Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.

BACKGROUND & AIMS: Alterations in the production of epithelial mucins have been correlated with advanced tumor stage in the colon, but direct evidence for a role of specific mucin genes in liver metastasis is lacking. The current study was designed to establish more directly the role of MUC2 in colon cancer metastasis. METHODS: MUC2 levels were manipulated in highly metastatic human colon cancer cells using eukaryotic expression constructs designed to express a portion of MUC2 complementary DNA in antisense orientation. To assess the effect of MUC2 levels on metastatic potential, liver colonization was assessed in athymic mice after splenic-portal inoculation. RESULTS: Stable integration of the MUC2 antisense construct into metastatic colon cancer cells (LS LiM6) resulted in an 80% reduction in MUC2-specific messenger RNA and a concomitant decrease in MUC2 apomucin protein. This reduction was associated with a 50% reduction in synthesis of mature glucosamine-labeled mucin, almost complete inhibition of secretion of sialyl-LeX and sialyl-Tn antigens, and a 40% decrease in binding of colon cancer cells to E-selectin. Reduction in MUC2 levels was associated with a marked decrease in liver colonization. CONCLUSIONS: This study provides direct evidence that MUC2 plays an important role in colon cancer metastasis.

Clinical differentiation of narrow QRS complex tachycardias.

Supraventricular tachycardias generally present with narrow QRS complexes and are quite commonly seen in the emergency department. Regular narrow QRS complex tachycardias occur in all age groups and may be associated with minimal symptoms, such as palpitations, or, present with hemodynamic compromise resulting in syncope. While history and physical examination are indispensable, they usually do not lead to a definitive diagnosis. The diagnosis is made by careful analysis of the 12-lead ECG. Therapy is based on hemodynamic assessment and understanding of the tachycardia mechanism.

Clinical approach to wide QRS complex tachycardias.

Wide QRS complex tachycardia is a frequently encountered arrhythmia in the emergency department and presents a diagnostic challenge to the emergency physician. The history, physical examination, chest radiograph, and electrocardiogram analysis are important in making the correct diagnosis. The diagnosis of ventricular tachycardia is supported by, 1) a history of prior myocardial infarction or congestive heart failure; 2) a physical examination showing cannon A-waves in the jugular venous pulsation or variable heart sounds; 3) a chest radiograph showing cardiomegaly or evidence of prior cardiac surgery; and 4) characteristic ECG features that include AV dissociation, fusion-capture beats, QRS concordance, or, typical morphologic features in leads V1 and V6. This article presents the diagnostic and therapeutic approaches to wide QRS tachycardias.

Permanent cardiac pacing.

Implantation of a permanent pacemaker is the most commonly performed surgical operation involving the heart. The modern cardiac pacemaker is a complex device that can sense and pace in both the atrium and ventricle. It also modulates the pacing rate based on sensed physiologic parameters. This article reviews the fundamental principles of pacemaker technology and provides the emergency physician with approaches to common pacemaker problems.

Implantable cardioverter defibrillators.

Implantable cardioverter defibrillators have proven to be an effective therapy for life-threatening ventricular arrhythmias. Given the ever-increasing number of patients who have these devices, increasing numbers of patients are likely to present to emergency departments with defibrillator-related problems. This article discusses normal device function, indications for implantation, and technique of implantation. It also focuses on the evaluation and management of patients with these devices presenting to the emergency department.

Solitary fibrous tumor. A cytologic-histologic study with clinical, radiologic, and immunohistochemical correlations.

