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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 127 records · Page 7Linked to original sources

Modulation of the biological functions of galectin-3 by matrix metalloproteinases.

Galectin-3 is an important intracellular and extracellular lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The exact physiological role of the protein is presently not known. We have previously demonstrated that recombinant human galectin-3 is a novel substrate for metalloproteinases, particularly MMP-2 and MMP-9. These enzymes are capable of efficiently cleaving the Ala62-Tyr63 bond of the ca. 30 kDa galectin-3, generating a 22 kDa fragment with intact carbohydrate recognition domain and a ca. 9 kDa polypeptide comprising the amino terminal end of the intact galectin-3. In this study, we analyzed interactions of the 22 kDa fragment of galectin-3 with immobilized laminins. We have also compared the hemagglutination as well as homodimerization potentials of this fragment with that of intact galectin-3. Our data suggest that cleavage of galectin-3 by metalloproteinases; (a) alters the carbohydrate recognition domain of the lectin so that it binds more tightly to the glycoconjugates and, (b) reduces selfassociation of the galectin molecules thereby abrogating the biological properties dependent on such associations or homodimerization.

Animals↗

Seven novel mutations in mut methylmalonic aciduria.

Methylmalonic aciduria (MMA) is an autosomal recessive inborn error of metabolism that results from functional defects in methylmalonyl CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses the vitamin B12 derivative, adenosylcobalamin (AdoCbl) as a cofactor. To date, 23 mutations have been identified at the MUT locus on the short arm of chromosome 6, causing the mut forms of MMA (mut complementation group; mut MMA, McKusick #251000). We now report seven novel mutations. Three were found inmut0 patients: R228Q (c759G-->A) was found as a heterozygous change; G312V (c1011G-->T) and 346delL (c1112delCTT) were both found as homozygous changes. Four mutations were found in mut patients: A191E (c648C-->A) and V633G (c1974T-->G) were found in the same patient; 684insL (c2128insCTC) and L685R (c2130T-->G) were both found as homozygous changes. The recent modelling of the human methylmalonyl CoA mutase allowed for an interpretation of the identified mutations.

Alleles↗

Sequence elements involved in the rescue of IBV defective RNA CD-91.

Deletion mutagenesis has been used to identify essential regions for rescue of coronavirus defective RNAs (D-RNAs). Using this technique on a cloned IBV D-RNA CD-91, we have identified a region potentially important in its rescue. Comparing the sequence of D-RNAs rescued with those not rescued we have deduced that a 72 base region corresponding to base number 13,824 to 13,896 in the viral genome is required for rescue. This may be an IBV D-RNA packaging signal or a cis-acting element involved in replication. Further experiments and modification of our techniques will be required to differentiate between the two processes.

Animals↗

Rescue of IBV D-RNA by heterologous helper virus strains.

Coronavirus defective RNA (D-RNA) vectors could be developed to deliver selected genes for the production of recombinant coronavirus vaccines. An IBV D-RNA, CD-61, derived from a naturally occurring IBV Beaudette D-RNA, CD-91, is being developed as a D-RNA vector for IBV. In order to use CD-61 as a vector it will require rescue by heterologous strains in addition to Beaudette. Rescue will be determined by recognition of replication and packaging signals within the D-RNA by the helper virus. The 5' and 3' UTRs are believed to contain sequences involved in replication and transcription. The 5' and 3' UTRs of six strains of IBV have been sequenced and experiments performed using six strains of helper virus for rescue of CD-61 to determine whether rescue correlates with sequence conservation within the 5' and 3' UTRs. Results indicate that all strains of helper virus rescued the D-RNA to varying degrees. Sequence comparisons show a high degree of sequence identity in the UTRs, but enough strain differences exist to be used as markers. The 5' and 3' UTRs of the D-RNAs rescued by the heterologous strains were also sequenced and leader switching between the helper virus and the Beaudette leader on the D-RNAs was observed.

3' Untranslated Regions↗

Is early kinetic positioning beneficial for pulmonary function in multiple trauma patients?

Body positioning (kinetic therapy) is known to improve oxygenation in patients with impaired pulmonary function and ARDS. We have used body positioning prophylactically in trauma patients whose injury and pattern predispose to ARDS. This retrospective study reports the effects of early prophylactic (group P) versus late (group L) axial rotation on pulmonary function and the incidence of ARDS. Both groups were comparable in age, injury severity and the degree of thoracic injury. Systemic oxygenation was significantly better and the incidence of ARDS significantly lower in group P (group P: 34.3 per cent, group T: 74.1 per cent, P < 0.05). There was a tendency towards a lower incidence of pneumonia and a better survival in group P, which did not reach statistical significance. The duration of kinetic therapy and of ventilation was comparable in both groups. In this retrospective evaluation early prophylactic kinetic therapy was associated with a significantly lower incidence of ARDS compared with that instigated later.

Adult↗

A comparison of two methods of securing an endotracheal tube.

