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Biomedical subjects

S Long

Publications and source records attributed to S Long.

At least 19 recordsLinked to original sources

Measurement of forces inside a three-dimensional pile of frictionless droplets.

We present systematic and detailed measurements of interparticle contact forces inside three-dimensional piles of frictionless liquid droplets. We measured long-range chainlike correlations of the directions and magnitudes of large forces, thereby establishing the presence of force chains in three dimensions. Our correlation definition provides a chain persistence length of 10 mean droplet diameters, decreasing as load is applied to the pile. We also measured the angles between contacts and showed that the chainlike arrangement arises from the balance of forces. Moreover, we found that piles whose height was comparable to the chain persistence length exhibited substantially greater strain hardening than did tall piles, which we attributed to the force chains. Together, the results establish a connection between the microscopic force network and the elastic response of meso- or macroscopic granular piles. The conclusions drawn here should be relevant in jammed systems generally, including concentrated emulsions and piles of sand or other heavy particles.

Journal Article↗

Telomerase reverse transcriptase (TERT) expression and proliferation in canine brain tumours.

Telomerase is a ribonucleoprotein enzyme complex that synthesizes telomere DNA. It is detected in 85-90% of malignant tumours in humans, but not in most somatic cells. Because telomerase plays a critical role in cell immortality, it represents an important target for anticancer therapies. We have previously shown that the dog is a potentially useful model for evaluating telomerase-based therapeutics. In this present study we analysed 93 canine brain tumours for telomerase reverse transcriptase (TERT) expression by immunohistochemistry. TERT immunoreactivity was detected in 16 of 50 grade 1 (32%) and 29 of 43 grade 2 tumours (67.4%), demonstrating a statistically significant association with histological grade (P = 0.00012). A subset of 51 tumours was also assessed for MIB-1 expression. The MIB-1 labelling index (LI) was found to correlate significantly with tumour grade, with a mean MIB-1 LI of 1.5% for grade 1 tumours, as compared with a mean MIB-1 LI of 21.7% for grade 2 tumours (P << 0.001). The MIB-1 LI was also significantly associated with TERT expression in all brain tumours (P << 0.001). These data further support the dog as a model for the preclinical development of telomerase-based therapeutics in brain tumours.

Animals↗

The canine telomerase catalytic subunit (dogTERT): characterisation of the gene promoter and identification of proximal core sequences necessary for specific transcriptional activity in canine telomerase positive cell lines.

Telomerase biology is complicated by studies that show that telomere expression and telomere biology differs between species, and that existing animal models do not closely resemble the human situation. We have previously reported a description of telomere/telomerase biology in the dog and have suggested this as an alternative model system. To further elucidate telomerase biology in this species we have cloned and characterised the canine reverse transcriptase (dogTERT) promoter. We demonstrate that core promoter activity is contained within a region extending approximately 300 bp upstream of the ATG codon. Transient transfections in telomerase-positive canine cell lines and telomerase negative fibroblasts showed that the promoter is only active in telomerase positive cell lines. Sequence analysis demonstrated that the 5' regulatory region is GC-rich and contains no TATA or CAAT box, similar to the human TERT promoter. Motif searches revealed the presence of multiple transcription factor binding sites common to both the human and canine TERT promoters, including a single E-box, Sp1, AP1, MZF-2 and ER/Sp1 binding sites. These findings suggest that the dogTERT gene shares similar transcriptional control to hTERT. Identification of the core promoter necessary for activity may allow the use of naturally occurring cancers in dogs as a preclinical testing ground for telomerase targeted therapies in human cancer patients.

Animals↗

Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.

A significant increase in tumor regression was induced in N-nitroso-N-methylurea-induced mammary tumors in rats treated with the combination of melatonin and 9-cis-retinoic acid (9cRA). Treatment groups included: control (ethanolic saline), 9cRA (30 mg/kg chow/day), melatonin 500 microg/day, melatonin 1000 microg/day, melatonin 500 microg/day+9cRA and melatonin 1000 microg/day+9cRA. Rats treated with the lower dose of melatonin 500 microg+9cRA show the greatest degree of tumor regression (78%), with 54% undergoing complete regression and a significant increase in apoptotic cells observed by TUNEL Assay. Furthermore, tumor multiplicity and burden were significantly decreased by the combination of melatonin and 9cRA.

Alitretinoin↗

Development and performance of the vehicle-mounted radiation monitoring equipment used in the Maralinga rehabilitation project.

