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G Reynolds

Publications and source records attributed to G Reynolds.

At least 19 recordsLinked to original sources
PubMed2007

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.

Adult↗
PubMed2006

Modulation of iron transport proteins in human colorectal carcinogenesis.

BACKGROUND AND AIMS: Total body iron and high dietary iron intake are risk factors for colorectal cancer. To date there is no comprehensive characterisation of iron transport proteins in progression to colorectal carcinoma. In this study, we examined expression of iron import (duodenal cytochrome b (DCYTB), divalent metal transporter 1 (DMT1), and transferrin receptor 1 (TfR1)) and export (hephaestin (HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma. METHODS: Perl's staining was used to examine colonocyte iron content. Real time polymerase chain reaction (PCR) and western blotting were used to examine mRNA and protein levels of the molecules of interest in 11 human colorectal cancers. Semiquantitative immunohistochemistry was used to verify protein levels and information on cellular localisation. The effect of iron loading on E-cadherin expression in SW480 and Caco-2 cell lines was examined by promoter assays, real time PCR and western blotting. RESULTS: Perl's staining showed increased iron in colorectal cancers, and there was a corresponding overexpression of components of the intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron exporter FPN was also overexpressed, but its intracellular location, combined with reduced HEPH levels, suggests reduced iron efflux in the majority of colorectal cancers examined. Loss of HEPH and FPN expression was associated with more advanced disease. Iron loading Caco-2 and SW480 cells caused cellular proliferation and E-cadherin repression. CONCLUSIONS: Progression to colorectal cancer is associated with increased expression in iron import proteins and a block in iron export due to decreased expression and aberrant localisation of HEPH and FPN, respectively. This results in increased intracellular iron which may induce proliferation and repress cell adhesion.

Antigens, CD↗
PubMed2004

Early versus delayed umbilical cord clamping in preterm infants.

BACKGROUND: Optimal timing for clamping of the umbilical cord at birth is unclear. Early clamping allows for immediate resuscitation of the newborn. Delaying clamping may facilitate transfusion of blood between the placenta and the baby. OBJECTIVES: To delineate the short- and long-term effects for infants born at less than 37 completed weeks' gestation, and their mothers, of early compared to delayed clamping of the umbilical cord at birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (2 February 2004), the Cochrane Neonatal Group trials register (2 February 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), PubMed (1966 to 2 February 2004) and EMBASE (1974 to 2 February 2004). SELECTION CRITERIA: Randomized controlled trials comparing early with delayed (30 seconds or more) clamping of the umbilical cord for infants born before 37 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Three reviewers assessed eligibility and trial quality. MAIN RESULTS: Seven studies (297 infants) were eligible for inclusion. The maximum delay in cord clamping was 120 seconds. Delayed cord clamping was associated with a higher hematocrit four hours after birth (four trials, 134 infants; weighted mean difference 5.31, 95% confidence interval (CI) 3.42 to 7.19), fewer transfusions for anaemia (three trials, 111 infants; relative risk (RR) 2.01, 95% CI 1.24 to 3.27) or low blood pressure (two trials, 58 infants; RR 2.58, 95% CI 1.17 to 5.67) and less intraventricular haemorrhage (five trials, 225 infants; RR 1.74, 95% CI 1.08 to 2.81) than early clamping. REVIEWERS' CONCLUSIONS: Delaying cord clamping by 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion and less intraventricular haemorrhage. There are no clear differences in other outcomes.

Blood Transfusion↗
PubMed2002

Reactivity and isotype profiling of monoclonal antibodies using multiple antigenic peptides.

The characterisation of monoclonal antibodies (MAbs) is essential for the development of assay systems particularly where antigens have been developed using synthetic peptides. Indeed some peptide-carrier conjugates fail to induce immune responses and may not generate antibodies that bind to native protein. As an alternative to peptide-carrier conjugates, multiple antigenic peptides (MAPs) have been used for immunization strategies, but with little regard to the characteristics of the MAbs produced. In this study, we used 3 MAPs of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) to immunise BALB/c mice. Overall, the polyclonal antibody responses from tail bleeds showed that MAPs evoked B-cell responses. However, on screening 144 hybridomas, 24 MAb supernatants exhibited weak to moderate reactivity in enzyme-linked immunosorbant assay (ELISA) and against cell cytospin preparations (B95.8 and AG876 LCL), respectively. Isotype profiling of hybridoma supernatants also showed that 11 out of 24 were IgM. Further characterization of 6 MAbs in Western blotting showed reactivity to recombinant LMP1 and only one MAb (B28D) showed weak reactivity to the malignant cells (Hodgkin/Reed-Sternberg; HRS cells) of an EBV+ Hodgkin's lymphoma using paraffin-embedded tissue. It is probable that these MAPs failed to augment T-cell help and contributed to the production of low affinity (IgM) antibodies. These observations may be of importance to future immunization strategies, where MAPs are used in the production of monoclonal reagents.

