PubMed Health⌕ Search

Biomedical subjects

N Jordan

Publications and source records attributed to N Jordan.

At least 19 recordsLinked to original sources
PubMed2003

The antiepidermal growth factor receptor agent gefitinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitro.

Although many estrogen receptor-positive breast cancers initially respond to antihormones, responses are commonly incomplete with resistance ultimately emerging. Delineation of signaling mechanisms underlying these phenomena would allow development of therapies to improve antihormone response and compromise resistance. This in vitro investigation in MCF-7 breast cancer cells examines whether epidermal growth factor receptor (EGFR) signaling limits antiproliferative and proapoptotic activity of antihormones and ultimately supports development of resistance. It addresses whether the anti-EGFR agent gefitinib (ZD1839/Iressa; TKI: 1 mum) combined with the antihormones 4-hydroxytamoxifen (TAM: 0.1 mum) or fulvestrant (Faslodex; 0.1 mum) enhances growth inhibition and prevents resistance. TAM significantly suppressed MCF-7 growth over wk 2-5, reducing proliferation detected by immunocytochemistry and fluorescence-activated cell sorter cell cycle analysis. A modest apoptotic increase was observed by fluorescence-activated cell sorter and fluorescence microscopy, with incomplete bcl-2 suppression. EGFR induction occurred during TAM response, as measured by immunocytochemistry and Western blotting, with EGFR-positive, highly proliferative resistant growth subsequently emerging. Although TKI alone was ineffective on growth, TAM plus TKI cotreatment exhibited superior antigrowth activity vs. TAM, with no viable cells by wk 12. Cotreatment was more effective in inhibiting proliferation, promoting apoptosis, and eliminating bcl-2. Cotreatment blocked EGFR induction, markedly depleted ERK1/2 MAPK and protein kinase B phosphorylation, and prevented emergence of EGFR-positive resistance. Faslodex plus TKI cotreatment was also a superior antitumor strategy. Thus, increased EGFR evolves during treatment with antihormones, limiting their efficacy and promoting resistance. Gefitinib addition to antihormonal therapy could prove more effective in treating estrogen receptor-positive breast cancer and may combat development of resistance.

Antineoplastic Agents, Hormonal↗
PubMed2003

Postmodern values, attitudes and the use of complementary medicine.

OBJECTIVES: To examine the relationship between postmodern values, demographic variables and people's attitudes towards and use of acupuncture, aromatherapy and naturopathy. DESIGN: One hundred and seventy-one adults completed a survey measuring postmodern values about health, attitudes towards and use of complementary and alternative medicine (CAM), age, gender, education, and current and recent health. SETTING: Griffith University, Gold Coast, Australia. MAIN OUTCOME MEASURES: Attitudes to CAM and use of CAM. RESULTS: Postmodern values significantly predicted attitudes to CAM and actual use of CAM. Age also significantly predicted attitudes to CAM. CONCLUSIONS: The results highlight the importance of patients' belief in natural remedies and in their active involvement in the healing process.

Adolescent↗
PubMed2003

The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population.

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 births and can be caused by mutations in 9 known genes, including that encoding the TSH receptor (TSHR). We report on two Welsh siblings, detected by neonatal screening, who had normal sized and placed glands but negative isotope uptake. Genomic DNA was obtained from both siblings and parents, the TSHR amplified using pairs of intronic and/or overlapping exonic primers and the PCR products sequenced automatically. Both siblings were homozygous for a previously described G to A transition producing a missense mutation, W546X, in the fourth membrane spanning region of the TSHR, rendering it unresponsive to TSH. Both parents were heterozygous and unrelated; furthermore, the W546X has been described in three further families (one of which is Welsh), suggesting that it may be a relatively common mutation. We genotyped 368 euthyroid Welsh individuals using single nucleotide primer extension, and found 366 homozygous wild-type (G:G) and 2 heterozygous (G:A) for the mutation. In conclusion, CH in the siblings is due to the missense mutation, W546X, in their TSHR gene. The W546X allele was detected in approximately 1 in 180 individuals and may be a major contributor to hypothyroidism in the Welsh population.

Alleles↗
PubMed2003

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo.

The thyrotrophin receptor (TSHR) provides an autoantigenic link between the thyroid and orbit in Graves' (GD) and thyroid eye diseases (TED). We measured TSHR transcripts in different fat depots to determine whether TSHR expression levels are influenced by the autoimmune/inflammatory process and/or thyroid hormone status, using quantitative real-time PCR. Nine intact or fractionated adipose samples, from patients with GD and/or TED, were analysed ex vivo. Eight expressed the TSHR, at levels approaching the thyroid, and one was at the limit of detection. Thirteen/fifteen orbital and abdominal fat samples from patients free of GD and TED, measured ex vivo, were negative for TSHR transcripts and two were at the limit of detection. All preadipocyte samples induced to differentiate in vitro expressed the TSHR. To investigate the influence of thyroid hormone status on adipose TSHR expression, we induced hyper- and hypothyroidism in BALBc mice by administering tri-iodothyronine and propylthiouracil respectively. In euthyroid animals, whole fat samples were at the limit of detection and were not altered by thyroid hormone status. The results show that adipose TSHR expression ex vivo indicates adipogenesis in progress in vivo and is associated with the autoimmune/inflammatory process in GD and TED but is not restricted to the orbit or influenced by thyroid hormone status.

