The advancement of a new human factors report--'The Unique Report'--facilitating flight crew auditing of performance/operations as part of an airline's safety management system.

This paper presents the findings of research relating to the specification of a new human factors report, conducted as part of the work requirements for the Human Integration into the Lifecycle of Aviation Systems project, sponsored by the European Commission. Specifically, it describes the proposed concept for a unique report, which will form the basis for all operational and safety reports completed by flight crew. This includes all mandatory and optional reports. Critically, this form is central to the advancement of improved processes and technology tools, supporting airline performance management, safety management, organisational learning and knowledge integration/information-sharing activities. Specifically, this paper describes the background to the development of this reporting form, the logic and contents of this form and how reporting data will be made use of by airline personnel. This includes a description of the proposed intelligent planning process and the associated intelligent flight plan concept, which makes use of airline operational and safety analyses information. Primarily, this new reporting form has been developed in collaboration with a major Spanish airline. In addition, it has involved research with five other airlines. Overall, this has involved extensive field research, collaborative prototyping and evaluation of new reports/flight plan concepts and a number of evaluation activities. Participants have included both operational and management personnel, across different airline flight operations processes. Statement of Relevance: This paper presents the development of a reporting concept outlined through field research and collaborative prototyping within an airline. The resulting reporting function, embedded in the journey log compiled at the end of each flight, aims at enabling employees to audit the operations of the company they work for.

Fractal organization of feline oocyte cytoplasm.

The present study aimed at verifying whether immature cat oocytes with morphologic irregular cytoplasm display self-similar features which can be analytically described by fractal analysis. Original images of oocytes collected by ovariectomy were acquired at a final magnification of 400x with a CCD video camera connected to an optic microscope. After greyscale thresholding segmentation of cytoplasm, image profiles were submitted to fractal analysis using FANAL++, a program which provided an analytical standard procedure for determining the fractal dimension (FD). The presentation of the oocyte influenced the magnitude of the fractal dimension with the highest FD of 1.91 measured on grey-dark cytoplasm characterized by a highly connected network of lipid droplets and intracellular membranes. Fractal analysis provides an effective quantitative descriptor of the real cytoplasm morphology, which can influence the acquirement of in vitro developmental competence, without introducing any bias or shape approximation and thus contributes to an objective and reliable classification of feline oocytes.

Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells.

BACKGROUND: We examined the effect of resveratrol (RS), a nonflavonoid polyphenolic phytoalexin found in grapes and red wine, and RS coincubated with the oxidant 2-deoxy-D-ribose (dR), on apoptosis and on the oxidative metabolic status of normal human peripheral blood mononuclear cells (PBMNCs) isolated ex vivo from healthy donors. MATERIAL AND METHODS: Apoptosis was measured by changes of membrane permeability to propidium iodide (PI), plasma membrane exposure of phosphatidylserine (PS) and intracellular caspase activity. Oxidative status was assessed by recording the intracellular glutathione concentration (GSH), the activities of the enzymes y-glutamyltransferase (y-GT) and glutathione-S-transferase (GST), and intracellular lipid peroxidation (MDA). RESULTS: Neither apoptotic nor oxidative parameters were affected by culturing PBMNCs in medium containing RS up to 20 micro M for 5 days, while the frequency of cells with intermediate permeability to PI (17% +/- 5) increased at 50 micro M of RS. Thus resveratrol was slightly toxic, but there was little apoptosis in these cells. Peripheral blood mononuclear cells were also grown first in medium plus RS for 24 h and then for 96 h in medium containing RS plus 10 mM of dR, an oxidant sugar that is apoptogenic for human lymphocytes. The apoptotic changes triggered by dR were counteracted by the phytoalexin in a dose-dependent manner, but RS activity was absent at the lowest concentration (5 micro M) and significantly reduced at the highest concentration used (50 micro M). In PBMNCs coincubated with 20 micro M of RS and 10 mM of dR the antioxidant effect of RS manifested with a significant reduction of caspases-3, -8, y-GT, GST activities and MDA content. CONCLUSIONS: Peripheral blood mononuclear cells acquire antioxidant capacity when treated with RS. Grape resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases.

