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Biomedical subjects

C Jones

Publications and source records attributed to C Jones.

At least 55 records · Page 3Linked to original sources
PubMed2004

Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast.

AIMS: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. METHODS: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. RESULTS: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p=0.0005). CONCLUSIONS: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.

Acid Anhydride Hydrolases↗
PubMed2003

Polarization transfer in the 4He(e-->,e'p-->)3H reaction up to Q2=2.6 (GeV/c)2.

We have measured the proton recoil polarization in the 4He(e-->,e(')p-->)4H reaction at Q(2)=0.5, 1.0, 1.6, and 2.6 (GeV/c)(2). The measured ratio of polarization transfer coefficients differs from a fully relativistic calculation, favoring the inclusion of a medium modification of the proton form factors predicted by a quark-meson coupling model. In addition, the measured induced polarizations agree reasonably well with the fully relativistic calculation indicating that the treatment of final-state interactions is under control.

Journal Article↗
PubMed2003

Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.

Aged↗
PubMed2003

Failure of immunotherapy to prevent, arrest or reverse diabetic lumbosacral plexopathy.

Three patients are described who had severe and progressive diabetic lumbosacral plexopathy despite active immunosuppressive therapy. One patient developed the condition while immunosuppressed for a cardiac transplant and two others progressed while receiving intravenous gamma globulin. The cases raise questions about current unsupported practices of treatment for this condition. Robust clinical trial evidence is required before immunosuppression can be recommended.

Adult↗
PubMed2003

Water and sanitation associated with improved child growth.

OBJECTIVE: To examine the relation between household water and sanitation, and the risk of stunting and reversal of stunting in Khartoum and Crezira regions, Sudan. DESIGN: Prospective cohort study. SETTING: A total of 25 483 children aged 6-72 months from rural Sudan enrolled in an 18-month field trial in 1988 to study the effect of vitamin A supplementation on child health and survival. RESULTS: The mean height-for-age z-scores at baseline and the end of study were -1.66 and -1.55, respectively, for the group with water and sanitation facilities, and -2.03 and -1.94 for the group without water and sanitation, after adjustment for age, region, gender, mother's literacy, intervention group (vitamin A vs placebo), family wealth, breastfeeding and cleanliness. Among children of normal height-for-age at baseline, the risk of stunting (<-2 height-for-age z-score) was lowest in the group that came from homes that had both water and sanitation compared to children from homes without these facilities (multivariate RR=0.79, 95% CI 0.69-0.90). Among children stunted at baseline, those coming from homes with water and sanitation had a 17% greater chance of reversing stunting than those coming from homes without either facility (adjusted RR=1.17, 95% CI 0.99-1.38). We did not detect a synergistic association between access to water and sanitation. CONCLUSIONS: Water and sanitation are independently associated with improved growth of children. SPONSORSHIP: None.

Body Height↗
PubMed2003

The utilitarian argument for medical confidentiality: a pilot study of patients' views.

OBJECTIVES: To develop and pilot a questionnaire based assessment of the importance patients place on medical confidentiality, whether they support disclosure of confidential information to protect third parties, and whether they consider that this would impair full disclosure in medical consultations. DESIGN: Questionnaire administered to 30 consecutive patients attending a GP surgery. RESULTS: Overall patients valued confidentiality, felt that other patients might be deterred from seeking treatment if it were not guaranteed, but did not think that they would withhold information for this reason themselves. CONCLUSIONS: When presented with brief details of five clinical situations in which a breach of confidentiality might be considered, a clear majority of subjects believed that doctors should disclose information in two of the situations, but subjects were not confident that doctors would do so. In three situations, about half felt that disclosure was justified--these included the only scenario in which disclosure was clearly mandated by statute. There was little change in patients' general attitude to confidentiality after considering the scenarios. However, the views expressed were often inconsistent with responses to the clinical scenarios, suggesting that complex opinions were not accurately reflected in the responses. The format of the questionnaire has been amended, and the study will be repeated with other groups of patients.

Automobile Driving↗
PubMed2003

Use of the Internet for patient care: a nationwide survey of Australian anaesthetists.