BACKGROUND: Solitary fibrous tumors (SFT) are rare neoplasms that most commonly involve the pleura, mediastinum, and lung. They are believed to be submesothelial in origin. Histologically, they are characterized by fibroblast-like cells and connective tissue in varying proportions. The "patternless pattern" and the hemangiopericytoma-like pattern are the most common arrangements. The majority of SFTs have been immunoreactive for CD34. Very little has been reported regarding the cytologic findings in these tumors. METHODS: The authors reviewed the radiographic findings and studied fine-needle aspiration biopsies performed on seven patients with SFT of the pleura, and examined subsequent histologic material. The cell blocks or smears of all cases were stained with a monoclonal antibody to CD34. RESULTS: The cytologic preparations showed varying degrees of cellularity. Smears were comprised of spindled cells in a bloody background with small amounts of collagen. The three malignant tumors had a greater number of cells, both dispersed and in clusters, with nuclear pleomorphism and prominent nucleoli. The cell blocks characteristically showed varying degrees of cellularity with thickened blood vessels and a hemangiopericytoma-like pattern. The cells from the four benign tumors tended to be smaller in size and grouped in more cohesive clusters than the malignant ones. CD34 stained the spindle tumor cells in the cell blocks or smears from five cases; one malignant and one benign case failed to stain. The corresponding histologic samples from these cases demonstrated the same CD34 staining pattern in all cases except one. CONCLUSIONS: The differential diagnosis of SFT includes neurogenic tumors, mesotheliomas, sarcomatoid carcinoma, synovial sarcoma, hemangiopericytoma, and fibrosarcoma. CD34, when present, may prove equally helpful as a positive marker in cytology and in histologic preparations in the differential diagnosis of SFT.

Computerized interactive morphometry in the differential diagnosis of irradiated prostates.

Radiation therapy is becoming a treatment of choice for many patients with prostatic carcinoma. Distinguishing radiation change in prostate glands from carcinoma may be difficult. In this study we objectively assessed, by morphometric methods, the nuclear characteristics of benign and malignant prostates with a history of radiation treatment (125I implant with or without prior external beam radiation). This is part of our continuing efforts to achieve difficult differential diagnoses by analyzing perimeter, diameter and nuclear profile area of cells or interest and applying methods of statistical classification. Biopsies were performed 18-36 months following implant therapy. Eleven cases with residual prostate tumor constituted the malignant group. These were compared to 20 benign cases (benign glands in the 11 carcinoma cases plus 9 other cases with no residual carcinoma). Immunohistochemical staining with keratin 903 was performed on all cases. Differences in the nuclear parameters were most evident in the average nuclear profile areas (32.5 microns 2 for the malignant groups vs. 39.6 for the benign) and in the mean maximal cord length (diameter) (7.4 microns for the malignant group vs. 9.0 for the benign). Classification, however, is based on the size distribution plots of nuclear profile areas, which, in the malignant cases, had a sharper peak at lower value, while the benign cases had higher value and a broader peak with a trailing off into the larger values. This study emphasized the marked nuclear alterations that occur in irradiated prostates.(ABSTRACT TRUNCATED AT 250 WORDS)

HMB-45 reactivity in renal angiomyolipoma and lymphangioleiomyomatosis.

Recent reports have elucidated the variety of tissue types that can react with HMB-45. Consistent positivity has been demonstrated in angiomyolipomas, but only in the smooth-muscle cells. In this report, we examine five renal angiomyolipomas and 20 mesenchymal lesions with similar morphological features and with a possibly similar histogenesis. These include one retroperitoneal lymphangioleiomyomatosis, five epithelioid leiomyomas, nine leiomyosarcomas with epithelioid features, and five alveolar soft part sarcomas. HMB-45 demonstrated a strong diffuse cytoplasmic positive reaction with the smooth-muscle component in all cases of renal angiomyolipoma and in the one case of lymphangioleiomyomatosis. All alveolar soft part sarcomas, leiomyomas, and leiomyosarcomas were uniformly negatively stained by this antibody. We discuss the widening spectrum of lesions that are reactive with HMB-45 and the relationship of angiomyolipoma and lymphangioleiomyomatosis.

Case report: fatal lymphoproliferative disease seven weeks after liver transplantation.

A 42-year-old man developed a lymphoproliferative disorder and died seven weeks after undergoing liver transplantation for primary biliary cirrhosis. At autopsy, diffuse large cell lymphoma was noted to involve almost every organ. Molecular analyses of DNA isolated from an enlarged periportal lymph node indicated the presence of Epstein-Barr virus sequences and several JH immunoglobulin gene rearrangements (consistent with the presence of more than one greatly expanded clone of lymphoid cells of B-cell lineage). This case underscores the possibility of the rapid emergence of lymphoproliferative disorder related to Epstein-Barr virus early after liver transplantation, masked by a concurrent episode of acute rejection.