Ultrastructural complexity of nuclear components during early apoptotic phases in breast cancer cells.

Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK-BR-3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 microM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process.

Spontaneous apoptosis, oxidative status and immunophenotype markers in blood lymphocytes of AIDS patients.

Peripheral blood mononuclear cells (PBMC) from 251 HIV-positive drug abusers of known clinical stage and from 40 healthy donors were tested for conventional immunologic markers (CD3, CD4, CD8, CD19, CD14, CD16/CD56, CD45 and HLA-DR). Additional cell parameters and the occurrence of spontaneous apoptosis (programmed cell death) were investigated on freshly isolated PBMC by flow cytometric measurement of either annexin-V bound to plasma membrane phosphatidylserine or propidium iodide uptake. The activity of gamma-glutamyltransferase (gamma-GT), an ectoenzyme contributing to the synthesis of the intracellular antioxidant glutathione (GSH) and involved in early apoptosis, was also determined in these cells. Immunocompetent T-cell counts were lower in HIV+ patients, with the exception of CD8+ and HLA-DR+ lymphocytes. The external binding of annexin-V was significantly higher in HIV+ PBMC and occurred in both CD8+ and CD4+ T-lymphocyte subsets. The activity of gamma-GT, was significantly lower in the PBMC from HIV+ patients, indicating that the redox status of PBMC may be affected in HIV+ individuals. Finally, the most dominant features characterising patients receiving antiretroviral therapy were greater long-term stability in the distribution of various cell parameters excepted the level of apoptosis.

Effects of steroid hormones on nuclear membrane and membrane-bound heterochromatin from breast cancer cells evaluated by fractal morphometry.

OBJECTIVE: To evaluate the effect of steroid hormones on the ultrastructure of nuclear heterochromatin and perinuclear membranes in human MCF-7 breast cancer cells. STUDY DESIGN: MCF-7 cells were cultured briefly (five minutes) in the presence of 10(-9) M estrogen 17 beta-estradiol, a stimulator of cell proliferation and/or 10(-9) M glucocorticoid dexamethasone. Changes in the morphologic complexity of nuclear membrane-bound heterochromatin (NMBHC) and nuclear membranes (ENM) were assessed by means of the fractal capacity dimension, D, a noneuclidean geometric descriptor of complex, irregular bodies. RESULTS: 17 beta-estradiol (10(-9) M) enhanced the ultrastructural irregularity of NMBHC, as documented by the increased value of D, whereas dexamethasone (10(-9) M) reduced it when compared to NMBHC from untreated MCF-7 control cells. In contrast, neither steroid modified ENM ultrastructure. Changes in the nuclear heterochromatin complexity induced by estrogen 17 beta-estradiol occurred concomitantly with functional changes at the cell periphery, such as activation of the phospholipase C, a cell membrane-associated enzyme involved in signal transduction. Dexamethasone reduced the ultrastructural complexity of NMBHC without affecting functional processes. CONCLUSION: Fractal morphometry proved its usefulness in quantifying early ultrastructural changes in nuclear components induced in MCF-7 cells by steroid hormones, 17 beta-estradiol and dexamethasone.

Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients.

We have compared the concentrations of intracellular glutathione (GSH), glutathione-dependent antioxidative enzymes, the cell death rate and immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy donors and from patients with insulin-dependent type II (NIDDM) diabetes mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte counts, whereas the percentages of CD3, CD4 adn CD8 T lymphocytes were significantly reduced. In contrast, the absolute number and percentage of B lymphocytes was higher in diabetic patients than in healthy donors. The low intracellular reduced glutathione(GSH) and the unbalanced profile of key enzymes involved in GSH metabolism, gamma-glutamyltransferase (gamma-GT) and glutathione-S-transferase (GST), account for the increased oxidative status of PBMC from diabetic patients. The plasma membranes of PBMC for diabetic patients were less permeable to propidium iodide than those of PBMC from healthy donors, indicating that the apoptotic cell death rate was lower in the cells from diabetic patients. These differences are potentially useful markers of pathogenic metabolic changes which occur during clinical diabetes and if they are confirmed could be use dot identify the onset of diabetes.