Animals↗
PubMed2001

Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial.

BACKGROUND: Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder. METHODS: We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis. FINDINGS: 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14). INTERPRETATION: Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis.

Double-Blind Method↗
PubMed2001

Generation and characterization of monoclonal antibodies to the neural crest.

The generation of monoclonal antibodies (MAbs) specific for quail neural crest may provide valuable tools for studying the differentiation of embryonic precursor cells. Unfortunately, relatively few antibodies are available because of the difficulty in obtaining sufficient cells for in vivo immunization strategies. We have overcome this problem by using intrasplenic immunization with formaldehyde-fixed cells harvested from neural crest cultures. In addition, booster injections of cultured whole-embryo cells were administered intraperitoneally. Following two fusions, a total of 18 hybridomas were generated with antibody reactivity to the cytoplasm of neural crest cells. Furthermore, 32 were reactive against both somite (a noncrest mesodermal control) and crest cultures, whilst 15 were not reactive. Out of those hybridomas reactive with neural crest, six designated 160D, 164D, OE, 12E, 120E and 124E were further characterized. Interestingly MAb supernatants OE, 12E, 120E, and 124E exhibited reactivity against some but not all neural crest cells suggesting that they might recognise subpopulations. Immunoglobulin isotyping of supernatants revealed that 4 (160D, 164D, OE, and 120E) were IgM and 2 (12E and 124E) were IgG(2b). On assessing their reactivity against human tissue sections, all six hybridoma supernatants cross-reacted with neuroendocrine cells within appendix, colon and rectum. These MAbs could provide novel reagents for the understanding of neural crest development.

Animals↗
PubMed1999

Effect of Epstein-Barr virus infection on response to chemotherapy and survival in Hodgkin's disease.

We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P =.05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P =.02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P =.18 and P =.40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Adsorption of Monoalkyl Phosphates at the Zircon-Aqueous Solution Interface.

The adsorption of a series of monoalkyl phosphates (MAP) of varying alkyl chain lengths (Cn) on a pure natural sample of zircon (ZrSiO4) at 25 degreesC has been studied as a function of concentration and pH. Electrokinetic (zeta-potential) studies showed a significant shift of the isoelectric point of zircon (pH approximately 5.7) to lower pH values, indicating specific interactions between zircon and MAP. Diffuse reflectance infrared Fourier transform spectroscopy and pH increment studies suggested that adsorption of MAP onto zircon proceeded via chelate formation. Adsorption was aided by an attractive lateral alkyl chain interaction energy (phi) of approximately -0.85kT per CH2 group, which suggested that surface aggregates form on the zircon surface. Adsorption isotherms were best described by a Langmuir model, indicating that attractive lateral alkyl chain interactions were compensated by repulsive headgroup interactions, resulting in a pseudo-ideal system. Copyright 1998 Academic Press.

Journal Article↗
PubMed1997

The effect of old age on the disposition and antinociceptive response of morphine and morphine-6 beta-glucuronide in the rat.

The aims of this study were to examine the effect of old age on the pharmacokinetics of morphine and morphine-6 beta-glucuronide (M6G) and their relationships to antinociceptive activity. Morphine (21.0 mumol/kg) or M6G (21.7 mumol/kg) were administered s.c. to young adult and aged male Hooded-Wistar rats. Antinociceptive effect was measured by the tail-flick method at various times up to 2.5 h or 6.5 h after morphine or M6G administration, respectively, and concentrations of morphine, morphine-3 beta-glucuronide (M3G) and M6G in plasma and brain were determined by HPLC. Creatinine clearance was significantly lower by 33% or 21% in aged compared to young adult rats receiving morphine or M6G, respectively. After morphine administration, the areas under the (i) antinociceptive effect-time curve, (ii) plasma morphine concentration-time curve, and (iii) brain morphine concentration-time curve were not different between young adult and aged rats. However, the AUC for plasma M3G was five-fold higher in the aged relative to young adult rats, which could not be accounted for by only a 33% lower creatinine clearance. M6G was not detected in any plasma or brain sample from rats administered morphine and no M3G was detected in brain. For M6G administration, the areas under the (i) antinociceptive effect-time curve, and (ii) plasma M6G concentration-time curve were 1.8- and 1.6-fold higher in aged compared to young adult rats, respectively. Concentrations of M6G in brain were below the limit of quantification. No morphine or M3G was detected in any of the plasma or brain samples of rats administered M6G. The results demonstrate no change in morphine antinociception and pharmacokinetics with age, and suggest that blood-brain barrier permeability and reception sensitivity to morphine are not altered in aged rats. Accumulation of M3G in plasma of aged rats is probably due to diminished renal clearance of M3G in addition to a reduction in the biliary excretion of M3G. The heightened sensitivity of the aged rats to M6G is probably due to the observed altered kinetics of M6G rather than a pharmacodynamic change.

