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Biomedical subjects

L Williams

Publications and source records attributed to L Williams.

At least 91 records · Page 5Linked to original sources
PubMed1998

Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration.

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.

Amino Acid Sequence↗
PubMed1998

Nitric oxide compartments in the mushroom bodies of the locust brain.

All insect brains contain mushroom-shaped neural bodies which are implicated in associative learning. Here we show that the mushroom bodies of the locust brain have a remarkable and hitherto undescribed neural organisation consisting of six tubular structures in which bundles of axons are enclosed by cylindrical walls of nitric oxide synthase (NOS) expressing processes. A dynamic temporo-spatial simulation shows that the tubular organization allows NO to attain and maintain locally elevated concentrations within highly structured domains in the CNS. A diffusible gaseous signalling molecule such as NO can therefore selectively affect computational processes occurring in discrete parallel channels of information flow in the brain. The implications of this are discussed in relation to the role of NO in a compartmental model of the mushroom bodies and more generally in the context of the targetting of diffusible messenger molecules in the brain.

Animals↗
PubMed1998

Molecular genetics of spectral tuning in New World monkey color vision.

Although most New World monkeys have only one X-linked photopigment locus, many species have three polymorphic alleles at the locus. The three alleles in the squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm, respectively, and the three alleles in the marmoset and tamarin have spectral peaks near 562, 556, and 543 nm, respectively. To determine the amino acids responsible for the spectral sensitivity differences among these pigment variants, we sequenced all exons of the three alleles in each of these four species. From the deduced amino acid sequences and the spectral peak information and from previous studies of the spectral tuning of X-linked pigments in humans and New World monkeys, we estimated that the Ala --> Ser, Ile --> Phe, Gly --> Ser, Phe --> Tyr, and Ala --> Tyr substitutions at residue positions 180, 229, 233, 277, and 285, respectively, cause spectral shifts of about 5, -2, -1, 8, and 15 nm. On the other hand, the substitutions His --> Tyr, Met --> Val or Leu, and Ala --> Tyr at positions 116, 275, and 276, respectively, have no discernible spectral tuning effect, though residues 275 and 276 are inside the transmembrane domains. Many substitutions between Val and Ile or between Val and Ala have occurred in the transmembrane domains among the New World monkey pigment variants but apparently have no effect on spectral tuning. Our study suggests that, in addition to amino acid changes involving a hydroxyl group, large changes in residue size can also cause a spectral shift in a visual pigment.

Amino Acid Substitution↗
PubMed1998

Emergency vaccination of pigs against foot-and-mouth disease: protection against disease and reduction in contact transmission.

The protective ability of two novel oil-based FMD vaccines in pigs was examined. Both vaccine formulations were shown to protect pigs against airborne challenge with homologous FMDV within four days of vaccination, but not at two and three days post-vaccination. Protection was associated with the induction of variable and low titre serum antibody responses. A transmission study showed that protective immunisation resulted in reduced virus excretion. Vaccination at seven days, but not at four days, prior to challenge prevented contact transmission of FMD. The two formulations tested in this study have the favourable characteristics of low viscosity, low reactivity and high potency emergency FMD vaccines for use in strategic vaccination campaigns to assist the control of outbreaks of FMD.

Adjuvants, Immunologic↗
PubMed1998

Trinucleotide (CAG) repeat length is positively correlated with the degree of DNA fragmentation in Huntington's disease striatum.

Recent studies using DNA fragmentation assays suggest a role for apoptosis in cell death in Huntington's disease. In this study, we investigated the relationship between the degree of DNA fragmentation and the number of trinucleotide (CAG) repeats of the Huntington's disease gene in striatal tissue from Huntington's disease brains. We used frozen striatal tissue from 27 post mortem Huntington's disease brains (graded 0-4 on the Vonsattel classification, post mortem delay ranging from 4 to 41 h), plus control sections which were age, sex and post mortem delay matched from neurologically normal and Alzheimer's diseased striatal tissue. Our results show a significant positive correlation between the number of CAG repeats in the Huntington's disease gene and the degree of DNA fragmentation in Huntington's disease striatum. These results suggest that expanded CAG repeats in the Huntington's disease gene may lead to neuronal degeneration in Huntington's disease through an apoptotic mechanism.

Adult↗
PubMed1998

Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach.

Previously in this journal, we reported an association of the dopamine D4 receptor gene (DRD4) and attention deficit hyperactivity disorder (ADHD). In a population-association (case-control) study of 39 children with a refined phenotype of ADHD and 39 ethnically matched controls, we observed an increased percentage of the 7 repeat allele (29% vs 12%) and the 7+ genotype (49% vs 21%) in the ADHD group compared to the control group. In a replication and an extension of our initial study, we recruited another sample of ADHD subjects and found percentages of the 7 repeat allele (28%) and the 7+ genotype (48%) consistent with our previous findings. We used a family-based approach to evaluate a predicted association of DRD4 and ADHD based on a test of allele transmission focused on the 7 repeat allele. We identified 52 families based on the diagnosis of the refined phenotype of ADHD in the proband and the availability of DNA from both biological parents as well as the proband. Haplotype relative risk (HRR) analysis was performed to test our a priori hypothesis and produced significant results (chi-square = 4.65, P < 0.035). This provides additional evidence that the DRD4 gene is associated with a refined phenotype of ADHD.