The rehabilitation of the former nuclear test site at Maralinga involved (among other processes) the removal of contaminated soil from an area of approximately 2.5 km2. The two most stringent rehabilitation criteria required measurements to ensure that no radioactive particle exceeding 100 kBq of 241Am activity, and no area of 1 ha exceeding 3 kBq/m2 of 241Am activity, remained in the rehabilitated area. The project timetable required that the area be scanned at the rate of approximately 3 ha/day. Two vehicle-mounted detection systems were developed and constructed to obtain the necessary measurements in the available timeframe. The scientific basis for the designs are presented, together with details of the selected equipment and technical solutions found. The performance of this equipment in the field is discussed in terms of both its scientific and technical operation. Based on the experience gained at Maralinga, improved versions of this equipment were produced under contract for the People's Republic of China.

Americium↗

Guidelines on the management of secondary prophylaxis of vascular events in stable patients in primary care.

Atherothrombosis, thrombus formation superimposed on an existing atherosclerotic plaque, is an acute process leading to ischaemic events such as myocardial infarction, stroke and critical limb ischaemia. Patients presenting with clinical conditions associated with atherothrombosis are at increased risk of subsequent vascular events. The beneficial effect of antiplatelet therapies for short-term and long-term secondary prevention of atherothrombotic events has been established. These guidelines aim to provide evidence-based recommendations that will assist in the antiplatelet-mediated secondary prophylaxis of vascular events in patients with stable cardiovascular disease treated in the primary healthcare setting. Medline and the Cochrane library were accessed using free-text strategies in the domains of antiplatelet agents and antithrombotics. Development of the guidelines was driven by a series of Steering Committee meetings, in which the quality of relevant studies was assessed and identified using narrative summary. These guidelines present evidence and recommendations for the treatment of numerous atherothrombotic indications depending on individual patient circumstances.

Acute Disease↗

Molecular identification and expression analysis of tumor necrosis factor in channel catfish (Ictalurus punctatus).

A tumor necrosis factor (TNF) alpha-like gene, encoding a propeptide of 230 amino acids and a mature (soluble) peptide of 162 amino acids, was identified in channel catfish (Ictalurus punctatus). While the catfish protein shared features in common with both mammalian TNFalpha and TNFbeta homologs, overall sequence identity/similarity was slightly higher vs. TNFalpha genes when mature TNF sequences were compared. Phylogenetic analysis placed catfish and other fish TNF sequences within their own cluster apart from mammalian TNFalpha and beta genes, and supported the suggestion that TNFalpha and beta genes separated after the divergence of mammals and teleosts. In contrast to trout and carp, but similar to flounder, catfish TNF was present as a single copy gene. Expression studies demonstrated that catfish TNFalpha mRNA was present in all tested tissues (i.e. liver, spleen, head kidney, mesonephros, gill, thymus, and PBLs) from an unstimulated fish. Moreover, catfish TNF was constitutively expressed in actively proliferating, but otherwise unstimulated, macrophage (42TA) and T cell (G14D; TS32.17) lines, but not in B cell (1G8 or 3B11) or fibroblast lines. TNF expression was upregulated in PBLs, and in G14D and 42TA cells, but not in 3B11 cells, by PMA/calcium ionophore treatment. These results demonstrate that a catfish homolog of TNFalpha has been identified, and indicate that catfish TNFalpha is expressed in catfish in a manner similar to that seen in mammals.

Amino Acid Sequence↗

Improving the quality of care of musculoskeletal conditions in primary care.

OBJECTIVE: To determine the support services general practitioners (GPs) need when working with patients who have musculoskeletal problems and their educational needs in order to deliver an improved service. METHODS: GPs (n=446) on the Sheffield and Barnsley principal lists were sent a questionnaire (53.8% response rate). Semistructured interviews of a purposive sample of 10 GPs were analysed qualitatively to increase understanding of the research objectives. RESULTS: GPs were self-confident in managing common musculoskeletal conditions such as gout (86% of GPs who replied), back pain (69%), osteoarthritis (62%) and sporting injuries (58%) entirely within the surgery. Despite high levels of confidence in diagnosing non-specific pain syndromes, 68% of GPs would refer to a rheumatologist. Most GPs (68%) were happy with their current referral rates to physiotherapists and 65% of GPs in this sample provided a personal injection service. Reduction of inappropriate prescribing of non-steroidal anti-inflammatory drugs would be helped by better patient education materials on treatments (90%) and more resources for the primary care physiotherapy service (85%). Half of the GPs had had specific musculoskeletal training within the last 5 yr. Half of the GPs planned to update their knowledge and skills in the next year, 64% of these preferring a taught interactive course, 50% wanting to sit in with a consultant in clinic and 46% preferring to learn as part of a personal learning plan. CONCLUSIONS: GPs feel confident managing the majority of musculoskeletal conditions within the surgery provided they have adequate support in terms of opportunities for appropriate education, particularly joint injection techniques, ongoing consultant support for complex cases with poor outcomes, particularly non-specific pain syndromes, adequate access to physiotherapy, and a multidisciplinary approach to pain control and inappropriate prescribing.