Steroid hormones modify nuclear heterochromatin structure and plasma membrane enzyme of MCF-7 cells. A combined fractal, electron microscopical and enzymatic analysis.

Ultrastructural features of the nuclear membrane envelope (ENM) and the nuclear membrane-bound heterochromatin (NMBHC) were investigated in MCF-7 human breast cancer cells by fractal morphometry. The fractal dimension D established by the box counting method proved to be effective for quantifying nuclear changes in MCF-7 cells treated with steroid hormones, namely the estrogen 17 beta-estradiol, which stimulates cell proliferation, and the glucocorticoid dexamethasone. When MCF-7 cells were briefly (5 min) cultured in the presence of 17 beta-estradiol (10(-9) M), the irregularity of the NMBHC outline was increased as documented by the increased fractal dimension D. Changes in the ultrastructural complexity of the nuclear heterochromatin were observed in concomitance with functional changes at the cell periphery, namely the modulation of the estrogen-induced activity of phospholipase C, a cell membrane-associated enzyme involved in the signal transduction pathway via phosphoinositides metabolism. Dexamethasone did not affect the in vitro proliferation, the phospholipase C activity nor the shape of the ENM of MCF-7 cells, but reduced the structural complexity of the nuclear membrane-bound heterochromatin.

Apoptotic cell death and the proliferative capacity of human breast cancers.

The proliferative capacity (%S-phase fraction), DNA ploidy, apoptosis frequency (DNA fragmentation) and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR) of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left-skewed frequency distribution and an overall median value of 1.64%, whilst the median %S-phase fraction was 8%. The median %DNA fragmentation and %S-phase fraction were 1.96% and 16% in hyperdiploid tumours (n = 29; DNA index >1.1) higher than in hypodiploid tumors (n = 10; DNA index <0.96), 0.38% and 7.5%. DNA diploid tumours (n = 71) had median %DNA fragmentation and %S-phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg) the median values in hyperdiploid (10.6 fmol/mg) and diploid tumours (14.6 fmol/mg). This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S-phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2) and diploid tumours (3.6). These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

Calcium Dobesilate protects human peripheral blood mononuclear cells from oxidation and apoptosis.

The antioxidant effects of Calcium Dobesilate (CD, Doxium) were investigated in relation to the oxidative status, apoptosis and in vitro proliferation of human peripheral blood mononuclear cells (PBMC) isolated from healthy donors. CD alone did not modify cell growth in vitrountil 10 microM. This molecule counteracted oxidative damages generated by the high reducing sugar dR and was shown to reduce apoptosis by delaying both membrane permeability changes and DNA fragmentation. CD 10 microM affected in a time-dependent dynamics several parameters representative of the cellular oxidative status. In particular, CD significantly increased the activity of glutathione S-transferase (GST) after three days of treatment and also, but to a lower extent, the activity of gamma-glutamyltransferase (gamma-GT). Both enzymes are known to be involved in the glutathione (GSH) metabolic cycle. This enzymatic behaviour was reversed at seven days of treatment, with a significant GST decrease and a gamma-GT activation. After seven days of CD exposure, the intracellular GSH content was enhanced and this resulted in a dramatic decrease in lipid peroxidation, underlining the powerful antioxidant properties of CD in human PBMC.

Treatment of fallopian tube carcinoma with cyclophosphamide, adriamycin, and cisplatin.

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.

Endometrial stromal sarcoma: analysis of treatment failures and survival.

