Early effects on restoration of evoked field potentials in the hippocampal CA(1) region after reversible hypoxia/hypoglycemia by the radical scavenger N-tert.-butyl-alpha-phenylnitron.

In transverse hippocampus slices a short period of hypoxia/hypoglycemia induced by perfusion with an O(2)/glucose-free medium caused early loss and incomplete restoration of evoked field potentials in the CA(1) region. In the present study a search was made for whether the formation of free oxoradicals immediately after starting the hypoxic phase could be part of the breakdown and incomplete restoration of the excitatory potentials (EPs). It was shown that preincubation and postischemic incubation with the radical scavenger PBN did not prevent the potential breakdown but significantly enhances potential restoration, even when PBN was added to the perfusion medium 40 min after hypoxia. Thus, free oxoradicals may damage membrane constituents such as receptors or channel proteins at a very early phase, before neuronal death is pronounced. The results also show that treatment with radical scavengers has a beneficial effect on early hypoxic damage.     

Anterior segment evaluation of infants with retinopathy of prematurity

To understand the mechanisms of glaucoma in retinopathy of prematurity (ROP), anterior segment evaluation is essential. The authors prospectively examined the anterior segment of 27 eyes of 17 premature infants with stages IV and V ROP. Twenty-six eyes received no previous surgery or treatment. Schi?tz and applanation tonometry were performed. Structural evaluation of each anterior segment was conducted by biomicroscopy and Koeppe gonioscopy. In the 26 eyes, angle closure of greater than 180 degrees was noted in 3 (12%). The authors noted prominent Schwalbe's line in 4 eyes (15%), high iris convexity in 15 (58%), hypopigmentation of the iris root in 19 (73%), translucent matrix in the angles ("Barkan's-type" membrane) in 18 (69%), posterior synechiae in 16 (62%), visible iris or angle vessels in 12 (46%), and pigment clumping in the angle recess in 12 (46%). This study identified structural abnormalities in the anterior segment of ROP infants, including pathologic changes and anatomic features that could have a developmental origin.     

Partner acceptance of health department notification of HIV exposure, South Carolina

To determine the acceptability of health department notification of sex and needle-sharing partners of persons infected with human immunodeficiency virus (HIV), we administered an anonymous questionnaire to partners notified of their exposure to HIV during the previous 2 years. Of the 202 partners notified, 132 (65%) were locatable and completed the questionnaire. Only 12 (9%) thought they may have been exposed to HIV before health department notification. When the 132 partners were asked if they thought the health department did the right thing in telling them about their exposure, 87% responded "yes;" when asked if the health department should keep notifying persons exposed to HIV, 92% responded "yes." Responses were similar for homosexual-bisexual men, heterosexuals, and intravenous drug users; men and women; and whites and blacks. We conclude that health department notification is acceptable to persons exposed to HIV in this rural South Carolina district.     

A 3-day estrogen treatment improves prefrontal cortex-dependent cognitive function in postmenopausal women

Estrogen secretion in young women follows a cyclic pattern characterized by a pronounced surge in estrogen around ovulation. The way in which this estrogen peak affects cognitive functioning is unclear. Short-term estrogen treatment for a few days mimicking normal pre-menopausal estrogen dynamics substantially enhanced cognitive functions in ovariectomized animals. Here, we provide evidence that inducing a single estrogen peak in postmenopausal women improves their cognitive abilities. Healthy women (51-64 yrs, n=14) received either 100 microg estrogen transdermally for 3 days or placebo in a double-blind within-subject design. The treatment caused a temporary rise in serum estrogen levels roughly comparable to the mid-cyclic changes in estrogen in young women. At the end of the treatment, the women completed two types of tests involving primarily hippocampus-dependent functions of memory retention or prefrontal cortex-dependent functions. Results revealed a clear beneficial effect of estrogen on tasks mainly involving the prefrontal cortex: performance on a digit-ordering task (p<0.05) and on a task requiring short-term memory of event sequences in an unfamiliar story (p<0.01) were improved, and susceptibility to interference in the Stroop test (p<0.05) was diminished after estrogen. On the other hand, estrogen did not affect hippocampus-dependent retention of a story, with delayed recall tested after 30 min or 1 week, although immediate recall was improved by estrogen. We conclude that in postmenopausal women, a transient increase in plasma estrogen concentration acutely improves prefrontal cortex-dependent cognitive functions, whereas hippocampus-dependent memory retention is less affected. Our results encourage future studies to investigate whether repeated induction of short-lasting estrogen peaks could enhance cognitive efficacy of hormonal replacement therapy.     

Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN

Inhibition of bcl-2 expression by antisense oligodeoxynucleotides (ODN) might render bcl-2 overexpressing malignant B cells more susceptible to chemotherapy. ODN containing unmethylated CG dinucleotides (CpG) are known to activate B cells. We studied the effects of two bcl-2 antisense ODN, with (G3139) or without CG dinucleotides (NOV 2009) within the sequence, and the effects of a nonantisense, CpG-containing ODN (ODN 2006) on activation and apoptosis of malignant B cell lines and primary B-CLL cells. Without cationic lipids, no antisense-mediated inhibition of bcl-2 synthesis was achieved with G3139 and NOV 2009. Instead, G3139, but not NOV 2009, induced similar changes as ODN 2006 in proliferation, expression of costimulatory and antigen-presenting molecules, as well as in bcl-2 and bcl-xL levels of primary B-CLL cells. G3139 and ODN 2006 inhibited in vitro, spontaneous apoptosis in B-CLL cells of patients with high serum thymidine kinase activity (s-TK, marker for proliferative activity of malignant B cells), whereas in patients with low s-TK activity, apoptosis was induced. In conclusion, our results suggest that modulation of malignant B cell apoptosis by G3139 depends on its immunostimulatory properties rather than on antisense-mediated reduction of bcl-2 expression. Immunostimulatory CpG ODN may have a therapeutic potential in patients with B-CLL, especially those with low s-TK activity.     

Interferon-producing cells: on the front line in immune responses against pathogens

Interferon-producing cells (IPC) constitute a small population of leukocytes that secrete high levels of type I interferons in response to viruses. Although human IPC have been known for almost two decades, murine IPC have been identified only recently. Furthermore, it has been shown that IPC correspond to the enigmatic 'plasmacytoid cells' identified in human lymph nodes during infections. These breakthroughs have brought IPC to the attention of immunologists for their role in innate immunity and in shaping T cell responses. Here we review recent progress and outstanding questions in the field.     

Prognostic value of [<Superscript>18</Superscript>F]FDG-PET imaging in small cell lung cancer

Positron emission tomography (PET) utilizing fluorine-18 fluorodeoxyglucose (FDG) has been used in the evaluation of non-small cell lung cancer (NSCLC). Recently its use in the staging of small cell lung cancer (SCLC) has been reported. However, the prognostic value of FDG-PET imaging in SCLC has not been studied. We performed a retrospective analysis to assess this, with the following hypotheses: (1) PET-positive patients would have a less favorable prognosis than PET-negative patients and (2) a high standardized uptake value (SUV) would be associated with a poor prognosis. Retrospective review of a mixed population of treated and untreated patients imaged between 1995 and 2000 was performed. Results of 62 scans in 46 patients were analyzed. There were 8 untreated and 38 treated patients. Findings were correlated with pathology, computed tomography/magnetic resonance imaging and clinical data. The sensitivity of PET scanning was 100% with pathological correlation. The prognostic value of a positive PET study was determined. Overall survival in PET-positive cases was significantly worse than that in PET-negative cases ( P=0.0108). Correlation of SUV(max) with survival showed a significant negative correlation ( P=0.0021). In the eight untreated patients, scans were strongly positive and in all cases the scan results concurred with the final clinical stage assigned on the basis of conventional methods. We conclude that FDG-PET imaging provides prognostic information in treated patients. A positive study and a high SUV(max) are significantly associated with poor survival. Additionally, FDG-PET may be helpful in staging and follow-up.