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Biomedical subjects

G A Clarke

Publications and source records attributed to G A Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Reducing hazard related falls in people 75 years and older with significant visual impairment: how did a successful program work?

BACKGROUND: In a randomized controlled trial testing a home safety program designed to prevent falls in older people with severe visual impairment, it was shown that the program, delivered by an experienced occupational therapist, significantly reduced the numbers of falls both at home and away from home. OBJECTIVES: To investigate whether the success of the home safety assessment and modification intervention in reducing falls resulted directly from modification of home hazards or from behavioral modifications, or both. METHODS: Participants were 391 community living women and men aged 75 years and older with visual acuity 6/24 meters or worse; 92% (361 of 391) completed one year of follow up. Main outcome measures were type and number of hazards and risky behavior identified in the home and garden of those receiving the home safety program, compliance with home safety recommendations reported at six months, location of all falls for all study participants during the trial, and environmental hazards associated with each fall. RESULTS: The numbers of falls at home related to an environmental hazard and those with no hazard involved were both reduced by the home safety program (n = 100 participants) compared with the group receiving social visits (n = 96) (incidence rate ratios = 0.40 (95% confidence interval, 0.21 to 0.74) and 0.43 (0.21 to 0.90), respectively). CONCLUSIONS: The overall reduction in falls by the home safety program must result from some mechanism in addition to the removal or modification of hazards or provision of new equipment.

Accidental Falls↗
PubMed2004

Cholesterol synthesis inhibition distal to squalene upregulates biliary phospholipid secretion and counteracts cholelithiasis in the genetically prone C57L/J mouse.

BACKGROUND AND AIMS: Newly synthesised cholesterol contributes poorly to biliary lipid secretion but may assume greater importance when the rate limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is upregulated. As this occurs in the gall stone susceptible C57L/J inbred mouse, we employed two cholesterol biosynthesis inhibitors, Tu 2208 and Ro 48-8071, potent inhibitors of squalene epoxidase and oxidosqualene-lanosterol cyclase, respectively, to assess their potential in preventing cholesterol cholelithiasis in the C57L/J mouse strain. Mice were fed a lithogenic diet comprising a balanced nutrient intake with 15% dairy fat, 1% cholesterol, and 0.5% cholic acid added. METHODS: We determined gall stone phenotype, HMGR activity, biliary lipid secretion rates, and counterregulatory events in male C57L/J mice and gall stone resistant AKR treated with Tu 2208 (30-60 mg/kg/day) or Ro 48-8071 (30-100 mg/kg/day), while ingesting chow or the lithogenic diet. RESULTS: Both agents reduced the gall stone prevalence rate from 73% to 17% in C57L/J mice, inhibited HMGR activity, and decreased hepatic cholesterol concentrations without appreciably influencing biliary cholesterol secretion. In C57L as well as AKR mice, both agents increased biliary phospholipid (which is mostly phosphatidylcholine) secretion rates and at the highest doses effectively reduced the biliary cholesterol saturation index. CONCLUSIONS: Cholesterol biosynthesis inhibitors acting distally to squalene do not reduce biliary cholesterol secretion rates despite reductions in cholesterol biosynthesis and hepatocellular levels. However, they effectively prevent gall stone formation through stimulation of pathways that lead to enhanced biliary phospholipid secretion.

Animals↗
PubMed2001

Tumour-derived mutated K-ras codon 12 expression in regional lymph nodes of stage II colorectal cancer patients is not associated with increased risk of cancer-related death.

This study examined the frequency of lymph node micrometastases detected by expression of mutant K-ras oncogene present in the respective primary tumour. The study population consisted of consecutive patients with stage II colorectal cancer (CRC) undergoing curative resection and with disease-free survival of 60 months or longer or CRC-related death. Of 27 patients found to have K-ras mutations at codon 12, 17 had genomic DNA suitable for PCR recovered from corresponding regional lymph node tissue. The same K-ras mutation was identified in the lymph nodes of 13 patients (76%), four of whom (30%) died of CRC recurrence within 5 years. A single patient in the negative group (25%) also died. Lymph node micrometastases detected by this technique thus show no relationship to mortality in stage II CRC. Further study of this technique is necessary before it can be used in the selection of patients for adjuvant chemotherapy.

Base Sequence↗
PubMed2001

The indications, utilization and safety of gastrointestinal endoscopy in an extremely elderly patient cohort.