The objective of this retrospective multicenter study was to assess the rates, times, and sites of recurrences of 26 patients with low-grade endometrial stromal sarcomas (ESS) (<10 mitoses per 10 high-power fields (HPF) and 40 patients with high-grade ESS (>10 mitoses/10 HPF). Surgery was the initial therapy for all patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 92 months (range, 4-167). Low-grade ESS: Of the 20 patients with disease confined to the uterus, 5 (25.0%) developed pelvic recurrence after a median of 36 months (range, 4-108). Of the 6 patients with disease outside the uterus, only one recurred in the pelvis after 93 months. High-grade ESS: Of the 20 patients with disease confined to the uterus, 11 (55.0%) developed recurrent disease after a median of 5 months (range, 2-76). The relapse occurred in the pelvis in 3 patients, in upper abdomen in 3, in upper abdomen and extraabdominal sites in 1, and in the pelvis and upper abdomen or extraabdominal sites in 4. Of the 12 patients with extrauterine disease confined to the pelvis, 9 (75.0%) developed recurrent disease after a median of 12 months (range, 1-49). The relapse occurred in the pelvis in 3 patients, in extraabdominal sites in 3, and in the pelvis and upper abdomen or extraabdominal sites in 3. Of the 8 patients with extrauterine disease outside the pelvis, 7 died of disease and 1 is currently alive with progressive disease after 24 months. The disease-free survival was significantly better for low-grade than that for high-grade ESS (P = 0.0001). By log-rank test the disease-free survival of high-grade ESS patients was related to stage (P = 0.0466) and mitotic count (P = 0.0014), but not to age. Cox model showed that mitotic count was the only independent prognostic variable for high-grade ESS (P = 0.006). In conclusion, low-grade and high-grade ESS have a completely different biological aggressiveness and clinical behavior.

Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer.

OBJECTIVE: To evaluate the antitumour activity of paclitaxel in patients with endometrial cancer pretreated with cisplatin, doxorubicin and cyclophosphamide (PAC). MATERIALS AND METHODS: Eligible patients had complete initial surgery, expected survival > or = 3 months, performance status < or = 1, measurable or evaluable disease. Paclitaxel was given over three hours at the dose of 175 mg/m2, repeated every 3 weeks. Tumour response was first evaluated after 3 cycles. A maximum of 10 cycles was given in responders. RESULTS: 19 patients entered the study and a total of 105 cycles were administered. Complete and partial responses were achieved in 2 and 5 patients, respectively, for an overall response rate of 37% (95% CI: 16%-62%). The response rate in patients refractory to platinum was 22%. One patient is alive without evidence of disease 16 months after the start of treatment. The most common side effects were mild to moderate myalgia and peripheral neuropathy, which occurred in 31% and 47% of patients, respectively. In only 1 patient treatment had to be discontinued because of severe myalgia. CONCLUSION: Paclitaxel is active in patients with endometrial cancer pretreated with PAC. Further studies with paclitaxel incorporated in the initial treatment for advanced disease are warranted.

Interferon-beta can induce progesterone receptors in human endometrial adenocarcinoma.

BACKGROUND: The induction of estrogen and progesterone receptors (ER and PGR) has been reported in breast and endometrial cancer cells exposed to human fibroblast interferon-beta (hIFN-beta). Clinical verification of this finding might provide the rationale for new therapeutic approaches. This study was designed to evaluate whether clinical treatment with high doses of hIFN-beta induced ER and PGR in patients with endometrial adenocarcinoma. METHODS: Two biopsies were obtained, 1 before and 1 after hIFN-beta treatment (3 x 10(6) i.m. every other day for 3 weeks) from 36 patients with endometrial adenocarcinoma. ER and PGR were determined with standard procedures using radiolabeled ligands. RESULTS: hIFN-beta treatment did not affect the proportion of ER-positive (i.e., >15 fmol/mg protein) or PGR-positive (i.e., >20 fmol/mg protein) cases. However, in patients with detectable ER and PGR at baseline, hIFN-beta raised the levels. Using a 35% difference before and after therapy as a cut-off, 72 and 79% of cases had increases in ER and PGR, respectively. The difference was highly significant for PGR. CONCLUSIONS: In patients with endometrial adenocarcinoma with undetectable ER or PGR, hIFN-beta did not induce the expression of these receptors. When the receptors were present they were upregulated by hIFN-beta. Whether this increase in receptor levels, particularly PGR, has therapeutic applications remains to be established.

