Primary heterologous carcinosarcoma of the ureter with necrotic malignant polyps. Report of a case and review of the literature

Carcinosarcoma is a rare and aggressive disease characterized by biphasic neoplasms with distinct mesenchymal and epithelial components. We report a case of ureteral carcinosarcoma with malignant necrotic polyps. The patient was a 58-year-old woman with painless hematuria, who was later diagnosed as having ureteral carcinosarcoma. Three long pendulous polypoid-shape tumors consisting of high-grade transitional cell carcinoma with chondrosarcomatous and osteosarcomatous elements were found. Two months after nephroureterectomy, the tumor relapsed in the bladder. Despite anterior exenteration, the patient died of local recurrence 6 months after her initial visit. To our knowledge, only 10 cases of this disease have been reported in the literature.     

Dexamethasone reduces lung eosinophilia,and VCAM-1 and ICAM-1 expression induced by Sephadex beads in rats

Airway eosinophilia is one of the key pathophysiologic features in asthma. The endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1), have previously been shown to play a crucial role in eosinophil recruitment into the inflamed airway. We have investigated the effects of dexamethasone on eosinophilia into the bronchoalveolar lavage fluid, and the upregulation of VCAM-1 and ICAM-1 expression, measured by immunoblotting, induced by i.v. injection of Sephadex beads into rats. The beads significantly increased the lung eosinophilia, and expression of VCAM-1 and ICAM-1 in the lung. Pretreatment with dexamethasone (0.1 to 2 mg/kg i.p.) strongly inhibited all the airway inflammatory events in a dose-dependent manner. In conclusion, glucocorticoids may be potent inhibitors of lung eosinophilia, at least in part, due to the prevention of the upregulation of VCAM-1 and ICAM-1 expression.     

Gingipains as the determinants of periodontopathogenicity

The arginine-specific cysteine proteinase (Arg-gingipain, Rgp) and lysine-specific cysteine proteinase (Lys-gingipain, Kgp) are produced by Porphyromonas gingivalis, an etiological bacterium of periodontal disease. Rgp and Kgp have been implicated as the major virulent factors because of their degrading activity to a broad range of host proteins and of the essential roles in bacterial cell viability. Recent studies have demonstrated the association of P. gingivalis with systemic diseases such as cardiovascular diseases, preterm birth, and low birth weight. The majority of gingipains exist as the membrane-associated complexes composed of the proteinase domains of both Rgp and Kgp, the C-terminal adhesin domains of RgpA and Kgp, phospholipids, and LPS. The complex induced potent viability loss of human endothelial cells and fibroblasts. As the suppression of Rgp and Kgp seems to be the most important to overcome the P. gingivalis-induced systemic disorders as well as the periodontal disease, we have thus designed and synthesized novel proteinase inhibitors specific to Rgp and Kgp on the basis of cleavage sites. Some of them suppressed the characteristic features of P. gingivalis associated with its pathogenicity such as degradation of host proteins, hemagglutination, enhancement of vascular permeability, disruption of leukocytes function, and induction of host cell death.     

A remnant tubal pregnancy after cloacal malformation repair

OBJECTIVE: Report of a remnant tubal pregnancy after cloacal malformation repair. DESIGN: Case report. SETTING: A university hospital. PATIENT: A woman with cloacal malformation repair. INTERVENTION: Laparoscopic surgery. MAIN OUTCOME MEASURE: Remnant tubal pregnancy. RESULT: Laparoscopic right salpingectomy. CONCLUSION(S): In this patient, ectopic pregnancy was caused by contralateral sperm transmigration to the remnant right tube, which was not connected with the left uterus.     

Effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin (LT H44A) as an adjuvant for nasal influenza vaccine

The effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin, LT H44A (His to Arg substitution at position 44 from the N-terminus of the A1 fragment of the A subunit) as an adjuvant for nasal influenza vaccine were examined. (1) When 0.2 microg of LT H44A, together with 0.2 microg of influenza A/PR/8/34 virus (PR8, H1N1) vaccine, was administered intranasally into BALB/c mice (twice, 4 weeks apart), anti-PR8 hemagglutinin (HA) IgA and IgG antibody (Ab) responses were induced at levels that were sufficient to provide either complete protection against infection with a small volume of PR8 virus suspension or partial protection against infection with a lethal dose of the suspension. The dose of the mutant LT and vaccine used here (0.2 microg/ 20 g doses mouse) corresponded to the estimated dose per person, i.e. 0.1 mg/10 kg body weight. (2) Using these vaccination conditions, no additional total IgE Ab responses were induced. (3) The mutant was confirmed to be less toxic than the native LT when the toxicity was analyzed either using Y1 adrenal cells in vitro (1/483 EC(50)) or by an ileal loop test. (4) One hundred micrograms of the mutant, administered intranasally or intraperitoneally into guinea-pigs (Heartley strain, 0.3-0.4 kg), caused no body-weight changes 7 days after administration, although 100 microg of the native LT administered intraperitoneally caused death in all guinea-pigs due to diarrhea within 2 days. The intranasal administration of 100 microg of the mutant resulted in almost no pathological changes in the nasal mucosa 3 days after administration. These results suggest that LT H44A, which can be produced in high yields in an E. coli culture (about 5 mg/l), could be used as one of the effective and safe adjuvants for nasal influenza vaccine in humans.     

Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome pathway in p53-mediated apoptosis of human cancer cells

Apoptosis is a morphologically distinct form of programmed cell death that plays a major role in cancer treatments. This cellular suicide program is known to be regulated by many different signals from both intracellular and extracellular stimuli. Here we report that p53 suppressed expression of the cellular FLICE-inhibitory protein (FLIP) that potentially blocks apoptotic signaling in human colon cancer cell lines expressing mutated and wild-type p53. In contrast, the expression of the death receptor KILLER/DR5 (TRAIL-R2) had no effect on FLIP expression, although exogenous p53 is known to induce KILLER/DR5 expression. In line with these observations, FLIP-negative cancer cells were sensitive to both p53- and KILLER/DR5-mediated apoptosis, whereas cells containing high levels of FLIP underwent apoptotic cell death when triggered by ectopic p53 expression but not by KILLER/DR5 expression. Treating the cells with a specific inhibitor of the proteasome inhibited the decrease of FLIP by p53, suggesting that p53 enhances the degradation of FLIP via a ubiquitin-proteasome pathway. Thus, the data indicate that p53-mediated downregulation of FLIP may explain the potent sensitization of human cancer cells to the apoptotic suicide program induced by wild-type p53 gene transfer.     

Adenosine A1 receptor blockade reverses dysmotility induced by ischemia-reperfusion in rat colon

This study was designed to assess whether adenosine A1 receptor antagonists [(R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] reverse dysmotility induced by ischemia-reperfusion in the rat colon. The gene of adenosine A1 receptor was expressed in the colon. Clamping (30 min) of the colonic marginal vessels was followed by reperfusion, and the propulsive colonic motility was evaluated. Propulsion was significantly slowed by ischemia-reperfusion, while FK352 and DPCPX abolished this delay. In contrast, the non-selective adenosine receptor antagonist, 8-phenyltheophylline, failed to affect the dysmotility. Thus, adenosine A1 receptor antagonists have potent therapeutic potential against ischemia-reperfusion-induced dysmotility in the colon.     

Receptors for sheep erythrocytes (E) and erythrocyte-antibody-complement complexes (EAC) on the lymphoblasts of childhood acute lymphoblastic leukemia

Two cell-surface markers, rosette formation with sheep erythrocytes (E-rosette) as a T-cell marker and rosette formation with bovine erythrocyte-antibody-complement complex (EAC-rosette) as a B-cell marker were determined on peripheral blood lymphocytes and lymphoblasts from normal and 89 children with acute lymphoblastic leukemia (ALL). In the majority of the patients (12/15 untreated patients and 6/11 patients in relapse), lymphoblasts exhibited neither E- nor EAC-rosette formation. Lymphoblasts from one untreated patient with mediastinal mass displayed E-(50%) and EAC-rosette formation (15%). In 3 of 11 patients in relapse, lymphoblasts displayed an increase in EAC-rosette formation with progressive disease. In the remaining patients with active disease, a small and variable proportion of lymphoblasts expressed E and/or EAC-rosette formation. In 63 patients in remission, percentages of E- and/or EAC-rosette were similar (p > 0.05) to those of control. The results indicate a wide heterogeneity with respect to expression of lymphocyte membrane markers in lymphoblasts and in normal lymphocytes in patients with active ALL.