PubMed Health⌕ Search

Biomedical subjects

Rodney J Taylor

Publications and source records attributed to Rodney J Taylor.

6 recordsLinked to original sources
PubMed2025

KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models.

PURPOSE: Neurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans. METHODS: Exome sequencing was used to detect genetic variants of KLHL13, which encodes Kelch like protein 13 (KLHL13), in four families segregating in an X-linked pattern. In silico protein modeling and overexpression in heterologous cells were used to determine the variant's impact. klhl13 loss of function was modeled in zebrafish, followed by rescue studies using human KLHL13 messenger RNA (mRNA) and an Aurora Kinase B (AURKB) inhibitor. RESULTS: We found one frameshift and three missense hemizygous variants of KLHL13 in individuals exhibiting NDD characteristics, such as intellectual disability (ID) and macrocephaly. Three-dimensional protein modeling simulation predicted the alteration of the KLHL13 protein folding for missense variants. Overexpression of NDD-associated variants in HEK293T cells revealed a significant impact on KLHL13-mediated cell-cycle regulation during mitosis, leading to genomic instability. Knocking down klhl13 in zebrafish resulted in developmental deficits, which were rescued by coinjection of human KLHL13WT messenger RNA but not by transcript encoding NDD variants. Treatment with AURKB selective inhibitor AZD1152-HQPA rescued genomic stability in heterologous cells and neurobehavioral deficits in zebrafish. CONCLUSION: Our results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapeutic approach to improve brain development and cognitive function.

Humans↗
PubMed2003

Multiple primary cancer, including transitional cell carcinoma of the upper uroepithelial tract in a multigeneration HNPCC family: molecular genetic, diagnostic, and management implications.

OBJECTIVE: We report a multigeneration family where colorectal cancer and cancer of multiple diverse anatomic sites, inclusive of transitional cell carcinoma of the upper uroepithelial tract, were manifested in several relatives. METHODS: A specific pattern of cancer of the colorectum, endometrium, ovary, small bowel, and transitional cell carcinoma, with a vertical distribution of this cancer phenotype through multiple generations, was consonant with a diagnosis of hereditary nonpolyposis colorectal cancer. RESULTS: Germline mutation testing identified the MSH2 mutation, which segregated with the cancer phenotype. This family study clearly demonstrates the value of genetic testing in the management and treatment decision process. CONCLUSIONS: We document, perhaps for the first time, how molecular genetic testing in hereditary nonpolyposis colorectal cancer can aid in the identification of a potential renal transplant donor for a relative with the MSH2 mutation who is experiencing renal insufficiency secondary to transitional cell carcinoma.

Adult↗
PubMed2002

Development and validation of the neck dissection impairment index: a quality of life measure.

OBJECTIVES: To validate a health-related quality-of-life (QOL) instrument for patients following neck dissection and to identify the factors that affect QOL following neck dissection. DESIGN: Cross-sectional validation study. SETTING: The outpatient clinic of a tertiary care cancer center. PATIENTS: Convenience sample of 54 patients previously treated for head and neck cancer who underwent a selective neck dissection or modified radical neck dissection (64 total neck dissections). Patients had a minimum postoperative convalescence of 11 months. Thirty-two underwent accessory nerve-sparing modified radical neck dissection, and 32 underwent selective neck dissection. MAIN OUTCOME MEASURE: A 10-item, self-report instrument, the Neck Dissection Impairment Index (NDII), was developed and validated. Reliability was evaluated with test-retest correlation and internal consistency using the Cronbach alpha coefficient. Convergent validity was assessed using the 36-Item Short-Form Health Survey (SF-36) and the Constant Shoulder Scale, a shoulder function test. Multiple variable regression was used to determine variables that most affected QOL following neck dissection RESULTS: The 10-item NDII test-retest correlation was 0.91 (P<.001) with an internal consistency Cronbach alpha coefficient of.95. The NDII correlated with the Constant Shoulder Scale (r = 0.85, P<.001) and with the SF-36 physical functioning (r = 0.50, P<.001) and role-physical functioning (r = 0.60, P<.001) domains. Using multiple variable regression, the variables that contributed most to QOL score were patient's age and weight, radiation treatment, and neck dissection type. CONCLUSIONS: The NDII is a valid, reliable instrument for assessing neck dissection impairment. Patient's age, weight, radiation treatment, and neck dissection type were important factors that affect QOL following neck dissection.

Aged↗
PubMed2002

Functional assessment using Constant's Shoulder Scale after modified radical and selective neck dissection.

BACKGROUND: Constant's Shoulder Scale is a validated and widely applied instrument for assessment of shoulder function. We used this instrument to assess which treatment and demographic variables contribute to shoulder dysfunction after neck dissection in head and neck cancer patients. METHODS: A convenience sample of 54 patients with 64 neck dissections and minimum follow-up of 11 months were evaluated. Thirty-two accessory nerve-sparing modified radical (MRND) and 32 selective neck (SND) dissections were performed. Multivariable regression analysis was used to determine the variables that were predictive for shoulder dysfunction. Clinical variables included age, time from surgery, handedness, weight, radiation therapy, neck dissection type, tumor stage, and site. RESULTS: Patients receiving MRND had significantly worse shoulder function than patients with SND (p =.0007). Radiation therapy contributed negatively, whereas weight contributed positively (p =.0001). CONCLUSIONS: The critical factors contributing to shoulder dysfunction after neck dissection were weight, radiation therapy, and neck dissection type.

Female↗
PubMed2002

Selective neck dissection for the treatment of neck metastasis from squamous cell carcinoma of the head and neck.

OBJECTIVE: Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. STUDY DESIGN: A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. METHODS: A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20-85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1-64 mo). Twenty-six patients had clinically negative (cNo) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. RESULTS: Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patientswere surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). CONCLUSIONS: With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.

Adult↗