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Biomedical subjects

G Jamieson

Publications and source records attributed to G Jamieson.

At least 19 recordsLinked to original sources

Cyclooxygenase-2 expression in squamous cell carcinoma of the esophagus.

Increased cyclooxygenase-2 expression has been reported to be a poor prognostic indicator in a number of cancers. In this study we investigated the relationship between COX-2 expression in squamous cell carcinoma of the esophagus and tumor characteristics and patient survival. The study group consisted of 90 men and 48 women who underwent esophagectomy for squamous cell carcinoma of the esophagus between October 1984 and May 1985. COX-2 expression was measured by immunohistochemistry in 138 primary cancers, 23 metastatic lymph nodes and 21 normal esophageal stumps. The relationship between the extent of staining for COX-2 and clinicopathological features and survival was determined. The extent of staining for COX-2 in both primary and metastatic cancers was higher than in normal squamous epithelia (P = 0.002 and P < 0.0001 respectively), and the grade of staining in the primary tumor correlated positively with the finding of lymph node metastases (P = 0.03). The 5-year survival rate in patients with less than 10% COX-2 positive cells was 47.5% compared to 23.2% in patients with more than 10% COX-2 positive cells (P = 0.0036). The relationship between survival and COX-2 staining was not due to COX-2 being a surrogate marker for TNM stage. Our results show that the expression of COX-2 is elevated in squamous cell carcinoma of the esophagus compared to normal epithelium and correlates with lymph node metastases. Survival was longer in those patients whose tumors expressed lower levels of COX-2.

Carcinoma, Squamous Cell↗

Relapse patterns after chemo-radiation for carcinoma of the oesophagus.

AIM: The detailed review of patterns of failure in this report was undertaken to identify the continuing obstacles to the successful management of oesophageal cancer, and to establish whether there is a case to compare definitive chemo-radiation (Def-CR) and surgery for patients with squamous cancer in a randomized controlled trial. MATERIALS AND METHODS: First and subsequent sites of failure were reviewed in 274 patients treated with Def-CR using two cycles of cisplatin, infusional fluorouracil and 60 Gy; and 92 patients with limited chemo-radiation (CR), using one cycle and 35 Gy, followed by surgery (CR-Surg). All were treated on prospective non-randomized trials run by the Trans-Tasman Radiation Oncology Group between 1985 and 1999. Failure patterns were analysed using competing risks methodology, and pre-treatment variables predicting survival were identified by proportional hazards modelling. RESULTS: Site, stage, performance status and gender were independently predictive of survival following Def-CR. Local failure was evident in 42.3% of patients, but distant failure in isolation occurred in an additional 18.1%. Lowest rates of local and distant failure at 5 years (29.9% and 26%) occurred in patients with squamous cancer (SCC) located in the upper-third, whose 5-year survival was also the most favourable (49.2%). Survival was least favourable in patients with adenocarcinoma (AC) in the lower two-thirds (18.1%) due to higher rates of local (51.5%) and distant (36.1%) failure. Local failure occurred in 31.5% of patients undergoing CR-Surg but distant failure in isolation was observed in a further 34.7%. Outcomes were least favourable in patients with AC of the lower-third in whom 57.7% failed distantly and 5-year survival was 3.8%. Response to pre-operative chemo-radiation was also strongly predictive of outcome. Patients with no residual cancer in the resection specimen had the lowest rates of local (0%) and distant (16.7%) failure and the best survival (64.9%). Survival in patients with residual cancer in nodes, however, was extremely poor (3.5%) with distant failure occurring in 66.7%. CONCLUSION: The concurrent administration of chemotherapy with radiotherapy seems to have improved loco-regional control and has exposed distant failure as an obstacle to further improvements in outcome. Site, histological subtype, gender and response to chemo-radiation may predict biological differences in oesophageal cancer (OC) that influence outcome. A good case for a randomized comparison between Def-CR and CR-Surg in patients with SCC in the lower two-thirds exists.

Adenocarcinoma↗

Putaminal hemorrhage and outcome.

Twenty-five patients (average age, 65 +/- 4.5 years) with spontaneous putaminal hemorrhage were studied to determine any independent predictors as to survival and level of disability. Based on the computed tomography (CT) findings, they were grouped according to their location and extent of the hemorrhage. The thalamus and the caudate were not involved. Univariate and multivariate regression analyses were done to determine any potential prognostic indicator. The groups were significantly different with regard to volume, intraventricular hemorrhage, midline shift, ambient cisterns, hydrocephalus, and disability score but not different with respect to pineal shift, side, gender, and age. The variables that arose as significant predictors of disability were intraventricular hemorrhage, midline shift, hydrocephalus, ambient cistems (all p < or = 0.001), pineal shift and age (both p < or = 0.04). Neither gender nor side was a significant predictor for disability score (p = 0.92 and p = 0.125, respectively). Multivariate regression model included volume, ambient cisterns, and age as significant predictors for disability score.

