Biomedical subjects
J Cole
Publications and source records attributed to J Cole.
An initiative to improve older women's health.
A project was undertaken to investigate the health concerns and needs of women aged 45 to 55 in Bradford. Health-care professionals, including nurses, offered one-to-one consultations on maintaining health in middle-age and later life.
Survival of bacteria during oxygen limitation.
Regulatory mechanisms that enable bacteria associated with food, drinks and the human body to adapt to changes in the availability of oxygen are reviewed. Excess oxygen induces two adaptive responses to oxidative stress. Five or more control circuits enable enteric bacteria to generate energy and grow well in anaerobic environments. Two sets of enzymes catalyse both nitrate and nitrite reduction, and dual two-component regulatory systems sense and respond to the available nitrate and nitrite in the environment. The periplasmic nitrate reductase enables bacteria to scavenge low concentrations of nitrate: similar systems are found in food-borne and other pathogens.
Mouse lymphoma thymidine kinase locus gene mutation assay: International Workshop on Genotoxicity Test Procedures Workgroup Report.
The Mouse Lymphoma Assay (MLA) Workgroup addressed and reached consensus on a number of issues. Discussion focused on five areas: (1) acceptable assay versions; (2) cytotoxicity measure; (3) 24-hr treatment; (4) microwell colony counting and sizing; and (5) data acceptability/statistical analysis. Although the International Conference on Harmonisation (ICH) indicated a preference for the microwell over the soft agar method, all of the workgroup members agreed that both versions of the MLA are equally acceptable. The workgroup agreed that it is desirable for both assay versions to use the same measure of cytotoxicity to define the acceptable and required concentration range. Currently, laboratories using the microwell version use the relative survival (RS) determined by cloning immediately after the treatment. Laboratories using the soft agar method do not obtain an RS but use the relative total growth (RTG), a combination of the relative suspension growth (RSG) during the expression period and the relative cloning efficiency determined at the time of mutant selection. The workgroup agreed to investigate the RSG, the RS, and the RTG and to develop further guidance. In the interim, the workgroup reached consensus that the RTG be used as the standard measure of cytotoxicity. The ICH recommended a 24-hr treatment in the absence of S9 when negative results are obtained with short (3-4 hr) treatments. The workgroup agreed to retain this requirement but acknowledged that more data are needed prior to making final recommendations concerning the need for and the specific protocol for the 24-hr treatment. Environ. Mol. Mutagen. 35:185-190, 2000 Published 2000 Wiley-Liss, Inc.
Molecular methods for the detection of mutations.
We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.
The role of proprioception and attention in a visuomotor adaptation task.
The role of proprioception in the control and adaptation of visuomotor relationships is still unclear. We have studied a deafferented subject, IW, and control subjects in a task in which they used single joint elbow extension to move to a visual target, with visual feedback of the terminal position provided by a cursor displayed in the plane of their movements. We report the differences in movement accuracy between the deafferented subject and controls in the normal task and when challenged with a cognitive load, counting backwards. All subjects were less accurate when counting; this was a small effect for the controls (<10% change) but much greater for the deafferented subject (>60% change). We also examined changes in movement kinematics when the instructed amplitude was altered via a changed gain between final arm position and presentation of the feedback cursor. The deafferented subject maintained temporal movement parameters stable and altered amplitude by scaling force (i.e. changed peak velocity), whereas the controls scaled both movement velocity and duration. Finally, we compared the subjects' adaptation of movement amplitude after a period of exposure to the changed visuomotor gain. The deafferented subject was able to adapt, but his adaptation was severely impaired by the counting task. These results suggest that proprioception is not an absolute requirement for adaptation to occur. Instead, proprioception has a more subtle role to play in the adjustment to visuomotor perturbations. It has an important role in the control of reaching movements, while in the absence of proprioception, attention appears necessary to monitor movements.
On the immunity principle: a view from a robot.
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In a medium containing glucose, lactate carbon is incorporated by gonococci predominantly into fatty acids and glucose carbon incorporation is increased: implications regarding lactate stimulation of metabolism.
The reason for stimulation by lactate of metabolism of gonococci growing in a medium containing glucose, which enhances pathogenicity by increasing growth rate, lipopolysaccharide (LPS) synthesis and protein formation, has been investigated. Tricine dodecylpolyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) on homogenates of gonococci grown in this medium with [14C]lactate showed that lactate carbon was preferentially incorporated into lipid and LPS. Nuclear magnetic resonance (NMR) spectroscopy on lipid extracted from gonococci grown in the glucose containing medium with [13C]lactate showed that lactate carbon was incorporated into fatty acid moieties and not into ethanolamine or glycerol moieties. In contrast, NMR on lipid from gonococci grown with [13C]glucose indicated glucose carbon in both moieties. When unlabelled lactate was added, lipid synthesis from [l3C]glucose was stimulated and small amounts of different fatty acids were formed. The NMR data shows that gluconeogenesis from lactate carbon does not occur in the presence of glucose, suggesting that lactate is used solely for rapid production, via pyruvate, of acetyl CoA, the precursor not only for fatty acid synthesis but also for the constituents and products of the citric acid cycle, including ATP. The rapid formation of a high level of acetyl CoA is the probable reason for the stimulation of metabolism and oxygen uptake by lactate. 14C label on LPS was detected in its fatty acids. Most proteins that stained with silver in tricine SDS-PAGE were not significantly labelled by [14C]lactate in the glucose-containing medium. Two of three appreciably labelled proteins were identified by N-terminal sequencing as GroEL and porin 1B, and one of the two less labelled proteins was similar to peroxiredoxin type proteins. There were no signs of specific induction of these proteins by lactate and their labelling was consistent with fatty acids in attached lipid.