The internet is an increasingly important source of information for anaesthetists. We sought to determine the extent and patterns of internet use among Australian anaesthetists, and to assess its effect on clinical decision-making. A postal survey of all Australian Fellows of the Australian and New Zealand College of Anaesthetists (n = 2344) was performed. The response rate was 48% (n = 1109) and 1066 responses were analysed. Ninety-seven per cent of respondents, much higher than the national average of 72%, had internet access at work or home. The majority used the internet at least once a month for patient care, and over 50% had made clinical decisions influenced by information found on the internet. In contrast, less than 20% had had any training in its use. In terms of access, rural Australia did not appear to be disadvantaged.

Adult↗
PubMed2002

Q2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a 3He target.

We present data on the inclusive scattering of polarized electrons from a polarized 3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference sigma(1/2)-sigma(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q2 of 0.1-0.9 GeV2.

Journal Article↗
PubMed2002

Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study.

PURPOSE: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. PATIENTS AND METHODS: From 1986 to 1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102 to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2 tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with astrocytoma dominant) in 32% of patients and oligodendroglioma (or oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast enhancement. Extent of resection was gross total in 14% of patients, subtotal in 35%, and biopsy only in 51%. RESULTS: At the time of the present analysis, 83 patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and 85% and 64%, respectively, with high-dose RT (log rank P =.48). Multivariate analysis identified histologic subtype, tumor size, and age as the most significant prognostic factors. Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed in seven patients, with one fatality in each treatment arm. The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5% with high-dose RT. CONCLUSION: This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.

Adult↗
PubMed2002

Analysis of bovine trigeminal ganglia following infection with bovine herpesvirus 1.

Following primary infection of the eye, oral cavity, and/or nasal cavity, bovine herpesvirus 1 (BHV-1) establishes latency in trigeminal ganglionic (TG) neurons. Virus reactivation and spread to other susceptible animals occur after natural or corticosteroid-induced stress. Infection of calves with BHV-1 leads to infiltration of lymphocytes in TG and expression of IFN-gamma (interferon-gamma), even in latently infected calves. During latency, virus antigen and nucleic acid positive non-neural cells were occasionally detected in TG suggesting there is a low level of spontaneous reactivation. Since we could not detect virus in ocular or nasal swabs, these rare cells do not support high levels of productive infection and virus release or they do not support virus production at all. Dexamethasone (DEX) was used to initiate reactivation in latently infected calves. Foci of mononuclear or satellite cells undergoing apoptosis were detected 6h after DEX treatment, as judged by the appearance of TUNEL+ cells (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling). BHV-1 antigen expression was initially detected in lymphocytes and other non-neural cells in latently infected calves following DEX treatment. At 24h after DEX treatment, viral antigen expression and nucleic acid were readily detected in neurons. Our data suggest that persistent lymphocyte infiltration and cytokine expression occur during latency because a low number of cells in TG express BHV-1 proteins. Induction of apoptosis and changes in cytokine expression following DEX treatment correlates with reactivation from latency. We hypothesize that inflammatory infiltration of lymphoid cells in TG plays a role in regulating latency.

Animals↗
PubMed2002

High-performance liquid chromatographic profiling of fluorescent labelled N-glycans on glycoproteins.

Monitoring protein glycosylation is becoming increasingly important as novel recombinant glycoprotein therapeutics, such as glycoprotein hormones, cytokines and clotting factors, are introduced into clinical use. In this report, we describe an HPLC strategy and an improved and simplified pre-column derivatization procedure to profile N-linked glycans obtained from a variety of commercially available glycoproteins as examples. N-Glycans were first released by peptide:N-glycosidase F and labelled with the fluorescent label, 4-aminobenzoic acid by reductive amination. The labelled N-Glycans were then resolved by normal-phase HPLC and the N-glycan profile could be further improved by separating the N-glycans first according to charge by anion-exchange HPLC prior to the normal-phase HPLC. If required, identification of the fractionated derivatized oligosaccharides can be determined by mass spectrometry. The whole profiling process is simple and can be implemented in most laboratories. Because of the high sensitivity, batch glycan-analysis of low-yield recombinant glycoproteins such as samples in ampoules or obtained in the early stage of production development is possible.

