Cell cycle regulators p27 and pRb in lymphomas – correlation with histology and proliferative activity

The cell cycle is a complex event in which multiple regulator-proteins participate. The G 1/S checkpoint of the cell cycle is controlled by pRb protein, which functions in its hypophosphorylated form as a negative regulator of growth. p27 (Kip1), a member of CIP/KIP family of cyclin inhibitory proteins, participates in inhibition of forming complexes that allow pRb to phosphorylate and lead the cell into mitosis. The expression of these important cell cycle regulator proteins was studied in a total of 96 non-Hodgkin’s lymphoma (NHL) samples, which were classified according to the REAL classification. The expression of p27, pRb and the cell proliferation marker Ki-67 (MIB-1) was evaluated in lymphomas using immunohistochemistry. This study showed that there were coordinate changes in the expression of p27 and pRb in NHL. When compared to low-grade lymphomas, high-grade lymphomas showed significantly reduced expression of p27 and inversely pRb expression was increased (P < 0.001). Increase in expression of Ki-67 was parallel with pRb expression, and was mainly seen in cells that lacked p27 expression (P < 0.0001). This study suggests that changes in the control of the cell cycle closely relate to the pathobiology of NHL. © 2000 Cancer Research Campaig

Circadian hormone secretory profiles in women with severe premenstrual tension syndrome.

The circadian secretory profiles of serum prolactin, growth hormone and cortisol were measured in two women suffering from severe premenstrual tension syndrome and in two asymptomatic control subjects. Subjects and controls were screened and included after a rigorous selection process. Blood samples were obtained every 30 min over a period of 24 h in each woman both on day 9 (follicular phase) and day 26 (luteal phase) of the menstrual cycle. There was no relationship between the hormonal secretory profiles and the premenstrual tension syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75119/1/j.1471-0528.1984.tb04785.x.pd

Antioxidant enzymes and lipid peroxidation in endometrium of patients with polyps, myoma, hyperplasia and adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Oxidative stress and impaired antioxidant system have been proposed as a potential factors involved in the pathophysiology of diverse disease states, including carcinogenesis. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of gynecological diseases in order to evaluate the antioxidant status in endometrium of such patients.</p> <p>Methods</p> <p>Endometrial tissues of gynecological patients with different diagnoses were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides.</p> <p>Results</p> <p>Superoxide dismutase activity was significantly decreased (50% in average) in hyperplastic and adenocarcinoma patients. Activities of both glutathione peroxidase and glutathione reductase were increased 60% and 100% on average, in hyperplastic patients, while in adenocarcinoma patients only glutathione reductase activity was elevated 100%. Catalase activity was significantly decreased in adenocarcinoma patients (47%). Lipid hydroperoxides level was negatively correlated to superoxide dismutase and catalase activities, and positively correlated to glutathione peroxidase and glutathione reductase activities.</p> <p>Conclusions</p> <p>This study provided the first comparison of antioxidant status and lipid peroxidation in endometrial tissues of patients with polyps, myoma, hyperplasia and adenocarcinoma. The results showed that patients with premalignant (hyperplastic) and malignant (adenocarcinoma) lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme activities than patients with benign uterine diseases, polyps and myoma, although the extent of disturbance varied with the diagnosis. Further investigation is needed to clarify the mechanisms responsible for the observed alterations and whether lipid hydroperoxide levels and antioxidant enzyme activities in uterus of gynecological patients might be used as additional parameter in clinical evaluation of gynecological disorders.</p

Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi

Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20degreesC. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection