were collected from 1,032 women 30 to 64 years of age residing in Dalarna county, in mid-Sweden. There were indications of a "dose-response relationship" between the conjectured sound exposure and reported symptoms, regardless of whether the female herself snored. Sleeping in separate bedrooms did not seem to give the women any alleviation. The results point to a possible contributory cause of disturbed sleep, morning headache, and daytime sleepiness among women living with a snoring spouse. The results also indicate that prevention and treatment of snoring are important issues for the couple as well as for the snorer.

Adult↗
PubMed2000

Bone mineral density in adults with Marfan syndrome.

OBJECTIVES: Reduced bone mineral density (BMD) has been reported in pre-menopausal women and children with Marfan syndrome (MFS). The bone mineral status of adult men with MFS is unknown. The objective of this study was to determine the BMD of adult men and women with MFS. METHODS: BMD (g/cm(2)) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4), femoral neck and total hip in 25 adults (12 male) who fulfilled the 1996 MFS diagnostic criteria. The results were compared with age- and sex-matched controls and expressed as S.D. from the population mean (z score). RESULTS: Overall, BMD was significantly reduced in the lumbar spine (z = -0.42 +/- 0.97, P < 0.05), total hip (z = -0.57 +/- 0.88, P < 0.005) and femoral neck (z = -0.51 +/- 0.88, P < 0. 005). In women alone, BMD was reduced at the femoral neck (z = -0.53 +/- 0.95, P < 0.05) and at the hip (z = -0.64 +/- 0.77, P < 0.005). In men, BMD was reduced at the femoral neck (z = -0.48 +/- 0.84, P < 0.05) with a non-significant trend to lower BMD at the hip (z = -0. 49 +/- 1.01, P = 0.054) and lumbar spine (z = -0.59 +/- 1.02, P = 0. 09). CONCLUSION: Axial BMD is lower than normal in Marfan adults. This reduction may contribute to fractures seen in the Marfan population.

Absorptiometry, Photon↗
PubMed2000

Sleep-disordered breathing and occupational accidents.

OBJECTIVES: The relationship between a common type of sleep disturbance, sleep-disordered breathing, and the risk of becoming involved in an occupational accident was studied. METHODS: A 10-year retrospective comparison was made of occupational injuries reported to the Occupational Injury Statistics Division of the Swedish National Board of Occupational Safety and Health. The injury rates for 704 consecutive patients suffering from sleep-disordered breathing were compared with the rates for an employed, age-matched random sample of 580 subjects, drawn from the general population. RESULTS: The risk of being involved in an occupational accident was about 2-fold among male heavy snorers and increased by 50% among men suffering from obstructive sleep apnea syndrome (OSAS). For females the risk increased by at least 3-fold among heavy snorers and OSAS patients. Reduced vigilance and attention due to sleep-disordered breathing are the proposed mechanisms behind the results. CONCLUSION: The early identification and treatment of persons suffering from sleep-disordered breathing would not only have positive impact on individual health and well-being but also on occupational safety.

Accidents, Occupational↗
PubMed1999

The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression.

Purine transport into the protozoan parasite Toxoplasma gondii plays an indispensable nutritional function for this pathogen. To facilitate genetic and biochemical characterization of the adenosine transporter of the parasite, T. gondii tachyzoites were transfected with an insertional mutagenesis vector, and clonal mutants were selected for resistance to the cytotoxic adenosine analog adenine arabinoside (Ara-A). Whereas some Ara-A-resistant clones exhibited disruption of the adenosine kinase (AK) locus, others displayed normal AK activity, suggesting that a second locus had been tagged by the insertional mutagenesis plasmid. These Ara-A(r) AK+ mutants displayed reduced adenosine uptake capability, implying a defect in adenosine transport. Sequences flanking the transgene integration point in one mutant were rescued from a genomic library of Ara-A(r) AK+ DNA, and Southern blot analysis revealed that all Ara-A(r) AK+ mutants were disrupted at the same locus. Probes derived from this locus, designated TgAT, were employed to isolate genomic and cDNA clones from wild-type libraries. Conceptual translation of the TgAT cDNA open reading frame predicts a 462 amino acid protein containing 11 transmembrane domains, a primary structure and membrane topology similar to members of the mammalian equilibrative nucleoside transporter family. Expression of TgAT cRNA in Xenopus laevis oocytes increased adenosine uptake capacity in a saturable manner, with an apparent K(m) value of 114 microM. Uptake was inhibited by various nucleosides, nucleoside analogs, hypoxanthine, guanine, and dipyridamole. The combination of genetic and biochemical studies demonstrates that TgAT is the sole functional adenosine transporter in T. gondii and a rational target for therapeutic intervention.

Adenosine↗
PubMed1999

Xanthine phosphoribosyltransferase from Leishmania donovani. Molecular cloning, biochemical characterization, and genetic analysis.

