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Biomedical subjects

J Cameron

Publications and source records attributed to J Cameron.

At least 19 recordsLinked to original sources
PubMed2006

Low-density lipoprotein receptor activity in Epstein-Barr virus-transformed lymphocytes from heterozygotes for the D374Y mutation in the PCSK9 gene.

OBJECTIVE: Missense mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been found to cause autosomal dominant hypercholesterolemia. The objective of this study was to investigate possible mechanisms by which mutation D374Y in the PCSK9 gene causes hypercholesterolemia. MATERIAL AND METHODS: Binding and internalization of low-density lipoprotein LDL in Epstein-Barr virus (EBV)-transformed lymphocytes from D374Y heterozygotes were examined. The autocatalytic activity of the D374Y mutant was studied in transiently transfected HEK293 cells. RESULTS: As determined by Western blot analysis of transiently transfected HEK293 cells, the autocatalytic activity of the D374Y mutant was approximately 95% of the wild-type. Levels of PCSK9 mRNA in EBV-transformed lymphocytes from D374Y heterozygotes and normal controls were similar and less than 1/1000 of the level in HepG2 cells. The amount of cell surface LDL receptors (LDLRs) in EBV-transformed lymphocytes from five D374Y heterozygotes was non-significantly increased by 17% compared with the amount in normal controls. LDLR-dependent binding and internalization of LDL in EBV-transformed lymphocytes from D374Y heterozygotes were non-significantly reduced by 11% and 12%, respectively, compared to the corresponding values in normal controls. CONCLUSIONS: LDLR-mediated endocytosis of LDL is not reduced in EBV-transformed lymphocytes from D374Y heterozygotes. Because of the extremely low levels of PCSK9 mRNA in EBV-transformed lymphocytes, it is possible that the LDLR-dependent endocytosis of LDL could be more severely affected in hepatocytes from D374Y heterozygotes than in EBV-transformed lymphocytes.

Cell Line, Transformed↗
PubMed2006

A study comparing two objective methods of quantifying the production of wound exudate.

OBJECTIVE: The objective assessment of chronic wound therapies for exudate management (WRAP study) tested a variety of methods that could be used to improve understanding of dressing performance in the presence of wound exudate, including measurement of the levels of exudate production. The aim of this study was to identify a valid and reliable method of measuring wound exudate production per unit area of wound surface. METHOD: Two methods were tested. Method A measured the weight of exudate collected in dressings by 'before and after' weighing of all dressing materials that came into contact with wound exudate. Method B measured wound exudate collected as part of topical negative pressure (TNP) therapy. RESULTS: Method A: Complete data were collected on three patients (at which point the study was halted), but it was only possible to obtain accurate measurements for two of these. Exudate production was 0.10g/cm2/24 hours and 0.21g/cm2/24 hours. It was time-consuming and required special equipment. Method B: Fifteen measurements from five patients were analysed and showed a mean exudate production of 1.3g/cm2/24 hours. CONCLUSION: There are problems with both methods of exudate measurement, but measuring wound fluid collected inTNP canisters seems simpler than weighing dressings and deserves further investigation.

Abscess↗
PubMed2005

Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab.

BACKGROUND: Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention (PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. METHODS: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. RESULTS: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC-1 (a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa (PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. CONCLUSIONS: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.

Abciximab↗
PubMed2005

Vascular dysfunction and metabolic parameters in polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and the metabolic syndrome; however, the cardiovascular (CV) manifestations of PCOS remain unclear. OBJECTIVE: The objective of this study was to examine the relationships between IR, metabolic parameters, androgens, and markers of early CV disease in PCOS. DESIGN: We conducted an observational study examining noninvasive markers of early CV disease in women with PCOS including structural [carotid intimal media thickness (IMT)] and functional measures (arterial function with pulse wave velocity and endothelial function with brachial arterial flow-mediated vasodilation). Metabolic parameters included insulin and glucose during an oral glucose tolerance test and lipid and androgen levels. SETTING: Participants were recruited from the general community. PATIENTS: Eighty overweight women with PCOS who were nonsmokers and not on oral contraceptives or other medications known to affect IR participated in the study. RESULTS: Stepwise regression analysis showed that after adjustment for age and body mass index, IMT was significantly correlated with blood pressure (BP) load (P = 0.03) and inversely with dehydroepiandrosterone sulfate (DHEAS) (P = 0.01). After correction for androgen status, IMT was correlated with fasting glucose and area under curve (AUC) insulin. Flow-mediated vasodilation was inversely related to lipids (P = 0.02), whereas pulse wave velocity was related to BP (P < 0.001), AUC insulin (P = 0.04), and AUC glucose (P = 0.035). CONCLUSION: In overweight women with PCOS, insulin resistance and BP interacted negatively with arterial structural and functional measures. DHEAS correlated inversely with arterial structure, suggesting possible cardioprotective effects of endogenous DHEAS in women with PCOS. Additional research is needed to clarify these findings.

Adolescent↗
PubMed2005

Comparison of two peri-wound skin protectants in venous leg ulcers: a randomised controlled trial.

OBJECTIVE: A randomised controlled trial was designed to determine whether or not early intervention with a suitable skin barrier preparation could prevent skin breakdown. This study was conducted to compare the efficacy and cost-effectivenss of two skin protectants, Cavilon No Sting Barrier Film (NSBF) (3M Health Care) and zinc paste compound, in the management of maceration and irritation of the peri-wound area of venous leg ulcers. METHOD: Thirty-five patients with venous leg ulcers and surrounding skin problems were randomised to receive either NSBF or zinc paste compound. The preparation was then applied at each dressing change for 12 weeks. All patients had been receiving compression bandaging before entering the study and continued wearing it throughout the 12-week study period. RESULTS: The decrease in wound area was 5.11+/-8.39cm2 in the NSBF group and 4.59+/-5.83cm2 in the zinc paste group. The healing rate was 0.046cm per week with NSBF and 0.039cm per week with zinc paste. There was a significant difference in the time required to remove and re-apply the skin protectants: an average of 0.19 (+/-0.17) minutes in the NSBF group and 5.53 (+/-2.10) minutes in the zinc paste group (p<0.0001). CONCLUSION: Both products were effective barrier preparations. However, NSBF was easy to apply and transparent. The zinc paste was messy to apply and difficult to remove, and thus took up considerably more nursing time than NSBF. DECLARATION OF INTEREST: This study was supported by 3M Health Care.

Aged↗
PubMed2004

DNM1DN: a new class of paralogous genomic segments (duplicons) with highly conserved copies on chromosomes Y and 15.

Screening a testis cDNA selection library for Y-linked genes yielded 79 cDNAs. Of these, 9 matched the 3' region of the dynamin 1 gene (DNM1) on chromosome 9q34 with >90% identity. Fluoresence in situ hybridisation and PCR amplification were used to localise a large number of DNM1-like sequences to human chromosomes 15 and Y. PCR amplification of overlapping Y-linked YACs allowed a more accurate mapping of the Y-linked DNM1-like cDNAs to a euchromatic locus in close proximity to heterochromatin at Yq11.23. A search of the genome database identified 64 highly homologous copies of the DNM1 fragment. Most of these copies were localised to chromosomes 15 and Y, but others mapped to chromosomes 5, 8, 10, 12, 19 and 22. These sequences exhibit all the major features of a duplicon and have been designated DNM1DN (DNM1 duplicon). Evolutionary studies using fluorescence in situ hybridisation indicate that transposition of the DNM1DN sequence to chromosome 15 took place earlier in primate evolution than the transposition to the Y chromosome. The translocation to the Y took place at a time following the divergence of a common ancestor from gorilla, approximately 4-7 million years ago.

Animals↗
PubMed2004

Methodology of the Cardiovascular Health and Age-Related Maculopathy (CHARM) Study.

Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. Epidemiological studies examining risk factors for AMD are needed to develop strategies for the prevention of blindness from this condition. A number of potentially modifiable risk factors for AMD have been identified; however, only smoking has been a consistent risk factor across the numerous studies. A growing body of evidence suggests that AMD and cardiovascular disease may have common risk factors. The Cardiovascular Health and Age Related Maculopathy (CHARM) Study was established to examine the risk factors for AMD and its progression, in particular risk factors associated with cardiovascular disease. Examining risk factors for prevalent AMD, cases with AMD were compared with age and gender matched controls with no AMD features. For the assessment of AMD progression, the study examined in 2001 and 2002 those participants with early AMD, or age-related maculopathy (ARM), who had undergone baseline examination between 1992 and 1995 and compared the characteristics of those who had progression of AMD with those who did not. The CHARM study involved both ophthalmic and cardiovascular examinations. Standardised clinical eye examination and grading of the macular stereo photographs were used to determine the AMD status and progression. To examine cardiovascular status, carotid artery ultrasound imaging analysis of systemic arterial compliance, augmentation index and pulse wave velocity were performed. The traditional and novel risk factors for CVD such as levels of glucose, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, fibrinogen, C-reactive protein, immunoglobulins A and M, homocysteine, oxidized LDL and the exposure to the Chlamydia Pneumonia infection were determined. DNA was collected for apolipoprotein E genotyping. The present paper outlines the primary aims of the CHARM study, the methodology involved and the recruitment results.

Age Factors↗
PubMed2004

Vascular dysfunction and autonomic neuropathy in Type 2 diabetes.

AIMS: To test the hypothesis that arterial dysfunction in Type 2 diabetes is related to autonomic neuropathy. METHODS: Arterial function and autonomic neuropathy were assessed over two consecutive days in 45 Type 2 diabetic and control subjects. Systemic arterial compliance (SAC), arterial stiffness (pulse-wave velocity, PWV) and carotid intima thickness (IMT) were assessed; these markers reflect early vascular disease and predict clinical vascular events. Autonomic neuropathy was assessed using heart rate variability with continuous ECG recording during various breathing and postural manoeuvres and an overall autonomic score was generated. Fasting metabolic parameters including glucose, insulin, HbA(1c) and lipid profile were measured. RESULTS: Autonomic neuropathy tests were all repeatable in diabetic subjects. Compared with controls, diabetic subjects had arterial dysfunction with increased PWV (P = 0.009), IMT (P < 0.001) and reduced SAC (P = 0.053). After adjustment for age, central PWV correlated with fasting insulin (r(2) = 0.45, P < 0.05) and autonomic score (r(2) = 0.44, P < 0.05), peripheral PWV correlated with autonomic score (r(2) = 0.51, P < 0.005) and IMT correlated with fasting insulin (r(2) = 0.5, P < 0.005). The presence of autonomic neuropathy correlated with fasting insulin (P = 0.015), but not age, duration diabetes, lipids or blood pressure. CONCLUSION: Using repeatable measures of autonomic neuropathy and vascular function in Type 2 diabetic subjects, we have demonstrated associations between autonomic neuropathy, vascular dysfunction and hyperinsulinaemia. This may help to explain the excess cardiovascular mortality seen in diabetic subjects with autonomic neuropathy.

Aged↗
PubMed2002

Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.

Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Journal Article↗
PubMed2002

Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.

The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Journal Article↗
PubMed2002

Venous leg ulcer recurrence: prevention and healing.

After a leg ulcer has healed, well-fitting compression stockings, patient education and regular check-ups are the basis for preventing recurrence. This article examines patterns in recurrence and subsequent healing among patients at an ulcer clinic.

Bandages↗
PubMed2001

Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1.

Dysregulation of imprinted genes on human chromosome 11p15 has been implicated in Beckwith-Wiedemann syndrome (BWS), an overgrowth syndrome associated with congenital malformations and tumor predisposition. The molecular basis of BWS is complex and heterogeneous. The syndrome is associated with alterations in two distinct imprinting domains on 11p15: a telomeric domain containing the H19 and IGF2 genes and a centromeric domain including the KCNQ1OT1 and CDKNIC genes. It has been postulated that disorders of imprinting in the telomeric domain are associated with overgrowth and cancer predisposition, whereas those in the centromeric domain involve malformations but not tumor development. In this study of 125 BWS cases, we confirm the association of tumors with constitutional defects in the 11p15 telomeric domain; six of 21 BWS cases with uniparental disomy (UPD) of 11p15 developed tumors and one of three of the rare BWS subtype with hypermethylation of the H19 gene developed tumors. Most importantly, we find that five of 32 individuals with BWS and imprinting defects in the centromeric domain developed embryonal tumors. Furthermore, the type of tumors observed in BWS cases with telomeric defects are different from those seen in BWS cases with defects limited to the centromeric domain. Whereas Wilms' tumor was the most frequent tumor seen in BWS cases with UPD for 11p15 or H19 hypermethylation, none of the embryonal tumors with imprinting defects at KCNQ1OT1 was a Wilms' tumor. This suggests that distinct tumor predisposition profiles result from dysregulation of the telomeric domain versus the centromeric domain and that these imprinting defects activate distinct genetic pathways for embryonal tumorigenesis.

