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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 37 records · Page 2Linked to original sources

Religious commitment and the construal of sources of help for emotional problems.

Religious commitment as an influence upon seeking help for psychological problems has not received the same level of research attention as variables such as sex, ethnicity and cultural background. The construing of members of a group of committed UK Christians was investigated, regarding their receiving such help from a variety of different helpers, professional and non-professional, secular and spiritual. Each participant was asked to interpret the factors statistically identified from construct and element relationships in a repertory grid that they had completed. Their commentaries formed the data for a qualitative thematic analysis, which gave rise to four main themes. From these, a tentative model is discussed. Possible implications for the acceptance of service provision by the substantial minority groups of religiously committed people in the UK are considered in the light of this model--and in the light of the further research that would be needed to establish it.

Adult↗

The assessment of a "nurse led" deliberate selfharm service.

OBJECTIVE: To determine the effectiveness of a nurse led deliberate selfharm assessment service. DESIGN: Nine month retrospective survey and comparison with previous system. SETTING: Stobhill General Hospital, North Glasgow. SUBJECTS: Two hundred and eighty three Medical inpatients referred following deliberate selfharm, with completed data on 272 cases. RESULTS: The service significantly reduced admissions to psychiatric inpatient care from 24% to 7%. A dedicated nurse led service, has led to consistency in parasuicide assessments, reduced stigma and negativity towards DSH patients, led to better joint working between Stobhill General Hospital and Psychiatric services and reduced inappropriate psychiatric outpatient referrals. CONCLUSIONS: A dedicated nurse led DSH assessment service benefits patients and reduces psychiatric hospital admissions. A member of the psychiatric staff working on a daily basis within the general medical wards enhances joint working, ensures smoother communication between helping agencies and increases treatment options.

Health Services Research↗

A telomerase component is defective in the human disease dyskeratosis congenita.

The X-linked form of the human disease dyskeratosis congenita (DKC) is caused by mutations in the gene encoding dyskerin. Sufferers have defects in highly regenerative tissues such as skin and bone marrow, chromosome instability and a predisposition to develop certain types of malignancy. Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing. Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif. Telomerase adds simple sequence repeats to chromosome ends using an internal region of its RNA as a template, and is required for the indefinite proliferation of primary human cells. We find that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomerase activity and have shorter telomeres than matched normal cells. The pathology of DKC is consistent with compromised telomerase function leading to a defect in telomere maintenance, which may limit the proliferative capacity of human somatic cells in epithelia and blood.

Adult↗

In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain.

Multi-echo Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.5 T and 4.0 T imaging systems to test their ability to measure in vivo multi-component T2 relaxation behavior in normal guinea pig brain. The known dependence of accurate T2 measurements on the signal-to-noise ratio (SNR) was explored in vivo by comparing T2 decay data obtained using three methods to increase SNR (improved RF coil design, signal averaging and increased magnetic field strength). Good agreement between T2 values of nickel-doped agarose phantoms was found between imaging and spectroscopic methods. T2 values were determined for gray matter (GM) and white matter (WM) locations from images of guinea pig brain in vivo. T2 measurements of GM were found to be monoexponential at both field strengths. The mean T2 times for GM were 71 ms at 1.5 T, and 53 ms at 4.0T. The highest average SNR was achieved using an improved RF coil at 4.0T. In this case, two peaks were extracted in WM, a "short" T2 peak at approximately 6 ms, and a "medium" T2 peak at approximately 48 ms. T2 values in GM and the major component of WM were significantly decreased at 4.0T compared to 1.5 T. The improved SNR attained with this optimized imaging protocol at 4.0T has allowed for the first time extraction of the myelin-sensitive T2 component of WM in animal brain in vivo.

Animals↗

Effects of combined shear and thermal forces on destruction of Microbacterium lacticum.

A twin-screw extruder and a rotational rheometer were used to generate shear forces in concentrated gelatin inoculated with a heat-resistant isolate of a vegetative bacterial species, Microbacterium lacticum. Shear forces in the extruder were mainly controlled by varying the water feed rate. The water content of the extrudates changed between 19 and 45% (wet weight basis). Higher shear forces generated at low water contents and the calculated die wall shear stress correlated strongly with bacterial destruction. No surviving microorganisms could be detected at the highest wall shear stress of 409 kPa, giving log reduction of 5.3 (minimum detection level, 2 x 10(4) CFU/sample). The mean residence time of the microorganism in the extruder was 49 to 58 s, and the maximum temperature measured in the end of the die was 73 degrees C. The D(75 degrees C) of the microorganism in gelatin at 65% water content was 20 min. It is concluded that the physical forces generated in the reverse screw element and the extruder die rather than heat played a major part in cell destruction. In a rotational rheometer, after shearing of a mix of microorganisms with gelatin at 65% (wt/wt) moisture content for 4 min at a shear stress of 2.8 kPa and a temperature of 75 degrees C, the number of surviving microorganisms in the sheared sample was 5.2 x 10(6) CFU/g of sample compared with 1.4 x 10(8) CFU/g of sample in the nonsheared control. The relative effectiveness of physical forces in the killing of bacteria and destruction of starch granules is discussed.

