Biomedical subjects

N Miller

Publications and source records attributed to N Miller.

At least 19 recordsLinked to original sources

PubMed2006

Molecular profiling techniques and bioinformatics in cancer research.

AIMS: Our aim was to describe the commonly used molecular profiling techniques in cancer research, to examine their limitations and to discuss the challenges of bioinformatics. METHODS: A literature search was performed using the PubMed database to identify publications relevant to this review. Citations from these articles were also examined to yield further relevant publications. RESULTS: We describe the use of DNA microarrays, comparative genomic hybridisation, tissue microarrays and digital differential display. The limitations of these technologies, their contribution to cancer research and the challenges of bioinformatics are also discussed. CONCLUSIONS: Although these high throughput technologies each have their own limitations they are rapidly developing and contributing significantly to our understanding of cancer genetics. They have also led to the emergence of bioinformatics as a rapidly developing and vital field.

Biomarkers, Tumor↗

PubMed2006

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Deltaproteobacteria↗

PubMed2006

Retention of the patella in total knee arthroplasty for rheumatoid arthritis.

AIM: To determine whether retention of the native patella during total knee arthroplasty is appropriate in patients with rheumatoid arthritis. METHODS: All patients undergoing total knee arthroplasty with a diagnosis of rheumatoid arthritis were identified between January 1997 and December 2000. Subsequently, each individual underwent both radiological and clinical assessments at a designated follow-up clinic. RESULTS: A total of 30 total knee arthroplasties were studied in 28 patients. Twenty-six patients (93%) were female with a mean age of 74.7 years (range 60-83 years). The average post-operative interval was 59.4 months (range 46-82 months). All individuals were noted to have satisfactory patellar tracking and bone stock at the time of surgery. No patient subsequently underwent revision surgery during follow-up and no episodes of implant sepsis were identified. The mean Patellar Score at final follow-up was 26.2 (range 22-30) with an average anterior knee pain score of 14.2 (range 10-15). The mean Oxford Knee Score was 18.7 (range 16-23) with a mean pain score component of 5.9. Patients were finally assessed with respect to the Knee Society Score. The mean Knee Score was 83.8 (range 71-96) with a mean Function Score of 79.7 (range 40-90). CONCLUSION: By retaining the native patella we were still able to obtain highly satisfactory medium-term results in terms of pain relief and function. In addition, the potential complications associated with prosthetic replacement of the patella were avoided.

Aged↗

PubMed2006

A prospective randomised controlled trial of the Kiwi Omnicup versus conventional ventouse cups for vacuum-assisted vaginal delivery.

OBJECTIVE: To evaluate the performance and safety of the Kiwi Omnicup and compare it to conventional vacuum cups in routine clinical practice. DESIGN: A randomised controlled trial of the Kiwi Omnicup versus conventional vacuum cups. SETTING: Queen Charlotte's and Chelsea Hospital, a tertiary referral hospital in London from April 2001 to March 2004. POPULATION: Women requiring assisted vaginal delivery by ventouse. METHODS: Women were randomised to the Kiwi Omnicup (n=206) or conventional vacuum cups (n=198). Data regarding maternal demographics, labour, mode of delivery and maternal and neonatal outcome were collected. MAIN OUTCOME MEASURES: Failure of delivery with instrument of first choice. RESULTS: The Kiwi Omnicup was less successful at delivery with instrument of first choice than the conventional ventouse, failure rate 30.1 versus 19.2% (RR 1.58; 95% CI 1.10-2.24). It was associated with a greater number of cup detachments (mean 0.68 compared with 0.28, with 44% compared with 18% having at least one detachment [P<0.0001]). There was no difference in the incidence of severe maternal trauma, and there were no cases of serious neonatal injury. CONCLUSIONS: The Kiwi Omnicup is less successful than conventional ventouse in achieving vaginal delivery, but its safety profile is comparable.

Adult↗

PubMed2006

Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Adult↗

PubMed2006

Effect of stage of lactation and parity on mammary gland cell renewal.

