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Biomedical subjects

J Hoeksema

Publications and source records attributed to J Hoeksema.

8 recordsLinked to original sources

Analysis of estrogen receptor interaction with a repressor of estrogen receptor activity (REA) and the regulation of estrogen receptor transcriptional activity by REA.

The transcriptional activity of nuclear hormone receptors is known to be modulated by coregulator proteins. We found that the repressor of estrogen receptor activity (REA), a protein recruited to the hormone-occupied estrogen receptor (ER), decreased the transcriptional activity of ER, both when ER was acting directly through DNA response elements as well as when it was tethered to other transcription factors. Administration of antisense REA resulted in a 2-4-fold increase in ER transactivation, implying that endogenous REA normally dampens the stimulatory response to estradiol. To define the interaction regions between ER and REA, we used glutathione S-transferase pull-down assays. We found that REA bound to the ligand-binding domain (E domain) of ER, but not to other regions of ER, and that REA interaction with ER involved a region in the C-terminal half of REA. REA and the coactivator SRC-1 were involved in a functional competition for regulation of ER transcriptional activity, which we show results from competition between these two coregulators for interaction with ER. REA contains an LXXLL motif near its N terminus, but this motif was not involved in its binding to ER. Rather, this sequence was required for the competitive binding of REA and SRC-1 to ER and thus for optimal repression of ER activity. Our findings show that the regions of REA required for its interaction with ER and for its repression of ER activity are different.

Amino Acid Motifs↗

Von Hippel-Lindau disease with multiple malignant renal tumors: the importance of genetic testing.

We present an adult man who, while being evaluated for gross hematuria, was found to have polycystic kidneys and multiple bilateral renal cell carcinomas. Further evaluation and the presence of a significant family history of cancer suggested the diagnosis of von Hippel-Lindau disease. Through the aid of genetic testing, this unusual diagnosis was confirmed and led to the identification of other family members with the von Hippel-Lindau gene. Patients with von Hippel-Lindau disease have an increased incidence of malignant carcinomas and the syndrome can mimic the presentation of other cystic diseases of the kidney. Early diagnosis and genetic screening of family members is essential to improve the prognosis and survival of those affected.

Adult↗

Development of a patient-centered preprocedure program.

Staff members at Blodgett Memorial Medical Center, Grand Rapids, Mich, developed and implemented a prototype for a new patient-centered preadmission testing (PAT) program. Using continuous improvement principles, an implementation team improved the existing PAT program by increasing patient satisfaction, reducing duplication of care and services, and avoiding delayed or canceled surgical procedures in the OR. The implementation team then designed a preprocedure learning process in which nurses performed patient assessments, coordinated information between departments, and made appropriate referrals.

Diagnostic Tests, Routine↗

The role of radiation therapy in the palliation of metastatic genitourinary tract carcinomas. A study of the Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group has conducted several randomized clinical trials to evaluate the efficacy of various radiation therapy schedules in palliating symptomatic brain and bone metastases. Among the patients entered in these studies, there were 225 patients with primary tumors of the genitourinary tract. Of these, 68 patients had cerebral metastases and 157 patients had osseous metastases. These patients were analyzed further as to the effectiveness of radiotherapy in palliation of their symptoms, and the results were compared to those for comparable metastases in patients with other primary sites. Relief of symptoms occurred in 54% of neurologic function (NF) Class III and 28% of NF Class II patients with cerebral metastases. This result compared favorably with those for the total group of patients consisting of patients with brain and bone metastases from various primary sites. Improvement was seen in 80% of patients with headaches and 88% of patients with convulsions. Motor loss improved in 62% of the patients. Of the patients with bone metastases, 81% with prostatic carcinoma and 59% with renal primaries had lessening of pain. Complete relief of pain at eight weeks occurred in 36% of the patients, compared to 24% in the total group. The median survival for patients with solitary bone metastases from a prostatic primary was 39 weeks, compared to 30 weeks for those with multiple metastatic sites.

Bone Neoplasms↗