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J Stewart

Publications and source records attributed to J Stewart.

At least 199 records · Page 11Linked to original sources
PubMed1997

Aging effects on the organic base transporter and stereoselective renal clearance.

OBJECTIVE: The organic base transporter is responsible for stereoselective renal excretion. Changes in activity of this system secondary to aging may affect the disposition of an organic base in a stereoselective manner. METHODS: Eight young men (age range, 22 to 33 years) and seven elderly men (age range, 62 to 79 years) were given 10 mg pindolol twice daily, pindolol with 200 mg trimethoprim once daily (a known inhibitor of organic base secretion) and pindolol with 1.5 gm ammonium chloride (NH4Cl) four times daily for 3 days on three occasions. On day 4, urine and plasma were collected over 24 hours to determine renal clearance (CLR) values of pindolol isomers. RESULTS: R(+)-Pindolol CLR values in young versus elderly men were 203 +/- 82 versus 150 +/- 87 ml/min, 128 +/- 51 versus 113 +/- 35 ml/min, and 480 +/- 248 versus 247 +/- 59 ml/min during the control, trimethoprim, and NH4Cl study phases, respectively. S(-)-Pindolol CLR values in young versus elderly were 279 +/- 81 versus 207 +/- 105 ml/min, 178 +/- 70 versus 136 +/- 42 ml/min, and 593 +/- 294 versus 276 +/- 49 ml/min during control, trimethoprim, and NH4Cl phases, respectively. NH4Cl increased R(+)-pindolol CLR by 138% (p < 0.05 versus pindolol alone) in young men, which was significantly greater than that observed in elderly subjects (66%; p < 0.05 versus pindolol alone; p = 0.016 young versus old). NH4Cl affected S(-)-pindolol CLR in a similar manner. Trimethoprim decreased R(+)-pindolol CLR in the young subjects by 37% (p < 0.05 versus pindolol alone), which was similar to that observed in the elderly subjects (26%; p < 0.05 versus pindolol alone; p = 0.94 young versus elderly). Trimethoprim affected S(-)-pindolol CLR in a similar manner. Stereoselective renal excretion of pindolol was unaffected by NH4Cl and trimethoprim, where the R(+)/S(-)-pindolol CLR ratio was unchanged (p = NS) from control in the young and elderly subjects. Comparison of the pindolol CLR isomer ratio between young and elderly groups showed no significant differences. Changes in pindolol clearance values resulted in significant changes in beta-blocking activity, assessed by isoproterenol (INN, isoprenaline) testing. CONCLUSIONS: Trimethoprim and NH4Cl significantly affect pindolol renal and total clearance values. Aging does not alter renal excretion of pindolol except for the magnitude by which renal excretion can be stimulated.

Adrenergic beta-Antagonists↗
PubMed1997

Sexually arousing events and relapse to heroin-seeking in sexually experienced male rats.

We have shown previously, using a reinstatement procedure, that both priming injections of heroin and exposure to footshock stress reinstate heroin-taking behavior following prolonged drug-free periods. In the present study, we examined the effect of another highly arousing event, exposure to a sexually active female, on reinstatement of heroin-seeking. Male rats were first given sexual experience, being allowed to copulate on 4 occasions with sexually active females and were then trained to self-administer heroin (100 micrograms/kg per infusion, IV) for 4 3-h sessions/day for 5-6 days and 1 6-h session/day for an additional 6 days. Extinction sessions were then given for 4 days, 6-h/day, during which saline was substituted for heroin. On tests for reinstatement, males were presented with: 1. The wire-mesh side of an empty cage (baseline condition), 2. the sight, odor, and smell of a sexually inactive female, 3. the sight, odor, and smell of a female in heat, 4. a female in heat, and allowed to copulate, 5. intermittent footshock (15 min, 0.5 mA, 0.5 s on, mean off period of 40 s), or 6. a priming injection of heroin (0.25 mg/kg, SC). Reinstatement of heroin-taking behavior was observed after exposure to the priming injection of heroin and to footshock stress. Reinstatement of heroin-taking behavior was not induced by exposure to the females in any of the conditions. Thus, motivational arousal, as such, does not appear to be a sufficient stimulus for relapse to heroin-taking.

Animals↗
PubMed1997

Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to incentives and stressors.

