Biomedical subjects

R Haydon

Publications and source records attributed to R Haydon.

4 recordsLinked to original sources

PubMed2002

Fluorescence-based functional assay for Wnt/beta-catenin signaling activity.

Aberrant activation of beta-catenin signaling has been implicated in the development of human cancers. As a Wnt signal transducer, beta-catenin forms a complex with the lymphocyte enhancer-binding factor/T cell factor transcription factor and activates downstream targets that promote cell proliferation. Here we developed a Wnt-dependent beta-catenin-mediated heterologous transactivation system, which consisted of a chimeric transcription factor constructed by fusing the GAL4 DNA-binding domain with the full-length beta-catenin, and a GAL4-responsive reporter expressing GFP. The chimeric transcription factor was highly unstable and exerted no detectable transactivating effect on the GAL4-responsive reporter. However, lithium and Wnt1 significantly stabilized this chimeric transactivator, indicating that this transactivation system is regulated by beta-catenin in a Wnt-responsive fashion. Thus, this transactivation system could be used as a functional reporter to identify potential upstream factors that deregulate beta-catenin signaling during tumorigenesis, as well as to screen for potential anti-cancer agents that specifically inhibit beta-catenin signaling in human tumors.

Adenocarcinoma↗

PubMed2001

Tetracycline-regulated gene expression mediated by a novel chimeric repressor that recruits histone deacetylases in mammalian cells.

Regulated gene expression will provide important platforms from which gene functions can be investigated and safer means of gene therapy may be developed. Histone deacetylases have recently been shown to play an important role in regulating gene expression. Here we investigated whether a more tightly controlled expression could be achieved by using a novel chimeric repressor that recruits histone deacetylases to a tetracycline-responsive promoter. This chimeric repressor was engineered by fusing the tetracycline repressor (TetR) with an mSin3-interacting domain of human Mad1 and was shown to bind the tetO(2) element with high affinity, and its binding was efficiently abrogated by doxycycline. The chimeric repressor was shown to directly interact with mSin3 of the histone deacetylase complex. This inducible system was further simplified by using a single vector that contained both a chimeric repressor expression cassette and a tetracycline-responsive promoter. When transiently introduced into mammalian cells, the chimeric repressor system exhibited a significantly lower basal level of luciferase activity (up to 25-fold) than that of the TetR control. When stably transfected into HEK 293 cells, the chimeric repressor system was shown to exert a tight control of green fluorescent protein expression in a doxycycline dose- and time-dependent fashion. Therefore, this novel chimeric repressor provides an effective means for more tightly regulated gene expression, and the simplified inducible system may be used for a broad range of basic and clinical studies.

Base Sequence↗

PubMed2001

The relationship between dysphonia and sinusitis: a pilot study.

Though some clinicians believe chronic sinusitis is associated with dysphonia, studies confirming such a relationship are not available. This pilot study investigated vocal characteristics of chronic sinusitis patients compared to those of nonsinusitis patients. Nineteen male patients were evaluated in a single-blind, nonrandomized, prospective study at a Department of Veterans Affairs Medical Center. After candidates for the experimental and control groups were thoroughly screened [nasal and laryngology examinations, sinus computed tomography (CT) scan, history], 10 chronic sinusitis patients were assigned to the experimental group, nine patients without chronic sinusitis were assigned to the control group. Visi-Pitch analysis of their speech evaluated fundamental frequency, intensity, and perturbation. The evaluator described voice quality and vowel prolongation. Videostroboscopic examination evaluated glottic closure, supraglottic activity, vocal fold edge, amplitude, mucosal wave, and nonvibrating portion. Visi-Pitch analysis and vowel prolongation for each group was compared using an independent t-test. The average fundamental frequency mean was 113.43+/-32.75 Hz for the control group and 112.29+/-19.71 for the experimental group. This study established methods and parameters to determine if a relationship between chronic sinusitis and dysphonia actually exists. It did not establish a relationship between these entities, possibly due to the small sample size enrolled in the study, but determined that 126 subjects would be necessary to achieve significant results.

Adult↗

PubMed1994

Use of standardized patients to identify deficits in student performance and curriculum effectiveness.

Much literature supports the value of performance-based tests for obtaining an overall assessment of clinical skills; however, these tests can also identify specific deficits in medical curriculum and student learning. This study, conducted over a period of 2.5 years, used standardized patients to identify deficiencies in medical students' evaluation of a patient with "hoarseness and cough." Each of 230 students performed a physical examination and took a medical history, and each was evaluated on 29 items according to predetermined criteria. We conclude the following: (1) When examining a patient complaining of hoarseness and cough, students frequently did not screen for hemoptysis, thyroid problems, and otalgia; (2) Overall test performance correlated positively with the time of year of the rotation, but screening for certain items (including hemoptysis, thyroid problems, and otalgia) appeared not to depend on rotation; (3) Several important items significantly differentiated the more knowledgeable student from the less knowledgeable student.

Clinical Clerkship↗