Female↗

Effects of high-calorie supplements on body composition and muscular strength following resistance training.

BACKGROUND: Seventy-three healthy, male subjects randomly divided into 3 groups participated in a study to determine the effects of 2 high-calorie nutritional supplements on body composition, body segment circumferences, and muscular strength following a resistance-training (RT) program. METHODS: In addition to their normal diets group 1 (CHO/PRO; n=26) consumed a 8.4 Mj x day(-1) (2010 kcal) high calorie, high protein supplement containing 356 g carbohydrate and 106 g protein. Group 2 (CHO; n=25) consumed a carbohydrate supplement that was isocaloric with CHO/PRO. Group 3 (CTRL; n=22) received no supplement and served as a control. All subjects were placed on a 4-day x week(-1) RT program for 8 weeks. RESULTS: Dietary analysis revealed no significant differences in total energy consumption or nutrients at any time in the non-supplemented diets of the 3 groups. Significant (p= or <0.05) increases in body mass (BM) and fat-free mass (FFM) were observed in CHO/PRO and CHO compared to CTRL. Mean (+/- SD) increases in BM were 3.1+/-3.1 kg and 3.1+/-2.2 kg, respectively. Fat-free mass significantly (p= or <0.05) increased 2.9+/-3.4 kg in CHO/PRO and 3.4+/-2.5 kg in CHO. Muscular strength, as measured by a one-repetition maximum in the bench press, leg press, and lat-pull down increased significantly (p= or <0.05) in all groups. No significant differences in strength measures were observed among groups following training. CONCLUSIONS: Results indicate that high-calorie supplements are effective in increasing BM and FFM when combined with RT. However, once individual protein requirements are met, energy content of the diet has the largest effect on body composition.

Adolescent↗

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene.

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Amino Acid Sequence↗

Dehydration, hydration behavior, and structural analysis of fenoprofen calcium.

Fenoprofen calcium (FC) is a nonsteroidal, anti-inflammatory, analgesic, and antipyretic agent. The dehydration behavior of FC dihydrate and the rehydration of the dried FC were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffractometry (PXRD). The stoichiometry, the crystal packing arrangement, and water environments in FC dihydrate were determined using single-crystal X-ray diffraction (XRD) analysis. The Arrhenius plot (natural logarithm of the dehydration rate constant versus the reciprocal of absolute temperature) for FC dihydrate from isothermal TGA is not linear. The activation energy of dehydration was 309 kJ/mol in the 50-60 degrees C range and 123 kJ/mol in the 60-80 degrees C range. The difference in activation energy can be explained from the crystal structure data where one water molecule is sandwiched between repeating polar carboxylate groups and the other water is in a slightly less polar region of the crystal. Single-crystal XRD analysis also indicated each calcium ion is coordinated to six oxygens. Two coordinating oxygens are provided by two water molecules and the other four oxygens are provided by the carboxylate group of four separate fenoprofen anions. Each fenoprofen anion, which can provide two oxygens for coordination, is associated with two different calcium ions. Hot-stage PXRD suggested that only a loss of 1 mole of water per mole of FC dihydrate (forming a monohydrate) was required to convert the material to a partially crystalline state. The monohydrate is not completely disordered as evidenced by a strong diffraction peak as well as some weaker peaks in the PXRD pattern. The rehydration of the anhydrous form of FC follows a solution-mediated transformation, prior to crystallizing as the dihydrate.

Anti-Inflammatory Agents, Non-Steroidal↗

Technetium-99 in the Irish marine environment.

Technetium-99 activity concentrations in seawater and biota from Irish coastal waters are presented. Time series measurements of 99Tc in seawater and Fucus vesiculosus from the western Irish Sea show that activity concentrations have increased in line with the increase in discharges of 99Tc from Sellafield. The peak in activity concentrations in both seawater and Fucus vesiculosus occurred in 1997 approximately two years after the peak in 99Tc discharges. The highest activity concentration recorded in Fucus vesiculosus showed a 29-fold increase over the mean concentration for the period 1988-1993. Technetium-99 activity concentrations were measured in fish, lobsters, prawns, mussels and oysters landed at major fishing ports on the east and northeast coasts of Ireland between 1996 and 1998. Concentration factors for 99Tc in the brown seaweed Fucus vesiculosus and certain species of fish, crustaceans and molluscs from the Irish Sea were estimated. In general, these concentration factors were higher than those in the literature which were derived from laboratory studies, but agreed well with values which were based on field studies. The mean committed effective doses to Irish typical and heavy seafood consumers due to 99Tc in the period 1996-1998 were 0.061 and 0.24 microSv, respectively.

Animals↗

Studying the epidemiology of attention-deficit hyperactivity disorder: screening method and pilot results.