Aging↗
PubMed1997

Concentration-effect relationships of morphine and morphine-6 beta-glucuronide in the rat.

1. The aims of the present study were to determine the relationship between the antinociceptive effect and concentrations of morphine and morphine-6 beta-glucuronide (M6G) in plasma and in the brain. 2. Morphine (14.0 and 28.0 mumol/kg) or M6G (8.67 and 17.3 mumol/kg) were administered s.c. to male Hooded-Wistar rats. The antinociceptive effect was measured by the thermal tail-flick method at various times up to 2 h and concentrations of morphine, morphine-3 beta-glucuronide (M3G) and M6G in plasma and in the brain were determined. 3. With a two-fold increment in morphine dose, the areas under the antinociceptive effect-, plasma morphine concentration- and brain morphine concentration-time curves increased by 1.9-, 2.3- and 2.3-fold, respectively. The area under the plasma M3G concentration-time curve increased 2.7-fold. Morphine-6 beta-glucuronide was not detected in any sample. For M6G, doubling of the dose led to a 1.7-fold increase in the area under the curve for plasma-time M6G concentrations but an 8.7-fold increase in the area under the curve for the antinociception-time effect. Concentrations of M6G in the brain were below the limit of quantification. The relationship between antinociceptive effect and plasma morphine or M6G were characterized by counter-clockwise hysteresis loops, probably reflecting a delay in crossing the blood-brain barrier. 4. Morphine-6 beta-glucuronide was approximately equipotent to morphine on the basis of dose, but substantially more potent on the basis of brain concentration.

Analgesics, Opioid↗
PubMed1997

Survival after gastrointestinal mucormycosis in a neonate.

Gastrointestinal mucormycosis has been reported more frequently in adults than in children. Due to the high mortality diagnosis is usually made at autopsy. Only one case of a neonate surviving this disease has been described. We report a premature infant presenting clinically with enterocolitis but lacking the radiological characteristics of necrotizing enterocolitis (NEC) Gastrointestinal mucormycosis was diagnosed on the histological specimen. The infant survived after surgery and 6 weeks of antifungal treatment. A high level of suspicion and early surgical intervention are necessary to make the correct diagnosis and commence appropriate treatment.

Anastomosis, Surgical↗
PubMed1996

Investigation of bone developmental and histopathologic changes from intraosseous infusion.

STUDY OBJECTIVE: To evaluate clinical and cellular changes of bone through the rapid growth phase of development after intraosseous infusion of hypertonic or isotonic solutions at slow or fast infusion rates in a pig model. METHODS: This was a prospective, randomized, partially blinded, comparative study using a porcine model in an urban teaching hospital laboratory with further development in a local farm environment. Sixty pigs weighing 12 to 30 kg were anesthetized and endotracheally intubated, and a no. 15 Jamshidi bone marrow needle was inserted into a front forelimb. Hypertonic (mannitol) or isotonic (saline) solutions of 8 mL/kg were infused through the intraosseous site at a rapid or slow infusion rate. Animals were observed for approximately 6 months, after which they were killed and the front forelimbs harvested for gross pathologic and histologic evaluation. RESULTS: No clinical complications were noted in any of the animal groups. No substantial histologic differences were found between the hypertonic and isotonic groups. Although gross pathologic lesions were found in 32% of the hypertonic groups and in fewer than 5% of the isotonic groups, this difference was not statistically significant. Equal bone changes were found in the slow- and rapid-infusion groups. CONCLUSION: The rate of intraosseous infusion and the osmolarity of the infused fluid did not appear to be related to any gross pathologic or histologic cellular or marrow changes or to any clinical complications in animal development in this study.

Animals↗
PubMed1996

What have the ACE-inhibitor trials in postmyocardial patients with left ventricular dysfunction taught us?