While a variety of methods exist for securing an endotracheal tube (ETT), there has been little research on their safety and efficacy. This study aimed to test the equivalence of two methods in three critical care settings by randomly assigning patients to receive either the knot, which requires scissors or blade to remove the ETT tape, or the bow, which can be removed manually. These methods were evaluated by comparing ETT movement, malposition, dislodgement, inadvertent extubation, reduced skin integrity, the cutting of the pilot tube and nurse satisfaction. The 5-month study was conducted in three critical care settings in a large tertiary hospital. Of the 230 patients enrolled, 222 completed the trial. Results, based on a randomised, active control equivalence design, demonstrated the two methods to be equally effective with regard to ETT movement > 2 cm (knot = 21 per cent, bow = 19 per cent; 95 per cent confidence interval for the [2 per cent] difference-8 to 12.5 per cent). The incidence of ETT-related complications was similar for both methods. No pilot tubes were cut using either method. Nurses found that patient mouth care was easier and patient comfort and skin integrity enhanced with the bow method. On the other hand, nurses perceived the knot-tying method to be more secure and easier to apply. Given the equivalence of the two methods, the bow would seem preferable for reasons of safety and comfort.

Adult↗

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants.

AIMS: To investigate (1) perinatal factors affecting condition at birth in very preterm infants (23-32 weeks) and (2) the relationship between poor condition at birth and neonatal respiratory morbidity and mortality. METHODOLOGY: Convenience sample (n = 479) drawn from a geographic population inception cohort. RESULTS: Antenatal steroid use reduced the risk of pH < or = 7.20 [Adjusted Odds Ratio 0.29 (95% CI 0.17, 0.50)], one minute Apgar < 4 [0.54 (0.33, 0.88)], and 5 min Apgar < 7 [0.44 (0.23, 0.84)]. Gestational age was significantly related to Apgar score but not cord arterial acid-base status. No other perinatal factor was significant. Poor condition at birth was associated with an increase in the incidence and severity of hyaline membrane disease and death. These effects were lessened in those exposed to steroids. CONCLUSION: Antenatal steroid use is associated with improved condition at birth and reduces the deleterious effects of poor condition at birth on early respiratory morbidity and mortality.

Acid-Base Equilibrium↗

Radiofrequency and microwave dielectric properties of aqueous cryoprotectant agents: dimethyl sulphoxide and 2,3-butanediol.

Earlier work on the dielectric properties of cryoprotectant agents is extended using a modified measuring cell and method of data reduction yielding results more efficiently over a temperature range from -75 to +25 degrees C at frequencies from 27 MHz to 3 GHz. Dimethyl sulphoxide and butanediol are investigated at lower aqueous concentrations than previously and the implications for electromagnetic rewarming of cryopreserved materials are discussed.

Butylene Glycols↗

Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome.

AIMS: To evaluate the effect of the administration of growth hormone on stature, body weight, and body composition in children aged between 4 and 10 years with Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were recorded in 25 children using standard anthropometric techniques at recruitment, and six months later, shortly before the start of daily subcutaneous injections of growth hormone. Body composition was assessed via a measurement of total body water using stable isotopes. Measurements were repeated at the end of the six months of growth hormone administration. Measurements of height, weight, and skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS: There was a significant reduction in the percentage of body fat after growth hormone treatment; height velocity doubled during treatment; body weight did not change significantly when expressed as an SDS. Skinfold thickness at both the triceps and subscapular site decreased in absolute terms and when expressed as an SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify a more prolonged trial of growth hormone treatment and an exploration of different dosage regimens in children with Prader-Willi syndrome.

Body Composition↗

Children's acquired aphasia screening test.

Diagnosis in acquired childhood aphasia (ACA) is a multi-stage process. After the medical condition has stabilised, the diagnostic evaluation requires careful assessment to establish a profile in the differential diagnosis of listening, understanding speaking, and gesture. Children with ACA were traditionally assessed on adapted batteries often used for adults. The Children's Acquired Aphasia Screening Test (CAAST) was specifically designed to evaluate linguistic and non-linguistic function in brain-damaged children aged between 3 and 7 years.

Aphasia↗

Substance use disorders in gay/bisexual men with HIV and AIDS.

The authors conducted a longitudinal study of psychological adaptation to AIDS in subjects with and without lifetime and current substance use disorders (SUD), in a cohort of HIV+ gay/bisexual subjects. A sample of HIV+ gay/bisexual men (n = 183) and an HIV- comparison group (n = 84) were assessed for SUD, depression, and anxiety disorders. Among HIV+ men, combined lifetime (42%) but not current (11.5%) SUDs were more prevalent than in HIV- men (27% and 10%, respectively). HIV+ men with current SUD reported more depression, distress and diminished quality of life than HIV+ men with no SUD, but HIV-illness severity did not differ. HIV+ men in recovery did not differ from men with no lifetime history. Most HIV+ gay/bisexual men with SUD discontinue or reduce substance use before or subsequent to knowledge of their HIV infection, probably in an attempt to adopt a healthier lifestyle. However, for some HIV+ men, persistent substance abuse/dependence is accompanied by higher levels of distress and diminished quality of life, underscoring their need for treatment intervention.