Brain metastases from endometrial carcinoma.

Central nervous system (CNS) involvement by endometrial carcinoma is uncommon. Among 1069 patients registered for endometrial carcinoma at our institution between 1982 and 1994, 10 (0,9%) developed brain metastases. Median age at the time of CNS metastasis diagnosis was 59 years. Median interval between diagnosis of endometrial cancer and documentation of brain involvement was 26 months. Clinical manifestation of brain metastasis included headache (80%), motor weakness (50%), seizures (20%), confusion (10%), balance (10%), and visual disturbances (10%). All lesions (4 multiple, 6 single) were contrast enhancing on computed tomography (CT) scans, and were located in the cerebrum in seven cases, in the cerebellum in one case, and in both in two cases. The CNS was the only site of detectable disease in six patients with recurrent disease. Nine patients died and one is alive with disease 3 months after surgical resection of a single cerebral deposit. Median survival from diagnosis of brain metastases for the entire series was 1 month (range 1-83). Six patients receiving only steroids died within 1 month from the diagnosis. One patient received radiotherapy (survival, 3 months) and two underwent surgical resection of solitary metastasis followed by radiotherapy (survival = 28 and 83 months). Prognosis of patients with CNS metastases from endometrial carcinoma appears poor; however, in a selected group of patients early diagnosis followed by multimodal treatment may result in a palliation of the disease.

Self-similarity and fractal irregularity in pathologic tissues.

The irregularity and self-similarity under scale changes are the main attributes of the morphologic complexity of cells and tissues, either normal or pathologic. In other words, the shape of a self-similar object does not change when scales of measure change because any part of it might be similar to the original object. Size and geometric parameters of an irregular object, however, differ when inspected at increasing resolution, which reveals more details. Significant progress has been made over the past three decades in understanding how to analyze irregular shapes and structures in the physical and biologic sciences. Dominant influences have been the discovery by B.B. Mandelbrot of a new, practical geometry of nature, now called fractal geometry, and the continuous improvements in computational capabilities. The application of the principles of fractal geometry, unlike the conventional Euclidean geometry developed for describing regular and ideal geometric shapes practically unknown in nature, enables one to measure the fractal dimension, contour length, surface area, and other dimensional parameters of almost all irregular and complex biologic tissues. During the past decade, a large amount of experimental evidence has accumulated showing that even in biomedical sciences fractal patterns could be observed. Through several examples borrowed from the recent literature, we focus on the application of the fractal approach to measuring irregular and complex features of pathologic cells and tissues and also on its potential role in the understanding of tumor biology.

Changes in membrane enzymes and glycosphingolipids in lymphocytes from HIV-1--infected and noninfected intravenous drug users.

The amounts of cell-surface glycosphingolipids and plasma membrane enzymes produced on the peripheral blood mononuclear cells (PBMNCs) isolated from 101 intravenous drug users (IDUs), of whom 91 were HIV-1 seropositive, were examined. Seronegative IDUs and age-matched healthy donors served as controls. The numbers of circulating CD3+, CD4+, and CD8+ T lymphocytes decreased during the advanced stages of the infection. There were also fewer CD4+ T-helper cells in HIV-1--seronegative IDU drug addicts. PBMNCs from HIV-1--seropositive subjects had abnormal surface enzyme kinetics. The phospholipase C had two pH optima, whereas the enzyme on normal cells has only one. The specific activity in cells from AIDS subjects was 4 times lower than that in normal PBMNCs. 5'-Nucleotidase showed a similar trend, whereas neutral endopeptidase activity did not correlate with the amounts of surface common acute lymphoblastic leukemia antigen (CALLA). These enzyme activities were decreased in HIV-seronegative IDUs. The subcellular distribution of enzymes and the profile of surface glycosphingolipids were also markedly changed, indicating the profound alterations in the membranes of PBMNCs from HIV-1--seropositive IDUs. These data suggest that intravenous drug use compromises the biochemical and structural integrity of the membrane surface of PBMNCs even before the onset of HIV.