A series of elegant experimental studies and careful clinical observation over a decade or more have led to the concept of 'infarct expansion' and 'remodelling' of the heart, culminating in a number of major mortality studies indicating the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in patients after myocardial infarction (MI). But has this concept been too narrow in predicting which patients might benefit from treatment with ACE inhibitors? Measurable infarct-expansion with progressive dilatation probably occurs in less than 20% of patients, whereas increase in volume and hypertrophy of the heart as responses to compromised function are likely wherever significant myocardial damage has occurred. Irrespective of infarct expansion, cumulative extensive damage can lead to an inevitable downward spiral with gross ventricular dilatation and death in heart failure. But in the majority of patients after MI a 'new equilibrium' is established in which initial dilatation and subsequently hypertrophy restore adequate function. Is it possible to distinguish patients in whom the cost and inconvenience of long-term therapy with an ACE inhibitor justify the likely benefit from treatment after an MI? The SAVE, AIRE and recent TRACE studies allow a rational approach for the clinician, indicating the effectiveness of these drugs in patients with evidence of impaired ventricular function. However, the prospect that ACE inhibitors prescribed long term might also prevent myocardial reinfarction could justify wider use. Post-MI patients are an easily identifiable high-risk group for a cost-effective programme of secondary prevention. Reinfarction in an already damaged ventricle carries a particularly poor prognosis and its prevention by ACE inhibitors could make a major contribution to the undoubted benefit from these agents. The recently completed TRACE study with its long-term follow-up may help resolve this issue, which is also being investigated in a number of long-term prospective studies in populations at high risk of cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Sexual behavior, sexually transmitted diseases, and risk of cervical cancer.

To explore sexually transmitted diseases and sexual behavior as risk factors for cervical cancer, we analyzed data from a population-based case-control study of breast and cervical cancer in Costa Rica. Data from 415 cases of cervical carcinoma in situ, 149 cases of invasive cervical cancer, and 764 controls were included in the analysis. Multivariate analysis showed that lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, herpes simplex virus type 2 seropositivity, and serologic evidence of previous chlamydial infection were predictors of carcinoma in situ. Serologic evidence of previous syphilis was not associated with carcinoma in situ. Predictors for invasive cervical cancer included lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, serologic evidence of previous syphilis, herpes simplex type 2 infection, and chlamydial infection. Cigarette smoking, socioeconomic status, self-reported history of sexually transmitted diseases, and douching were not associated with either carcinoma in situ or invasive cervical cancer.

Adult↗
PubMed1994

Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease.

Monoclonal antibodies directed against the Epstein-Barr virus nuclear protein 1 (EBNA1) were used to examine conventional paraffin sections from a series of EBV-associated lymphoproliferative disorders by immunohistochemistry. The presence of latent EBV infection in tumor cells was determined by in situ hybridization for the Epstein-Barr virus early RNAs (EBERs). Of those EBER-positive cases a total of 28 of 40 cases of Hodgkin's disease, 3 of 3 cases of Burkitt's lymphoma, and 8 of 8 cases of human immunodeficiency virus-associated cerebral B-cell lymphoma expressed detectable amounts of EBNA1. In the positive cases, expression was confined to the tumor cells. No reactivity was detected in EBV-negative cases of the above tumors or in 8 cases of EBV-negative cases of large cell anaplastic non-Hodgkin lymphoma. This report provides the first unequivocal evidence for the expression of the EBNA1 protein in the tumor cells of Hodgkin's disease and validates an important reagent with which to analyze the role of EBV in various virus-associated malignancies.

Amino Acid Sequence↗
PubMed1994

HIV and lesbian sex.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cuffed endotracheal tubes in pediatric intensive care.

We prospectively studied 282 consecutive tracheal intubations (243 patients) in a pediatric intensive care unit during a 7-month period to compare cuffed and uncuffed endotracheal tube (ETT) utilization and outcome. The incidence of postextubation stridor in each ETT group was the major outcome measure after controlling for various patient risk factors. Patients whose ETTs were inserted in the operating room, who were less than 1 year of age, or who had ETTs in place for less than 72 hours were more likely to have had insertion of an uncuffed ETT. Patients whose ETTs were inserted in the emergency department or who were more than 5 years of age were more likely to have had insertion of a cuffed ETT. Those who had a cuffed ETT were older (mean 8.1 vs 2.5 years) and had ETTs in place longer (mean 6.1 vs 3.7 days) than patients with an uncuffed ETT. Of the 188 patients who subsequently had removal of their ETTs, the overall incidence of postextubation stridor was 14.9%, with no significant difference between the two ETT groups even after controlling for patient age, duration of intubation, trauma, leak around ETT before extubation, and pediatric risk of mortality score. Two patients in the cuffed ETT group and four patients in the uncuffed ETT group required reintubation for severe postextubation stridor. Long-term follow-up identified 33 patients (17%) who required hospital readmission. None of these was admitted with an upper airway problem. Two patients who previously had insertion of a cuffed ETT subsequently received tracheostomies for the primary purpose of long-term mechanical ventilation unrelated to any problem with the upper airway. We conclude that cuffed endotracheal intubation is not associated with an increased risk of postextubation stridor or significant long-term sequelae.

Child↗