OBJECTIVE: As part of a larger epidemiologic study of risk factors for attention-deficit hyperactivity disorder (ADHD), this pilot study combined parent and teacher information to estimate ADHD prevalence among elementary school children in a North Carolina county. The methods developed for this study and the pitfalls we encountered illustrate the challenges involved in conducting population-based studies of ADHD. METHODS: We employed 2-stage screening using DSM-IV criteria. Teachers completed behaviour-rating scales for all children. We then administered a structured telephone interview to parents of potential cases. We screened 362 of 424 (85%) children in grades 1 to 5 in 4 schools. RESULTS: According to parent reports, 43 children (12%) had previously been diagnosed with ADHD by a health professional. Thirty-four children (9%) were taking ADHD medication. Forty-six children (12.7%) met study case criteria for ADHD, based on combined teacher and parent reports. Of the 46 cases, 18 (39%) had not been previously identified. Eight previously diagnosed children, however, did not meet case criteria. After we adjusted for nonresponse, the estimated prevalence was 16% (95%CI, 12% to 20%). CONCLUSIONS: These data suggest that the DSM-IV prevalence of ADHD has been substantially underestimated, although the true prevalence in this population may be less than the 16% estimated here. Population-based studies of ADHD are feasible and may provide important information about practice and treatment patterns in community settings, as well as a broader understanding of the etiology and life course of this common disorder.

Attention Deficit Disorder with Hyperactivity↗

Molecular cloning, sequencing analysis and expression of the catalase-peroxidase gene from Halobacterium salinarum.

The gene encoding catalase-peroxidase was cloned from chromosomal DNA from the Archaea, Halobacterium salinarum. The nucleotide sequence of a 3.5 kb fragment, containing the catalase-peroxidase gene and its flanking regions was determined. A 2.16 kb open reading frame was obtained, encoding the enzyme which was comprised of 720 amino acid residues with a calculated molecular weight of 80 kDa. The deduced amino acid sequence of the H. salinarum catalase-peroxidase showed a high degree of identity to other bifunctional catalase-peroxidases. A transcriptional start site was identified 183 bp upstream of the translational start codon. Southern blot analysis indicated that catalase-peroxidase was a single copy gene. The Archaeal catalase-peroxidase gene was expressed in Escherichia coli, and the expressed fusion protein exhibited both catalase and peroxidase activities.

Amino Acid Sequence↗

Long-term care hospitals under Medicare: facility-level characteristics.

Though accounting for only a small percentage of total Medicare spending, long-term care hospitals (LTCHs) (defined as having an average length of stay [LOS] of 25 days or more) have been growing, in number and in Medicare expenditures, at a rapid rate in recent years. Because they have not been widely studied, we conducted research to describe the characteristics of this increasingly important Medicare provider type. We found that most LTCHs specialize in the provision of respiratory care or rehabilitation. Information from this study can help inform the development of a Medicare prospective payment system for LTCHs.

Aged↗

[Effects of manganese, zircon and lithium alone on rat liver lipid peroxidation].

Lipid peroxide (LPO) in rat liver was detected by malondiadehyde (MDA) colorimetry. The effect of manganese, zircon and lithium alone on lipid peroxidation in rat liver was also studied. The results showed that manganese and zircon at the doses of (9.862-1.972) x 10(-4) and (0.1972-9.862) x 10(-5) nmol/L respectively decreased LPO in rat liver(P < 0.01). Lithium inhibited lipid peroxidation at the dose of (19.72-1.972) x 10(-4) nmol/L, and induced lipid peroxidation at higher concentration.

Animals↗

[Effect of cadmium on the phagocytic function of polymorphonuclear leukocyte in mice tested by chemiluminescence of whole blood].

The effect of cadmium chloride on the immunological toxicity of polymorphonuclear leukocyte (PMN) and on lipid peroxidation in liver were measured by using the chemiluminesence of whole blood and thiobarbituric acid (TBA) method. The results showed that 0.1 and 10 mmol/L of cadmium chloride could accelerate the chemiluminesence of whole blood in vitro, but 1000 mmol/L of cadmium chloride inhibit the chemiluminesence. Two hours after the injection of cadmium chloride through caudal vein, chemiluminesence of whole blood was induced obviously at the dose of cadmium 1 and 100 micrograms/kg BW in vivo, but the chemiluminesence was inhibited at the dose of 500 and 1000 micrograms/kg BW. At the dose of 1 microgram/kg BW, the peroxidation of liver lipids was induced. The results suggested that cadmium at low concentration accelerated the immunity of PMN, while high concentration was toxic to PMN, cadmium at low concentration could accelerate the phagocytic function of phagocytes. Phagocytosis brings about excessive active oxygen in organism and intensifies the action of active oxygen on the lipid peroxidation in tissue cells, at last, results in organic oxidation injury.

Animals↗