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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 19 recordsLinked to original sources
PubMed2001

Upconverting phosphor reporters in immunochromatographic assays.

Immunochromatographic assays have become popular diagnostic tools in a variety of settings because they are sensitive, fast, and easy to use. Here, we describe the use of a novel reporter, upconverting phosphors (UCP), in this assay format. UCP are submicron-sized, inorganic crystals that are excited with infrared light and that emit photons in the visible range depending on the ion composition of the crystal. Using human chorionic gonadotropin (hCG) as a model analyte to describe the properties of phosphors in immunochromatographic assays, a detection limit of 10 pg hCG in a 100-microl sample has been achieved on a regular basis, with occasional detection of 1 pg hCG. This represents at least a 10-fold improvement over conventional reporter systems such as colloidal gold or colored latex beads. Quantitation of analytes is possible over at least 3 orders of magnitude. Furthermore, an example is given of how UCP can be used for analyte multiplexing using a two-plexed wick for the detection of mouse IgG and ovalbumin. Thus, UCP lateral flow assays can be used for applications that are currently limited by assay sensitivity, and they can increase the probability of a diagnosis by verifying the presence of several analytes in the same sample.

Chorionic Gonadotropin↗
PubMed2001

Traumatic myiasis of geese in Hungary.

Five geese flocks were surveyed to gather data on the prevalence and clinical manifestation of traumatic myiasis and the fly species involved. Myiasis was recorded in all the flocks and the total number of infested geese was 26 (ca. 0.1% of the total numbers). The first cases were observed at the end of May, the last ones in August. Most birds (16/26) were infested in August. Each affected goose had only one lesion, which was located more frequently on the wings (14/26) than on any other body. In seven geese, Wohlfahrtia magnifica (Diptera: Sarcophagidae) was the only myiasis-causing species. In these cases the detransformed mean number of larvae per wound was 18.1 (range 5-40). Lucilia sericata (Diptera: Calliphoridae) was found to be solely responsible for the lesions of 12 birds, with detransformed mean of 94.0 (range 2-893) larvae per goose. The larvae of this species appeared to be generally less invasive than those of W. magnifica, but in three cases they were also deeply embedded in the wounds. In seven geese larvae of both fly species developed together in and around the wounds. With the exception of one lesion, there were more larvae of W. magnifica (detransformed mean of 21.8 with a range of 1-55) than that of L. sericata (detransformed mean of 11.2 with a range of 2-61) in these mixed infections. Predisposing conditions for development of traumatic myiasis in geese included plucking of feathers, other injuries and bacterial infections (e.g. inflammation of the phallus).

Animals↗
PubMed2001

Dissociable lexical and phonological influences on serial recognition and serial recall.

The impact of the lexicality of memory items on memory performance was compared in two paradigms, serial recall and serial recognition. Experiments 1 to 3 tested 7- and 8-year-old children. Memory accuracy was only mildly impaired in lists containing nonwords compared with words in a serial recognition task involving judgments of whether the items in two sequences were in the same order (Experiment 1), although a substantial advantage for word over nonword items from the same stimulus pool was found in serial recall (Experiment 2). A stronger influence of lexicality on serial recall than serial recognition was further demonstrated in Experiments 3A and 3B, and in 4A and 4B using adult participants. These experiments also established comparable degrees of sensitivity to the phonological similarity of the memory sequences in the two paradigms. The phonological similarity effect in serial recall was found to arise from increased phoneme order errors, whereas the lexicality effect was due principally to the greater frequency of phoneme identity errors for nonwords. It is proposed that the lexicality effect originates in the redintegration of item information just prior to recall, and that this process is largely bypassed in serial recognition.

Adult↗
PubMed2000

Reduced acute rejection and superior 1-year renal allograft survival with basiliximab in patients with diabetes mellitus. The Global Simulect Study Group.