BACKGROUND: In developed nations, increasing proportions of the population now reach advanced age. Physicians may be reluctant to refer such patients for non-critical diagnostic and therapeutic interventions, on the basis of perceived diminution of tolerance, safety and substantive benefits in these patients. We aimed to review the utility and safety of gastrointestinal endoscopy in an extremely elderly cohort. METHODS: The study involved 214 consecutive participants aged 85 years or more, between 1995 and 1997. They were identified using a prospective database linked to the endoscopy reporting system. Procedure type, indication, use of sedation, complications, and outcomes were evaluated. RESULTS: The median age was 87 (85-94, sigma = 2). The female:male ratio was 3:2; 185 had undergone one procedure and 29 two or more; and 65% of procedures were performed on an outpatient basis. Of the inpatient procedures, 10% of all procedures were performed emergently, predominantly for upper gastrointestinal hemorrhage. Midazolam was administered to 129 patients (60%), at a median dose of 2 mg (range 1-11); of these, 75 (35%) also received a median dose of 25 microg fentanyl (range 12.5-125). Colonoscopy (n = 95) was the most frequently performed procedure, followed by esophagogastroduodenoscopy (EGD) (n = 64) and endoscopic retrograde cholangiopancreatography (ERCP) (n = 21). There was no procedure-related mortality. The incidence of post-ERCP pancreatitis was 5%, colonic perforation 1%, and cardiopulmonary complications in sedated patients, 0.6%. The majority underwent procedures which related to active management of ongoing medical problems, and procedures were performed for palliative indications in only 15 (7%) patients. CONCLUSIONS: Gastrointestinal endoscopy is extremely safe and well tolerated in extremely elderly patients. Age alone should not influence decisions relating to its utilization.

Aged↗
PubMed2001

A simple automated solution for removing and applying sealing microplate lids.

With the improved reliability and efficiency of automation, there has been an increased desire to integrate automated sample management with automated screening systems. In order to store samples "on line" for an extended period of time, an automation-compatible means for sealing and unsealing microplates is necessary. Numerous commercial solutions are available for removing loose-fitting microplate lids; however, the task of removing a tight-fitting matted lid such as the RoboLid is more challenging. This paper discusses the design of an automated workstation for the application and removal of such tight-fitting microplate lids.

Equipment Design↗
PubMed1997

GP55 inhibits both cell adhesion and growth of neurons, but not non-neuronal cells, via a G-protein-coupled receptor.

There is compelling evidence for the role of inhibitory molecules in guiding neurons to their appropriate targets. Furthermore, continued expression of these molecules in the adult could explain why there is little regeneration of neurons in the central nervous system. We have previously identified a family of glycosyl phosphatidylinositol-linked glycoproteins (GP55) from adult chicken brain that has been shown to inhibit neurite outgrowth from dorsal root ganglion and forebrain neurons. GP55 consists of two or more glycoproteins and belongs to a subgroup of the lg superfamily which contains OBCAM, LAMP, neurotrimin and CEPU-1. We now show that GP55 is anti-adhesive, blocking the adhesion of neurons to normally adhesive substrata in a concentration dependent manner. The anti-adhesive effect can be blocked using antiserum raised against GP55 and pertussis toxin (PTX) but not the beta oligomer alone. In contrast, the adhesion of fibroblasts and Schwann cells to the substrata is not affected by GP55. Indeed, non-neuronal cells spread and grow normally. These results would suggest that both the anti-adhesive effect and the inhibition of outgrowth by GP55 is specific to neurons and is mediated by a PTX sensitive, G-protein-coupled receptor.

Animals↗
PubMed1996

A family of glycoproteins (GP55), which inhibit neurite outgrowth, are members of the Ig superfamily and are related to OBCAM, neurotrimin, LAMP and CEPU-1.

We have previously identified a glycosylphosphatidylinositol-linked glycoprotein of 55 kDa (GP55) which inhibits neurite outgrowth. We now provide evidence that GP55, isolated from adult chick brain, consists of at least two bands, both of which are active, i.e., block outgrowth of neurites from chick dorsal root ganglion neurons. An antiserum raised against the adult proteins reverses the inhibition and preliminary experiments suggest that GP55 is restricted to the nervous system, increases during development from very low levels at embryonic day 10 and is most abundant after hatching. Immunofluorescence reveals that GP55 is expressed on neurons cultured from an embryonic day 14 chick brain but is barely detectable on embryonic day 10 dorsal root ganglion neurons or embryonic day 8 forebrain neurons; the neurons which respond to substrate-bound GP55. Peptide sequencing revealed considerable homology with OBCAM, a protein previously identified on the basis of binding opiates. Nested polymerase chain reaction using primers to the OBCAM sequence and internal primers to GP55 peptides produced two different polymerase chain reaction fragments with homology to OBCAM. A full length clone (E19S) corresponding to one polymerase chain reaction product and a partial length clone (E14S) corresponding to the second have been isolated from an embryonic chick brain library. Both are members of the immunoglobulin superfamily and have (or are expected to have) three C2 domains. E19S has 90% homology with LAMP at the amino acid level. This sequence only partially matches the peptides from the adult protein and hence is probably not a major component of the adult proteins. E14S (GP55-A) has 83% homology to OBCAM at the amino acid level over the region sequenced. The sequence matches several of the peptides from the adult protein and is hence likely to correspond to a major component of the adult proteins. Thus members of the GP55 family are related to OBCAM, neurotrimin, LAMP and a recently discovered chick protein CEPU-1. Our results suggest molecules within this family are capable of acting as cell adhesion molecules and inhibitors of neurite outgrowth.

