Background. There is increasing evidence linking development and progression of cancer to an accumulation of mutations at the genomic level. The most frequently mutated gene known to date in sporadic breast cancer appears to be the tumor suppressor gene p53. This study was designed to determine the frequency of p53 gene mutations in primary breast cancer, to correlate the presence of p53 mutations with established clinicopathologic parameters, including the estrogen receptor (ER) and progesterone receptor (PR) status, and to assess the prognostic significance of p53 mutations regarding patient survival. Methods. We examined the p53 gene in genomic DNA samples from 192 primary breast cancers. Using denaturant gradient gel electrophoresis, the authors analyzed exons 5–9 in all tumors for mutations and performed DNA sequencing in 20 tumors to identify the exact nature of the p53 mutations. Results. p53 gene alterations were identified in 43 of the 192 tumors (22%), the majority localized in exons 5 and 6. DNA sequencing showed mostly missense mutations resulting from G or C substitutions. p53 mutations were found more often in tumors of younger women (P = 0.002), Afro‐American women (P = 0.05), and in tumors lacking ER (P = 0.03), PR (P = 0.04), or both (P = 0.06). There were no significant correlations with family history, tumor size, histologic grade or type, nodal status, or disease stage. The overall survival rates showed no significant difference between patients with mutant and wild‐type p53 tumors. The same was true when the comparison was limited to node‐negative patients or patients with ER‐positive or ER‐negative tumors. Finally, there was no significant difference in survival between patients with tumors harboring mutations in exons 5 and 6 versus exons 7–9. Conclusions. The results of this and other studies demonstrate a consistent relationship between ER‐positive tumors and wild‐type p53 on one hand and ER‐negative cancers and p53 mutations on the other. Our data do not support a significant prognostic role for p53 mutations in predicting survival.
The presently accepted methods for evaluation of splenic reticuloendothelial (RE) function include ""Tc sulfur colloid spleen scan, antibodycoated autologous erythrocyte clearance, and pocked erythrocyte count. All methods involve special equipment and/or risk and inconvenience to patients. A simple method of assessing splenic RE function was developed by counting erythrocytes with argyrophilic inclusions using a simple silver stain and an ordinary microscope.To test the validity of this method, blood samples were collected from patients suspected of having hyposplenia or asplenia, including patients with history of splenectomy, sickle cell disease or trait, and newborns. Blood samples were also collected from normal adults and from patients without hyposplenia or asplenia as controls. The samples were tested Reticuloendothelial (RE)) function is one of the many functions of the spleen, the importance of which is highlighted by the substantial risk of severe bacterial, systemic infection in asplenic individuals. Removal of the spleen for trauma increases the risk of death from overwhelming sepsis.1 Hyposplenia and asplenia occur in sickle cell disease and are associated with varying degrees of risk of bacterial sepsis.2 Hyposplenia also occurs in patients with bone marrow transplants, 3 alcoholic liver disease, 4 inflammatory bowel disease, 5 and in elderly people. 6 The tests often employed to evaluate splenic function include 99m Tc sulfur colloid spleen scan, antibody-coated autologous erythrocyte clearance, and pocked erythrocyte count. time consuming, involving patient inconvenience, or requiring special equipment.During our study of the argyrophilic nucleolar organizer region, we noticed that many erythrocytes from patients with histories of splenectomy or sickle cell disease contained argyrophilic inclusions. This prompted us to evaluate this feature as an indicator of splenic RE function. Toward this end, we compared the argyrophilic inclusion positive erythrocyte (AE) count with the pocked erythrocyte (PE) count for sensitivity, specificity, and correlation. We also studied the interobserver and intraobserver agreement for AE count. MATERIALS AND METHODSThirty-five EDTA anticoagulated blood samples were collected from patients with possible hyposplenia or asplenia. These included newborns up to 3 months of age (13 cases) and patients with histories of sickle cell disease (9 cases), sickle cell trait (2 cases), splenectomy (9 cases), chronic granulocytic leukemia (1 case), and autoimmune hemolytic anemia (1 case). Some of the cases first attracted our attention because of the presence of red cell inclusion bodies such as Howell Jolly (HJ) bodies and/or Pappenheimer (PH) bodies in their Wright-stained peripheral blood smears. The last two cases were selected 548 Downloaded from https://academic.oup.
Background: Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate 3 H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.
This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.
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