Aging↗
PubMed1997

Philadelphia chromosome in chronic myelogenous leukemia: confirmation of cytogenetic diagnosis in Ph positive and negative cases by fluorescence in situ hybridization.

In this study, patients with Philadelphia (Ph) negative and positive chronic myelogenous leukemia (CML) were analyzed by unicolor- and dual color- (DC) fluorescence in situ hybridization (FISH) using abl and bcr cosmid probes. Unicolor- and DC-FISH analysis revealed a BCR-ABL fusion in a Ph-negative patient. DC-FISH to interphase nuclei revealed the BCR-ABL fusion, even though no metaphases were available for metaphase-FISH and conventional cytogenetic analysis. In the remaining cases, the findings of FISH were in agreement with the cytogenetic results.

DNA, Neoplasm↗
PubMed1997

Identification of variant translocations in chronic myeloid leukemia by fluorescence in situ hybridization.

We studied two cases of chronic myeloid leukemia (CML) having variant complex translocations detected by trypsin G-banding and fluorescence in situ hybridization (FISH). Application of dual color- (DC-) FISH using abl and bor cosmid probes permitted us to detect the bor-abl fusion event on both interphase nuclei and metaphase spread. Furthermore, FISH using combinatorial hybridization (centromeric-library and library-library probes) demonstrated the content and the position of the translocations in CML patients with variant (complex type) Ph-positive rearrangements. FISH analysis appears to be superior than conventional cytogenetic analysis.

Chromosomes, Human, Pair 6↗
PubMed1997

Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions.

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.

Amphetamine↗
PubMed1997

Recovery of function is associated with increased spine density in cortical pyramidal cells after frontal lesions and/or noradrenaline depletion in neonatal rats.

Rats were given medial frontal lesions at 7 days of age and were tested as adults on tests of forelimb use, forelimb tactile sensitivity, tongue use, hindleg use, and in a spatial navigation task. The brains were processed with a modified Golgi-Cox procedure and dendritic arborization and spine density was measured. The animals showed recovery only on the spatial task and this was associated with an increase in the number of spines per unit length of dendrite. We also reanalyzed Golgi-Cox stained material from an experiment in which animals were depleted of cortical noradrenaline (NA) in infancy and then given frontal lesions on day 7. The NA depletion blocked the recovery from frontal lesions. Analysis of dendritic morphology showed that in otherwise intact rats, NA depletion decreased dendritic arbor but increased spine density to the level of frontal operates. Depleted frontal-operates showed no additional increase in spine density and also showed a decrease in dendritic arborization. These results suggest that recovery from neonatal cortical injury and from neonatal noradrenaline depletion may be supported by changes in both the dendritic arborization and the spine density in the remaining cortex.

Animals↗
PubMed1997

Somatosensory evoked potentials in adults with cortical dysgenesis and epilepsy.

Cortical dysgenesis (CD) is a well-recognised cause of epilepsy, but its functional anatomy is not fully understood. We recorded cortical somatosensory evoked potentials (SEPs) in 13 adult patients with epilepsy and various CDs excluding diffuse gyral malformations as diagnosed by MRI. The CD involved the perirolandic/perisylvian region in 7 patients. Six patients had neurological signs but only 3 had sensory dysfunction (astereognosis). As compared with 12 control subjects, SEPs were considered definitely abnormal in 7 patients (including the 6 with neurological signs) and equivocally abnormal in 2. The abnormalities ranged from defects affecting single components to absence of all potentials of cortical origin in one patient with hemiparesis and astereognosis. In this case it appears that gross sensory function must have been mediated by subcortical structures or through diffuse cortical projections. The initial cortical potentials (N20/P20) were absent in 6 patients, 5 of whom had CD in zones involving or bordering on the primary sensory cortex. Parietal potentials following N20 were absent or attenuated in 4 patients and of abnormally wide distribution, spreading to frontal, midline and ipsilateral electrodes, in 3 frontal components following P20 were absent, attenuated, delayed or distorted by abnormal spread of the parietal activity in 5 patients. Five patients with unilateral CD showed definite or equivocal SEP abnormalities to stimulation of both arms, suggesting there may be more widespread disturbance of cortical organisation and/or synaptogenesis, beyond the resolution of present day neuroimaging.

Adolescent↗
PubMed1997

Inhibition of Listeria monocytogenes and Salmonella enteriditis by combinations of plant oils and derivatives of benzoic acid: the development of synergistic antimicrobial combinations.