Amino Acid Sequence↗
PubMed1996

Gallium-67 imaging of pericardial lymphoma in AIDS.

A 33-yr-old homosexual man with acquired immune deficiency syndrome (AIDS) and Mycobacterium avium intracellulare (MAI) infection presented with fever, sweats, lethargy and dyspnea. A chest radiograph showed cardiomegaly and an echocardiograph revealed a large pericardial effusion. After pericardial aspiration, which confirmed T cell non-Hodgkin's lymphoma, he remained dyspneic. Gallium-67 imaging was performed to determine whether the patient's residual dyspnea was related to pulmonary MAI infection or lymphomatous infiltration of the heart. Planar 67Ga scintigraphy revealed intense tracer uptake in two areas within the mediastinum and surrounding the entire heart shadow but no evidence of pulmonary MAI infection. SPECT 67Ga scintigraphy precisely localized the two mediastinal abnormalities and demonstrated the tracer uptake around the heart to be pericardial rather than myocardial. Gallium-67 scintigraphy suggested that pericardial lymphoma was the likely basis of the patient's dyspnea.

AIDS-Related Opportunistic Infections↗
PubMed1995

A reappraisal of current methods for the assessment of planar gamma camera performance.

This study reappraises the acquisition parameters defined by three current protocols for the specification of planar gamma camera performance. These are the manufacturer Standards of the National Electrical Manufacturers' Association [1] and the International Electrotechnical Commission [2], and the user-orientated protocol of the UK Department of Health (DoH, formerly DHSS) Gamma Camera Performance Assessment Group [3]. The study looks specifically at three major planar performance characteristics: intrinsic non-uniformity, intrinsic spatial resolution and intrinsic non-linearity (spatial distortion). Acquisition parameters specified for these characteristics are investigated by testing a range of values for each parameter around those figures currently advocated by the three protocols. Those acquisition parameters which may be relaxed without loss of data integrity are identified and the adoption of revised parameters for some measurements within the DoH assessment protocol is suggested. Reviewing the data obtained, observations are made regarding the accuracy of some tests performed regularly for quality control purposes. The feasibility and advantages of incorporating some suitably modified DoH performance assessment tests within a routine quality assurance protocol for the gamma camera are also discussed.

Gamma Cameras↗
PubMed1994

Clinical experience with a multidetector SPET system (Toshiba GCA-9300A).

The clinical experience with the Toshiba GCA-9300A single photon emission tomography (SPET) system is discussed along with typical acquisition protocols for various SPET studies. The system was used to perform SPET studies in normals and in a variety of brain and body disorders. Its three Anger-type gamma cameras forming a triangular aperture offer a substantial increase in sensitivity compared to a single rotating gamma camera. This has allowed the routine use of lead fanbeam super high-resolution collimators (SHR FB) for 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain SPET studies and high-resolution parallel-hole collimators (HR PH) for cardiac and other body studies. The resulting improvement in spatial resolution coupled with the ease of patient positioning and the greater patient throughput compared to a conventional tomographic gamma camera, will enhance the role of brain and body SPET for both routine and research purposes.

Bone and Bones↗
PubMed1994

Identification of a novel protein from adult chicken brain that inhibits neurite outgrowth.

