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Biomedical subjects

J R Ellis

Publications and source records attributed to J R Ellis.

At least 19 recordsLinked to original sources
PubMed2006

Adult small intestinal stem cells: identification, location, characteristics, and clinical applications.

There are few systems which enable adult tissue stem cells to be studied. However, the gastrointestinal tract with its high degree of polarity, well-defined cell migratory pathways, and dynamic cell replacement is a model tissue providing unique opportunities for stem cell study. Lineage tracking indicates that all cell replacement originates at well-defined stem cell positions, with an associated slower cell cycle. Radiobiological studies suggest a hierarchical stem cell compartment (actual and potential stem cells). Actual stem cells have an intolerance of genotoxic damage and die via apoptosis. Stem cells also selectively sort the old and new DNA strands at division, retaining the replication error free strands in the stem cell daughter. High genotoxic sensitivity and selective sorting of old and new DNA strands, provides extremely effective protective mechanisms against both replication and random errors. This provides a new explanation for the low cancer risk in the small intestine.

Adult↗
PubMed2006

High genetic diversity in a rare and endangered sunflower as compared to a common congener.

Determining the genetic structure of isolated or fragmented species is of critical importance when planning a suitable conservation strategy. In this study, we use nuclear and chloroplast SSRs (simple sequence repeats) to investigate the population genetics of an extremely rare sunflower, Helianthus verticillatus Small, which is known from only three locations in North America. We investigated levels of genetic diversity and population structure compared to a more common congener, Helianthus angustifolius L., using both nuclear and chloroplast SSRs. We also investigated its proposed hybrid origin from Helianthus grosseserratus Martens and H. angustifolius. Twenty-two nuclear SSRs originating from the cultivated sunflower (Helianthus annuus L.) expressed sequence tag (EST) database, and known to be transferable to H. verticillatus and its putative parental taxa, were used in this study thereby allowing for statistical control of locus-specific effects in population genetic analyses. Despite its rarity, H. verticillatus possessed significantly higher levels of genetic diversity than H. angustifolius at nuclear loci and equivalent levels of chloroplast diversity. Significant levels of population subdivision were observed in H. verticillatus but of a magnitude comparable to that of H. angustifolius. Inspection of multilocus genotypes also revealed that clonal spread is highly localized. Finally, we conclude that H. verticillatus is not of hybrid origin as it does not exhibit a mixture of parental alleles at nuclear loci, and it does not share a chloroplast DNA haplotype with either of its putative parents.

Base Sequence↗
PubMed2004

Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans.

Impairments in early information processing are a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and Alzheimer's disease (AD). Several lines of evidence implicate a dysfunction of the cholinergic system in these disorders, particularly in AD where there is known degeneration in major cholinergic pathways. Inspection time (IT), a measure of early visual information processing speed, has been shown to be sensitive to cholinergic manipulation. The current study employed the IT task to (1) examine the independent roles of nicotinic and muscarinic receptors in modulating information processing and (2) investigate the interaction of nicotinic and muscarinic receptor systems in modulating information processing. Twelve healthy participants completed a randomized, double-blind, placebo-controlled study under four drug conditions; (1) placebo, (2) mecamylamine (15 mg; oral), (3) scopolamine (0.4 mg, s.c.), (4) mecamylamine (15 mg) + scopolamine (0.4 mg). IT measures were examined at baseline and 2.5 h post drug administration. Selective blockade of nicotinic receptors with mecamylamine did not significantly impair IT, whereas selective blockade of muscarinic receptors with scopolamine produced a significant but small impairment in IT. Combined blockade of both receptor types with scopolamine and mecamylamine produced a large impairment in IT performance. The results indicate that both nicotinic and muscarinic receptors are involved in modulating IT, and that the two systems may function synergistically to modulate early visual information processing. These findings suggest that functional abnormalities in both nicotinic and muscarinic systems may underlie deficits in early visual information processing seen in disorders such as Alzheimer's disease and schizophrenia.

Adult↗
PubMed2001

Is the SLC7A10 gene on chromosome 19 a candidate locus for cystinuria?

