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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 217 records · Page 12Linked to original sources
PubMed1999

Predicting conduct problems: can high-risk children be identified in kindergarten and grade 1?

Externalizing behavior symptoms (EBS) in childhood are a strong predictor of future conduct problems. This study evaluated their predictive accuracy using logistic regression and receiver operating characteristic curve techniques. EBS, alone and in combination with other child and familial risk factors, were used to predict conduct problems 30 months later in a nonclinic population of kindergartners and Grade 1 children. The sensitivity (Sn) and positive predictive value (PPV) of EBS alone were below preset criteria of > or = 50% for each (prevalence < or = 15%). Sn and PPV increased when other child and familial factors were combined with symptoms but did not exceed the preset criteria. From a developmental perspective, substantial stability of EBS exists over time. However, from the perspective of prevention science, significant levels of misclassification will occur when EBS are used to designate high-risk status under the low-prevalence conditions of normal populations.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein-Barr virus (EBV)-based mini-chromosome vectors in mdx mice.

Gene transfer by direct intramuscular injection of naked plasmid DNA has been shown to be a safe, simple but relatively inefficient method for gene delivery in vivo. Eukaryotic plasmid expression vectors incorporating the Epstein-Barr virus (EBV) origin of replication (oriP) and EBNA1 gene have been shown to act as autonomous episomally replicating gene transfer vectors which additionally provide nuclear matrix retention functions. Prolonged expression of a LacZ reporter gene and recombinant human dystrophin was shown using EBV-based plasmid vectors transfected into C2C12 mouse myoblast and myotube cultures. Intramuscular injection of EBV-based dystrophin expression plasmids into nude/mdx mice resulted in significant enhancement in the number of muscle fibres expressing recombinant dystrophin compared with a conventional vector. This effect was observed for over 10 weeks after a single administration. These results indicate the potential advantage of EBV-based expression vectors for focal plasmid-mediated gene augmentation therapy in Duchenne muscular dystrophy (DMD) and a range of other gene therapeutic applications.

Animals↗
PubMed1999

Internalization and recycling of the CB1 cannabinoid receptor.

Tolerance develops rapidly to cannabis, cannabinoids, and related drugs acting at the CB1 cannabinoid receptor. However, little is known about what happens to the receptor as tolerance is developing. In this study, we have found that CB1 receptors are rapidly internalized following agonist binding and receptor activation. Efficacious cannabinoid agonists (WIN 55,212-2, CP 55,940, and HU 210) caused rapid internalization. Methanandamide (an analogue of an endogenous cannabinoid, anandamide) was less effective, causing internalization only at high concentration, whereas delta9-tetrahydrocannabinol caused little internalization, even at 3 microM. CB1 internalized via clathrin-coated pits as sequestration was inhibited by hypertonic sucrose. Internalization did not require activated G protein alpha(i), alpha(o), or alpha(s) subunits. A region of the extreme carboxy terminus of the receptor was necessary for internalization, as a mutant CB1 receptor lacking the last 14 residues did not internalize, whereas a mutant lacking the last 10 residues did. Steps involved in the recycling of sequestered receptor were also investigated. Recovery of CB1 to the cell surface after short (20 min) but not long (90 min) agonist treatment was independent of new protein synthesis. Recycling also required endosomal acidification and dephosphorylation. These results show that CB1 receptor trafficking is dynamically regulated by cannabimimetic drugs.

Acids↗
PubMed1999

The effect of 'non-critical' (<50%) stenosis on vein graft longitudinal resistance and impedance.

