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Biomedical subjects

R Stratton

Publications and source records attributed to R Stratton.

At least 19 recordsLinked to original sources

Macro- and nanoscale observations of adhesive behavior for several E. coli strains (O157:H7 and environmental isolates) on mineral surfaces.

Subsurface biobarriers can be conceived to attenuate the migration of pathogens by adhesion to mineral surfaces. Candidate biobarrier materials of varied surface characteristics (dolomite, alpha-alumina, silica, pyrophyllite, and Pyrax (a composite form of pyrophyllite, mica, and silica)) were tested for Escherichia coli adhesive capacity in macroscale continuous-flow columns. Atomic force microscopy (AFM) was used to determine nanoscale interaction energies. Predicted attractive interaction energies correlated well with macroscale adhesive behavior for tested E. coli strains. AFM measurements confirmed ExDLVO model predictions of attachment in the primary minima for E. coli O157:H7 and two environmental isolates E. coli (UCFL339 and UCFL-348) with MOPS conditioned Pyrax. In macroscale column experiments, pyrophyllite and Pyrax demonstrated significantly higher bacterial retention, higher deposition coefficients and lower initial cell breakthrough values for E. coli O157:H7 than did alpha-alumina, silica, or dolomite (pyrophyllite, 0.93, 3.56 h(-1), 3.2% ODo; Pyrax, 0.95, 3.73 h(-1), 2.8% ODo; alpha-alumina, 0.74, 1.60 h(-1), 33% ODo; silica, 0.63, 0.43 h(-1), 73% ODo; and dolomite, 0.33, 0.17 h(-1), 89% ODo, respectively). Bacterial hydrophilicity impacted cell retention in Pyrax columns with the relatively hydrophobic E. coli isolate UCFL-339 (0.99, 6.13 h(-1), 0.4% ODo) retained better than the more hydrophilic E. coli isolate UCFL348 (0.94, 3.70 h(-1), 3.6% ODo). The strong adhesive behavior of Pyrax was attributed to the hydrophobic (deltaGiwi = -32.4 mJ/m2) pyrophyllite component of the mineral. Vicinal water appears poised between the bacterial and the mineral surface during initial attachment. Overall, observed behavior of the various E. coli strains and the selected mineral surfaces was consistent with surface analyses, conducted at both the macro- and nanoscale.

Aluminum Oxide↗

N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma.

BACKGROUND: Over-expression of connective tissue growth factor (CTGF) is a hallmark of fibrotic disease, including scleroderma. CTGF acts with the pro-fibrotic cytokine TGFbeta to promote sustained fibrotic responses in vivo. Elevated production of CTGF might be responsible for maintenance of the fibrotic phenotype in scleroderma. Assays of CTGF or of its fragments are potential non-invasive measures of the fibrotic response in scleroderma. AIM: To determine the utility of whole, N-terminal, and C-terminal CTGF as surrogate markers for fibrosis in scleroderma. DESIGN: Cross-sectional controlled study. METHODS: Plasma was collected prospectively from 47 scleroderma patients (26 diffuse scleroderma, 21 limited scleroderma) and 18 healthy controls. At the same time, dermal interstitial fluid was derived by a suction blister technique from the lesional skin of scleroderma patients, and from the forearm skin of healthy controls. Whole, N-terminal, and C-terminal CTGF were assayed by ELISA, using monoclonal antibodies specific for N- and C-terminal epitopes. RESULTS: N-terminal cleavage products of CTGF were present at elevated levels in the plasma and dermal interstitial fluid of scleroderma patients, compared to healthy controls. N-terminal CTGF levels in plasma and dermal interstitial fluid correlated with severity of skin disease and (negatively) with disease duration. Whole and C-terminal CTGF levels were low in blister fluid and plasma levels were not elevated in disease. DISCUSSION: These results support a role for CTGF in scleroderma-associated fibrosis and the utility of N-terminal CTGF as a marker of fibrosis.

Adult↗

Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.

The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.

Adolescent↗

Description and evaluation of a Newton-based electronic appetite rating system for temporal tracking of appetite in human subjects.

This study assessed the reliability and validity of a palm-top-based electronic appetite rating system (EARS) in relation to the traditional paper and pen method. Twenty healthy subjects [10 male (M) and 10 female (F)] - mean age M=31 years (S.D.=8), F=27 years (S.D.=5); mean BMI M=24 (S.D.=2), F=21 (S.D.=5) - participated in a 4-day protocol. Measurements were made on days 1 and 4. Subjects were given paper and an EARS to log hourly subjective motivation to eat during waking hours. Food intake and meal times were fixed. Subjects were given a maintenance diet (comprising 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6xResting Metabolic Rate (RMR), as three isoenergetic meals. Bland and Altman's test for bias between two measurement techniques found significant differences between EARS and paper and pen for two of eight responses (hunger and fullness). Regression analysis confirmed that there were no day, sex or order effects between ratings obtained using either technique. For 15 subjects, there was no significant difference between results, with a linear relationship between the two methods that explained most of the variance (r(2) ranged from 62.6 to 98.6). The slope for all subjects was less than 1, which was partly explained by a tendency for bias at the extreme end of results on the EARS technique. These data suggest that the EARS is a useful and reliable technique for real-time data collection in appetite research but that it should not be used interchangeably with paper and pen techniques.

Adult↗

Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients.

Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-beta to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-beta.

Cells, Cultured↗

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings.

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal:noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.