Chromatography, High Pressure Liquid↗
PubMed2002

A novel precursor ion discovery method on a hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer for studying protein phosphorylation.

A tandem quadrupole time-of-flight (Q-TOF) mass spectrometer has been programmed such that phosphorylated peptides can automatically be discovered and identified in a way similar to that of the use of precursor ion or neutral loss scanning, but without the need to scan the quadrupole mass filter. Instead, the method capitalizes on the innate capability of the Q-TOF to record mass spectra and product ion spectra quickly, with good sensitivity and with good mass accuracy. Alternate mass spectra, with and without fragmentation, are recorded at high and low collision energy with the quadrupole operating in wideband mode. The method of analysis is both compatible with and dependant on liquid chromatography for separation of complex mixtures. The method has been demonstrated by searching for the neutral loss of 98 Da (H3PO4) from phosphoserine and phosphothreonine residues, or for the phosphorylated immonium ion at m/z 216 from phosphotyrosine. The method also incorporates acquisition of the product ion spectrum from any candidate precursor ions, thereby allowing confirmation of the neutral loss or product ion and providing additional sequence information to assist identification of the protein and assign the site of phosphorylation.

Caseins↗
PubMed2002

Surgical blepharoptosis--the bridle suture factor?

AIMS: To evaluate the role of the superior rectus bridle suture in the development of post cataract blepharoptosis. METHODS: We compared the incidence of postoperative ptosis in two groups of patients undergoing cataract extraction. In the first group (32 patients), a temporal corneal approach was employed with no superior rectus bridle suture. In the second group (38 patients), a superior approach with a bridle suture was used. Both groups of patients underwent phacoemulsification with the use of peribulbar anaesthesia, a pressure lowering device and a speculum. We recorded the lid position at least 12 weeks following surgery and determined the degree of postoperative ptosis. Two-sided Fischer's Exact Test was used to test for significant difference between the two groups (using a statistical software package Instat Version 3.0 for Windows). RESULTS: Taking 2 mm of ptosis as a significant change, 11.5% of those undergoing temporal section sustained postoperative ptosis whilst it occurred in 12.9% of those who underwent a superior approach. CONCLUSIONS: The presence or absence of the superior rectus bridle suture and the site of the ocular wound do not significantly contribute to the incidence of postoperative ptosis. We would suggest that the causative factors are peribulbar anaesthesia, a pressure lowering device and the use of the speculum.

Aged↗
PubMed2002

Significant dissociation of brain and plasma kinetics with antipsychotics.

Current dosing regimens of psychotropic drugs are based on plasma kinetic considerations, although it is unclear whether plasma levels faithfully reflect brain kinetics of drugs.(1,2) To examine this, we compared the kinetics of plasma levels of two widely used antipsychotics, olanzapine and risperidone, vs the time course of their effects in the brain. We used positron emission tomography (PET) and [(11)C]-labeled ligands to quantify striatal and extra-striatal dopamine-2 (D(2)), and cortical serotonin-2A (5-HT(2A)) receptor occupancy in healthy subjects after a single dose, and in patients chronically treated for psychosis. We found a significant dissociation of brain and plasma kinetics. Mean plasma elimination half-lives of single doses of olanzapine and risperidone were 24.2 and 10.3 h, respectively, whereas it took on average 75.2 h with olanzapine, and 66.6 h with risperidone to decline to 50% of their peak striatal D(2) receptor occupancy. We found similar discrepancies between the time course of plasma levels and extra-striatal D(2) as well as 5-HT(2A) receptor occupancy. Our results question the current reliance on plasma kinetics as the main basis for dosing regimens of antipsychotics. Studies of brain kinetics may provide a sounder basis for determining dosing schedules of psychotropic medications.

Adult↗
PubMed2002

Cocaine related chest pain: are we seeing the tip of an iceberg?

The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed.

Chest Pain↗