Acquired Immunodeficiency Syndrome↗

Safety and efficacy of DEET and permethrin in the prevention of arthropod attack.

Many preventable diseases affecting troop strength are directly attributed to disease-carrying insects. The first line of defense against arthropod vectors is the use of personal protective measures. The concurrent application of DEET (N,N-diethyl-m-toluamide) repellent on the skin and permethrin [(3-phenoxy-phenyl)methyl(+/-)cis,trans-3-(2,2-dichloroethenyl)-2, 2- dimethylcyclopropane-carboxylate] insecticide on the battle dress uniform, while the uniform is worn properly, is a personal protective strategy officially known as the DOD Insect Repellent System. It is important for troop commanders and field leaders to enforce the use of personal protective measures to prevent insect-borne infectious diseases and to ensure troop and soldier readiness. DEET is a safe and effective repellent. Permethrin is a synthetic pyrethroid insecticide and repellent. Used in conjunction with proper clothing and other personal protective equipment, these repellents provide the best known protection available and are critical in minimizing the occupational health threat of arthropod-borne diseases to troops in the field.

DEET↗

The association of peripheral monocyte derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly.

OBJECTIVE: To examine the association of peripheral blood mononuclear cell (PBMC) derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor alpha (TNF-alpha), and radiographic osteoarthritis (OA) in the elderly. METHODS: A total of 703 subjects (436 women, 267 men, mean age 78.5+/-4.5 yrs) had both knee and hand radiographs, and cytokines were measured during the 22nd biennial examination of the Framingham Cohort. PBMC derived IL-1beta , IL-1Ra, and TNF-alpha production was assessed using a non-cross reacting polyclonal radioimmunoassay. Knee OA was defined as a score of > 2 using a modified Kellgren and Lawrence scale. The presence of osteophytes and joint space narrowing were scored separately on a 0-3 scale, in which disease was defined a priori as a score > 0 for each feature. Sex-specific odds ratios were calculated for knee OA after adjusting for weight, history of knee injury, and use of estrogen and nonsteroidal antiinflammatory drugs. RESULT: No uniform associations were found for IL-1beta or IL-1Ra in men, or for TNF-alpha production and radiographic OA in either sex. We found possible associations for the highest levels of IL-1beta production and the presence of knee osteophytes [OR=2.0 (1.2-3.5)] and joint space narrowing [OR=1.7 (1.1-2.8)] in women. Our data suggested a possible protective effect for IL-1Ra production and hand OA in women [OR=0.6 (0.4-1.0)]. CONCLUSION: We found no consistent association of PBMC cytokine production and radiographic OA. However, women with the highest production of IL-1beta and IL-1Ra had respectively higher rates of knee OA and lower rates of hand OA than expected.

Aged↗

Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham.

STUDY DESIGN: A 25-year follow-up study of 606 members of the population-based Framingham cohort, who had received lateral lumbar radiographs in 1967-1968 and 1992-1993, and completed an interview on back symptoms at the second examination. OBJECTIVES: To evaluate whether calcific lesions in the posterior wall of the abdominal aorta, the source of the feeding arteries of the lumbar spine, are associated with disc degeneration or back pain, which would suggest that ischemia of the lumbar spine leads to disc degeneration. METHODS: The presence of radiographic aortic calcification was ascertained in front of each lumbar segment from L1 through L4, and disc degeneration at intervertebral spaces from L1-L2 through L4-L5. The associations between aortic calcification, disc degeneration, and back pain were tested using logistic regression with adjustment for age and sex. RESULTS: At the baseline examination, aortic calcification was significantly associated with general disc degeneration, that is, disc space narrowing or endplate sclerosis at any lumbar level (odds ratio 1.6; 95% confidence interval 1.0-2.5; P = 0.034). In longitudinal, level-specific analyses, comparing local aortic calcifications with disc degeneration at the matching level, aortic calcifications predicted disc deterioration, that is, a decrease in disc space or appearance of endplate sclerosis, between the examinations (odds ratio 1.5; 95% confidence interval 1.3-1.8; P < 0.001). Furthermore, subjects in whom aortic calcifications developed between the examinations had disc deterioration twice as frequently as those in whom aortic calcifications did not develop (odds ratio 2.0; 96% confidence interval 1.2-3.5; P = 0.013). Also, individuals with severe (Grade 3) posterior aortic calcification in front of any lumbar segment were more likely than others to report back pain during adult life (odds ratio 1.6; 95% confidence interval 1.1-2.2; P = 0.014). CONCLUSIONS: Advanced aortic atherosclerosis, presenting as calcific deposits in the posterior wall of the aorta, increases a person's risk for development of disc degeneration and is associated with the occurrence of back pain.

Aged↗