Milk production is a function of the number and activity of mammary epithelial cells, regardless of stage of lactation. Milk yield is generally higher in multiparous cows than in primiparous cows, but persistency is usually greater in the latter group. We compared several measures related to metabolic activity, apoptosis, and endocrine control of mammary cell growth in 8 primiparous and 9 multiparous cows throughout lactation. Mammary gland biopsies were taken in early [10 d in milk (DIM)], peak (50 DIM), and late (250 DIM) lactation to evaluate gene expression and determine DNA and fatty acid synthase (FAS) content. Milk samples taken the day before the biopsies were used to detect protease activities and to determine stanniocalcin-1 (STC) concentrations. Blood samples served to measure insulin-like growth factor-1, prolactin, and STC concentrations. Milk yield was higher in multiparous cows than in primiparous cows at the 10 DIM (32.8 +/- 1.3 and 25.2 +/- 0.8 kg/d) and 50 DIM (38.0 +/- 1.2 and 29.8 +/- 1.1 kg/d), but it was the same for both groups at 250 DIM (23.9 +/- 1.5 and 23.8 +/- 1.1 kg/d). Except for stearoyl-coenzyme A desaturase, expression of genes related to milk synthesis was not affected by stage of lactation. However, gene expression of acetyl-coenzyme A carboxylase, beta-casein, and FAS was lower in early lactation in primiparous cows. Expression of both proapoptotic bax and antiapoptotic bcl-2 genes was higher in primiparous cows, whereas the bax-to-bcl-2 ratio was not changed. Mammary DNA concentration was higher in multiparous cows, as was the amount of FAS protein in early lactation. Two bands of protease activity were found in milk samples, and one of the bands had an apparent molecular weight similar to gelatinase A and was dependent on the stage of lactation. Serum insulin-like growth factor-1 increased with day of lactation and was higher in primiparous cows. Serum prolactin decreased in late lactation, but peak values were observed in early lactation for primiparous cows and peak lactation for multiparous cows. Milk STC content increased with advancing lactation. The results are consistent with a lower degree of differentiation and a greater capacity for cell renewal in the mammary gland of primiparous cows.

Animals↗

PubMed2005

Pathological and molecular predictors of the response of rectal cancer to neoadjuvant radiochemotherapy.

AIMS: The prediction of sensitivity and resistance to neoadjuvant therapy has great potential value for many tumour sites. A neoadjuvant regimen is increasingly the gold standard in rectal cancer management and the aim of this review was to highlight predictive markers currently assessed and evaluate their clinical utility. METHODS: A systematic search of Medline was conducted using the following keywords 'colorectal', 'neoadjuvant', 'molecular', 'predict' and 'radiotherapy'. Original manuscripts from all relevant listings were sourced. These were hand searched for further articles of relevance. RESULTS: Conventional indices including tumour stage and grade were unable to predict histological response. Immunohistochemical assessment of P53 gene, Bcl 2, Bax and microsatellite instability are of no predictive value. Studies utilising molecular response predictors from archival pre-treatment tumour tissues have identified several promising predictive markers including p21, spontaneous apoptosis and direct sequencing of the p53 gene. Global gene expression from fresh pre-treatment tissue using cDNA microarray has only recently been assessed but identified expression differences between 54 genes and was able to predict response with 78% sensitivity and 86% specificity. CONCLUSIONS: Currently there are no clinically useful predictors of response based on standard pathological assessment and immunocytochemistry. Direct gene sequencing of p53, studies of apoptosis and global gene sequencing may hold promise.

Biomarkers, Tumor↗

PubMed2005

Psychiatric comorbidity in gender identity disorder.

OBJECTIVE: Despite being recognized as an important prognostic factor for the outcome in gender identity disorder (GID), psychiatric comorbidity has rarely been assessed by means of standardized diagnostic instruments. The aim of this study was to assess current and lifetime psychiatric comorbidity in patients with GID. METHODS: A cross-sectional sample of 31 patients who were treated for GID was assessed by the structured clinical interview for Axis I and II (SCID-I/II) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Twenty-nine percent of the patients had no current or lifetime Axis I disorder; 39% fulfilled the criteria for current and 71% for current and/or lifetime Axis I diagnosis. Forty-two percent of the patients were diagnosed with one or more personality disorders. CONCLUSIONS: Lifetime psychiatric comorbidity in GID patients is high, and this should be taken into account in the assessment and treatment planning of GID patients.

Adult↗

PubMed2003

Molecular identification and expression analysis of tumor necrosis factor in channel catfish (Ictalurus punctatus).