Aged↗

Critical illness neuropathy.

Critical illness neuropathy frequently accompanies the septic syndrome in intensive care units. Another entity that may occur independently or concurrently in critically ill patients is a myopathy, giving rise to difficulties in distinguishing between them. The two patients described had sensorimotor axonal peripheral neuropathy. Axonopathy as a rule has a poor prognosis for recovery, which is slow and often incomplete. There are few reports of the functional outcome after rehabilitation therapy. The two patients described had 5-6 weeks of active rehabilitation therapy with improvement from moderate/severe disability at the onset to slight debility at the end of therapy.

Activities of Daily Living↗

High affinity interaction of HIV-1 integrase with specific and non-specific single-stranded short oligonucleotides.

Retroviral integrase (IN) catalyzes the integration of double-stranded viral DNA into the host cell genome. The reaction can be divided in two steps: 3'-end processing and DNA strand transfer. Here we studied the effect of short oligonucleotides (ODNs) on human immunodeficiency virus type 1 (HIV-1) IN. ODNs were either specific, with sequences representing the extreme termini of the viral long terminal repeats, or nonspecific. All ODNs were found to competitively inhibit the processing reaction with Ki values in the nM range for the best inhibitors. Our studies on the interaction of IN with ODNs also showed that: (i) besides the 3'-terminal GT, the interaction of IN with the remaining nucleotides of the 21-mer specific sequence was also important for an effective interaction of the enzyme with the substrate; (ii) in the presence of specific ODNs the activity of the enzyme was enhanced, a result which suggests an ODN-induced conformational change of HIV-1 IN.

DNA Primers↗

Affinity of antibodies to MUC1 antigens.

The binding affinity of a monoclonal antibody to its ligand has been often used as a qualitative and quantitative measure for the specificity of the antibody. The aim of this paper was to assess the affinity of binding to recombinant and synthetic MUC1 peptides of 52 monoclonal antibodies as part of the ISOBM TD-4 Workshop. Affinity of binding was assessed using a surface plasmon resonance biosensor (BIAcore). The monoclonal antibodies exhibited variable affinity to MUC1 peptides, and overall 25/52 antibodies showed significant binding to the test peptides with affinities ranging from 2.4 x 10(6) to 3.1 x 10(8) M-1. Affinities calculated by analysis of kinetic biosensor data agreed well with affinities determined by equilibrium binding analysis of radiolabelled antibodies. The affinity measurements may provide help when determining the use of various monoclonals in tumour biology research.

Amino Acid Sequence↗

Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein.

Mucin 1 (MUC1) is a large complex glycoprotein that is highly expressed in breast cancer, and as such could be a target for immunotherapy. In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection. On this basis, a clinical trial was performed in which 25 patients with advanced metastatic carcinoma of breast, colon, stomach, or rectum received mannan-MUC1 in increasing doses. After 4 to 8 injections, large amounts of IgG1 anti-MUC1 antibodies were produced in 13 out of 25 patients (with antibody titers by ELISA of 1/320-1/20,480). Most of the antibodies reacted to the epitopes STAPPAHG and PAPGSTAP. In addition, T cell proliferation was found in 4 out of 15 patients, and CTL responses were seen in 2 out of 10 patients. Mannan-MUC1 can immunize patients, particularly for antibody formation, and to a lesser extent, cellular responses. It remains to be seen whether such responses have antitumor activity.

Adenocarcinoma↗

The relationship between wheezing and lung mechanics during methacholine-induced bronchoconstriction in asthmatic subjects.