Adipose Tissue↗
PubMed2002

Impact of acid secretion, gastritis, and mucus thickness on gastric transfer of antibiotics in rats.

BACKGROUND AND AIMS: The success of Helicobacter pylori eradication regimens depends on gastric pH, inflammation, and mucus thickness. Our aim was to investigate the effects of acid secretion, inflammation, and mucolysis on gastric antibiotic transfer. SUBJECTS AND METHODS: A total of 134 anaesthetised rats were given metronidazole, amoxicillin, or clarithromycin intravenously and gastric contents were aspirated via an indwelling cannula. Acid secretion was controlled by either omeprazole or pentagastrin while gastritis was induced by infection with H pylori or dosing with iodoacetamide. Mucolysis was achieved by instilling pronase into the gastric lumen. RESULTS: Metronidazole transfer increased with acid secretion and fell with omeprazole, independently of gastric pH. Clarithromycin was also transferred with acid but was then rapidly degraded. Omeprazole prevented this degradation, raising gastric luminal concentrations. Omeprazole did not alter amoxicillin transfer. Gastritis induced by H pylori did not alter gastric transfer of metronidazole and amoxicillin but that of clarithromycin was increased by 23%. However, gastritis induced by iodoacetamide reduced clarithromycin transfer without any effect on metronidazole or amoxicillin transfer. Pronase treatment increased amoxicillin transfer fourfold and metronidazole by 66% but reduced clarithromycin transfer by 35%. CONCLUSIONS: Metronidazole and clarithromycin are predominantly transferred with gastric acid rather than by an acid trapping mechanism. Pronase increases the appearance of amoxicillin and metronidazole in gastric secretions.

Amoxicillin↗
PubMed2001

Primary congenital glaucoma: three case reports on novel mutations and combinations of mutations in the GLC3A (CYP1B1) gene.

PURPOSE: To describe three patients with congenital glaucoma homozygous and compound heterozygous for different mutations and benign sequence variants in the cytochrome P 450 1B1 (CYP1B1) gene. METHODS: All patients were examined by slit-lamp biomicroscopy, gonioscopy, measurement of the cornea and optic disc, ultrasound biometry, and automated static threshold perimetry when possible. Direct sequence analysis was performed on DNA extracted from peripheral blood from the patients and their parents. RESULTS: For patient 1, a newborn boy with buphthalmos and an opaque cornea, a novel homozygous C/T transition in codon 355 (CGA>TGA) led to a predicted nonsense codon Arg355X truncating the protein by 188 amino acids. For patient 2, a 24-year-old man, a compound heterozygous mutation 1410-1422del/1546-1555dup was found. For patient 3, a 34-year-old man, two novel heterozygous missense mutations resulting in an Ala443Gly and a Glu229Lys amino acid exchange and five benign sequence variants were found. CONCLUSION: Our results confirm the crucial role of CYP1B1 mutations for congenital glaucoma.

Adult↗
PubMed2000

Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.

Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes.

Arabidopsis↗
PubMed1999

Effects on blood pressure of drinking green and black tea.