Alleles↗
PubMed1998

Contextual influences and goal perspectives among female youth sport participants.

This study investigated two research questions: (1) do goal involvement and state anxiety vary between athletic games and athletic practices? and (2) do goal orientations change over the course of a competitive season as a function of the perceived team motivational climate? Middle school athletes (n = 127) were assessed on goal orientations, goal involvement, state anxiety, and motivational climate. Results indicated that athletes were more task involved and less anxious in practice than in game situations, and task goal orientation changed over the season relative to perceptions of mastery and performance climates. These results may indicate that sport offers an environment different from the academic setting and that mainstream psychology theories need to be adapted for the sport context.

Adolescent↗
PubMed1998

Multidimensional correlates of falls in older women.

Older women who had fallen within the last year (n = 63) were compared with those who had not fallen (n = 67) on several psychological and motor measures. Both fallers and nonfallers demonstrated high levels of functioning. Discriminant analysis results indicated that a combination of variables, including physical activity and both psychological (general well-being, self-efficacy) and motor (functional reach, mobility) measures differentiated fallers and nonfallers. Results suggest that falling is a multidimensional phenomenon, that small declines on multiple factors may increase risk of falls, and that multifaceted interventions may help maintain high levels of functioning and prevent declines often associated with increased age.

Accidental Falls↗
PubMed1998

Pre-school assessment project comparing assessment in the clinic or home.

From clinical experience it has been found that it is often difficult to assess young children in a clinical environment. Therefore, the aim of this project was to assess the communication of children in either the home or the clinic environment and to determine whether a more realistic impression of the child's language was obtained from home initial assessment. The results of this study suggest that for children who are 39 months old or less on the date of referral to speech and language therapy, a more representative sample of communication skills does emerge from initial assessment in the home environment. The conclusions drawn also indicate that the attendance rates for home assessments were significantly better than those for clinic appointments and this in turn meant that there was a subsequent cost saving to the department.

Child, Preschool↗
PubMed1998

Quality care for cardiology patients.

To evaluate outcome measures in a cardiology unit, patient satisfaction was measured. Patients consistently related problems in two areas: pain management and the waiting period before their procedure. After a major system change, patient satisfaction increased 16% and 29% respectively.

Heart Diseases↗
PubMed1998

Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting.

In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.

Adolescent↗
PubMed1998

Analog classroom assessment of Adderall in children with ADHD.

OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.

Adolescent↗
PubMed1998

Complement factor H or a related protein is a marker for transitional cell cancer of the bladder.

The BTAstat and BTA TRAK tests are new immunoassays that detect and measure an antigen in the urine of individuals diagnosed with bladder cancer. As described in this report, the monoclonal antibodies used in these kits were developed by immunizing mice with partially purified protein preparations derived from the urine of patients with bladder cancer. The antigen that is recognized by the monoclonal antibodies was purified from the urine of bladder cancer patients by immunoaffinity chromatography and identified as being either complement factor H (FH) or a closely related protein (CFHrp) by partial amino acid sequence analysis. Like serum FH, the urine antigen was demonstrated to have a complement factor C3b binding site and to accelerate the degradation of C3b in the presence of complement factor I. The culture supernatants from several human bladder, cervical, and renal cancer cell lines contained antigen as determined by immunoassay, and antigen affinity-purified from HeLaS3 culture media was shown to have FH activity. Moreover, the cell lines were shown to make products of the expected sizes by reverse transcription-PCR using FH-specific primers. In contrast, normal human epithelial keratinocytes, a myeloid leukemia cell line, and the colon cancer line LS174T were negative for production of a FH-like protein (CFHrp). We propose that the expression of proteins with FH-like activities may confer a selective growth advantage to cancer cells in vivo by decreasing complement activity, thus aiding their escape from lysis by immune surveillance. Identification of these proteins as cancer products also suggests avenues of chemotherapy or immunotherapy of some cancers.

Amino Acid Sequence↗
PubMed1998

Physician use of an ambulatory medical record system: matching form and function.

An ambulatory medical record system was implemented as a pilot project to determine the clinical and operational impacts of using interactive, computer-based systems in the outpatient setting. Of the 58 physicians who attempted to use the AMR system, 28 continue as active users. Physicians who discontinued use of the system reported a variety of reasons for their dissatisfaction. As a result of the pilot, the AMR implementation team and physicians understand better how to fit the AMR system to a physician's specific requirements, as well as enhance the operation of the physician's practice. Armed with the experience gained during the early phases of the implementation, the Cleveland Clinic Foundation now intends a cautious expansion and continued evaluation of the AMR system, with the objective of meeting organizational needs with appropriate technical functions.

Ambulatory Care Information Systems↗