This study describes inhibitory properties of combinations of oil of fennel, oil of anise or oil of basil with either benzoic acid or methyl-paraben against Listeria monocytogenes and Salmonella enteriditis. Micro-organisms were cultured at 37 degrees C in broth and viable counts measured over a 48-h period. S. enteriditis was particularly sensitive to inhibition by a combination of oil of anise, fennel or basil with methyl-paraben where there was < 10 CFU/ml after 1 h. L. monocytogenes was less sensitive to inhibition by each combination however there was a significant reduction in growth of 4-8 log by combinations of all oils and methyl-paraben at 8, 24 and 48 h. Synergistic inhibition by one or more combinations was evident against each micro-organism.

Anti-Bacterial Agents↗
PubMed1997

Hypereosinophilic syndrome or chronic eosinophilic leukemia: report of a case with a lytic bone lesion.

Some cases of hypereosinophilic syndrome and myeloproliferative disorders exhibit common features and thus pose diagnostic and therapeutic problems. We describe a 68-year-old patient who presented with such features and developed lytic lesion in the tibia. Based on our case and a review of literature we suggest that cases like ours should be classified and treated as chronic eosinophilic leukemia (a myeloproliferative disorder) rather than as a hypereosinophilic syndrome or as an atypical chronic myeloid leukemia.

Aged↗
PubMed1997

Distribution of p53 and K-ras mutations in human lung cancer tissues.

Studies were performed to examine the mutational pattern of K-ras exons 1 and 2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese patients (10 smokers, 17 non-smokers) using single-stranded conformational polymorphism and DNA sequencing. K-ras mutations were found in 13/27 tumors (48%); all mutations were clustered in exon 1 and distributed between codons 9 and 32. The frequency and number of patients with K-ras mutations between smokers and non-smokers were not different, except that a high frequency of G --> A transitions (11/11) was found in non-smokers. Among cell types, K-ras mutations were found in 7/13 (54%) squamous cell carcinoma (SC) and 5/12 (42%) adenocarcinoma (AC) patients. A --> T transversions (all six transversions) were present only in SC. In p53, 18/27 (67%) tumors contained mutations in exons 7 and 8, frequently at codons 226, 270, 275 and 281. The number of tumors with p53 mutations in smokers (70%) and in non-smokers (65%) was similar, and the mutation frequency did not differ except for a higher number of G --> A (6/7) and T --> C (5/6) transitions in non-smokers. Among cell types, the number of tumors with p53 mutations was 9/13 (69%) in SC and 8/12 (67%) in AC. The A --> G (11/16) transitions and A --> C (4/4) transversions in p53 were more frequent in SC than in AC (P < 0.04 for A --> G; P < 0.02 for A --> C). The varying mutation patterns in both the K-ras and p53 genes between smokers and non-smokers and among cell types suggest that other than cigarette smoke, environmental and dietary factors may also be involved in the genesis of lung cancer among these patients.

Adult↗
PubMed1997

Ankylosing spondylitis and secretor status: a re-evaluation.

Non-secretion of ABO blood group substances in body fluids is associated with susceptibility to some bacterial infections. Non-secretors were previously found to be over-represented in patients with ankylosing spondylitis (AS) (49%) compared to controls (27%). Re-evaluation of secretor status in a population of 92 AS patients and 103 controls revealed identical proportions of non-secretors (28%). Of 43 patients studied in both surveys, 6/22 typed initially as non-secretors proved to be secretors using both haemagglutination inhibition assay (HAI) and enzyme-linked immunosorbent assay (ELISA) techniques. Loss of secreted blood group antigens in the saliva is the cause of this mis-typing. Careful attention to the method of collection, handling and preservation of saliva specimens is essential for accurate assessment of secretor status. Therefore, there is no link between secretor status and AS.

ABO Blood-Group System↗
PubMed1997

Priming of neutrophil respiratory burst activity by lipopolysaccharide from Burkholderia cepacia.