Xanthine phosphoribosyltransferase (XPRT) from Leishmania donovani is a unique enzyme that lacks a mammalian counterpart and is, therefore, a potential target for antiparasitic therapy. To investigate the enzyme at the molecular and biochemical level, a cDNA encoding the L. donovani XPRT was isolated by functional complementation of a purine auxotroph of Escherichia coli that also harbors deficiencies in the prokaryotic phosphoribosyltransferase (PRT) activities. The cDNA was then used to isolate the XPRT genomic clone. XPRT encodes a 241-amino acid protein exhibiting approximately 33% amino acid identity with the L. donovani hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and significant homology with other HGPRT family members. Southern blot analysis revealed that XPRT was a single copy gene that co-localized with HGPRT within a 4.3-kilobase pair (kb) EcoRI fragment, implying that the two genes arose as a result of an ancestral duplication event. Sequencing of this EcoRI fragment confirmed that HGPRT and XPRT were organized in a head-to-tail arrangement separated by an approximately 2.2-kb intergenic region. Both the 3.2-kb XPRT mRNA and XPRT enzyme were significantly up-regulated in Deltahgprt and Deltahgprt/Deltaaprt L. donovani mutants. Genetic obliteration of the XPRT locus by targeted gene replacement indicated that XPRT was not an essential gene under most conditions and that the Deltaxprt null strain was competent of salvaging all purines except xanthine. XPRT was overexpressed in E. coli and the recombinant protein purified to homogeneity. Kinetic analysis revealed that the XPRT preferentially phosphoribosylated xanthine but could also recognize hypoxanthine and guanine. K(m) values of 7.1, 448.0, and >100 microM and k(cat) values of 3.5, 2.6, and approximately 0.003 s(-1) were calculated for xanthine, hypoxanthine, and guanine, respectively. The XPRT gene and XPRT protein provide the requisite molecular and biochemical reagents for subsequent studies to validate XPRT as a potential therapeutic target.

Amino Acid Sequence↗
PubMed1999

Coupled chemical and mechanical reaction steps in a processive Neurospora kinesin.

We show using single molecule optical trapping and transient kinetics that the unusually fast Neurospora kinesin is mechanically processive, and we investigate the coupling between ATP turnover and the mechanical actions of the motor. Beads carrying single two-headed Neurospora kinesin molecules move in discrete 8 nm steps, and stall at approximately 5 pN of retroactive force. Using microtubule-activated release of the fluorescent analogue 2'-(3')-O-(N-methylanthraniloyl) adenosine 5'-diphosphate (mantADP) to report microtubule binding, we found that initially only one of the two motor heads binds, and that the binding of the other requires a nucleotide 'chase'. mantADP was released from the second head at 4 s(-1) by an ADP chase, 5 s(-1) by 5'-adenylylimidodiphosphate (AMPPNP), 27 s(-1) by ATPgammaS and 60 s(-1) by ATP. We infer a coordination mechanism for molecular walking, in which ATP hydrolysis on the trailing head accelerates leading head binding at least 15-fold, and leading head binding then accelerates trailing head unbinding at least 6-fold.

Adenosine Diphosphate↗
PubMed1999

Splicing mutations in KCNQ1: a mutation hot spot at codon 344 that produces in frame transcripts.

BACKGROUND: Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these. METHODS AND RESULTS: We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript. CONCLUSIONS: The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.

Child, Preschool↗
PubMed1999

Lytic Paget disease as a cause of orbital cholesterol granuloma.

A case of histologically confirmed Paget disease of the orbit produced a lesion that appeared both clinically and histologically similar to a cholesterol granuloma. This case is unique because of the unusual location of the lesion, its presentation in a patient with no other manifestations of Paget disease, and the histological picture produced by the disease.

Cholesterol↗
PubMed1999

Intravenous therapy for women in labor: implementation of a practice change.

BACKGROUND: Intravenous therapy for women in labor has been routinely administered in many North American hospitals since the 1950s. The purpose of this study was to evaluate a change in intravenous therapy practice. METHODS: The evaluation study, using a posttest, quasi-experimental design, examined the responses of women in labor and nurses to a questionnaire. Proxy prestudy cohort data were used for comparison of some patient outcomes. The convenience sample comprised 219 women admitted to the labor and delivery unit of a community hospital in Toronto, Ontario, between August and October 1997. RESULTS: Under the new intravenous therapy protocol, 26 percent of the women in labor did not receive intravenous therapy compared with 100 percent under the old protocol. The primary reasons for therapy were to enable administration of prescribed medication and bolus intravenous administration associated with epidural anesthesia. At the first after-delivery void, 61 percent of study women-65 percent of those who received intravenous therapy and 50 percent of those who received no intravenous therapy-tested negative for ketonuria. All 119 comments from nurses indicated comfort with their judgments related to the initiation of intravenous therapy. CONCLUSIONS: The change in the intravenous therapy protocol was supported by the study findings. Nurses should increase patient education about drinking and eating adequately throughout labor if appropriate, and resuming adequate fluid and food intake as quickly as possible after childbirth.

Attitude of Health Personnel↗
PubMed1999

Validation of a geologically based radon risk map: are the indoor radon concentrations higher in high-risk areas?

Since geographically coded information is frequently used in studies of the relationships between environmental factors and illness at the population level and by authorities for promotion of mitigation, knowledge about the validity of proxy measures is essential. This study was an evaluation of a geologically based map describing the risk for high radon levels, which was used by the municipal authorities to determine the necessity of remedial actions. Annual mean radon gas concentrations for a random sample of one-family homes selected from high-risk areas (n = 252) were compared with those of a random sample of homes from normal and low-risk areas (n = 259). No difference in geometric mean radon concentration was found between the areas, 101 Bq m(-3) and 103 Bq m(-3), respectively. The proportion of homes in each area with radon gas concentrations above the current Swedish administrative limit value for mitigation (400 Bq m(-3)) was similar, approximately 10%. We conclude that the radon risk map was unsuitable for identifying areas of concern. The findings also indicate that geologically based and geographically coded information as a proxy for human exposures can be safely used for scientific and administrative purposes only following validation.

Air Pollution, Indoor↗