OBJECTIVE: vein graft stenoses <50% cause minimal flow impairment, velocity elevation, or symptomatology and are therefore usually assumed to be "non-critical". The purpose of this study was to assess the effect of <50% vein graft stenosis on vein graft longitudinal impedance, as elevated impedance has been found to correlate with clinical graft failure. METHODS: eight segments of non-reversed cryopreserved vein (mean length 23+/-1 cm; mean outer diameter 4.7+/-0.2 mm) were saline-perfused in vitro utilising a variable pulsatile perfusion pump, Windkessel, and clamp resistor simulating the haemodynamic conditions of arterial bypass. Proximal (Pprox) and distal (Pdist) pressure were continuously measured by fluid-filled catheter transduction, and flow (Q) by ultrasonic transit-time flowmetry. Waveforms were digitally recorded at 200 Hz at pulse rates ranging from 60-180 b.p.m. with mean flow (Q) of 154 ml/min and mean proximal pressure (Pprox) of 100 mmHg (max/min 120/90). Graded mid-graft stenoses of <50% were created using an inflatable vascular occluder and measured by the corresponding changes in mean pressure gradient (DeltaP=Pprox-Pdist) and Q (%stenosis=1-{DeltaPbaselineQstenosis/Delta PstenosisQbaseline}1/4). Vein graft longitudinal resistance (RL) was calculated as DeltaP/Q. After Fourier transformation, vein graft longitudinal impedance (ZL) was calculated as DeltaP/Q at each harmonic, with ZL determined by integration over 0-4 Hz. Results are reported as mean+/-S.E.M. RESULTS: the desired levels of pressure and flow were established in all vein segments. Graded inflation of the occluder resulted in vein graft stenosis of 23+/-3% and 39+/-3%. This was accompanied by a mild reduction in Q (12% and 30%) and considerable increases in both RL (180% and 710%) and ZL (140% and 430%). CONCLUSIONS: "non-critical" vein graft stenosis (<50%) causes minimal change in mean flow, but substantial elevations in longitudinal resistance and impedance. The contribution of "non-critical" stenosis to vein graft failure may be under-appreciated.

Blood Vessel Prosthesis↗
PubMed1999

Chronic pyelonephritis in association with neuropathic bladder.

Progressive chronic pyelonephritis (CPN) leading to renal failure was, in the past, a mode of death in children with meningomyelocele (MMC). With more sophisticated management modalities, renal failure is now uncommon, but the problem of CPN still remains. In this series of 100 children with MMC, 39% have CPN. It is significantly more common in girls than in boys. There is a strong relationship between CPN and vesico-ureteric reflux (VUR). There is no association with raised bladder pressure. The majority of CPN arises in children under the age of 4 years, but damaged kidneys can continue to deteriorate. Although chronic renal failure is rarely seen in children with MMC, there is a risk that this may merely be postponed into adulthood.

Chronic Disease↗
PubMed1999

The Melbourne Acuity Screening Test (MAST).

The Melbourne Acuity Screening Test (MAST) is a vision screening technique which combines the features of a linear presentation, incorporating a crowding effect with a pass/fail test protocol. It is a simple, quick screening test which can be used for both literate and illiterate people. This paper reports on the preliminary results of a comparison of the pass/fail method with that of the measurement of threshold linear acuity. The evaluation consisted of four parts: (1) test-retest and reliability of the MAST and Sheridan Gardiner (SG) linear test; (2) concurrent validity of the MAST compared with the SG linear test; (3) a limited negative predictive study, and (4) a comparison of the time taken to perform the MAST versus the measurement of threshold acuity. The test-retest reliability for both tests was high. The agreement, determined by Cohenthorn s kappa, ranged between 0.71 and 0.79. The agreement between the MAST and the SG linear test was also high, ranging between 0.88 and 0.89. The negative predictive value was 100%. The positive predictive value was 85.7%. The MAST was also significantly quicker to perform, taking approximately half the time of the SG linear test.

Child↗
PubMed1999

Indirect evidence of human skeletal muscle damage and collagen breakdown after eccentric muscle actions.

Indirect markers of muscle damage and collagen breakdown were recorded for up to 9 days after a bout of concentric, followed by a bout of eccentric, muscle actions. Nine untrained participants performed two bouts of 50 maximum effort repetitions on an isokinetic dynamometer (angular velocity 1.05 rad x s(-1), range of motion 1.75 rad). An initial concentric bout of muscle actions was followed by an eccentric bout 21 days later, using the same knee extensors. Concentric actions induced no changes in maximum voluntary isometric contraction force (MVC), nor induced any changes in the serum enzyme activities of creatine kinase, a lactate dehydrogenase isoenzyme (LDH-1), or alkaline phosphatase. Similarly, concentric actions induced no change in markers of collagen breakdown, namely plasma hydroxyproline and serum type 1 collagen concentration. In contrast, eccentric actions induced a 23.5+/-19.0% (mean+/-s) decrease in MVC immediately post-exercise (P < 0.05), and increased the serum enzyme activities of creatine kinase and LDH-1 to 486+/-792 and 90+/-11 IU.l(-1) respectively on day 3 post-exercise, and to 189+/-159 and 96+/-13 IU x l(-1) respectively on day 7 post-exercise (all P< 0.05). Eccentric actions induced no significant changes in plasma hydroxyproline, but increased collagen concentration on days 1 and 9 post-exercise (48.6% and 44.3% increases above pre-exercise on days 1 and 9 respectively; both P < 0.05). We conclude that eccentric but not concentric actions may result in temporary muscle damage, and that collagen breakdown may also be affected by eccentric actions. With caution, indices of collagen breakdown may be used to identify exercise-induced damage to connective tissue.