A tumor necrosis factor (TNF) alpha-like gene, encoding a propeptide of 230 amino acids and a mature (soluble) peptide of 162 amino acids, was identified in channel catfish (Ictalurus punctatus). While the catfish protein shared features in common with both mammalian TNFalpha and TNFbeta homologs, overall sequence identity/similarity was slightly higher vs. TNFalpha genes when mature TNF sequences were compared. Phylogenetic analysis placed catfish and other fish TNF sequences within their own cluster apart from mammalian TNFalpha and beta genes, and supported the suggestion that TNFalpha and beta genes separated after the divergence of mammals and teleosts. In contrast to trout and carp, but similar to flounder, catfish TNF was present as a single copy gene. Expression studies demonstrated that catfish TNFalpha mRNA was present in all tested tissues (i.e. liver, spleen, head kidney, mesonephros, gill, thymus, and PBLs) from an unstimulated fish. Moreover, catfish TNF was constitutively expressed in actively proliferating, but otherwise unstimulated, macrophage (42TA) and T cell (G14D; TS32.17) lines, but not in B cell (1G8 or 3B11) or fibroblast lines. TNF expression was upregulated in PBLs, and in G14D and 42TA cells, but not in 3B11 cells, by PMA/calcium ionophore treatment. These results demonstrate that a catfish homolog of TNFalpha has been identified, and indicate that catfish TNFalpha is expressed in catfish in a manner similar to that seen in mammals.

Amino Acid Sequence↗

PubMed2003

A randomized, double-blind trial of the efficacy and safety of 10 or 20 mg rabeprazole compared with 20 mg omeprazole in the maintenance of gastro-oesophageal reflux disease over 5 years.

BACKGROUND: Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year. AIM: To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years. METHODS: Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease. RESULTS: One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated. CONCLUSIONS: Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Short-term natural history of isolated gastrocnemius and soleal vein thrombosis.

OBJECTIVE: Lower extremity deep vein thrombosis is often isolated to the sinusoidal veins draining the gastrocnemius and soleus muscles. The purpose of this study was to establish the incidence rate of propagation of isolated gastrocnemius and soleal vein thrombosis (IGSVT) into the deep veins of the calf and thigh. METHODS: All patients who were referred for color flow duplex ultrasonography (CFDU) for suspected deep vein thrombosis were prospectively evaluated for IGSVT. Patients with IGSVT received no systemic anticoagulation therapy and underwent serial CFDU at 5, 9, 14, 30, and 90 days after recruitment. The incidence and extent of IGSVT propagation were noted. Factors predictive of IGSVT extension were sought, including age, gender, side, symptoms, ambulatory status, and the presence of comorbid illness, including cardiac disease, cancer, hypercoagulable states, recent surgery or trauma, and previous venous disease. RESULTS: One hundred thirty-five limbs with IGSVT were studied for 3 months, and 16.3% of cases with IGSVT extended the thrombus to the level of the adjacent tibial, or peroneal, veins or higher. Only 3% of the cases with IGSVT propagated as cephalad as the popliteal vein, and 90.9% of IGSVT propagation occurred within 2 weeks of CFDU diagnosis. No IGSVT propagated to the level of the popliteal vein beyond 2 weeks from the time of CFDU diagnosis. No IGSVT extended into the deep veins of the thigh. By the end of the 3-month study period, 45.9% of thrombi had completely resolved. Only the presence of cancer was prognostic for IGSVT progression. CONCLUSION: During the 3-month study period, the short-term incidence rate of untreated IGSVT propagation to the level of the popliteal vein, even in the presence of cancer, was only 3%. Follow-up imaging to detect IGSVT propagation beyond 2 weeks from the time of diagnosis may not be necessary.

Adult↗

PubMed2003

Myocardial performance during maximal exercise in adolescents with anorexia nervosa.

AIM: To examine cardiac responses and indicators of myocardial function during maximal exercise in adolescent girls with anorexia nervosa. METHODS: Eight girls (mean age 16.3+/-2.7 years) who satisfied criteria for the diagnosis of anorexia nervosa underwent maximal cycle testing. Cardiac stroke volume and peak aortic velocity and mean acceleration of flow (markers of myocardial contractility) were assessed using Doppler echocardiography and compared to healthy control subjects. Gas exchange variables were measured using open circuit spirometry techniques. RESULTS: Resting and maximal heart rates were less in the patients, and maximal oxygen uptake was significantly lower than controls. Maximal stroke index was greater in the patients than controls, with a normal pattern of response to progressive exercise. Peak aortic velocity and mean acceleration of flow were similar in the two groups when adjusted for heart rate. CONCLUSION: Findings of low heart rate and aerobic fitness previously described in patients with anorexia nervosa were confirmed. However, there was no evidence of abnormal myocardial performance during maximal exercise testing.

Adolescent↗

PubMed2002

Isolation of the provisionally named Desulfovibrio fairfieldensis from human periodontal pockets.

