Sporadic adult-onset brainstem hyperkalemic periodic paralysis masquerading as recurrent transient ischemic attacks.

We report a case of adult-onset, sporadic, hyperkalemic periodic paralysis with primary brainstem musculature symptoms masquerading as recurrent transient ischemic attacks. Unilateral brainstem weakness could be induced with rapid eye blinking, which was followed by lower extremity weakness and cramping. Treatment with acetazolamide and albuterol ameliorated the patient's attacks.

Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 µg.

The importance of mitochondria in the tumourigenic phenotype: gliomas as the paradigm (review).

Cancer arises from the accumulation of nuclear and cytoplasmic abnormalities, a phenomenon allowing for the expression of the tumourigenic phenotype. Gliomas represent the most frequently diagnosed tumours of the central nervous system in adults. Warburg hypothesized the importance of glycolysis in cancer cells, and implicated additional roles of mitochondria in neoplasia. Recent data have shown the importance of mitochondria in the tumourigenic phenotype, in particular, within the apoptotic process. There have been a variety of studies conducted on brain tumours revealing significant alterations of mitochondria within the tumourigenic phenotype. This review describes some of the more recent findings of mitochondria and gliomas, correlating findings to those observed in other cancers. Alterations in mitochondrial DNA copy number and location, as well as dependence of the cancer cell phenotype on mitochondria are emphasised. In addition to its role in apoptosis, the mitochondrion serves as an important element in the tumourigenic phenotype, and clinical approaches targeting this organelle have potential for the development of effective treatment regimens for patients with glioma and other neoplastic diseases.

Increased expression but not sensitivity to Fas/CD95 in glioblastoma cells depleted of mitochondrial DNA.

Mitochondria and Fas (CD95) play a role in tumorigenicity and apoptosis. In the present study, the functional relationship of mitochondria to Fas in mediating apoptosis was investigated. Glioblastoma cells (DBTRGO5MG, U87) were depleted of mitochondrial DNA (mtDNA) by treatment with ethidium bromide (Rho(-) cells). Compared to Rho(+) cells, Rho(-) cells showed enhanced expression of Fas at the cell surface. Indeed, when Rho(+) cells were treated with mitochondrial respiratory chain complex inhibitors, Fas cell surface expression was noted to increase in a similar fashion to the depletion of mtDNA in both cell lines. However, when cells were evaluated for sensitivity to apoptosis using Fas-engagement, there was no difference between the Rho(+) and Rho(-) cells in either cell line. By contrast, sensitivity to the cytotoxic agent cis-diammine-dichloroplatinum (cisplatin) was markedly increased in the Rho(-) cells, which expressed higher levels of cell surface Fas. Expression of Fas is increased with the depletion of mtDNA and respiratory complex inhibitors. However, this increase in expression does not necessarily translate to an increase in sensitivity to Fas-engagement, although there is an increase in the sensitivity of depleted cells to cytotoxic agents such as cisplatin.

Radioimmunotherapy of non-Hodgkin's lymphoma: clinical development of the Zevalin regimen.

Zevalin (ibritumomab tiuxetan; IDEC Pharmaceuticals Corporation, San Diego, CA, USA) was approved by the United States Food and Drug Administration on February 19, 2002, following 9 years of clinical development. Six clinical studies supported the Zevalin Biologics License Application. The Zevalin regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), and for those with follicular NHL refractory to Rituxan (rituximab, MabThera; IDEC Pharmaceuticals Corporation, San Diego, CA and Genentech, South San Francisco, CA). In the year following FDA approval, approximately 1300 patients were treated in clinical trials or with the commercially available product.

Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6.

The Kruppel-like transcription factor KLF6 is a novel tumor-suppressor gene mutated in a significant fraction of human prostate cancer. It is localized to human chromosome 10p14-15, a region that displays frequent loss of heterozygosity in glioblastoma multiforme (GBM). Indeed, mutations of the KLF6 gene have recently been reported in this tumor type. In this study, we report that the expression of KLF6 is attenuated in human GBM when compared with primary astrocytes. Expression of KLF6 in GBM cells reverts their tumorigenicity both in vitro and in vivo, which is correlated with its transactivation of the p21/CIP1/WAF1 promoter. Additionally, KLF6 inhibits cellular transformation induced by several oncogenes (c-sis/PDGF-B, v-src, H-Ras, and EGFR) that are components of signaling cascades implicated in GBM. Our results provide the first evidence of functional tumor suppression by KFL6, and its loss may contribute to glial tumor progression.