Adult↗
PubMed1999

Trichome cell growth in Arabidopsis thaliana can be derepressed by mutations in at least five genes.

Leaf trichomes in Arabidopsis are unicellular epidermal hairs with a branched morphology. They undergo successive endoreduplication rounds early during cell morphogenesis. Mutations affecting trichome nuclear DNA content, such as triptychon or glabra3, alter trichome branching. We isolated new mutants with supernumerary trichome branches, which fall into three unlinked complementation groups: KAKTUS and the novel loci, POLYCHOME and RASTAFARI. They map to chromosomes IV, II, and V, respectively. The trichomes of these mutants presented an increased DNA content, although to a variable extent. The spindly-5 mutant, which displays a constitutive gibberellin response, also produces overbranched trichomes containing more nuclear DNA. We analyzed genetic interactions using double mutants and propose that two independent pathways, defined by SPINDLY and TRIPTYCHON, act to limit trichome growth. KAKTUS and POLYCHOME might have redundant actions mediating gibberellin control via SPINDLY. The overall leaf polysomaty was not notably affected by these mutations, suggesting that they affect the control of DNA synthesis in a tissue- or cell type-specific manner. Wild-type tetraploids also produce overbranched trichomes; they displayed a shifted polysomaty in trichomes and in the whole leaf, suggesting a developmental program controlling DNA increases via the counting of endoreduplication rounds.

Alleles↗
PubMed1999

Building community for the long-term: an intergenerational commitment.

Intergenerational visitation programs have demonstrated advantages for the young and old, but few programs last more than a year or two. Weaving long-term intergenerational programs into the fabric of both school curricula and community cultural life was the goal of a project launched in 1988 in Phoenix, Arizona. Classrooms of children visit weekly or biweekly with nearby nursing home residents, developing friendships while pursuing educational activities. Carefully planned and widespread community support through board participation, donations, and publicity has allowed the program to continue to expand, while the budget has decreased. Materials are available which facilitate program replication.

Aged↗
PubMed1999

Y chromosome microdeletion in a father and his four infertile sons.

Microdeletions of Yq are associated with azoospermia and severe oligozoospermia. In general, men with deletions are infertile and therefore deletions are not transmitted to sons unless in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are performed. We report an unusual family characterized by multiple members with infertility and Yq microdeletion. Complete reproductive history, semen analyses and blood samples were elicited from relevant family members. DNA preparation and quantification were performed using commercial kits. A total of 27 pairs of sequence tagged sites based primer sets specific for the Y microdeletion region loci were used for screening. Southern blots using deleted in azoospermia (DAZ) and ribosomal binding motif (RBM) cDNAs were then analysed for confirmation. The proband, his three brothers and father were all found to be deleted for DAZ but not RBM. At the time of analysis, the proband's father was azoospermic whereas his four sons were either severely oligozoospermic or azoospermic. Unlike their father, the four sons are infertile and have no offspring, except for one of them who achieved a daughter only after IVF/ICSI treatment for infertility. Microdeletions of Yq involving the DAZ gene are associated with a variable phenotypic expression that can include evidently normal fertility.

Blotting, Southern↗
PubMed1999

Necrosis, apoptosis, cytostasis and DNA damage in human lymphocytes measured simultaneously within the cytokinesis-block micronucleus assay: description of the method and results for hydrogen peroxide.

A method is described for the inclusion of apoptotic and necrotic cells in the cell counts obtained in the cytokinesis-block micronucleus (CBMN) assay, which is conventionally used solely for the assessment of chromosome breakage, chromosome loss and frequency of dividing cells. The morphological criteria for the recognition and discrimination between necrotic, apoptotic and viable cells are described. Using this comprehensive method we have evaluated the cytotoxic and genotoxic effects of hydrogen peroxide (0-100 microM) in lymphocytes exposed in RPMI 1640 medium. The results obtained indicated significant (P < 0.05) correlations between hydrogen peroxide concentration and the frequency of micronucleated cells (r = 0.39), necrotic cells (r = 0.73), apoptotic cells (r = -0.26) and binucleated cells (r = -0.55). Almost similar results were obtained using the cytosine arabinoside modification of the CBMN assay, which enables excision-repaired sites to be converted to micronuclei. Some of the above end-points were significantly (P < 0.05) correlated with each other (necrosis and apoptosis, R = -0.39; necrosis and micronucleated cell frequency, R = 0.46; necrosis and binucleated cells, R = -0.78; apoptosis and binucleated cells, R = 0.32). It was therefore necessary to use multiple regression analysis to identify the main event induced by hydrogen peroxide, which was necrosis (beta = 0.57, P = 0.0001) and not micronucleus formation (beta = 0. 15, P = 0.1332). Using an ELISA assay we showed that hydrogen peroxide did not induce 8-hydroxydeoxyguanosine. Our data show that the proposed comprehensive test system may provide a better procedure for classifying potential toxic chemicals and enable discrimination between agents that primarily induce cytotoxic effects as opposed to genotoxic effects. The integration of apoptosis and necrosis into the micronucleus assay may also be of practical use in radiosensitivity studies.

