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Biomedical subjects

Bryan R Haugen

Publications and source records attributed to Bryan R Haugen.

24 records · Page 2Linked to original sources
PubMed2002

Quantitative analysis of telomerase hTERT mRNA and telomerase activity in endometrioid adenocarcinoma and in normal endometrium.

OBJECTIVES: In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomerase repeat amplification protocol (TRAP) assay were correlated with tumor grade in endometrial carcinomas and with the histologic phase of normal endometrium. METHODS: Twenty-six samples of endometroid adenocarcinoma and 20 cases of benign endometrium were obtained from hysterectomy specimens. Total RNA was extracted from each tissue sample and used for quantitative real-time RT-PCR of hTERT mRNA and the levels were standardized to the levels of ribosomal RNA. Quantitative determination of telomerase activity was performed by the polymerase chain-based TRAP assay and the levels of expression were defined by the ratio of radioactivity incorporated into the 6-bp telomerase amplification products versus the radioactivity incorporated into an internal standard (telomerase/ITAS x 100 = 1 RU). Statistical analyses were performed using the Fisher exact test or chi2 test, a Wilcoxon rank sum test, and a linear regression analysis. RESULTS: hTERT mRNA and telomerase activity levels showed a linear association in the study group (P = 0.006, R2 = 0.139). hTERT mRNA levels and telomerase activity levels were significantly higher in endometrial cancer (179 pg/ng rRNA, 44 relative units (RU)) than in normal endometrium (45 pg/ng), (15 RU) (P = 0.009, P = 0.006). In normal endometrium, hTERT mRNA and telomerase activity levels were highest in the proliferative phase (74 pg/ng rRNA, 25 RU) and were relatively low in secretory (13 pg/ng rRNA, 6 RU) and atrophic endometrium (9 pg/ng rRNA, 2 RU). CONCLUSION: These results suggest that the quantitative analysis of hTERT and telomerase activity may have potential roles as diagnostic or prognostic adjuncts for both premenopausal and postmenopausal patients with endometrial cancer.

Adult↗
PubMed2002

Correlation of survivin mRNA detection with histologic diagnosis in normal endometrium and endometrial carcinoma.

BACKGROUND: The objective of this study was to determine if survivin mRNA expression is a marker of endometrioid adenocarcinoma and if survivin mRNA levels correlate with tumor grade and stage. METHODS: Twenty-six samples of endometrioid adenocarcinoma and 18 cases of benign endometrium were obtained at surgery. RNA was extracted from tissues and was used for quantitative real-time RT-PCR, targeting a 91-bp sequence of survivin mRNA and the levels were standardized to the levels of ribosomal RNA. Statistical analysis of the correlation between histologic diagnosis and the corrected survivin mRNA levels was performed by the Fisher Exact test and the Kruskal-Wallis test. RESULTS: Survivin mRNA was detected in all specimens. Survivin mRNA levels were increased in proliferative endometrium (P = 0.0509) and was increased in correlation with ascending grade in endometrioid adenocarcinoma (P = 0.01). CONCLUSION: Survivin mRNA is not a specific marker of endometrial cancer, but may reflect an important mechanism in tumor progression of the endometrial mucosa.

Adenocarcinoma↗
PubMed2002

Excessive survivin expression in thyroid lymphomas.

Thyroid lymphoma occurs most commonly in the thyroid glands with a background of Hashimoto's thyroiditis. Therefore, it is occasionally difficult to distinguish lymphoma from Hashimoto's thyroiditis because of some cellular and histologic similarities. We have examined whether survivin or human telomerase reverse transcriptase (hTERT) expression can differentiate between the 2 disorders. Surgically removed tissue samples from 6 patients with thyroid lymphoma and 6 patients with Hashimoto's thyroiditis were analyzed for mRNA levels of survivin and hTERT by real-time quantitative reverse-transcription polymerase chain reaction. Expression of survivin protein was examined by immunohistochemical stain using a polyclonal antibody. Survivin mRNA levels were greater in thyroid lymphoma than in Hashimoto's thyroiditis: 49.1 +/-36.4 versus 6.6 +/-2.7 pg/ng rRNA (mean +/- SD) (P <0.005). Immunohistochemical stain confirmed an abundance of survivin protein in lymphoid cells of thyroid lymphoma. The amount of hTERT mRNA did not differ in the 2 disorders. Our study shows that measuring survivin mRNA levels or immunohistochemistry of the protein expression can be useful to aid the diagnosis of thyroid lymphoma when histologic diagnosis is difficult.

Biomarkers, Tumor↗
PubMed2002

Congenital isolated central hypothyroidism caused by a "hot spot" mutation in the thyrotropin-beta gene.

Two adult siblings presented to our practice with a known history of congenital central isolated hypothyroidism. Their growth, development, and general health had been normal. Although the disorder was known to result from thyrotropin (TSH) deficiency, providers in the past had made multiple adjustments in their levothyroxine replacement doses in attempts to normalize serum TSH levels. This suggests a need for better education of providers who care for patients with central hypothyroidism. We performed DNA sequencing of the TSHbeta gene and identified a homozygous single base deletion in codon 105, on exon 3, resulting in a frameshift and a premature termination signal at codon 114. This same mutation (C105FS114X) has been previously reported in South America and Europe and appears to be the most common genetic mutation associated with congenital isolated TSH deficiency. The identification of this mutation for the first time in the United States suggests that this disorder, now described in patients from countries on multiple continents, is more common than previously appreciated and may be a mutational "hot spot."

Amino Acid Sequence↗
PubMed2002

Clinical comparison of whole-body radioiodine scan and serum thyroglobulin after stimulation with recombinant human thyrotropin.

Sensitive monitoring for thyroid cancer recurrence or persistence includes whole-body radioiodine scanning (WBS) and measurement of serum thyroglobulin (Tg) after endogenous or exogenous thyrotropin (TSH) stimulation. We reviewed our experience using recombinant human thyrotropin (rhTSH) in 83 patients to compare the clinical relevance of a positive WBS and/or Tg. Ten patients had a positive WBS; eight of these patients had activity limited to the thyroid bed. rhTSH-stimulated Tg was 2 ng/mL or more in 25 and 5 ng/mL or more in 13 patients. Of the patients with a negative WBS, 11 of 20 patients with a Tg 2 ng/mL or more and 7 of 9 patients with a Tg 5 ng/mL or more received therapy or further evaluation based on the Tg alone. Conversely, only 1 of 5 patients with a serum Tg less than 2 ng/mL received therapy or further evaluation based on a positive WBS alone. Three of the patients who did not receive therapy or further evaluation, had subsequent negative WBS 10-12 months later, suggesting lack of clinically significant disease. Twenty patients had a negative WBS and serum Tg 2 ng/mL or more. Eleven of 20 patients had a Tg less than 5 ng/mL and 4 of these patients had further evaluation with a neck ultrasound. One patient had a biopsy-proven recurrence (rhTSH-stimulated Tg 4 ng/mL). Subsequent evaluations (> or = 6 months later) have been negative for 8 patients. Of the nine patients with a Tg 5 ng/mL or more and a negative WBS, 7 had further evaluation and 6 of 7 had identified disease. In summary, rhTSH-stimulated WBS and Tg are complementary, but Tg is a more sensitive indicator of disease recurrence or persistence. In our practice, an rhTSH-stimulated Tg greater than 4-5 ng/mL often resulted in further evaluation, while a Tg less than 4 ng/mL rarely resulted in further immediate evaluation.

Algorithms↗