PubMed · 14184738
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R DEGOS, J GUILAINE. [DEEP ANNULAR GRANULOMAS].. https://pubmed.ncbi.nlm.nih.gov/14184738/
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BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) regulates cellular responses to hypoxia and is rapidly degraded under normoxia through von Hippel-Lindau (VHL) mediated ubiquitination. Although HIF-1alpha stabilization appears to be the molecular basis for VHL-associated cancers, stabilizing mutations in HIF-1alpha have not been reported. METHODS: A series of 15 metastatic androgen independent prostate cancers were examined for mutations in the oxygen-dependent domain (ODD) of HIF-1alpha by PCR amplification and DNA sequencing. RESULTS: A somatic proline to serine mutation in codon 582 (P582S) was identified in one sample. Transfection studies with a HIF-1alpha regulated reporter gene showed increased transcriptional activity that correlated with higher mutant HIF-1alpha protein expression. Increased expression of the P582S mutant induced by iron chelation, which blocks proline hydroxylation of wild-type HIF-1alpha, was markedly attenuated. The mutant also showed increased stability under normoxic versus hypoxic conditions. CONCLUSION: The P582S HIF-1alpha is a stable variant and HIF-1alpha mutation is a mechanism for enhancing HIF-1alpha activity in human cancer. The recent identification of the identical P582S HIF-1alpha as a polymorphism suggests that this variant may increase tumor susceptibility or cause more aggressive biological behavior.
PURPOSE: To retrospectively evaluate whether recall, biopsy, and positive biopsy rates for a group of radiologists who met requirements of Mammography Quality Standards Act of 1992 (MQSA) demonstrated any change over time during a 27-month period (nine consecutive calendar quarters). MATERIALS AND METHODS: Institutional review board approved study protocol, and informed consent was waived. All screening mammograms that had been interpreted by MQSA-qualified radiologists between January 1, 2001, and March 31, 2003, were reviewed. Group recall rates, biopsy rates, and detected cancer rates for nine calendar quarters were computed and attributed to performance date of original screening mammogram. Type of biopsy performed was classified as follows: stereotactic vacuum-assisted biopsy, ultrasonography (US)-guided core biopsy, US-guided fine-needle aspiration biopsy, surgical excision, and multiple biopsies. chi(2) Test for trend (two sided) and linear regression were used to assess trends over time for recall and biopsy rates, biopsy rates according to type of biopsy performed, and percentage of biopsy results positive for cancer. RESULTS: Group recall rate did not show a statistically significant trend during period studied (P = .59). Biopsy rates increased significantly from 13.02 to 20.12 per 1000 screening examinations (P < .001). A corresponding substantial decrease was seen in percentage of biopsies in which malignancy was found, although this trend was not statistically significant (P = .24). A significant increase (from 4.72 to 9.88 per 1000 screening examinations) was found in rate of stereotactic vacuum-assisted 11-gauge core biopsies performed (P < .001). CONCLUSION: Observed increase in biopsy rates reinforces the need to carefully select patients for biopsy to achieve efficient, efficacious, and cost-effective programs for early detection of breast cancers.
HISTORY: A 56-year-old man complain of chronic cough for 6 months without further clinical problems. The patient was otherwise in good health and showed only a moderate bronchial sound at the left ventral paracordial region. INVESTIGATIONS: Thorax X-ray revealed an infiltrate in the lingula with segmental borders. The CT scan showed air bronchogramms and bilateral more small infiltrates. DIAGNOSIS, TREATMENT, CLINICAL COURSE: Bronchoscopic transbronchial biopsies revealed a BALT-lymphoma. A seven years old chest X-ray showed the lingual infiltrate in nearly the same extension as the current X-ray. Because of the disseminated manifestation, the slow course and the good performance status we did not start a palliative chemotherapy so far. CONCLUSION: Any pulmonary infiltrate which looks like pneumonia must be given a definite diagnosis if there are no clinical signs of infection.