Beckwith-Wiedemann Syndrome↗
PubMed2001

Measurement of the rate of nu(e) + d --> p + p + e(-) interactions produced by (8)B solar neutrinos at the Sudbury Neutrino Observatory.

Solar neutrinos from (8)B decay have been detected at the Sudbury Neutrino Observatory via the charged current (CC) reaction on deuterium and the elastic scattering (ES) of electrons. The flux of nu(e)'s is measured by the CC reaction rate to be straight phi(CC)(nu(e)) = 1.75 +/- 0.07(stat)(+0.12)(-0.11)(syst) +/- 0.05(theor) x 10(6) cm(-2) s(-1). Comparison of straight phi(CC)(nu(e)) to the Super-Kamiokande Collaboration's precision value of the flux inferred from the ES reaction yields a 3.3 sigma difference, assuming the systematic uncertainties are normally distributed, providing evidence of an active non- nu(e) component in the solar flux. The total flux of active 8B neutrinos is determined to be 5.44+/-0.99 x 10(6) cm(-2) s(-1).

Journal Article↗
PubMed2001

A potent, nonpeptidyl 1H-quinolone antagonist for the gonadotropin-releasing hormone receptor.

Extensive development of the structure-activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 10(4)-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.

Animals↗
PubMed2001

Identification and characterisation of a novel gene, TSGA10, expressed in testis.

We describe the isolation of a novel gene, TSGA10, by differential mRNA display which is expressed solely in adult human testis. It seems likely that the gene is expressed during spermatogenesis possibly in spermatocytes. The gene is composed of 19 exons extending over more than 80 kb. The complete cDNA contains an open reading frame of 2094 nucleotides, which appears to encode a novel protein. It has been mapped by polymerase chain reaction on a panel of somatic cell hybrids and by fluorescence in situ hybridization to chromosome 2q11.2.

3' Untranslated Regions↗
PubMed2001

Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population.

OBJECTIVE: Our goal was to compare the prevalence of mental illness and its impact on functional status in an indigent uninsured primary care population with a general primary care sample. We also hoped to assess patient preferences about mental health and medical service integration. STUDY DESIGN: We compared a survey of consecutive primary care adults in April and May 1999 with a 1997-98 survey of 3000 general population primary care patients. Both studies used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire and the 20-question Medical Outcomes Study Short Form. POPULATION: The patients were from a private nonprofit primary care clinic in Grand Junction, Colorado, that served only low-income uninsured people. We approached a total of 589 consecutive patients and enrolled 500 of them. MAIN OUTCOME MEASURE: The main outcomes were the prevalence of psychiatric illnesses and the relationship with functional impairment. We compared our findings with a more generalizable primary care population. RESULTS: This low-income uninsured population had a higher prevalence of 1 or more psychiatric disorders (51% vs 28%): mood disorders (33% vs 16%), anxiety disorders (36% vs 11%), probable alcohol abuse (17% vs 7%), and eating disorders (10% vs 7%). Having psychiatric disorders was associated with lower functional status and more disability days compared with not having mental illness. Patients indicated a preference for mental health providers and medical providers to communicate about their care. CONCLUSIONS: This low-income uninsured primary care population has an extremely high prevalence of mental disorders with impaired function. It may be important in low-income primary care settings to include collaborative care designs to effectively treat common mental disorders, improve functional status, and enhance patient self-care.

Adolescent↗