Neutrophil activation may play an important role in the pathogenesis of respiratory disease in Burkholderia cepacia-colonized cystic fibrosis (CF) patients. As bacterial lipopolysaccharides (LPS) are potent immunostimulatory molecules, we investigated the role of B. cepacia LPS in neutrophil activation processes. LPS extracted from a highly transmissible and virulent strain of B. cepacia (J2315) was found to increase neutrophil surface expression of the beta2 integrin, complement receptor 3, and to prime neutrophil respiratory burst responses to the neutrophil-activating agent fMet-Leu-Phe. By contrast, LPS extracted from a nonmucoid Pseudomonas aeruginosa strain isolated from a patient with CF showed little or no priming activity. As B. cepacia is currently being developed as a biocontrol agent for large-scale agricultural release, we compared LPS molecules from a range of bacterial strains for their proinflammatory ability. Priming activity was demonstrated in LPS extracts from all B. cepacia strains tested, with one environmental strain, J2552, showing the highest activity. These findings indicate (i) that B. cepacia LPS may contribute to the inflammatory nature of B. cepacia infection in CF patients, both by promoting increased neutrophil recruitment and by priming neutrophil respiratory burst responses, and (ii) that environmental strains of B. cepacia may have considerable inflammatory potential in susceptible individuals.

Burkholderia cepacia↗
PubMed1997

Evolutionary transitions and artificial life.

A major challenge for artificial life is to synthesize the evolutionary transitions that have repeatedly formed differentiated higher-level entities from cooperative organizations of lower-level entities, producing the nested hierarchical structure of living processes. This article identifies the key elements and relationships that must be incorporated or synthesized in an artificial life system if these transitions are to emerge. The processes currently included in artificial life systems are unable to provide an adequate basis for the emergence of the complex cooperative organization that is essential to the transitions. A new theory of the evolution of cooperative organization is developed that points to the additional processes that must be included in artificial life systems to underpin the emergence of the transitions.

Biological Evolution↗
PubMed1997

Electrocardiographic prediction of hyperinflation in children.

The mean frontal P wave axis in an electrocardiogram (ECG), which reflects the atrial orientation in the thorax, is altered by the relationship between atria and the diaphragm and, therefore, by hyperinflation. To examine this relationship, 102 children (ages 6-18) with asthma were prospectively studied. Lung volumes were estimated by plethysmography and a standard ECG obtained before and after bronchodilator. The mean thoracic gas volume (TGV) was 120.7 +/- 2.1% of predicted and the mean P axis was 54.9 +/- 1.5 degrees. Sixty-two subjects (61%) had a "vertical" P axis (> or = 60 degrees). Of 27 subjects with moderate or severe hyperinflation (TGV > or = 130% predicted), 23 (85%) had a vertical P axis. As a measure of significant hyperinflation, a vertical P axis had a sensitivity of 85%, specificity of 49%, positive predictive value of 38% and a negative predictive value of 90%. After nebulized albuterol, the mean TGV decreased to 96.4 +/- 1.3% predicted and the mean P axis decreased by 7.1 +/-1.6 degrees. Sixty-two of 76 subjects (82%) with > or = 15% decrease in TGV also had a decrease in P axis, and 62/67 subjects (93%) with a decrease in P axis also had > or = 15% decrease in TGV. The sensitivity was 82%, specificity 81%, and positive predictive value 93% for a decrease in P axis as a measure of decrease in TGV. A vertical P axis combined with a decrease in P axis after bronchodilator is highly sensitive and predictive for hyperinflation in children.

Adolescent↗
PubMed1997

Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group.

PURPOSE: To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS: Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS: There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION: Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.

Aged↗
PubMed1997

Potential use of image analysis for the evaluation of cellular predicting factors for therapeutic response in breast cancers.

OBJECTIVE: To summarize the current literature on the association between biologic prognostic factors and therapeutic implications. STUDY DESIGN: To illustrate how these biologic factors are determined and how they can affect treatment, three patients' biologic profiles and their implications for the patients' choice of therapeutic approaches were analyzed. Immunohistochemical techniques combined with image analysis was used to evaluate estrogen receptors, progesterone receptors, proliferation index and erbB-2. Visual assessment was used to evaluate P glycoprotein (MDR1), EGFR and p53. RESULTS: Data from the literature stress the importance of biologic profiles for defining tumor behavior and patient management. The examples of patients' biologic factors illustrated the possible importance of these factors for helping to design treatment. CONCLUSION: Today the data on the association of patient response to chemotherapy and molecular markers are only starting to accumulate. A larger database is needed for a more precise estimation of response probability in order to help physicians decide between treatment options.

Adult↗