Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines

The architecture of normal colonic mucosa suggest that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.     

Overexpression, purification, and characterization of SHPTP1, a Src homology 2-containing protein-tyrosine-phosphatase

A protein-tyrosine-phosphatase (PTPase; EC 3.1.3.48) containing two Src homology 2 (SH2) domains, SHPTP1, was previously identified in hematopoietic and epithelial cells. By placing the coding sequence of the PTPase behind a bacteriophage T7 promoter, we have overexpressed both the full-length enzyme and a truncated PTPase domain in Escherichia coli. In each case, the soluble enzyme was expressed at levels of 3-4% of total soluble E. coli protein. The recombinant proteins had molecular weights of 63,000 and 45,000 for the full-length protein and the truncated PTPase domain, respectively, as determined by SDS/PAGE. The recombinant enzymes dephosphorylated p-nitrophenyl phosphate, phosphotyrosine, and phosphotyrosyl peptides but not phosphoserine, phosphothreonine, or phosphoseryl peptides. The enzymes showed a strong dependence on pH and ionic strength for their activity, with pH optima of 5.5 and 6.3 for the full-length enzyme and the catalytic domain, respectively, and an optimal NaCl concentration of 250-300 mM. The recombinant PTPases had high Km values for p-nitrophenyl phosphate and exhibited non-Michaelis-Menten kinetics for phosphotyrosyl peptides.     

Mammographic findings of recurrent breast cancer after lumpectomy and radiation therapy: comparison with the primary tumor

PURPOSE: To compare the mammographic findings of recurrent breast cancer with those of the primary tumor in patients who underwent lumpectomy and radiation therapy. MATERIALS AND METHODS: Mammograms were reviewed of primary and recurrent tumors in 25 patients (26 lesions). Mammographic appearance, location, and histopathologic characteristics were retrospectively compared between primary and recurrent tumors. RESULTS: Primary and recurrent tumors were mammographically similar in 21 (81%) of the 26 lesions. Of 14 primary tumors with calcifications, 12 (86%) recurred with calcifications, and of the 12 masses, nine (75%) recurred as masses. Recurrent tumors that occurred in the lumpectomy quadrant were more often similar in mammographic appearance to the primary tumor (20 of 22 tumors) than those in other quadrants (one of four tumors) (P < .02). CONCLUSION: After conservative treatment of breast cancer, the majority of recurrent tumors appear to be mammographically similar to primary tumors. It is prudent to review preoperative mammograms during follow-up of patients after lumpectomy and radiation therapy.     

In vivo surface analysis of titanium and stainless steel miniplates and screws

OBJECTIVE: To determine the results peranal excision for rectal carcinoma. DESIGN: Retrospective case series. SETTING: A university-affiliated hospital. PATIENTS: Of 178 patients who presented for curative resection of rectal carcinoma between 1975 and 1993, 19 (10.7%) were deemed suitable for local excision. There were 10 men and 9 women with a mean age of 71.2 years. The follow-up ranged from 13 to 184 months. INTERVENTION: Peranal excision. MAIN OUTCOME MEASURES: Histologic differentiation, gross morphology, depth of invasion and size of the carcinoma, adequacy of margins of excision, complications of operation, rates of recurrence, results of salvage therapy and 5-year survival. RESULTS: There were no intraoperative complications. Postoperative complications included urinary retention (one patient) and bleeding (one patient). There were five local recurrences (26%). Salvage operations were performed in three (60%) patients and were successful in two of them. The 5-year cancer-specific survival rate was 82%. The recurrence rate was higher in patients with inadequate margins of excision and ulcerative lesions. Neither size nor grade of the carcinoma correlated with recurrence. CONCLUSIONS: Local excision of rectal carcinoma can be performed successfully in selected patients. Diligent follow-up is required, because up to 60% of local recurrences can be treated successfully.     

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.     

Risk stratification using the Society of Thoracic Surgeons Program

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.     

Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA.     

Ultrastructural and biochemical changes of hepatocytes during ether and fluothane anesthesia under experimental conditions

A study was made of a possibility of using Soviet made membranes "Vladipor" with a pore diameter of 16--17 nm for the purpose of concentration and purification of antigenic extracts from stab cultures of S. typhi obtained by the action of typsin, hydrogen peroxide and detergents. Preparations, complete by antigenic structure, were obtained by ultrafiltration, with a good yield. The maximal rate of ultrafiltration was noted in case of "peroxide" antigenic preparations. The use of diafiltration provided a significant reduction of the ash content in the end products.