BACKGROUND: The flavonoid components of tea have been associated in epidemiological studies with a decreased risk of cardiovascular disease. Flavonoids have been shown to have antioxidant and vasodilator effects in vitro; we therefore postulated that drinking green or black tea attenuates the well-characterized acute pressor response to caffeine and lowers blood pressure during regular consumption. OBJECTIVE: To determine whether green and black tea can attenuate the transient pressor effect of caffeine, or lower blood pressure during regular consumption. METHODS: In the first study, the acute effects of four hot drinks - green tea and black tea (at a dose equivalent to four standard cups), water matched to the teas for caffeine content ('caffeine') and water - were assessed in 20 normotensive men using a Latin-Square designed study. Clinic blood pressure was measured before and 30 and 60 min after each drink had been ingested. In the second study, the effects on blood pressure of regular green and black tea ingestion were examined in 13 subjects with high-normal systolic blood pressure and mild systolic hypertension (systolic blood pressure in the range 130-150 mmHg) using a three-period crossover study. Five cups per day of green tea, black tea and caffeine (in hot water and matched to the teas) were consumed for 7 days each, in random order. Twenty-four hour ambulatory blood pressure was measured at the end of each seven-day intervention. Results are presented as means and 95% confidence intervals (CI). RESULTS: An acute pressor response to caffeine was observed. Relative to caffeine, there were further acute increases in systolic and diastolic blood pressure at 30 min among those drinking green tea [5.5 mmHg (95%CI -1.4 to 12.4) and 3.1 mmHg (95%CI -0.1 to 6.3), respectively] and black tea [10.7 mmHg (95%CI 4.0 to 17.4) and 5.1 mmHg (95%CI 1.8 to 8.4), respectively]. The changes in blood pressure at 60 min were not significant The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [increases of 1.7 mmHg (95%CI -1.6 to 5.0) and 0.9 mmHg (95%CI -1.3 to 3.1), respectively] or black tea [increase of 0.7 mmHg (95%CI -2.6 to 4.0) and decrease of 0.7 mmHg (95%CI -2.9 to 1.5), respectively] was not significant relative to caffeine. CONCLUSIONS: Contrary to our initial hypothesis, tea ingestion caused larger acute increases in blood pressure than caffeine alone. However, any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption.

Adult↗
PubMed1998

Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised.

BACKGROUND: It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. AIMS: To clarify the effects of H pylori infection on the mucus gel barrier in vivo. METHODS: Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. RESULTS: There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) micron, 106 (30) micron, respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) micron, p=0.03) compared with those without atrophy. CONCLUSIONS: A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

Aged↗
PubMed1998

Sexually transmitted diseases in Ulaanbaatar, Mongolia.

Although human immunodeficiency virus (HIV) rates are increasing rapidly in Asia, a full understanding of the extent of other sexually transmitted diseases (STDs) in many of these areas is lacking. There have been anecdotes of rising rates of STDs in Mongolia, a country thus far relatively unaffected by HIV. To further the understanding of STDs, a prevalence study was conducted in the STD clinic in Ulaanbaatar, the capital and largest city in Mongolia. Among 260 patients, the prevalence of gonorrhoea, chlamydia and syphilis was 31.1%, 8.1% and 8.6% respectively for males and 10.3%, 9.9% and 6.0% for females. Sixty-seven per cent of females had trichomoniasis and 19.7% of males had non-gonococcal urethritis (NGU). Forty-two per cent of gonococcal isolates had plasmid mediated resistance to penicillin, and chromosomal resistance to penicillin, tetracycline, and ciprofloxacin was documented. No patients were infected with HIV. STDs are a significant problem in Mongolia. Improved control efforts are urgently needed to prevent the emergence of HIV.

Adolescent↗
PubMed1998

Goals for Alzheimer's care in nursing homes: what kind of differences do special care units expect to make?

Special Care Units (SCUs) for people with dementia have been enthusiastically promoted although many residents with dementia live elsewhere in their nursing home. In response to open-ended questions during personal interviews, coordinators of all 64 SCUs in Minnesota nursing homes described their goals and criteria for success. They then rated the importance of a list of possible goals and their unit's success in achieving them. Unit coordinators of 173 nursing home units in facilities with SCUs and 135 units in facilities without SCUs answered the same questions about people with dementia in their own units. When unprompted, respondents both in and outside SCUs were varied, sparse (averaging 3.1 goals per person), vague, process-oriented rather than outcome-oriented, and sometimes unrealistic. Yet, respondents later strongly endorsed most of the 24 goals the researchers suggested. ANOVA and regression analyses revealed few statistically significant differences according to unit type, although SCU coordinators were more likely to aspire to fewer medications, reduced disruptive behavior, and reduced agitation and anxiety, and were less likely to want residents to sleep through the night. Some differences were only between SCUs and non-SCUs in facilities without SCUs. Characteristics of facilities, coordinators, and case mix (e.g., proportion of dementia on the unit) were as predictive of goals and perceptions of success as SCU units. Findings reinforce the lack of conceptual clarity about expectations for direct and indirect effects of SCUs.

Aged↗
PubMed1998

A novel method for the visualization of the in situ mucus layer in rat and man.

1. The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa. 2. In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 degreesC) and the use of a water-soluble mountant. 3. A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) micrometer; B, 179 (48) micrometer; C, 184 (50) micrometer; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) micrometer. 4. This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.

Aged↗
PubMed1997

Effectiveness and economic impact of antidepressant medications: a review.