BACKGROUND: Renal allograft recipients with diabetes mellitus often demonstrate poorer clinical outcomes than nondiabetic patients. Basiliximab (Simulect), a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection in renal allograft recipients in 2 multicenter, placebo-controlled, phase III trials. METHODS: An analysis of pooled results from the 2 trials was conducted to compare the efficacy and safety of basiliximab with placebo in renal transplant recipients with and without prior diabetes. Patients received either basiliximab (20 mg on day 0 and day 4 posttransplantation) or placebo in combination with cyclosporine for microemulsion (Neoral) and steroids. RESULTS: A total of 722 patients (150 diabetic, 572 nondiabetic) were eligible for intent-to-treat analysis. At 12 months, basiliximab as compared with placebo reduced the proportion of patients experiencing first acute rejection by 41% in diabetics (P<0.01) and by 29% in nondiabetics (P<0.001). Biopsy-confirmed rejection was reduced by 44% in diabetics (P<0.01) and by 26% in nondiabetics (P<0.01). The first acute rejection episode requiring augmented immunosuppression other than steroids was reduced by 49% in diabetics (P<0.01) and by 41% in nondiabetics (P<0.001); death, graft loss, or first rejection episode was reduced by 43% in diabetics (P=0.001) and by 22% in nondiabetics (P<0.01). Superior graft survival was maintained in diabetic recipients treated with basiliximab versus placebo (96% vs. 86%; P=0.022). There were no significant differences in safety between basiliximab and placebo in both diabetic and nondiabetic patients. CONCLUSIONS: Basiliximab is associated with a significant reduction in acute rejection and an excellent safety profile in renal transplant recipients with and without diabetes mellitus. Superior graft survival was evident in diabetic patients.

Acute Disease↗
PubMed2000

Paraoxonase activity is reduced by a pro-atherosclerotic diet in rabbits.

Serum paraoxonase (PON1) is believed to protect against the development of atherosclerosis because of its ability to retard the oxidation of low-density lipoprotein (LDL) by hydrolysing LDL-associated phospholipid and cholesteryl-ester hydroperoxides. We have examined the relationship between PON1 and atherosclerosis development in transgenic rabbits overexpressing human apolipoprotein (apo) A-I and nontransgenic littermates fed a pro-atherogenic diet. PON1 activity was higher in transgenic (4006.1 +/- 716.7 nmol/min/ml) compared to control (3078.5 +/- 623.3 nmol/min/ml) rabbits (P < 0.01) while high-density lipoprotein (HDL) cholesterol was 1.84 +/- 0.54 mmol/L in transgenic rabbits and 0.57 +/- 0.21 mmol/L in control rabbits (P = 0.0001). After feeding rabbits a high-cholesterol diet for 14 weeks HDL-cholesterol fell by 70% in both transgenic and control rabbits (P < 0.001 compared to week 0) PON1 activity fell by 50% in both groups of rabbits (P < 0. 01 compared to week 0). The amount of thoracic aortic surface area covered by lesions was 29 +/- 16% in the control group and 26 +/- 15% in the transgenic group (P = NS). A pro-atherosclerotic diet reduces PON1 which may exaggerate the effects of the diet on the development of atherosclerosis.

Animals↗
PubMed2000

Child pedestrian injury prevention project: student results.

BACKGROUND: Few comprehensive pedestrian safety interventions for primary-school-age children have been developed and evaluated. This paper reports the impact of the 3-year (1995-1997) Child Pedestrian In jury Prevention Project (CPIPP) on a cohort of 1603 children followed from age 6 to 9 years. This multicomponent project comprised an educational intervention for students, their parents and teachers, and the local community, as well as several environmental interventions. The primary aim of CPIPP was to improve children's road-related behavior and to enhance the safety of their road environment. METHODS: Three communities were assigned to the treatment conditions: (1) high-education, community, and environmental interventions; (2) moderate-education intervention only; and (3) comparison (usual road safety education). Children's pedestrian knowledge and road crossing and playing behaviors were assessed using a pre- and posttest self-report questionnaire. Their self-reported road crossing behaviors were validated using an observational schedule and brief interview. RESULTS: Children in the high and moderate intervention groups were significantly more likely to cross the road with adult supervision (P = 0.013) and play away from the road (P = 0.000) than the comparison group. No differences were detected in children's pedestrian safety knowledge between the intervention and comparison groups. CONCLUSIONS: While several methodological limitations may have influenced the study outcomes, these data nonetheless indicate that in the study sample the CPIPP educational intervention deaccelerated the natural increase in children's pedestrian-related risk behavior.

Accident Prevention↗
PubMed2000

Methods for evaluating a mature substance abuse prevention/early intervention program.