Wheeze is a classic sign of airflow obstruction but relatively little is known of its mechanism of production or its relationship to the development of airflow obstruction. We studied eight asthmatic subjects age (mean +/- 5D) 42 +/- 5 yr, FEV1 2.46 +/- 0.36 L during an extended, symptom-limited methacholine challenge test. Breath sounds were detected by a microphone over the right upper anterior chest. Spectral analysis was by a fast Fourier transform algorithm. Mean FEV1 fell by 51 +/- 14% to 1.28 +/- 0.61 L during the challenge and airways resistance increased by 119 +/- 50%. There were no consistent changes in breathing pattern or tidal volume during the challenge. Wheeze occurred late in the challenge at the highest concentration of methacholine administered and only after expiratory tidal flow limitation had been reached. Five subjects developed wheeze on tidal breathing, the remaining three only wheezed on deep breathing. Wheezing sounds were reproducible between breaths, coefficient of variation of starting sound frequency was 4.2% and ending frequency 12%. Mean frequency of expiratory wheezes was 669 +/- 100 Hz and inspiratory wheezes 710 +/- 76 Hz. Expiratory wheeze fell in pitch during a breath (mean fall in sound frequency 187 +/- 43 Hz) but inspiratory wheezes were more variable. Expiratory wheezes occurred late in the respiratory cycle at a mean of 58% of the maximal tidal expiratory flow, whereas inspiratory wheezes occurred around maximal tidal inspiratory flows, suggesting that the mechanisms of production of inspiratory and expiratory wheezes may be different. In this model, the presence of wheeze during tidal breathing was a sign of severe airflow limitation.

Adult↗

A new series of pyridinone derivatives as potent non-nucleoside human immunodeficiency virus type 1 specific reverse transcriptase inhibitors.

4-(Arylthio)-pyridin-2(1H)-ones variously substituted in their 3-, 5-, and 6-positions have been synthesized as a new series of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)-pyridinone hybrid molecules. Biological studies revealed that some of them show potent HIV-1 specific reverse transcriptase inhibitory properties. Compounds 16 and 7c, the most active ones, inhibit the replication of HIV-1 at 3 and 6 nM, respectively.

Antiviral Agents↗

Short-term training, muscle glycogen, and cycle endurance.

The objective of this study was to test the hypothesis that the increased glycogen concentration found in the working muscles following short-term training would result in an increase in endurance performance. Endurance performance was examined in 8 active but untrained males who cycled until fatigue at 65% VO2max prior to and following 3 consecutive days of training. Training consisted of cycling for 2 hrs a day at the same power output used in the prolonged fatigue trials. A 39% increase in cycle time, from 103 +/- 7.7 to 143 +/- 14 min (p < 0.05), was observed following training. At fatigue prior to training, glycogen concentration in the vastus lateralis muscle was depleted by 75% (317 +/- 17 to 78.8 +/- 32 mmol.glucosyl units .kg-1 d.w). Following training, glycogen concentration at a comparable work time was 2.3 times higher. The elevated glycogen level following training was due both to higher glycogen at rest and during exercise. The energy cost of the activity as measured by the VO2 at selected intervals was unchanged with training. No change (p > 0.05) in exercise time was observed in a control group who were subjected to similar exercise protocols approximately 1 to 2 weeks apart. It is concluded that short-term training at least in untrained individuals (VO2max averaging 43.6 +/- 2.9 ml.kg-1.min-1) substantially elevates submaximal exercise tolerance and that the increase in resistance to fatigue is related to the elevated availability of glycogen.

Energy Metabolism↗

Metabolic adaptations to short-term training are expressed early in submaximal exercise.

In previous studies we have been able to demonstrate tighter metabolic control of muscle metabolism during prolonged steady-state exercise 5 to 6 days after the initiation of training and well before changes in oxidative potential. To examine whether the metabolic adaptations are manifested during the non-steady-state adjustment to submaximal exercise, 11 male subjects (Vo2 peak, 45 +/- 2.4 mL.kg(-1). min(-1), X +/- SE) performed 98 min of cycle exercise at 67% of Vo2 peak prior to and following 3 to 4 days of training for 2 h per day. Analysis of lactate concentration (mmol/kg dry weight) in samples rapidly extracted from vastus lateralis indicated reductions (p < 0.05) of 44% at 3 min ( 42.1 +/- 7.1 vs. 23.6 +/- 7.7), 29% at 15 min (35.4 +/- 6.4 vs. 25.0 +/- 6.0), and 32% at 98 min (22.9 +/- 6.9 vs. 15.6 +/- 3.2) with training. Training also resulted in higher phosphocreatine and lower creatine and P(i) values that were not specific to any exercise time point. In addition, Vo2 was not altered either during the non-steady state or during the steady-state phases of exercise. These results suggest that at least part of the tightening of the metabolic control and the apparent reduction in glycogenolysis and glycolysis in response to short-term training occurs during the adjustment phase to steady-state exercise.

Adenine Nucleotides↗

Coupling of muscle phosphorylation potential to glycolysis during work after short-term training.