CT-determined intracranial volume for a normal population.
Intracranial volume comparisons of patients with craniosynostosis and normal have been contrary to expectations, leading to questioning of the validity of the current normal reference material. Computed tomography-determined intracranial volume is presented for a white normal population. Specifically, intracranial volumes for 157 subjects (82 female and 75 male) were measured from computed tomography data using the Cavalieri estimator: volume determination was based on measuring the area in each computed tomography section. Monomolecular and Gompertz models were applied to find curves of best fit to the intracranial volume as a function of the age. The best fit was obtained using the monomolecular model when the response variable was the logarithmically transformed intracranial volume, and the independent variable was the logarithm of the age from conception. For example, the mean (standard deviation) for male subjects at 1 year and 20 years were 1,125.6 (89.6) ml and 1,472.9 (117.2) ml, respectively, and for female subjects 1,024.9 (84.0) ml and 1,321.7 (108.3) ml, respectively. Although the shape and rate of increase of the female and male curves is similar, the female mean is 1.3 standard deviations below the male mean at 20 years. These curves were compared with the commonly referenced curves of Blinkov (1941), Lichtenberg (1960), and Dekaban (1977). Our male curve is substantially higher than these curves in the age range 8 months to 4 years. Our female curve, however, is approximately 1 standard deviation below Lichtenberg's curve from birth to 7 months. There are then only minor differences between our female curve and Lichtenberg's curve until his curve crosses ours at 41 months, where they significantly diverge from approximately 4.5 years. Our curves indicate that 95% of the final intracranial volume has been attained by 42 months for girls and 46 months for boys.
Terminal restriction fragment length polymorphism analysis program, a web-based research tool for microbial community analysis.
Rapid analysis of microbial communities has proven to be a difficult task. This is due, in part, to both the tremendous diversity of the microbial world and the high complexity of many microbial communities. Several techniques for community analysis have emerged over the past decade, and most take advantage of the molecular phylogeny derived from 16S rRNA comparative sequence analysis. We describe a web-based research tool located at the Ribosomal Database Project web site (http://www.cme.msu.edu/RDP/html/analyses. html) that facilitates microbial community analysis using terminal restriction fragment length polymorphism of 16S ribosomal DNA. The analysis function (designated TAP T-RFLP) permits the user to perform in silico restriction digestions of the entire 16S sequence database and derive terminal restriction fragment sizes, measured in base pairs, from the 5' terminus of the user-specified primer to the 3' terminus of the restriction endonuclease target site. The output can be sorted and viewed either phylogenetically or by size. It is anticipated that the site will guide experimental design as well as provide insight into interpreting results of community analysis with terminal restriction fragment length polymorphisms.
Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice.
While nephrologists often observe reduced hematocrit associated with inhibitors of angiotensin-converting enzyme (ACE), the basis for this effect is not well understood. We now report that two strains of ACE knockout mice have a normocytic anemia associated with elevated plasma erythropoietin levels. (51)Cr labeling of red cells showed that the knockout mice have a normal total blood volume but a reduced red cell mass. ACE knockout mice, which lack tissue ACE, are anemic despite having normal renal function. These mice have increased plasma levels of the peptide acetyl-SDKP, a possible stem cell suppressor. However, they also show low plasma levels of angiotensin II. Infusion of angiotensin II for 2 weeks increased hematocrit to near normal levels. These data suggest that angiotensin II facilitates erythropoiesis, a conclusion with implications for the management of chronically ill patients on inhibitors of the renin-angiotensin system.
Peer-based differences among boys with ADHD.
Examined the peer interactions and peer acceptance of three groups of boys ages 8 to 11 1/2 years: attention deficit hyperactivity disorder (ADHD), predominantly inattentive type; ADHD, combined type; and nonclinical controls (N = 45). Peer nominations were obtained from each boy's classroom. Newly acquainted peers consisting of boys from each of the 3 groups were observed for 3 play sessions, after which peer nominations were obtained. Both ADHD groups were more likely than nonclinical controls to receive lower social preference scores from peers in the classroom but not in the play groups. In both settings, boys from the predominantly inattentive group were more likely to be nominated as very shy, whereas boys from the combined type group were more likely to be nominated for starting fights and arguments. Observations of the play group showed that boys from the predominantly inattentive group displayed a marked pattern of social withdrawal. The findings suggest that the peer rejection experienced by these 2 groups may result from very different social behavior patterns.
Insights derived from ACE knockout mice.