Adult↗
PubMed1999

A mutation in the second transmembrane region of the CB1 receptor selectively disrupts G protein signaling and prevents receptor internalization.

We mutated a conserved aspartate in the second transmembrane domain of the cannabinoid CB(1) receptor to asparagine (D164N), stably transfected it into AtT20 cells, and examined the coupling of this mutant receptor to several intracellular effectors that are targets of wild-type CB(1) receptor activation. We found that the D164N receptor binds the CB(1) agonist WIN 55,212-2 with an affinity matching that of the wild-type CB(1) receptor and inhibits Ca(2+) currents and cAMP production with an equivalent potency and efficacy. This mutation, however, blocks coupling of the receptor to the potentiation of inwardly rectifying potassium channel (KIR) currents and prevents internalization of the receptor after exposure to agonist. Although the mutant receptor did not internalize, we found it was still capable of activating p42/44 MAP kinase. In addition, we made a reciprocal mutation that exchanged the aspartate with an asparagine in the seventh transmembrane region (D164N/N394D). In other seven-membrane-spanning receptors, this reciprocal mutation is known to restore functions disrupted by the mutation of the single conserved aspartate. However, activation of D164N/N394D did not potentiate KIR current, nor did it internalize. We conclude that D164 is necessary for potentiation of KIR current and internalization of receptor but not necessary for agonist binding, inhibition of cAMP production, inhibition of Ca(2+) currents, or activation of p42/44 MAP kinase. Furthermore, CB(1) receptor internalization is not necessary for MAP kinase activation.

Animals↗
PubMed1999

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Animals↗
PubMed1999

Efficacy of an international exchange via the Internet.

Nursing education is lacking in international and computer experiences needed in the current global health care system. No nursing studies were found that use international exchanges together with computer use as a teaching strategy to help students become more culturally competent as well as more knowledgeable in electronic information communication. Knowles' adult learning theory, Kolb's experiential learning theory, and Campinha-Bacote's cultural competence model undergird this pilot study. The study used a one-group, posttest design to measure the effectiveness of an international exchange via the Internet, designed to enhance global awareness and computer use of 25 nursing students enrolled in a rural university in the southeastern United States. Data were obtained on a 24-item Internet Exchange Evaluation Questionnaire at the end of the course. Descriptive statistics were used to analyze the data. International exchange via the Internet was determined to be an effective strategy for heightening international awareness and increasing Internet use. This pilot study suggests fostering international exchanges and improving computer use can be developed further through more sophisticated approaches. A model of improving global health through shared knowledge and professional collaboration will be pursued further.

Adult↗
PubMed1999

Nurse-mediated serum cholesterol reduction and health locus of control--a device for targeting health promotion?

Varying intensities of nurse-mediated health education advice were administered to subjects over a three-month period. Mean serum total cholesterol was calculated for each group at the outset and completion of the study. A multidimensional health locus of control (MHLC) scales questionnaire was self-completed by subjects at the outset. A highly significant association between internality and reduction in serum total cholesterol in the high-intensity intervention group was observed. The completion of a MHLC scale questionnaire may assist health professionals in identifying which subjects may most benefit from high-intensity health education advice when raised serum total cholesterol is prevalent.

Adult↗
PubMed1999

A specialized apperception test for ambulatory-impaired adolescents.

A specialized apperception test for physically impaired adolescents was developed, and a pilot was conducted using ten nonimpaired and ten impaired adolescents. Ten cards depicting various scenes with physically impaired male and female models were designed to elicit themes that may be particularly relevant for this adolescent population. Two raters evaluated how well each card elicited issues identified in the literature as pertinent to physically challenged adolescents.

Activities of Daily Living↗