Appetite↗

Growth hormone improves weight velocity and height velocity in prepubertal children with cystic fibrosis.

We undertook this study to determine if growth hormone treatment of prepubertal children with cystic fibrosis could improve their height and weight. Nine prepubertal children with cystic fibrosis were treated with human recombinant growth hormone for one year. Results obtained during this year were compared to similar measurements made for each patient for the one year prior to the treatment year. Anthropometric data including: height, height velocity, weight, weight velocity and skin fold thickness were measured at three month intervals. Pulmonary function and skeletal muscle strength were measured at three month intervals. Glucose tolerance was evaluated by HbAlc and by fasting blood glucose and insulin levels every three months. Our results demonstrate that growth hormone treatment resulted in significant improvement in height velocity and height Z scores. Weight increased in all subjects, with a significant increase in weight velocity (year prior to treatment = 1.7+/-1.0 kg/yr, treatment year = 3.8+/-1.6 kg/yr; p=0.03). Measurements of skin fold thickness suggests that lean body mass improved with growth hormone treatment. Pulmonary function improved in all but two patients, whose pulmonary function remained the same and muscle strength improved in all subjects. These results suggest that growth hormone used in prepubertal children with cystic fibrosis can improve height and weight and may improve lean body mass.

Autoantibodies↗

The value of SPECT scans in identifying back pain likely to benefit from facet joint injection.

Lumbar facet disease is sometimes implicated in low back pain. Identification is difficult and this may account for a variable response. Single photon emission computerized tomography (SPECT) is a scanning technique which enables localization of facet joint pathology. We determined whether recognition of facet disease by this method improved the response to corticosteroid injection treatment. Fifty-eight patients with low back pain and displaying accepted clinical criteria for facet joint disease were evaluated by SPECT. Twenty-two had facetal uptake of isotope. These and the tender facet joints of 36 scan-negative patients were injected with 40 mg methylprednisolone and 1 ml 1% lignocaine under X-ray control. Pain was assessed by a blind observer using the McGill questionnaire (MGQ), Present Pain Intensity score (PPI) and a Visual Analogue Scale (VAS). VAS, PPI and MGQ were reduced in the scan-positive patients at 1 month (P = 0.05, P = 0.0005, P = 0.005) and MGQ at 3 months (P = 0.01), whilst scan-negative patients were unchanged. The percentage of scan-positive patients who reported improvement was 95% at 1 month and 79% at 3 months, significantly greater than the control group (P = 0.0005, P = 0.01). Within 6 months, pain improvement in the SPECT-positive group was no longer statistically significant. Tenderness did not correlate with increased uptake on SPECT scan. Osteoarthritis of the facets was more common in the SPECT-positive patients (P < 0.001), but did not correspond with sites of increased uptake on SPECT scan. These results suggest that SPECT can enhance the identification of back pain sufferers likely to obtain short-term benefit from facet joint injection.

Adolescent↗

Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype.

The critical importance of dosage compensation is underscored by a novel human syndrome ("XYXq syndrome") in which we have detected partial X disomy, demonstrated supernormal gene expression resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq- karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all three cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline.

Abnormalities, Multiple↗

Nucleotide sequence of the gene coding for a 130-kDa mosquitocidal protein of Bacillus thuringiensis israelensis.

The nucleotide sequence of pVB131 containing the gene coding for a 130-kDa Bacillus thuringiensis israelensis (B.t.isr) mosquitocidal protein was determined. The pVB131 plasmid was constructed by Sekar and Carlton [Gene 33 (1985) 151-158]. Our sequencing revealed only one open reading frame large enough to code for a protein of 130 kDa. The translation start site was determined by sequencing the protein isolated from B.t.isr. The amino acid sequence of the protein was deduced from the nucleotide sequence, and its Mr was determined as 128,505. Immunological and biochemical analyses of B.t.isr mosquitocidal proteins indicated that the 130-kDa protein coded by pVB131 was indeed expressed in B.t.isr. Comparing the peptide sequence of the 130-kDa B.t.isr toxin with the sequences of other B.t. toxins having activities specific to lepidopteran species showed that several domains were highly homologous. This suggests that they are evolutionarily related to each other, and in the evolutionary process the sequences in the homologous domains that are important to the insecticidal activity have been conserved.

Amino Acid Sequence↗

Correlates of biopsy-studied nephropathy in young patients with insulin-dependent diabetes mellitus.

We have correlated pathologic findings in kidney biopsies from 12 adolescents with proteinuria or hypertension with severity of limited joint mobility (LJM) and retinopathy. We compared mean glucosylated hemoglobin (GHB) and clinical findings in these patients with those in patients without proteinuria or hypertension. Severity of LJM correlated with basement membrane thickening. Protein excretion correlated with degree of mesangial matrix increase and basement membrane changes. Retinal changes were related to basement membrane thickness and duplication. Despite treatment, blood pressures were significantly higher in patients with nephropathy than in the comparison group. Glycemic control status was generally poor and did not correlate with pathologic changes. The narrow spectrum of control did not permit assessment of possible effects of milder metabolic derangement. However, the similarity of GHB values in the groups with and without nephropathy implicates other factors. The group with clinical nephropathy had more LJM than did the comparison group, reaffirming LJM as a risk factor for early microvascular disease. Biopsy changes of nephropathy may begin relatively early in the course of diabetes (less than 7 years in three of our patients) and is already advanced when proteinuria appears.

Adolescent↗