To examine whether the metabolic adaptations to short-term training are expressed over a range of submaximal levels of mitochondrial respiration, seven untrained male subjects [maximal O2 uptake (VO2max) = 45.9 +/- 1.9 (SE) ml.kg-1.min-1] performed a progressive three-stage protocol of cycle exercise at 60% (20 min), 79% (20 min), and 92% (11 min) of pretraining VO2max before and after training. Training consisted of 5-6 days of cycling for 2 h/day at 65% VO2max. Muscle tissue rapidly obtained from the vastus lateralis by needle biopsy indicated that training blunted (P < 0.05) the increase in lactate observed at 60% (23.4 +/- 6.5 vs. 12.4 +/- 2.9 mmol/kg dry wt), 79% (48.9 +/- 5.1 vs. 25.6 +/- 5.2 mmol/kg dry wt), and 92% (68.3 +/- 6.4 vs. 41.5 +/- 6.5 mmol/kg dry wt) of VO2max. Training also resulted in a higher phosphocreatine and lower creatine and P(i) concentrations at both 79% (P < 0.05) and 92% (P < 0.05) of VO2max and higher muscle glycogen levels (P < 0.05). These changes were accompanied by small but significant reductions (P < 0.05) in O2 uptake at the two higher exercise intensities. Given that the lactate-to-pyruvate ratio and the calculated free ADP and AMP were also reduced (P < 0.05), it would appear that short-term training results in a tighter metabolic control over a range of mitochondrial respiratory rates.

Adult↗

Surgical bypass for palliation of malignant oesophageal obstruction.

It is possible to achieve satisfactory palliation for most patients with malignant oesophageal obstruction by endoscopic means, surgical resection or radiotherapy. Despite these options, a small group of patients remains for whom another alternative should be considered. Fifteen patients presenting with extensive tumour, a non-dilatable stricture, or a tracheo-oesophageal fistula, not suitable for any of the standard methods of palliation, underwent palliative surgical bypass using stomach or colon. The hospital mortality was 33% and the median survival 6 months. Anastomotic leakage occurred in six patients and the median postoperative stay was 28 days (range 20-42 days). All patients who survived surgery, except one, achieved satisfactory palliation. The nature of these patients is such that whatever is done, mortality will almost inevitably be high. The authors believe that all patients in this series were better off than they would have been if left untreated, and oesophageal bypass should be considered for patients with distressing dysphagia due to disease not amenable to standard palliative methods.

Adult↗

An enzymic method of preparing plant chromosomes for in situ hybridization.

A method of preparing chromosomes from plant root tips for in situ hybridization with tritiated DNA is described. The technique relies on the enzymic hydrolysis of plant cell walls with a pectinase-cellulase mixture. It is shown that, despite the enzymic mixture possessing nuclease activity, there is no detectable degradation of DNA within fixed root tips. To demonstrate the suitability of this method of preparing plant chromosomes for in situ hybridization, a cloned repetitive DNA sequence has been hybridized to Allium sativum chromosomes. Chromosomes prepared using this technique also can be readily C-banded.

Chromosomes↗

Gas Chromatography-Mass Spectrometry of N- Heptafluorobutyryl Isobutyl Esters of Amino Acids in the Analysis of the Kinetics of [N]H(4) Assimilation in Lemna minor L.

Rapid, sensitive, and selective methods for the determination of the (15)N abundance of amino acids in isotopic tracer experiments with plant tissues are described and discussed. Methodology has been directly tested in an analysis of the kinetics of [(15)N]H(4) (+) assimilation in Lemna minor L. The techniques utilize gas chromatography-mass spectrometry selected ion monitoring of major fragments containing the N moiety of N-heptafluorobutyryl isobutyl esters of amino acids. The ratio of selected ion pairs at the characteristic retention time of each amino acid derivative can be used to calculate (15)N abundance with an accuracy of +/-1 atom% excess (15)N using samples containing as little as 30 picomoles of individual amino acids. Up to 11 individual amino acid derivatives can be selectively monitored in a single chromatogram of 30 minutes. It is suggested that these techniques will be useful in situations where the small quantities of N available for analysis have hitherto hindered the use of (15)N-labeled precursors.

Journal Article↗

Alteration in esophageal motility after laryngectomy.

Ten laryngectomees underwent esophageal motility studies to assess the effect of laryngectomy on esophageal function. When these patients are compared with controls, marked derangements in esophageal motility were noted in the upper esophageal sphincter (UES) and in the body of the esophagus. Lower esophageal sphincter (LES) function did not differ significantly from the controls. Dysphagia developed postoperatively in five of the ten laryngectomees. This preliminary analysis suggests that esophageal motility disturbances may be relatively frequent after laryngectomy and that these disturbances may be clinically significant. The theoretical basic for the motility abnormalities and areas of future research are discussed.

Aged↗