The authors describe methods for work in progress to evaluate four workplace prevention and/or early intervention programs designed to change occupational norms and reduce substance abuse at a major U.S. transportation company. The four programs are an employee assistance program, random drug testing, managed behavioral health care, and a peer-led intervention program. An elaborate mixed-methods evaluation combines data collection and analysis techniques from several traditions. A process-improvement evaluation focuses on the peer-led component to describe its evolution, document the implementation process for those interested in replicating it, and provide information for program improvement. An outcome-assessment evaluation examines impacts of the four programs on job performance measures (e.g., absenteeism, turnover, injury, and disability rates) and includes a cost-offset and employer cost-savings analysis. Issues related to using archival data, combining qualitative and quantitative designs, and working in a corporate environment are discussed.

Absenteeism↗
PubMed2000

The gapped xylem mutant identifies a common regulatory step in secondary cell wall deposition.

The phenotype of the novel gapped xylem (gpx) mutant is described. gpx plants exhibit gaps in the xylem in positions where xylem elements would normally be located. These gaps are not part of the transpiration stream and result in gpx plants having fewer functional xylem elements. The gaps are due to the absence of a secondary cell wall in developing xylem elements, resulting in complete degradation of these elements during cell death, and illustrate the importance of the secondary cell wall in retaining a functional xylem element following programmed cell death. Consequently the gpx phenotype suggests that the processes of secondary cell wall formation and cell death are independently regulated in developing xylem. gpx plants also exhibit a highly irregular pattern of secondary cell wall thickening in interfascicular cells, with some cells apparently undergoing little or no secondary cell wall deposition. Secondary cell wall deposition in plants involves the co-ordinate regulation of several complex metabolic pathways. The gpx mutant identifies a key step involved in regulating the deposition of secondary cell wall material in both xylem and interfascicular cells, and suggests that a common regulatory step controls secondary cell wall formation in these diverse cell types. The gpx mutant offers a unique opportunity to elucidate the mechanism by which the complex processes involved in secondary cell wall formation are co-ordinately regulated.

Arabidopsis↗
PubMed2000

Sulfakinin neuropeptides in a crustacean. Isolation, identification andtissue localization in the tiger prawn Penaeus monodon.

The sulfakinin (SK) family of neuropeptides are characterized by a C-terminal octapeptide sequence that begins with two acidic residues (most commonly DD), and ends with YGHMRF-NH2, usually with the tyrosyl residue sulfated. So far, sulfakinins have only been identified in insects and the present study was initiated to investigate if the family is more widely distributed within the arthropods. Purification of an extract of the central nervous system of the giant tiger prawn Penaeus monodon has revealed three novel members of the sulfakinin peptide family. One of the peptides, Pem SKI, has the sequence <QFDEY(SO3H)GHMRF-NH2, where <Q denotes a pyroglutamic acid residue, and is for all criteria typical of insect sulfakinins, several of which also have an N-terminal pyroglutamic acid. Tyrosyl O-sulfation was verified by mass spectrometry. The two other peptides have a hitherto unknown L/M variation at position three from the C-terminus. One of these, Pem SKII, has a particularly glycine-rich N-terminus, AGGSGGVGGEYDDYGHLRF-NH2. The other, Pem SKIII, is a truncated form of Pem SKII, with the sequence VGGEYDDYGHLRF-NH2. Mass spectrometry of the latter two peptides indicated that only one of the two tyrosyl residues is sulfated. By analogy, it is suggested that the sulfation is located at the residue in position six from the C-terminus. A small amount of a nonsulfated variant of Pem SKII was also present in the extract. Immunocytochemical studies with sulfakinin antisera show a sparse neuronal distribution pattern, similar to that of insects. A prominent pair of large (approximately 25 micrometer) cells and 6-8 pairs of smaller (approximately 10 micrometer) cells are present in the protocerebrum. The larger cells have prominent neurites that give rise to varicosities in the centre of the brain. Their axons exit the brain via the circumoesophageal connectives and continue along the intersegmental connectives. Each of the thoracic and abdominal ganglia has sulfakinin-immunoreactive arborizations as a result of branching from the intersegmental nerves. This distribution pattern strongly suggests a role in neurotransmission or neuromodulation, although it remains to be elucidated what the exact role(s) is. However, on account of the conservation of peptide structure during the evolutionary period spanning the insect/crustacean lineage, especially between Pem SKI and insect sulfakinins, it may be assumed that the sulfakinins have a significant physiological role.

Amino Acid Sequence↗
PubMed2000

Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: A clinicopathological study.

