Perforin-positive cytotoxic lymphocytes in pregnancy.

OBJECTIVE: To investigate whether perforin-positive, cytotoxic lymphocytes are present in the first and second trimester as well as at term during normal gestation. STUDY DESIGN: A monoclonal antibody raised against human perforin was used to detect perforin expression in mononuclear cells in first-trimester abortion, second-trimester preterm labor due to cervical incompetence and term placentas obtained after normal delivery. Fresh frozen tissue sections containing first- and second-trimester decidua and placental tissues as well as decidua of maternal and fetal surfaces of term placenta were stained using an immunoperoxidase method. RESULTS: Occasional perforin-positive lymphocytes were present in stroma of chorionic villi of term placenta, while most were found in decidua and coagulated blood in maternal vessels and intervillous spaces. The majority of these lymphocytes were CD3-, CD2+ and CD56+. Quantitative comparison of decidual perforin-positive lymphocytes demonstrated a relative increase in these lymphocytes in decidua of second-trimester and term placentas. CONCLUSION: The presence of perforin-positive cytotoxic lymphocytes in maternal blood and decidua during gestation suggests their roles in pregnancy.

3,4-Dichloroisocoumarin serine protease inhibitor induces DNA fragmentation and apoptosis in susceptible target cells.

3,4-Dichloroisocoumarin (DCI) inhibition of serine proteases generates reactive intermediates that have been theorized to affect apoptosis. To examine this possibility various target cells were treated with different concentrations of DCI and assessed for intracellular nuclear DNA fragmentation and apoptosis. DCI treatment caused oligonucleosomal DNA fragmentation in cell lines expressing high levels of protease activity (LAK cells, NK-92, CTLL-2, L929, 3T3). This DNA breakdown characteristic of apoptosis occurred in a dose-dependent fashion within 4-6 hr of treatment and was confirmed by electron microscopy. In cell lines expressing low levels of protease activity (unstimulated human peripheral blood mononuclear (PBMN) cells, YAC-1 cells), DCI effectively inhibited protease activity without inducing oligonucleosomal DNA fragmentation. ZN2+ ions significantly inhibited DCI-induced DNA degradation. The mixture of DCI and BLT esterase active NK cell lysate triggered DNA fragmentation in isolated YAC-1 nuclei. Degree of DNA fragmentation in YAC-1 nuclei was proportional to the level of BLT esterase activity. Cell lysate protease activity, initially inhibited by DCI acylation, was restored by hydroxylamine deacylation, thus preventing DCI-mediated DNA fragmentation. Our results suggest that DCI treatment of cells expressing high levels of protease activity generates toxic levels of acyl-enzyme intermediates. These intermediates may trigger nuclear DNA breakdown and apoptosis by activating endogenous endonucleases. This effect may compromise the analysis of apoptosis in experimental systems using high concentrations of DCI for extended periods.

Myxoid change in nondecidualized cutaneous endometriosis resembling malignancy.

Cutaneous endometriosis infrequently arises in the absence of pelvic disease. Rare features such as myxoid change can resemble malignancy and may pose a challenging histological diagnosis. We are not aware of any previous cases involving nondecidualized cutaneous endometriosis with myxoid change associated with an abdominal surgical scar. We report the first such case in which a 24-year-old woman presented with a steadily growing, firm, tender, painful, subcutaneous cicatrical mass that had appeared shortly after cesarean section 1 year previously. The mass was removed and permanent sections revealed foci of large, irregular endometrial glands embedded within prominent myxoid stroma and acellular mucin pools, with fibrosis and pseudoinfiltration of the fascia. No evidence of malignancy was identified. This case demonstrates that nondecidualized cutaneous endometriosis with myxoid change should be considered in the differential diagnosis of histologically similar malignancies such as mucinous adenocarcinoma and pseudomyxoma peritonei.

Ovarian mucinous cystadenoma associated with mural leiomyomatous nodule and massive ovarian edema.

Mural nodules associated with mucinous and serous tumors of the ovary may represent a reactive process, a benign tumor, or a malignant neoplasm. Mural leiomyomatous nodule in mucinous cystadenoma is extremely rare. Two such cases had been described previously. In this case a 43-year-old white female presented with 24-h history of left quadrant pain and a left adenexal cystic mass on ultrasound examination. An exploratory laparotomy revealed a left ovarian mass with torsion on its pedicle. Frozen section of the cystic mass showed a mucinous cystadenoma with mural smooth muscle proliferation. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histologic examination of the mass revealed a mucinous cystadenoma with a mural leiomyomatous nodule and an enlarged ovary with massive stromal edema. This is the first case of a mural leiomyomatous nodule in association with a mucinous cystadenoma in an ovary with massive edema. This case broadens the histologic spectrum in which a mural leiomyomatous nodule may be encountered.

Impairment of left ventricular function by acute cardiac lymphatic obstruction.

OBJECTIVES: We performed the following study to define the effects of acute cardiac lymphatic obstruction on left ventricular (LV) systolic and diastolic function. METHODS: Cardiac lymphatic obstruction was created in 8 pentobarbital-anesthetized dogs by identifying (Evans blue) and ligating the right and left epicardial lymphatics, the afferent and efferent lymphatics associated with the pretrachael and cardiac lymph nodes, and the thoracic duct. Left ventricular function was assessed by analysis of micromanometer-conductance catheter-derived LV pressure-volume relationships. Contractility was assessed by preload recruitable stroke work (PRSW). The active and passive phases of LV relaxation were assessed by the time constant o isovolumic relaxation (tau) and the end-diastolic pressure-volume relationship (stiffness), respectively. RESULTS: PRSW decreased significantly and tau increased significantly from baseline at 1, 2, and 3 h after cardiac lymphatic obstruction (n = 8), but stiffness did not change. Cardiac lymphatic obstruction had similar effects on LV function in a group of autonomically blocked dogs (n = 5). Left ventricular function did not change in sham treated controls (n = 8). Cardiac lymphatic obstruction induced a significant increase in LV wet/dry weight ratios (3.58 +/- 0.01) when compared to the control group (3.53 +/- 0.02). Histopathology of the myocardium in the lymphatic obstruction groups revealed significant lymphangiectasis and increased interstitial spacing when compared to controls. CONCLUSIONS: Acute cardiac lymphatic obstruction depresses contractility and active relaxation and causes mild LV myocardial edema, but does not alter diastolic stiffness.

Posttransplantation lymphoproliferative disorder in cardiac transplant allografts.

Posttransplantation lymphoproliferative disorder occurs in 1.5% to 13% of heart transplant recipients and rarely involves the allograft. We report a case of posttransplantation lymphoproliferative disorder restricted to the mitral valve in a heart transplant recipient. Thirteen cases of cardiac allograft involvement by posttransplantation lymphoproliferative disorder are reported in the literature. None are restricted to the allograft. Five specify sites of cardiac involvement. Valvular masses without infection necessitate evaluation for posttransplantation lymphoproliferative disorder involvement of the cardiac allograft valve.