Sulfate-reducing bacteria have recently been associated with periodontitis and proposed to play a role in the pathogenesis of this chronic inflammatory process. Eight isolates of sulfate-reducing bacteria belonging to the genus Desulfovibrio were obtained from the periodontal pockets of five out of seven patients presenting with active periodontitis. A multiplex PCR was devised for their identification at the species level. All isolates were identified as Desulfovibrio fairfieldensis, a recently proposed new species. This finding reinforces the suggestion that Desulfovibrio fairfieldensis is a human bacterium that may present a pathogenic potential.

Adult↗

PubMed2002

Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects.

AIM: To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two-way crossover, clinical pharmacology study. METHODS: Twenty-four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1-5, with a 14-day 'wash-out'. Intragastric pH was recorded continuously, and serum gastrin measured, on days 0, 1 and 5. RESULTS: On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5-11, 14-24 and 0-24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0-14, 14-24 and 0-24 h. On day 5, mean serum gastrin AUC0-4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h). CONCLUSION: In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58.

Agrobacterium tumefaciens is a plant pathogen capable of transferring a defined segment of DNA to a host plant, generating a gall tumor. Replacing the transferred tumor-inducing genes with exogenous DNA allows the introduction of any desired gene into the plant. Thus, A. tumefaciens has been critical for the development of modern plant genetics and agricultural biotechnology. Here we describe the genome of A. tumefaciens strain C58, which has an unusual structure consisting of one circular and one linear chromosome. We discuss genome architecture and evolution and additional genes potentially involved in virulence and metabolic parasitism of host plants.

Agrobacterium tumefaciens↗

PubMed2001

Extraordinary variation in a diversified family of immune-type receptor genes.

Immune inhibitory receptor genes that encode a variable (V) region, a unique V-like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in two lineages of bony fish. In the present study, eleven related genes encoding distinct structural forms have been identified in Ictalurus punctatus (channel catfish), a well characterized immunological model system that represents a third independent bony fish lineage. Each of the different genes encodes an N-terminal V region but differs in the number of extracellular Ig domains, number and location of joining (J) region-like motifs, presence of transmembrane regions, presence of charged residues in transmembrane regions, presence of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails. Variation in the numbers of genomic copies of the different gene types, their patterns of expression, and relative levels of expression in mixed leukocyte cultures (MLC) is reported. V region-containing immune-type genes constitute a far more complex family than recognized originally and include individual members that might function in inhibitory or, potentially activatory manners.

Amino Acid Sequence↗

PubMed2001

Time-resolved imaging of spatiotemporal patterns in a one-dimensional dielectric-barrier discharge system.

A makeshift streak camera produces time-resolved images of filament patterns in a one-dimensional dielectric-barrier discharge system. The images reveal a variety of spatial and temporal structures, including temporally distinct discharge stages that occur at specific phases of the 12.5 kHz driving oscillation and spatially periodic filament arrays that are generated during the discharge stages. The data answer recent questions regarding time-averaged images of a similar system. Most notably, all but the simplest time-averaged images are due to the integration of multiple filament patterns generated in different discharge stages. Disordered states of the system are also examined. Some of these are spatially disordered but display temporal structure; others appear to lack both spatial and temporal order. Possibilities are suggested for investigations of surface-charge spreading and pattern stability in similar systems.

Journal Article↗

PubMed2001

Rapid and specific detection of the Mycobacterium tuberculosis complex using fluorogenic probes andreal-time PCR.

A rapid and sensitive strategy for the specific identification of Mycobacterium tuberculosis (TB) was designed and evaluated using crude mycobacterial lysates. The speed of real-time polymerase chain reaction (PCR) was combined with the sensitivity of fluorogenic probes to confirm the presence of mycobacteria as well as specifically identify the presence of members of the mycobacteria tuberculosis complex (MTC) in a single-tube assay. Oligonucleotides were designed to amplify the internal transcribed spacer (ITS) from several mycobacterial species. Specific fluorogenic probes were included in the PCR reaction for the identification of TB as well as Mycobacterium bovia and Mycobacterium africanum in bacterial lysates. The combination of TB-specific fluorogenic probes with real-time PCR formed an approach determined to be fast (less than 40 min), sensitive (less than 800 copies of DNA) and reliable for the specific detection of the MTC. Our data demonstrate the use of real-time PCR and fluorogenic probes in a rapid and sensitive assay to distinguish members of the MTC from other mycobacterial species.

DNA Primers↗