Cell cycle effects of the novel topoisomerase I inhibitor NU/ICRF 505 in a panel of Chinese hamster ovary cell lines

The effect of the novel topoisomerase I inhibitor NU/ICRF 505 (20 microM, approximate IC50 concentration) on the cell cycle was studied by flow cytometry in four Chinese hamster ovary (CHO) cell lines. Postdrug treated cells were incubated with optimal concentrations of cytochalasin B to prevent re-entry of daughter cells into the cell cycle. NU/ICRF 505 had no significant effect on cell cycle distribution in the parent cell line (CHO-K1) and two mutants hypersensitive to topo II inhibitors (ADR-1, ADR-3), all of which express similar levels of topo I protein. In the drug-resistant variant ADR-r, which overexpresses topo I 2-fold, a significant accumulation of cells in G1 phase was recorded. These results are broadly consistent with the cell cycle effects expected in CHO cells by a classic topo I poison (camptothecin) and add weight to the view that NU/ICRF 505 induces cell death primarily through topo I inhibition.     

Ozone therapy of diffuse peritonitis in the early postoperative period

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.     

Daniel's story: congenital central hypoventilation syndrome

Central hypoventilation syndrome (CHS) is a disorder characterized by little or no ventilatory or arousal sensitivity to hypercapnia and variable reactivity to hypoxemia, with little or no hypoxic arousal responsiveness. CHS may be congenital or acquired and can be idiopathic or secondary to a known central nervous system abnormality. Infants often present with life-threatening apnea during quiet sleep and develop severe respiratory acidosis because of the inadequate response to hypercapnia and hypoxia. Long-term treatment usually involves use of mechanical ventilation during sleep.     

Detachment of the continent ileostomy poucn from the anterior abdominal wall: report of two unusual cases

The cases of two patients with continent ileostomies are presented. These illustrate the problems encountered with detachment of the pouch from the abdominal wall resulting in angulation of the efferent loop of the pouch in relation to the nipple valve and difficulty intubating the pouch. Both patients required operative correction of the separation. Several suggestions are made in order to prevent or decrease the incidence of the complications. Removal of a peritoneal strip around the efferent loop of the pouch appears to facilitate adequate fixation of the pouch to the anterior abdominal wall.     

Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.     

kDNA and rDNA sequences reveal a phylogenetic cluster of species originally placed in different genera of trypanosomatids

Hybridization using kDNA and rDNA sequences as probes was performed to study phylogenetic relatedness of different species of trypanosomatids. Using this approach, we identified five organisms which had been classified as Phytomonas and Herpetomonas that were more closely correlated to each other phylogenetically than to any other species or isolates from either genera. These findings raise doubts about the validity of the current classification of Trypanosomatidae. Finally, we demonstrated the usefulness of kDNA sequences as an alternative to genomic sequences in obtaining phylogenetic information on trypanosomatids.     

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group

BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values. RESULTS: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.     

Childhood leukemia in Belarus before and after the Chernobyl accident

Childhood leukemia (ICD 204-208 [1]) incidence rates in the different regions of Belarus are reported for a period before and after the Chernobyl accident (1982-1994). There are, at this point, no recognizable trends towards higher rates.