We describe 21 affected individuals from a kindred with early-onset autosomal dominant familial Alzheimer's disease caused by an intronic presenilin-1 mutation (in intron 4). Mean age at onset of symptoms was 37.4 years [95% confidence interval (CI): 36.6-38.2 years], mean age at death was 44.7 years (95% CI: 43.1-46.3 years) and mean duration of illness was 7.3 years (95% CI: 5.9-8.7 years). Myoclonus and seizures were prominent features of this pedigree. In the four cases for whom neuropsychometric data were available, verbal memory impairment preceded visual memory deficits; naming was relatively preserved until late in the disease. One of these four cases underwent serial volumetric MRI scans demonstrating in vivo brain tissue loss of 3.9% (38.9 ml, annualized rate of atrophy: 1. 7%) over 22 months of follow-up. The four individuals who had necropsies demonstrated the neuropathological hallmarks of Alzheimer's disease. Apolipoprotein E (APOE) status was assessed in five individuals: the case with the youngest age at onset at 33 years of age was found to be homozygous epsilon4/epsilon4, > 1 SD below the mean age of onset for those of known APOE genotype (36.4 +/- 2.3 years, mean +/- SD), and > 2 SDs below the mean age of onset for the pedigree as a whole (37.4 +/- 1.7 years, mean +/- SD). APOE genotype may therefore modulate age at onset in this pedigree.

Adult↗
PubMed2000

Are differences in interleukin 10 production associated with joint damage?

OBJECTIVE: Constitutive differences between individuals in cytokine production may determine the variation in the course of inflammatory arthritis. METHODS: The association between interleukin 10 (IL-10) production and joint destruction was studied by comparing IL-10 mRNA content in synovial biopsies from seven patients with destructive joint disease and six patients with non-destructive joint disease. The IL-10 mRNA content was 0.4 +/- 0.6 arbitrary units in erosive joints compared with 2.3 +/- 1.2 arbitrary units in non-erosive joints (P: < 0.03, Mann-Whitney U:-test). As this difference suggested that IL-10 production was associated with joint destruction, we tested whether the IL-10 locus determined the extent of joint damage. RESULTS: Innate differences in IL-10 production are locus-dependent. In line with these data, we showed that innate differences in IL-10 protein production were also present as differences in IL-10 mRNA levels. We tested if polymorphisms in the promoter of IL-10 were associated with the extent of joint damage. DISCUSSION: In a cohort study of female rheumatoid arthritis patients followed for 12 yr, the extent of joint destruction differed significantly between patients with different IL-10 genotypes. In patients with the -1082AA genotype who were studied prospectively, the mean increase in radiographic damage score (modified Sharp score of X-rays of hands and feet) during the first 6 yr was 9 +/- 9 per yr vs 19 +/- 16 per yr for patients with the genotype -1082GG (P: < 0.02). In line with these data, cultures of endotoxin-stimulated whole blood from 158 donors showed that the presence of the allele associated with less joint destruction correlated with slightly higher IL-10 production. CONCLUSIONS: Both the immunogenetic and the synovial biopsies suggest that a variation in IL-10 production is associated with joint destruction.

Adult↗
PubMed2000

Guidelines in gynaecology: evaluation in menorrhagia and in urinary incontinence.

OBJECTIVE: To evaluate the effectiveness of national guidelines and local protocols in improving hospital care (process and outcome) for women with menorrhagia and for women with urinary incontinence. DESIGN: 2 x 2 balanced incomplete block controlled before and after study. SETTING: Gynaecology units in four district general hospitals across Scotland. INTERVENTION: National guidelines were adapted locally to protocols, which were disseminated at specific local educational meetings and implemented by placing a copy of the appropriate protocol in women's hospital casenotes prior to consultation. POPULATION: Four hundred and ninety-seven women with menorrhagia and 449 women with urinary Incontinence. MAIN OUTCOME MEASURES: Process of care within six key areas of clinical practice: initial hospital assessment; appropriate use of hospital investigations; inappropriate use of hospital investigations; appropriate first line treatments; appropriate pre-surgery assessment; and use of surgical treatments. Outcome of care using condition-specific outcome measures and four domains of SF-36 at zero, six and twelve months following intervention. RESULTS: There were significant improvements with the introduction of guidelines and protocols in two (initial hospital assessment and appropriate pre-surgery assessment) of the six key areas of clinical practice assessed. In the other areas there were no significant improvements or deteriorations observed. There was no evidence of effect of guidelines and protocols on the condition-specific outcome measures or on the four domains of the SF-36. CONCLUSIONS: There were only very modest benefits observed from the introduction of guidelines and protocols on the hospital management of the two conditions. The reasons for this lack of impact of the guidelines is unclear. Experience of this study raises important methodological issues for future research in this area.