Actinomycetales↗

A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3' end.

Simple sequence repeat telomeric DNA is maintained by a specialized reverse transcriptase, telomerase. The integral RNA subunit of telomerase contains a template region that determines the sequence added to chromosome ends. Aside from providing the template, little is known about the role of the telomerase RNA. In addition, no hypotheses have been suggested to account for the striking evolutionary divergence in size and sequence between telomerase RNAs of ciliates, yeasts, and mammals. We show that the two- to threefold increase in size of the mammalian telomerase RNAs relative to ciliate telomerase RNAs is due to the presence of an extra domain resembling a box H/ACA small nucleolar RNA (snoRNA). The human telomerase RNA (hTR) H/ACA domain is essential in vivo for hTR accumulation, hTR 3' end processing, and telomerase activity. By substituting the U64 box H/ACA snoRNA for the hTR H/ACA domain, we demonstrate that a heterologous snoRNA can function to promote chimeric RNA accumulation and 3' end processing but not telomerase activity. In addition, we show that maturation of full-length hTR and its assembly into active telomerase occur from an mRNA promoter-driven RNA polymerase II transcript but not from a U6 snRNA promoter-driven RNA polymerase III transcript. Finally, we show that a small percentage of hTR is associated with nucleoli. These results have implications for the biogenesis and structure of hTR and the human telomerase ribonucleoprotein complex. They also expand the structural and functional diversity of the box H/ACA snoRNA motif.

Animals↗

Reduced visual evoked responses in multiple sclerosis patients with optic neuritis: comparison of functional magnetic resonance imaging and visual evoked potentials.

The limited application of functional magnetic resonance imaging (fMRI) for investigations of multiple sclerosis (MS) patients has already shown that deficits of the motor, cognitive and visual systems may be identified by differences in the patterns of activation in response to a suitable stimulus. In MS patients with unilateral optic neuritis, the area of activation in the primary visual cortex, measured by fMRI techniques, is dramatically reduced in response to stimulation of the affected eye. The latency of the major positive component of the visual evoked potential (VEP) recorded upon stimulation of the affected eye is significantly increased in these patients, as compared to the unaffected eye and normal volunteers. We have found a correlation between the neural response measured using fMRI and the latency of the VEP. fMRI signal responses have the potential to provide more detailed topographic information relating to functional deficits in MS.

Evoked Potentials, Visual↗

Sonographic surveillance of abdominal aortic aneurysms: what is the smallest change in measured diameter that reliably reflects aneurysm growth?

OBJECTIVE: The decision to repair an abdominal aortic aneurysm may be based on an apparent increase in aneurysm diameter seen in successive sonographic examinations. However, true aneurysm growth can be diagnosed only if the measured increase in aneurysm diameter exceeds the variability inherent in the measurement. This study uses analysis of variance to determine the smallest change between 2 successive, independent sonographic measurements of aneurysm diameter that reliably indicates aneurysm growth. METHODS: Pairs of independent observers examined 63 patients with abdominal aortic aneurysms. Each observer obtained a sonographic measurement of the anteroposterior aneurysm diameter in the transaxial and longitudinal scan planes, and the transverse aneurysm diameter in the transaxial scan plane. Analysis of variance yielded the total variance associated with each type of measurement as well as the contributions made by variance among aneurysms, variance between observers and residual variance. These components were used to estimate interobserver standard error of measurement, interobserver reliability and the smallest measurement change needed to diagnose true aneurysm growth. RESULTS: Differences among aneurysms made the largest contribution to overall variance. Interobserver reliability was excellent, ranging from 0.89 to 0.94 (with perfect reliability being 1.00). The smallest difference between 2 successive, independent anteroposterior diameter measurements that indicated aneurysm growth at the 95% confidence level was 0.78 cm in the transaxial scan plane and 0.92 cm in the longitudinal scan plane. The smallest difference between 2 successive, independent transverse diameter measurements that indicated aneurysm growth at the same confidence level was 1.05 cm. CONCLUSION: Despite high interobserver reliability, only changes in measured aneurysm diameter greater than or equal to 0.78 cm indicate aneurysm growth at the 95% confidence level. Smaller changes in measured diameter may not be real, but due to variability in measurement.

Aged↗

Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography.

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.

Adult↗

Maillard induced complexes of bovine serum albumin--a dilute solution study.

