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Biomedical subjects

J M Chase

Publications and source records attributed to J M Chase.

9 recordsLinked to original sources

Atopic dermatitis is associated with a low-producer transforming growth factor beta(1) cytokine genotype.

BACKGROUND: Atopic dermatitis (AD) is associated with hyperresponsiveness of lymphocytes to allergens. In acute AD only T(H)2-type lymphocytes are activated, whereas in more chronic forms of AD, the activity of both T(H)1- and T(H)2-type lymphocytes increases. IL-10 and transforming growth factor beta(1) (TGF-beta(1)) are immunosuppressive cytokines that inhibit the activity of both T(H) cell types in human subjects. OBJECTIVE: The aim of this study was to determine whether children with moderately severe chronic AD had IL10 or TGFB1 genotypes known to be associated with low cytokine production. METHODS: Using amplification refractory mutation screening PCR, we examined TGFB1 and IL10 gene polymorphisms, which are known to affect cytokine production, in 68 children with moderately severe AD and in 50 nonatopic children. RESULTS: The odds ratio of children with AD having a low TGFB1 producer genotype was 4.8 (95% CI, 2.4--9.7) compared with the control subjects (P <.0001). There were no differences in the frequency of IL10 gene polymorphisms between groups. CONCLUSION: TGFB1 genotype may partly explain the strong genetic predisposition to AD.

Adolescent↗

Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy.

Mouse mutants have a key role in discerning mammalian gene function and modelling human disease; however, at present mutants exist for only 1-2% of all mouse genes. In order to address this phenotype gap, we have embarked on a genome-wide, phenotype-driven, large-scale N-ethyl-N--nitrosourea (ENU) mutagenesis screen for dominant mutations of clinical and pharmacological interest in the mouse. Here we describe the identification of two similar neurological phenotypes and determination of the underlying mutations using a novel rapid mapping strategy incorporating speed back-crosses and high throughput genotyping. Two mutant mice were identified with marked resting tremor and further characterized using the SHIRPA behavioural and functional assessment protocol. Back-cross animals were generated using in vitro fertilization and genome scans performed utilizing DNA pools derived from multiple mutant mice. Both mutants were mapped to a region on chromosome 11 containing the peripheral myelin protein 22 gene (Pmp22). Sequence analysis revealed novel point mutations in Pmp22 in both lines. The first mutation, H12R, alters the same amino acid as in the severe human peripheral neuropathy Dejerine Sottas syndrome and Y153TER in the other mutant truncates the Pmp22 protein by seven amino acids. Histological analysis of both lines revealed hypo-myelination of peripheral nerves. This is the first report of the generation of a clinically relevant neurological mutant and its rapid genetic characterization from a large-scale mutagenesis screen for dominant phenotypes in the mouse, and validates the use of large-scale screens to generate desired clinical phenotypes in mice.

Animals↗

Coronal fracture of the hamate body.

A case of a displaced coronal fracture of the hamate body with a 1-month delay in diagnosis is presented with a review of the literature regarding hamate-body fractures. Mechanism, diagnosis, and treatment options are discussed. This diagnosis should be suspected on initial review of plain radiographs, which must include an oblique view in any patient presenting with pain after blunt trauma to the hand. Open reduction with internal fixation is reserved for unstable, displaced fractures. Care should be taken to preserve the vascular supply to the displaced fragment, and a two-incision technique is recommended to minimize risk to the motor branch of the ulnar nerve.

Adult↗

Toward the therapeutic editing of mutated RNA sequences.

If RNA editing could be rationally directed to mutated RNA sequences, genetic diseases caused by certain base substitutions could be treated. Here we use a synthetic complementary RNA oligonucleotide to direct the correction of a premature stop codon mutation in dystrophin RNA. The complementary RNA oligonucleotide was hybridized to a premature stop codon and the hybrid was treated with nuclear extracts containing the cellular enzyme double-stranded RNA adenosine deaminase. When the treated RNAs were translated in vitro, a dramatic increase in expression of a downstream luciferase coding region was observed. The cDNA sequence data are consistent with deamination of the adenosine in the UAG stop codon to inosine by double-stranded RNA adenosine deaminase. Injection of oligonucleotide-mRNA hybrids into Xenopus embryos also resulted in an increase in luciferase expression. These experiments demonstrate the principle of therapeutic RNA editing.