Adult↗
PubMed1999

Characterisation using microphysiometry of CRF receptor pharmacology.

We have assessed the utility of the Cytosensor microphysiometer for studying the pharmacology of recombinant CRF receptors. Chinese hamster ovary cells stably expressing the human CRF1 or CRF2 receptor were perfused in the Cytosensor with bicarbonate-free Hams F12 (pH 7.4) containing 0.2% bovine serum albumin. The rank order of potencies of agonist peptides were CRF = sauvagine = urocortin = urotensin at CRF1 (pEC50 values 11.16 +/- 0.17, 11.37 +/- 0.14, 11.43 +/- 0.09 and 11.46 +/- 0.13; n = 4), and urocortin = sauvagine > urotensin > CRF at CRF2 (pEC50 values 10.88 +/- 0.12, 10.44 +/- 0.05, 9.36 +/- 0.12 and 8.53 +/- 0.07; n = 7-9). alpha-Helical CRF (9-41) was a competitive antagonist at the CRF2 receptor (pK(B) = 6.99 +/- 0.08, n = 4), but was a partial agonist at the CRF1 receptor (pEC50 = 6.85 +/- 0.08, Emax = 33%, n = 3). CP 154,526 was a competitive antagonist at the CRF1 receptor (pK(B) = 8.17 +/- 0.05, n = 6), but was inactive at the CRF2 receptor. These data are consistent with established CRF receptor pharmacology and show that the Cytosensor is a viable method for assessing the functional activity of CRF-receptor agonists and antagonists.

Acid-Base Equilibrium↗
PubMed1999

High sensitivity immunoassays using particulate fluorescent labels.

The use of polystyrene fluorescent microspheres as sensitive labels in direct-detection (not enzymatically amplified) heterogeneous equilibrium "sandwich" immunoassays in 96-well plates is described. With mouse IgG as a model antigen, a fluorescent particulate label is more sensitive than a corresponding soluble reporter. The limit of detection of mouse IgG in the multiparametrically optimized assay was 0.2 ng/ml (7.6 x 10(8) antigens/ml) for the particulate reporter and 50 ng/ml (1.9 x 10(11) antigens/ml) for the soluble reporter. The sensitivities of assays using the particulate label were dependent on the surface densities of the capture and reporter antibodies and the concentration of reporter beads. Sensitivity was improved by adding the preformed reporter antibody/fluorescent microsphere complex to trapped antigen on the well surfaces instead of sequentially adding the reporter antibody and then the fluorescent microspheres. Maximal (equilibrium) binding of the particulate reporter to captured antigen occurred after 20 h with a concentration of 1.4 x 10(9) reporter beads/ml. Thus, particulate fluorescent labels provide high sensitivity in direct-detection immunoassays.

Animals↗
PubMed1999

The crayfish plasma clotting protein: a vitellogenin-related protein responsible for clot formation in crustacean blood.

Coagulation in crayfish blood is based on the transglutaminase-mediated crosslinking of a specific plasma clotting protein. Here we report the cloning of the subunit of this clotting protein from a crayfish hepatopancreas cDNA library. The ORF encodes a protein of 1,721 amino acids, including a signal peptide of 15 amino acids. Sequence analysis reveals that the clotting protein is homologous to vitellogenins, which are proteins found in vitellogenic females of egg-laying animals. The clotting protein and vitellogenins are all lipoproteins and share a limited sequence similarity to certain other lipoproteins (e.g., mammalian apolipoprotein B and microsomal triglyceride transfer protein) and contain a stretch with similarity to the D domain of mammalian von Willebrand factor. The crayfish clotting protein is present in both sexes, unlike the female-specific vitellogenins. Electron microscopy was used to visualize individual clotting protein molecules and to study the transglutaminase-mediated clotting reaction. In the presence of an endogenous transglutaminase, the purified clotting protein molecules rapidly assemble into long, flexible chains that occasionally branch.

Amino Acid Sequence↗