Association of bovine serum albumin (BSA) on heating in the presence and absence of 2% xylose has been studied using dynamic light scattering and sedimentation velocity. When 3% solutions of the protein alone are heated at 95 degrees C association products are formed with molar masses of approximately 2 x 10(6) g/mol, a value which is independent of the time of heating. These aggregates can be dissociated in solvents that disrupt non-covalent bonds. When the reducing sugar xylose is present there is a continuous change in the hydrodynamic properties with time. After 80 min a molar mass in excess of 7 x 10(6) g/mol is obtained. This increase in molar mass is attributed to additional non-disulphide linkages resulting from the Maillard reaction. Information about the gross conformation of the Maillard induced association products has been obtained from MHKS (Mark-Houwink-Kuhn-Sakarada) double logarithmic plots of D20,w and S20,w against molar mass. The values of the MHKS coefficients obtained are most consistent with a linear rod: i.e. the association is of an end-to-end type.

Animals↗

The variability of manual and computer assisted quantification of multiple sclerosis lesion volumes.

The high resolution and excellent soft tissue contrast of Magnetic Resonance Imaging (MRI) have enabled direct, noninvasive visualization of Multiple Sclerosis (MS) lesions in vivo. This has allowed the quantification of changes in the appearance of lesions in MR exams to be used as a measure of disease state. Nevertheless, accurate quantification techniques are subject to inter- and intra-operator variability, which may hinder monitoring of disease progression. We have developed a computer program to assist an experienced operator in the quantification of MS lesions in standard spin-echo MR exams. The accuracy of assisted and manual quantification under known conditions was studied using exams of a test phantom, while inter- and intra-operator reliability and variability were studied using exams of a MS patient. Results from the phantom study show that accuracy is improved by assisted quantification. The patient exam results indicate that assisted quantification reduced inter-operator variability from 0.34 to 0.17 cm3, and reduced intra-operator variability from 0.23 to 0.15 cm3. In addition, the minimum significant change between two successive measurements of lesion volume by the same operator was 0.64 cm3 for manual quantification and 0.42 cm3 for assisted quantification. For two different operators making successive measurements, the minimum significant change was 0.94 cm3 for manual quantification, but only 0.47 cm3 for assisted quantification. Finally, the number of lesions to be monitored for an average change in volume at a given power and significance level was reduced by a factor of 2-4 by assisted quantification. These results suggest that assisted quantification may have practical applications in clinical trials, especially those that are large, multicenter, or extended over time, and therefore require lesion measurements by one or more operators.

Analysis of Variance↗

Quantification of multiple sclerosis lesion volumes in 1.5 and 0.5 T anisotropically filtered and unfiltered MR exams.

Recently, guidelines for the use of MRI in the monitoring of MS have recommended the use of imaging systems with mid-field (0.5-1.0 T) or high-field (greater than 1.0 T) strengths. Higher field strengths provide many advantages, including increased signal-to-noise ratios (SNR). SNR also may be increased by post-processing algorithms that reduce noise. In this paper we evaluate the impact on operator variability of (a) lesion quantification in high-field (1.5 T) versus mid-field (0.5 T) exams; and (b) an anisotropic diffusion filter algorithm that reduces image noise without blurring or moving object boundaries. Inter- and intra-operator reliability and variability were studied using repeated quantification of lesions in 1.5 and 0.5 T filtered and unfiltered MR exams of a MS patient. Results indicate that inter-operator variability in 1.5 T unfiltered exams was 0.34 cm3 and was significantly larger than that in 1.5 T filtered (0.27 cm3), 0.5 T unfiltered (0.26 cm3), and 0.5 T filtered (0.24 cm3) exams. Similarly, intra-operator variability in 1.5 T unfiltered exams was 0.23 cm3 and was significantly larger than that in 1.5 T filtered (0.19 cm3), 0.5 T unfiltered (0.19 cm3), and 0.5 T filtered (0.18 cm3) exams. In addition, the minimum significant change between two successive measurements of lesion volume by the same operator, was 0.64 cm3 in 1.5 T unfiltered exams, but 0.53 cm3 or less in other exams. For two different operators making successive measurements, the minimum significant change was 0.94 cm3 in 1.5 T unfiltered exams, but only 0.75 cm3 or less in other exams. Finally, the number of lesions to be monitored for an average change in volume at a given power and significance level was greater by 30%-60% for quantification in 1.5 T unfiltered exams. These results suggest that inter- and intra-operator variability are reduced by anisotropic filtering, and by quantification in 0.5 T exams. Reduced operator variabilities may result from higher detail signal-to-noise ratios (dSNRs) in 0.5 T and filtered exams.

Analysis of Variance↗

Differential scanning calorimetry of lupin and soy proteins.