One of the genes (SLC7A9) that causes cystinuria, an inborn error of amino acid transport, is localized to 19q13. Close examination of human genomic DNA sequences has identified a similar gene (SLC7A10) that also maps to the 19q13.1 region and is highly expressed in kidney. The homologies between SLC7A9 and SLC7A10 are likely the result of gene duplication. SLC7A10 is known to encode a protein with a function similar to that of the SLC7A9 gene product. To determine if mutations in the SLC7A10 gene could also cause cystinuria, we characterized the primary genomic structure and sequenced the 11 exons and surrounding sequences from 10 unrelated patients with cystinuria. We identified one missense mutation which may account for cystinuria in one family. We also observed one intronic change, as well as one silent mutation, that were seen only in cystinuria patients. We therefore suggest that the SLC7A10 gene warrants further investigation as another candidate gene for cystinuria.

Amino Acid Sequence↗
PubMed2001

Lung cancer screening.

Prior attempts to screen for lung cancer using chest radiography and sputum cytology have proved unsuccessful. Recent reports have investigated the role of spiral CT in early lung cancer detection and have suggested that screening would be of value. Prior to the introduction of a national lung cancer screening programme, it would be essential to demonstrate that this would reduce mortality and would be cost effective.

Evidence-Based Medicine↗
PubMed1999

Histologic and immunologic associations of an HPV16 variant in LoSIL smears.

BACKGROUND: Human papillomavirus type 16 variants have been described and may have different biologic activities: this has implications for the design of HPV vaccines. OBJECTIVES: The aim of this study was to see if the HPV16 variant E-G 131 can be detected in women with preinvasive disease and to consider the histological and immunological implications of such infection. DESIGN: A prospective observational cross-sectional study on a cohort of women with minor cervical cytological abnormalities was performed. METHODS: Samples were tested for HPV DNA by polymerase chain reaction and restriction enzyme digestion. Blood samples were tested for antibodies to HPV16 virus-like particles (VLP) and to determine class I HLA types. Women found to have abnormal colposcopy were treated by large-loop excision of the transformation zone on a see-and-treat basis. RESULTS: Two hundred forty-one women were included in the study. Infection with the variant was detected in 20. 9% of cases and was not associated with any specific HLA type. These cases were more likely to have high-grade CIN than those with wild-type HPV16 or no HPV16 (chi2 = 18.85, P < 0.001). There were significant differences in seropositivity to HPV16 virus-like particles between the three groups (chi2 = 32.43, P < 0.001). CONCLUSIONS: The E-G 131 variant may have increased oncogenic potential by evading host immune responses, but its identification is only weakly predictive of high-grade disease in stepwise logistic regression. The lack of seropositivity to HPV16 VLP has implications for the design of prophylactic vaccines based on VLP to HPV16.

Adult↗
PubMed1995

The role of coronary revascularization in recipients of an implantable cardioverter-defibrillator.

The impact of adjuvant coronary revascularization was studied in a group of 138 recipients of an implantable cardioverter-defibrillator, all of whom had ischemic heart disease as the cause of their arrhythmias. Patients chosen for revascularization had more severe anatomic, symptomatic, or physiologic evidence of active ischemia. There were no operative deaths among 23 patients who actually underwent coronary artery bypass combined with cardioverter-defibrillator implantation; however, operative mortality by the intention-to-treat principle was 8% (2/25). Total cardiac survival was better for patients who underwent revascularization than for those patients who had "high-risk" characteristics and did not undergo revascularization. Stratified subgroup analysis demonstrated significant survival advantages favoring revascularization in patients with three-vessel or left main coronary artery disease, class III or IV angina, and an ejection fraction greater than 25%. Multivariate analysis revealed that low ejection fraction and left main coronary artery disease were independent predictors of decreased survival.

Adult↗
PubMed1995

Transvenous versus transthoracic cardioverter-defibrillator implantation. A comparative analysis of morbidity, mortality, and survival.

The hypothesis that transvenous implantation of a cardioverter-defibrillator is associated with less morbidity than use of a transthoracic approach was investigated in a retrospective series of 146 patients. None of these patients had concomitant heart procedures, and the preoperative characteristics of the two groups were similar. When analyzed by actual technique used (transvenous, 57 patients; transthoracic, 89 patients) and by the intention-to-treat method (transvenous, 65 patients, 8 of whom actually underwent thoracotomy; thoracotomy, 81 patients), transvenous implantation was associated with a lower incidence of postoperative respiratory complications and atrial fibrillation. Total cardiac mortality and freedom from sudden cardiac death in the transvenous and transthoracic groups were comparable at 2 years.

Aged↗
PubMed1995

The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer.

HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus (HPV) oncogene products may be important in the control of the HPV infections associated with the development of cervical cancer. We have identified, in HLA-B7 individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which alters an HLA-B7 peptide binding epitope in a way likely to influence immune recognition by CTLs. These results illustrate a biologically relevant mechanism for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both HLA type and HPV16 strain variation need to be considered in the screening of at-risk individuals and for the rational design of anti-HPV vaccines.

Amino Acid Sequence↗
PubMed1995

Squamous cell carcinoma of the ovary.

Benign cystic teratoma is a very common ovarian lesion; and it commonly occurs during a woman's reproductive years and most often is benign. In approximately 1% to 2% of cases, however, it can undergo a malignant transformation with a very poor prognosis. This is especially the case when disseminated disease is present. Usually the associated malignancy is squamous cell carcinoma, and radical surgery is recommended. An American Samoan woman was air-evacuated to Tripler Army Medical Center for further evaluation and therapy after having undergone an exploratory laparotomy and right ovarian cystectomy. Her pathology at the time of her initial procedure revealed a mature cystic teratoma with a malignant degenerative component. Her diagnostic evaluation upon arrival was unremarkable except for her physical exam and pelvic CT. She subsequently underwent a radical surgical procedure to include a surgical staging procedure, revealing disseminated squamous cell carcinoma with FIGO stage III disease. Whereas malignant transformation of a benign cystic teratoma is a rare occurrence, a high index of suspicion should be maintained whenever a preoperative diagnosis is encountered; a radical surgical approach with en bloc resection should be employed. Adjuvant therapy with radiation or chemotherapeutic agents in general has not been shown to improve the outcome, especially in disseminated disease.

Carcinoma, Squamous Cell↗
PubMed1994

Appropriate sensing of ventricular fibrillation after failed shocks in a transvenous cardioverter-defibrillator system.

BACKGROUND: Reduction in R-wave amplitude immediately after defibrillation shocks in an integrated shock/sense transvenous cardioverter-defibrillator (TCD) lead system has prompted concerns regarding adequate sensing after failed shocks. We therefore studied redetection characteristics for ventricular fibrillation after unsuccessful defibrillation shocks in a TCD system to determine if these observations have clinical relevance. METHODS AND RESULTS: Fifty patients with this shock/sense TCD lead system underwent conversion testing of their TCD at several time intervals. There were a total of 142 failed shocks events recorded, including 10, 15, 70, and 47 events at implantation, predischarge, and 2- and 6-month testing, respectively. Initial detection time (IDT) and redetection time (RDT) for ventricular fibrillation were measured from event markers for all unsuccessful defibrillation shocks. To assess the effect of failed shocks on electrogram quality, 54 failed shock episodes were evaluated in 37 of the 50 patients by measuring electrograms during VF before and after shock. Mean RDT for the entire group was 5.3 +/- 3.5 seconds compared with an IDT of 4.5 +/- 3.3 seconds (P = NS). There were no significant differences between IDT and RDT at implantation or any follow-up testing period, despite a significant decline in R-wave amplitude from 8.1 +/- 3.5 to 6.8 +/- 2.8 mV (P < .0001) measured 3 to 6 seconds after shock delivery. Analysis of 8 individuals with any extended RDT (> or = 10 seconds) showed no significant differences in clinical or implantation characteristics when compared with 42 individuals without extended RDT. CONCLUSIONS: In this integrated shock/sense TCD lead system, unsuccessful shock delivery has no significant effect on redetection of ventricular fibrillation at device implantation or up to 6 months of follow-up, despite an observed reduction in postshock R-wave amplitude. Therefore, the reported reduction in electrogram quality after a shock is of no practical importance because sensing of ventricular fibrillation does not appear to be compromised in this particular TCD system. Whether this applies to other implantable cardioverter-defibrillator pulse generators and lead systems with different sensing characteristics requires further evaluation.

Aged↗
PubMed1993

Low energy as part of a flexible strategy in hospital design.

It is well recognised that energy utilisation in hospitals often forms a significant element of the operation and revenue costs of such facilities. Whilst much attention continues to be focused on low energy, the importance of combining this within a flexible design strategy is often less well acknowledged. This paper highlights the need to consider energy when addressing flexibility in the design and planning of hospitals. It also shows how such an approach has been adopted in the UK's first low energy hospital, completed in 1990.

Air Conditioning↗