Enzymatic, biophysical and ultrastructural changes of plasma membranes in chemical-induced rat hepatoma.

Plasma membranes from liver of control rats or from chemical-induced hepatoma were prepared. The basal activity of adenylate cyclase was increased significantly in the rat plasma membranes of DEN-induced hepatoma compared to normal tissue. The glucagon-induced response on the cellular effector systems via guanine nucleotide-binding regulatory proteins (G proteins) was inhibited in hepatoma plasma membranes. These findings suggest that in hepatoma membranes, unlike normal hepatic membranes, the response to hormonal stimuli through regulatory G proteins results in a loss of response to glucagon, as well as to GTP plus glucagon or to GTP gamma S. However, the activating effects of forskolin, which catalyses the formation of cyclic AMP from ATP acting on the catalytic subunit, were to some extent retained. The methyltransferase-I behaved in the opposite direction to the adenylate cyclase, showing a decreased activity in hepatoma plasma membranes compared to control membranes. In contrast, the activity of the ecto-5'-nucleotidase was significantly increased in hepatoma. These enzymatic changes have been found to influence the membrane fluidity and to be responsible for the ultrastructural modifications of hepatoma plasma membranes which are induced by chemical carcinogens.

Limited invasiveness to assess retroperitoneal spread in stage I-II ovarian carcinoma.

OBJECTIVE: To evaluate the incidence of retroperitoneal metastases, survival rate and site of recurrence in early ovarian tumors undergoing limited retroperitoneal surgery. METHOD: Three hundred seventy-three consecutive patients underwent assessment of the retroperitoneum consisting of intraoperative palpation with or without biopsies. RESULTS: Retroperitoneal metastases were detected in 10 stage-I tumors (3.2%) and in 10 stage-II tumors (16%). The risk was inversely related to tumor differentiation. Palpation revealed metastases in 10 cases. During follow-up, none of the borderline tumors (1.9% of stage-I grade-1 node-negative, 2.7% of grade-2 and 7.0% of grade-3 tumors) recurred in the retroperitoneum. In stage II, two recurrences were observed in grade-2 tumors (11%) and one in grade 3 (4.5%). CONCLUSION: Limited retroperitoneal surgery enables satisfactory outcome in early ovarian cancers. Risk of retroperitoneal recurrence is minimal in grade 1 and non-existent in borderline tumors. Less differentiated tumors have low risk but further investigation of the therapeutic role of lymphadenectomy is justified.

Apoptosis in human lymphoblastoid cells induced by acivicin, a specific gamma-glutamyltransferase inhibitor.

We examined the effects of acivicin, a specific inhibitor of the ectoenzyme gamma-glutamyltransferase (gamma-GT), on gamma-GT activity and apoptosis in 2 human T-lymphoblastoid CEM cell lines, CCRF and VBL-100. In both cell lines, acivicin was found to cause morphological and biochemical changes of apoptosis in a dose-dependent manner. There was a close correlation between inhibition of gamma-GT activity and the emergence of apoptotic cells. However, VBL-100 cells had a 50% higher gamma-GT basal activity than CCRF-CEM cells, their enzyme activity was more inhibited, and, they had a greater apoptotic response to acivicin. The gamma-GT-specific activity in apoptotic/dead cells was also almost totally inhibited, while that of cells that remained alive after 5 days of acivicin treatment was not. These findings confirm that gamma-GT is implicated in the process of apoptosis of CEM cells.