Differential scanning calorimetry (DSC) was used to study the 7S and 11S globulin fractions extracted from lupin seed (Lupinus luteus) flour. In agreement with previous work on other lupin species, the isolate showed three denaturation peaks compared to the two observed with soy. By comparison with the isolated globulin fractions, the denaturation peaks at the two higher temperatures in the lupin isolate were assigned to the 11S and 7S globulins. The denaturation temperature of the lupin 7S globulin was about 10 K higher than that for the corresponding soy globulin, whereas the values for the 11S globulin were similar. All globulins displayed increasing thermal stability with decreasing moisture contents. Possible reasons for the differences in behaviour of soy and lupin protein isolates are discussed.

Calorimetry, Differential Scanning↗

A study of glycerolphosphate acyltransferase in rat liver mitochondria-submitochondrial localization and some properties of the solubilized enzyme.

1. Glycerolphosphate acyltransferase (GPAT) was solubilized from the rat liver mitochondrial membranes using sodium cholate. Dithiothreitol was necessary to stabilize the solubilized enzyme on storage. 2. Unlike the enzyme in situ in mitochondrial membranes, the solubilized mitochondrial GPAT was susceptible to inhibition by N-ethylmaleimide; a property more characteristic of the distinct microsomal form of GPAT. 3. Solubilized mitochondrial GPAT retained its very high preference for saturated acyl-CoA substrate (palmitoyl-CoA) and had no activity whatever with any tested concentration of the unsaturated substrate oleoyl-CoA. 4. Solubilization increased the affinity of mitochondrial GPAT for palmitoyl-CoA whilst decreasing the Km for glycerol phosphate. 5. After separation of liver mitochondrial outer and inner membranes and estimation of cross-contamination by appropriate markers it was concluded that the mitochondrial inner membrane contains significant GPAT activity. This was established with preparations from fed, 48 hr-starved and streptozotocin-diabetic rats.

Animals↗

The response of brown adipose tissue mitochondrial glycerolphosphate acyltransferase to cold-exposure in hypothyroidism, after adrenalectomy and after treatment with cycloheximide.

1. Exposure to cold has previously been shown to considerably increase the activity of the mitochondrial form of glycerolphosphate acyltransferase (GPAT) in brown adipose tissue (A. C. Darnley, C. A. Carpenter and E. D Saggerson, Biochem. J. 253, 351-355, 1988; J. R. D. Mitchell and E. D. Saggerson. Biochem. J. 277, 665-669, 1991). 2. Both adrenalectomy and chemically-induced hypothyroidism increased mitochondrial GPAT activity in rats maintained at 21 degrees C. This increase was similar to that caused by exposing rats to the cold (4 degrees C) for three days. Whereas exposure of hypothyroid rats to cold (4 degrees C) resulted in a further increase in GPAT activity, no further increase in activity was observed after exposure of adrenalectomized rats to the cold. 3. Administration of triiodothyronine (T3) to rats maintained at 21 degrees C had no effect on mitochondrial GPAT activity. 4. Prior treatment with cycloheximide abolished 60-70% of the increase in GPAT activity caused by cold-exposure.

Acclimatization↗

Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low dose aspirin.

OBJECTIVES: Concern has been expressed about possible neonatal side effects after the use of maternal anti-platelet agents in pregnancy, particularly low dose aspirin treatment. We have studied neonatal platelet behaviour using whole blood techniques, and assessed the neonatal effect of the maternal ingestion of 60 mg aspirin daily. DESIGN: Cross sectional and randomised, double-blind, placebo-controlled. SETTING: University hospital. SUBJECTS: 1. Eight normal women, studied before conception, and their infants. 2. Twenty-four infants whose mothers had been randomised to receive either 60 mg aspirin daily, or placebo, in double-blind fashion. METHODS: The Clay Adams Ultra Flo 100 whole blood single platelet counter was employed to measure platelet aggregation in response to various agonists. The platelet release reaction was also measured in whole blood, and serum thromboxane B2 (TxB2) production was measured by radio-immunoassay. Umbilical cord blood samples were obtained at delivery. RESULTS: 1. Neonatal platelet aggregation induced by adrenaline, ADP and platelet activating factor was reduced in comparison with their mothers (P < 0.01), whereas the neonatal platelet release reaction was reduced when stimulated by collagen and U46619 (a thromboxane mimetic) (P < 0.01). Serum TxB2 production was similar in mothers and babies. 2. Neonatal platelet aggregation, release reaction and serum TxB2 production were not significantly reduced in infants exposed to maternal aspirin in comparison with those neonates exposed to maternal placebo. This is in contrast to the effect on maternal platelets. CONCLUSIONS: Although only a small number of patients were studied, we interpret this as a relative sparing of neonatal platelet reactivity due to the presystemic action of low dose aspirin.

Adult↗