Glycoproteins that inhibit neurite outgrowth may guide growth cones during development by acting as a barrier and closing off inappropriate routes. Their continued expression in the adult central nervous system may be a key factor in preventing regeneration of central nervous system neurons. A glycoprotein of 55 kDa has been isolated from the detergent-insoluble membrane skeleton from adult chicken brain. Initial experiments showed that dorsal root ganglion neurons would not adhere to or extend neurites on a substratum coated with GP55. Furthermore, GP55 will act as a barrier to the advance of established growth cones in the presence of poly-L-lysine, laminin or G4. Central nervous system neurons from forebrain as well as dorsal root ganglion neurons from the peripheral nervous system are inhibited by GP55. GP55 is also effective in blocking the initial adhesion of neurons to a substratum of poly-L-lysine and, particularly, laminin. In contrast to the inhibition of neurite outgrowth, neuronal adhesion is concentration independent over the range tested. A preliminary investigation of the mechanism by which GP55 inhibits outgrowth suggests that a pertussis toxin-sensitive G protein is required. Preliminary evidence suggests that GP55 is anchored in the membrane by a glycosyl phosphatidylinositol moiety. GP55 is distinct from previously identified inhibitory proteins, based on the source and molecular mass, and is thus a new member of this rapidly expanding family.

Animals↗
PubMed1994

Stimulatory and inhibitory action of nitric oxide donor agents vs. nitrovasodilators on reactive oxygen production by isolated polymorphonuclear leukocytes.

Nitrovasodilators, particularly the nitric oxide donor agents, are known to inhibit leukocyte functions such as chemotaxis, adherence, migration and proteolytic enzyme release. In this study, we investigated the modulatory role of nitric oxide donor agents on reactive oxygen production by canine polymorphonuclear leukocytes using luminol-enhanced chemiluminescence (LDCL). LDCL was measured before and after activation using 1 mg/ml of opsonized zymosan in the absence or presence of various agents. Unlike the nitrovasodilators, nitroglycerin and nicorandil, the nitric oxide donor agents, 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside, both produced enhanced stimulation of LDCL following zymosan at low concentrations of the agonist and inhibition at high concentrations of the agonist. SIN-1 and sodium nitroprusside (but not nitroglycerin or nicorandil) also produced LDCL before activation of cells with zymosan. This increase was blocked by superoxide dismutase or catalase but not by the hydroxyl radical scavenger, mannitol. SIN-1c, the inactive product of SIN-1 produced no LDCL. Furthermore, incubation of 10 microM SIN-1 or nitroprusside with luminol in the absence of cells produced no chemiluminescence at these drug concentrations. The stimulation of LDCL in the prezymosan phase was partially inhibited by methylene blue and L-nitroarginine methyl ester. In zymosan-stimulated cells, the enhanced LDCL induced by SIN-1 was prevented with superoxide dismutase, catalase (but not mannitol) and reversed with L-nitroarginine methyl ester. Thus, nitric oxide donor agents may either stimulate or inhibit oxygen radical production by isolated neutrophils depending on the drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10.

We cloned a mouse histidase cDNA to identify the mutation in histidinemic mice (his/his) and to determine the relationship of the histidase locus (Hal) both to Chromosome 10 markers and to Hsd, the histidase activity variant locus. The his mutation, a G to A transition at nucleotide +965, changes Arg-322 to Gln (R322Q). Expression of the R322Q allele in COS cells resulted in proportionately reduced amounts of histidase protein and activity compared to the wildtype allele. Hal maps approximately 4 cM distal to the insulin-like growth factor-1 locus and approximately 10 cM proximal to steel. Hsd was found to be tightly linked to Hal, and the low-histidase-activity Hsd allele was associated with reduced histidase mRNA. These studies indicate that the R322Q allele reduces the stability of histidase, position Hal on the Chromosome 10 linkage map, and provide further evidence that Hsd is allelic to Hal.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Substrate-bound GP130/F11 will promote neurite outgrowth: evidence for a cell surface receptor.

GP130/F11 is a neuronal cell adhesion molecule belonging to the Ig superfamily. Preliminary evidence suggests that it may be important for the fasciculation of axons and cell-cell interactions during synaptogenesis. Previous work has shown that when F3 (the mouse homologue) is transfected into Chinese hamster ovary (CHO) cells it will act as a substrate for neuronal growth and adhesion. In this study we have shown that isolated GP130/F11 will also act as a substrate for the growth of chick dorsal root ganglia cell neurons. The concentration of GP130/F11 on the surface of sympathetic neurons, grown for one day in culture was approximately 40 ng cm-2 which was comparable to the levels required to stimulate neurite outgrowth. Deglycosylation of GP130/F11 or partial denaturation by boiling did not abolish the activity. However, after treatment with dithiothreitol, GP130/F11 was no longer capable of stimulating neurite outgrowth. GP130/F11 will also stimulate neurite outgrowth from forebrain neurons from 7 to 9-day-old embryos. These do not express GP130/F11 until around day 10, providing further evidence that GP130/F11 interacts with an as yet unknown cell surface receptor.