The evaluation of ACE knockout mice has illustrated the tremendous physiologic importance of the RAAS. We have discussed how interruption of this system influences blood pressure, renal function, renal development, serum and urine electrolyte composition, haematocrit and male reproductive capacity. This body of data underlines the modelling of the RAAS as a type of biological machine that is positioned to respond to environmental insult and to maintain a homeostasis of blood pressure, blood volume and electrolyte composition. These data also emphasise Harry Goldblatt's seminal observation that the kidney and the RAAS are intimately linked in the regulation of normal blood pressure.
Home versus hospice inpatient care: discharge characteristics of palliative care patients in an acute care hospital.
This prospective survey was initiated to identify factors that helped and hindered home discharge for 100 consecutive patients who did not require further specialist palliative or acute care. Information was collected on demographics, functional ability (using the Palliative Performance Scale [PPS] and Karnofsky Performance Scale [KPS]), cognitive function at discharge as measured by the Mini-Mental State Examination (MMSE), home support circumstances, and patient and family preference for discharge. 59 patients were discharged home and 41 were transferred to a hospice. Younger patients with younger caregivers were discharged home more often. Patients with better MMSE and better functional ability (PPS and KPS) were also more likely to go home. Patients going home were more likely to be married. Preference for site of discharge was met for 76% of patients and 90% of families. Of the patients going to a hospice, 24% of patients and 7% of families preferred a home discharge. More physical support at home could have facilitated a home discharge for 13 patients. Functionally dependent and cognitively impaired patients were generally unable to return home. To support patients and their families in an environment of their choice, access to increased physical support in the home must be addressed.
Radiographic analysis of femoral tunnel position in anterior cruciate ligament reconstruction.
Successful reconstruction of the anterior cruciate ligament (ACL) depends on anatomic placement of a graft ligament substitute. This study examined the accuracy of a plain radiograph in determining femoral tunnel position during ACL reconstruction. Nine cadaveric distal femurs had six separate tunnels made in each specimen: 12:00 (high position), 1:30 (anatomic position), and 3:00 (low position) in the left femora and 12:00 (high), 10:30 (anatomic), and 9:00 (low) in the right femora. At each position on the clock face, two 9-mm tunnels were drilled, leaving 2 mm (correct) and 12 mm (incorrect) of posterior wall intact. With a radiopaque tunnel dilator in each tunnel, a true lateral radiograph, a 10 degree externally rotated lateral radiograph, and a 10 degree internally rotated lateral radiograph were obtained. All radiographs were analyzed for femoral tunnel placement in the anteroposterior plane with the four-quadrant method described by Harner et al and the ratio method described by Aglietti et al. Statistically significant differences could only be distinguished between anatomic (10:30), anterior (12-mm rim), and posterior (2-mm rim) positions. There were no statistically significant differences for any of the other positions when comparing true laterals to true laterals, true laterals to internal or external oblique views, or when comparing internal and external oblique views. A malpositioned anterior tunnel (12-mm rim posterior), which was "low" at 9:00 or "high" at 12:00 in the notch (malplaced), could not be distinguished reliably from an anatomically correct placed tunnel with a single-plane lateral radiograph.
The relationship between the scarf ratio and subsequent motor performance in infants born preterm.
The relationship between the scarf ratio and subsequent motor performance in Thai infants born preterm was the focus of this study. The scarf ratio was measured in 61 infants at 36 and 40 weeks postconceptional age (PCA). At 40 weeks PCA, one-, two-, three-, and four-months adjusted age, the infants were evaluated using the Test of Infant Motor Performance. Pearson product moment correlations revealed significant positive correlations between the scarf ratio and the infants' later motor performance. Because the scarf ratio can be a useful measure of shoulder girdle muscle tone, it may provide a valuable indicator of subsequent motor performance in infants born preterm who might be considered to be at risk for developmental delay.
El Niño and the related phenomenon Southern Oscillation (ENSO): the largest signal in interannual climate variation.
El Niño and the related phenomenon Southern Oscillation (ENSO) is the strongest signal in the interannual variation of ocean-atmosphere system. It is mainly a tropical event but its impact is global. ENSO has been drawing great scientific attention in many international research programs. There has been an observational system for the tropical ocean, and scientists have known the climatologies of the upper ocean, developed some theories about the ENSO cycle, and established coupled ocean-atmosphere models to give encouraging predictions of ENSO for a 1-year lead. However, questions remain about the physical mechanisms for the ENSO cycle and its irregularity, ENSO-monsoon interactions, long-term variation of ENSO, and increasing the predictive skill of ENSO and its related climate variations.
Variability of presentation in hereditary neuropathy with liability to pressure palsy results in underrecognition.
The genetic defect responsible for hereditary neuropathy with liability to pressure palsy (HNPP) is located in the same segment that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A). HNPP had been presumed to be rare until an epidemiological study found a much higher incidence than was expected; the researchers suggested that HNPP was underrecognized because many affected persons have mild symptoms. We believe that another reason for underdiagnosis of HNPP is the marked phenotypic variability of the disease. We recommend, therefore, that DNA analysis for the 17p11.2 deletion be considered in patients with unexplained demyelinating neuropathy regardless of family history.