Adenosine Deaminase↗

Patella infera following arthroscopic anterior cruciate ligament reconstruction.

Fifty patients who had an arthroscopic anterior cruciate ligament reconstruction for chronic insufficiency were reviewed at an average of 13.6 months following surgery. Among these patients, 32% complained of anterior knee pain that interfered with daily activities. Radiographic patella infera was present in 12% of patients using the Insall-Salvati ratio and in 16% using the Blackburne-Peel ratio. Radiographic patella infera did not correlate with the clinical problem of postoperative anterior knee pain. However, loss of knee extension of greater than 5 degrees correlated highly with pain (p=0.002).

Adolescent↗

Distinguishing between haloperidol's and decamethonium's disruptive effects on operant behavior in rats: use of measurements that complement response rate.

The behavioral effects of haloperidol (0.04 to 0.16 mg/kg) and nonparalytic doses of decamethonium (0.2 to 0.8 mg/kg) were studied with operant methods that permitted the measurement of response rate, peak force of response, duration of response, and duration of the rat's head entry into the reinforcement dipper well. Type of operant response topography (forelimb press or forelimb grasp-and-pull) and peak force (low or high) required for reinforcement delivery were independent variables. The low-force, press-topography condition yielded qualitatively different profiles for the two drugs. Haloperidol increased peak force and duration of operant response, increased maximum head entry duration, and temporally dissociated forelimb and head entry behavior. Decamethonium decreased force and duration of operant response, did not appreciably affect maximum head entry duration, and did not influence the normal temporal coupling of forelimb and head entry responses. The haloperidol effects were seen as reflections of pseudo-Parkinsonism, not muscle weakness, which appeared to be the primary source of decamethonium's behavioral effects.

Animals↗

Specificity of run training on VO2 max and heart rate cganges during running and swimming.

To further evaluate the specificity of aerobic training, maximum physiologic measures (VO2, VE, HR, and R) and submaximal exercise heart rate were determined in control (N = 8) and experimental (N = 11) subjects prior to and following 10-week interval run training. Experimental subjects significantly increased (P less than 0.01) treadmill VO2 max by 252 ml O2 or 6.3%. This was siginificantly larger (P less than 0.01) than the 87 ml O2 or 2.6% increase (P less than 0.05) observed during swimming. Max HR decreased significantly in both forms of exercise. In addition, heart rate at two submaximal work levels during running and swimming was significantly lower after training. No changes in metabolic and physiologic measures were demonstrated for the controls after the 10-wk period. These results further support the concept of the specificity of the metabolic adaptation to aerobic training and strongly suggest that local adaptations in skeletal muscle significantly contribute to improvement in VO2 max. However, running may produce a general training adaptation in maximal and submaximal heart rate.

Adolescent↗

Peer-Led Alcohol Education program: a pharmacy student-led program for seventh-graders.

OBJECTIVE: To delay or discourage the use of alcohol by seventh-grade students through peer-led education. Peer-Led Alcohol Education (PLAE) program objectives were to: (1) educate students about alcohol use and (2) assess the differences between pharmacy student presenters and high school student (peer) presenters. SETTING: Middle schools in rural Nebraska. DESIGN: PLAE focuses on normative beliefs, personal values, and pledging. Pharmacy students and high school students were trained to deliver alcohol education presentations to seventh-grade students. Evaluation results were compared among groups of seventh-grade students who received PLAE presentations from peer presenters and from pharmacy student presenters. RESULTS: PLAE presentations were made to 342 seventh-grade students at 11 schools. Evaluation results suggest that pharmacy students projected more confidence in their presentations, used more creative prop selections, and were more effective communicators. High-school presenters had a greater ability to "relate" to the seventh-graders and thus were deemed more on-target with the information. CONCLUSION: Evaluation findings suggest that rural seventh-grade students in Nebraska perceived that the PLAE program provides useful information to aid them in their decisions regarding alcohol use.

Alcohol Drinking↗