Animals↗
PubMed1993

Physical performance evaluation of the Toshiba GCA-9300A triple-headed system.

The physical performance of the Toshiba GCA-9300A triple-headed SPECT system has been assessed. Using a water-filled cylinder containing 99mTc, the tomographic volume sensitivity was 33.8 and 34.8 kcps/(MBq/ml)/cm for the high-resolution, parallel-hole (HR-PH) collimator and the super high-resolution, lead fanbeam (SHR-FB) collimator, respectively, excluding the rotation time(s) during scanning when data are not acquired. The tomographic spatial resolution at the center, in air, with 132 mm radius of rotation was 10.2 and 7.8 mm FWHM with the HR-PH and SHR-FB collimators, respectively; in water it was 11.0 and 7.8 mm. Reconstructed relative activity concentrations were accurate for both collimator sets if attenuation correction was used. With the SHR-FB collimators, the average peak-to-valley ratio of five-line sources in water improved significantly when an asymmetric energy window was used. Using the three-dimensional Hoffman brain phantom which simulates a 4:1 grey matter-to-white matter ratio and the usual choice of acquisition and processing parameters for brain studies, the reconstructed grey matter-to-white matter ratio was only about 1.7 for total counts typically acquired in a 99mTc-HMPAO study (4.0 M counts) and only 2.3 for 40 M counts. There was a qualitative improvement with an asymmetric energy window.

Brain↗
PubMed1992

Preoperative imaging of colorectal cancers. Targeting the epithelial membrane antigen with a radiation-labeled monoclonal antibody.

The epithelial membrane antigen (EMA) is expressed by the majority of colorectal cancers but has not previously been investigated as a target for radiation-labeled monoclonal antibodies (MoAb) in the imaging of patients with colorectal cancer. A rat IgG2a MoAb that recognizes EMA, ICR2, was labeled with Indium-111 (100 megabecquerel per milligram [MBq/mg]MoAb) using the bicyclic anhydride of the chelating agent diethylene triamine pentacetic acid (ccDTPA) and was administered intravenously to 22 patients known to have or thought to have colorectal cancer. Daily gamma camera imaging was performed for 3 days during the time between the administration of the radiation-labeled antibody and surgical procedure. At operation, the biopsies were done of the tumors and the normal colon, and the uptake of radiation-labeled MoAb was measured in a gamma well-counter. Immunocytochemistry for EMA expression also was done on resected tumors. Independent unblinded and blinded reporting was done on all scans. The sensitivity of 111In-ICR2 for detecting cancers preoperatively was 80% and 60%, respectively, on unblinded and blinded reporting, and the corresponding specificity 20% and 60%. The low unblinded specificity was attributable to a false-positive localization in severely dysplastic benign tumors (n = 2) and inflammatory tissue (n = 2). Liver metastases present in three patients were cold relative to normal liver. Lymph node metastases were localized in 1 of 6 patients preoperatively. The mean absolute uptake of 111In-ICR2 in tumor tissue was 7.75 +/- 3.77 x 10(-3) percent of injected dose per gram, and the ratio to normal colon was 2.10 +/- 0.92:1. On immunohistochemistry, EMA was expressed by 16 of the 17 primary cancers, both dysplastic adenomas, and all nodal metastatic deposits. EMA-negative tumors (1 cancer + 1 colonic lipoma) had negative antibody scans, and patients whose tumor was negative or only focally positive for EMA expression had lower tumor/normal colon ratios of radioactivity (1.30 +/- 0.26 versus 2.45 +/- 0.65, P = 0.005) on gamma well-counting of excised specimens. These results suggest a possible role for 111In-ICR2 in the detection of colorectal cancer and metastases but not its liver deposits.

Aged↗
PubMed1990

Effects of inhibitors on proteinase activities in gels following isoelectric focussing.

Homogenates of rat submandibular glands were electrophoresed on isoelectric focussing gels and bands of proteinase activity demonstrated by means of overlay membranes impregnated with fluorogenic oligopeptide substrates. Inhibition characteristics of individual proteinase bands were tested within the gels and after excision and subsequent elution from the gels. Some bands of activity were resistant to inhibition by pre-incubation of the gel with certain inhibitors, but were subsequently found to be inhibited when tested with the same substrate after elution. These inconsistencies were influenced by the use of different substrates. The results indicate that, though some useful screening information may be obtained by applying inhibitors to the gels, this system does not permit a reliable assessment of inhibition characteristics which require subsequent elution and assay.

Amino Acid Sequence↗