This article reviews the existing literature on the pharmacoeconomics and effectiveness of antidepressant medications. Although selective serotonin reuptake inhibitors (SSRIs) have not proved to be more efficacious than the older tricyclics, and their prescription costs are significantly higher, they provide superior effectiveness; ie, patients are less likely to discontinue taking them or switch antidepressants. Pharmacoeconomic studies consistently demonstrate a relationship between this superior effectiveness and reductions in overall treatment costs, often through decreased utilization of medical and hospital services. The most conservative study found a cost offset that more than negated the extra cost of drugs, although the cost savings were not statistically significant. Other studies found statistically significant lowering of utilization costs by using SSRIs rather than tricyclics. Studies comparing SSRIs with each other present conflicting findings, although fluoxetine appears to have an edge over sertraline and paroxetine with regards to effectiveness and pharmacoeconomics. More studies employing a prospective outcome design and naturalistic study setting need to be conducted with SSRIs and other new antidepressants.

Antidepressive Agents, Second-Generation↗
PubMed1997

Mucus and H. pylori.

A continuous, adherent mucus gel layer with mucosal bicarbonate secretion is the initial protective barrier in the stomach and duodenum against erosion by the gastric juice. H. pylori resides within the adherent mucus gel layer close to the epithelial surface. The barrier function of the mucus layer in vivo depends on (i) its thickness, and (ii) its gel structure, a property which is linearly dependent on the polymeric mucin content. We have shown in vivo that H. pylori colonisation alone did not decrease the thickness of the adherent gastric mucus barrier, although there was a mean 20% decrease in mucus thickness in those H. pylori positive subjects with underlying gastric atrophy. There was, however, a significant mean 18% reduction in the gel-forming polymeric mucin content of mucus from H. pylori subjects, independent of underlying atrophy. Studies in vitro suggest this loss of gel structure might arise from a H. pylori mediated, high local pH generated by urease activity rather than by proteolysis. This study shows that H. pylori infection alone does not compromise the overall integrity of the mucus barrier in vivo. However, in the immediate environment of the organism there appears to be a localised loss of mucus gel structure. The mucus barrier is compromised if H. pylori associated gastric atrophy or peptic ulceration follows.

Animals↗
PubMed1996

The reinforcing effects of brief exposures to nitrous oxide in healthy volunteers.

The reinforcing and subjective effects of brief (about 1.5 min) exposures to nitrous oxide, ranging from inspired concentrations of 20-80% in oxygen, were examined in 11 healthy volunteers. A choice procedure was used in which during each of four sessions, subjects first sampled a given concentration of nitrous oxide and placebo oxygen, and then chose between the two. 20, 40, 60 and 80% nitrous oxide were chosen by five, four, three, and three subjects, respectively--these choice levels did not exceed that of chance. All concentrations had psychoactive effects, and in general, concentration-related subjective effects were found. We conclude that in a medical setting, nitrous oxide inhaled in a manner similar to that when used recreationally in a naturalistic setting, does not function as a reinforcer across a wide range of concentrations, in subjects with a modest lifetime history of psychoactive drug use.

Adult↗
PubMed1996

Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes.

BACKGROUND: Regulation of the inflammatory response within the human lung is essential to prevent this important part of the normal host defence response becoming a pathological process. Tumour necrosis factor alpha (TNF-alpha) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis in many organ systems including the lung. Interleukin 10 (IL-10) has been proposed as having an inhibitory effect on the production of several inflammatory cytokines including TNF-alpha. METHODS: The effect of IL-10 administration on TNF-alpha production was explored in human alveolar macrophages and peripheral blood monocytes from matched individuals. The effects of IL-10 on TNF-alpha protein production were determined by sandwich enzyme linked immunosorbant assay (ELISA), whereas the TNF-alpha mRNA response was established by Northeren blotting using a TNF-alpha specific oligonucleotide probe. The protein synthesis inhibitors actinomycin D and cyclohexamide were utilised to monitor IL-10 effects on mRNA degradation and de novo protein synthesis, respectively. RESULTS: The lipopolysaccharide-mediated TNF-alpha production in alveolar macrophages was reduced from 3.508 (0.629) to 2.035 (0.385) ng/ml by 100 U/ml IL-10. Lipopolysaccharide-induced TNF-alpha production in peripheral blood monocytes was reduced from 2.035 (0.284) to 0.698 (0.167) ng/ml. TNF-alpha gene expression was also inhibited in both alveolar macrophages and peripheral blood monocytes; lipopolysaccharide-induced TNF-alpha mRNA was reduced by 47.8 (15.2)% and 83.1 (4.2)%, respectively, by IL-10. The IL-10 mediated suppression of TNF-alpha mRNA was unaffected by addition of cyclohexamide, suggesting that de novo protein synthesis was not required for TNF-alpha inhibition. mRNA stability experiments indicated no acceleration in lipopolysaccharide-induced TNF-alpha mRNA degradation in response to IL-10. CONCLUSIONS: These findings suggest that IL-10 is a potent inhibitor of TNF-alpha expression and release from alveolar macrophages and peripheral blood monocytes, and thus it may have an important role in the cytokine network of the pulmonary immune response.

Adult↗