Expression of BCL-2 oncoprotein on tumor cells and tumor-infiltrating lymphocytes (TIL) in meningiomas

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3–). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto- oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas. Received: 10 June 1998 / Accepted: 23 February 1999     

Evidence for preferential repair of 3-carbethoxypsoralen plus UVA induced DNA lesions in the active MAT{alpha} locus in Saccharomyces cerevisiae using the UvrABC assay

The occurrence of preferential repair in Saccharomyces cerevisiaeof the active MAT locus compared with the inactive HML locuswas confirmed after 254 nm UV irradiation. Experiments carriedout using the UvrABC excinuclease assay with the monofunctionalfurocoumarin 3-carbethoxypsoralen (3-CPs) plus UVA radiationwhich induce mainly monoadducts in DNA demonstrated preferentialrepair of the active MAT locus compared with the inactive HMLlocus in a SIR⁺ strain. However, as after 254 nm UV irradiation,no difference in the rate of removal of 3-CPs plus UVA inducedlesions was observed between the two loci in the sir-3 mutantin which both loci are active. Thus, it appears that 3-CPs plusUVA induced monoadducts as well as pyrimidine dinners a e subjectto preferential repair. ³To whom correspondence should be addressed     

Nursing as a lesbian

Minority status within any larger group is often difficult. Lesbian nurses face a dilemma of choice—whether or not to come out of the closet to their colleagues and patients. This essay describes the professional reflections of one lesbian nurse.     

The pharmacokinetics of high-dose medroxyprogesterone acetate (MPA) in the therapy of advanced breast cancer

Summary Oral MPA 1.5 g/day leads to plasma concentrations between 1 and 12 g/ml, with a broad intra-and interindividual variance. The plateau state is reached in between 4 and 16 days. Plasma concentrations in the plateau state are very sensitive to dose modifications. After cessation of administration, the decline in plasma levels seems to proceed in two phases, with half-times of about 20 h and 4 days. Extraction procedures reveal no benefit in discriminating between MPA and its metabolites.     

Combined endovascular therapy of ruptured aneurysms and cerebral vasospasm

We describe two patients with subarachnoid haemorrhage due to a ruptured intracranial aneurysm and severe symptomatic vasospasm. The aneurysm was occluded with detachable coils followed by intra-arterial infusion of papaverine to treat vasospasm as an one-stage procedure. There was significant resolution of the vasospasm. The long-term clinical outcome in one patient was excellent, the other still has minor deficits. Combined endovascular aneurysm therapy followed by intra-arterial spasmolysis with papaverine is a technically feasable therapeutic alternative in patients with symptomatic vasospasm. Received: 5 November 1999/Accepted: 12 July 2000     

A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels.

Toxins from cone snail (Conus species) venoms are multiple disulfide bonded peptides. Based on their pharmacological target (ion channels, receptors) and their disulfide pattern, they have been classified into several toxin families and superfamilies. Here, we report a new conotoxin, which is the first member of a structurally new superfamily of Conus peptides and the first conotoxin affecting vertebrate K+ channels. The new toxin, designated conotoxin ViTx, has been isolated from the venom of Conus virgo and comprises a single chain of 35 amino acids cross-linked by four disulfide bridges. Its amino acid sequence (SRCFPPGIYCTSYLPCCWGICCSTCRNVCHLRIGK) was partially determined by Edman degradation and deduced from the nucleotide sequence of the toxin cDNA. Nucleic acid sequencing also revealed a prepropeptide comprising 67 amino acid residues and demonstrated a posttranslational modification of the protein by releasing a six-residue peptide from the C-terminal. Voltage clamp studies on various ion channels indicated that the toxin inhibits the vertebrate K+ channels Kv1.1 and Kv1.3 but not Kv1.2. The chemically synthesized product exhibited the same physiological activity and identical molecular mass (3933.7 Da) as the native toxin.     

Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats

The present study addresses the effects of moderate posttraumatic hypothermia (32 degrees C) on the temporal and regional profile of polymorphonuclear leukocyte (PMNL) accumulation after traumatic spinal cord injury (SCI). We hypothesized that posttraumatic hypothermia would reduce the degree of inflammation by reducing PMNL infiltration. Rats underwent moderate spinal cord injury at T10 using the NYU impactor device. In the first study, the temporal profile of myeloperoxidase (MPO) activity (a marker of neutrophil accumulation) under normothermic (37 degrees C) conditions was determined. The animals were allowed to survive for 3 or 24 h, or 3 or 7 days after SCI. Spinal cords were dissected into five segments rostral and caudal to the injury site. Additional animals were studied for the immunocytochemical visualization of MPO. In the second study, rats were sacrificed at 24 h after a monitoring period of normothermia (36.5 degrees C/3 h) or hypothermia (32.4 degrees C/3 h) with their controls. In the time course studies, MPO enzymatic activity was significantly increased at 3 and 24 h within the traumatized T10 segment compared to controls. MPO activity was also increased at 3 h within the rostral T8 and T9 segments and caudal T11 and T12 segments compared to controls. At 24 h after trauma, MPO activity remained elevated within both the rostral and caudal segments compared to control. By 3 days, the levels of MPO activity were reduced compared to the 24-h values but remained significantly different from control. Neutrophils that exhibited MPO immunoreactivity were seen at 6 and 24 h, with a higher number at 3 days. PMNLs were located within the white and gray matter of the lesion and both rostral and caudal to the injury site. Posttraumatic hypothermia reduced MPO activity at 24 h in the injured spinal cord segment, compared to normothermic values. The results of this study indicate that a potential mechanism by which hypothermia improves outcome following SCI is by attenuating posttraumatic inflammation.