Sociodemographic indicators and risk of brain tumours.

Background: To better understand patterns of occurrence or diagnosis of brain tumours in different segments of the population, we evaluated associations between sociodemographic variables and the relative incidence of brain tumours as part of a multi-faceted case-control study.

Methods: The study was conducted at hospitals in three US cities between 1994 and 1998. In all, 489 glioma cases (354 high-grade, 135 low-grade), 197 meningioma cases, 96 acoustic neuroma cases, and 799 controls admitted to the same hospitals for any of a variety of non-neoplastic diseases or conditions were enrolled and interviewed.

Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.

p73 transcription factors are members of the p53 family and participate in developmental processes and DNA damage response. p73 expression was shown to be regulated during the cell cycle, suggesting that p73 might play a role in cell growth and might be a target for cyclin-dependent kinases. Consistent with this hypothesis, we discovered that p73 interacts physically with various cyclins (A, B, D, and E).

Development and evaluation of the nuclisens basic kit NASBA for the detection of RNA from Candida species frequently resistant to antifungal drugs.

We describe a Nucleic Acid Sequence Based Amplification (NASBA) protocol to detect 6 different Candida species (Candida krusei, Candida glabrata, Candida inconspicua, Candida dubliniensis, Candida norvegensis, Candida lusitaniae) and compare it to a PCR assay. NASBA showed a sensitivity of 1 Colony Forming Unit and detected RNA from all 6 Candida species within 1 working day. All 5 patients with documented candidiasis showed identical results by both methods.

Laterality of brain tumors.

Tumor laterality was evaluated with respect to presenting symptoms and demographic factors among 489 adults with histologically confirmed glioma (354 high-grade, 135 low-grade), 197 with meningioma, and 96 with acoustic neuroma. The ratio of left-sided to right-sided tumors did not differ significantly from 1.00 for any of the major tumor types.

Selective E2F-dependent gene transcription is controlled by histone deacetylase activity during neuronal apoptosis.

The alteration of chromatin through histone acetylation and deacetylation participates in the regulation of gene expression. We have investigated the effects of histone deacetylase inhibition on neuronal fate. We show that treatment of primary neurones with trichostatin A (TSA) or sodium butyrate (NaBu) induces typical features of apoptosis, a cell death that relies on specific genetic programmes.

Antifungal drug resistance.

The increasing incidence of invasive fungal infections is the result of many factors, including an increasing number of patients with severe immunosuppression. Although new drugs have been introduced to combat this problem, the development of resistance to antifungal drugs has become increasingly apparent, especially in patients who require long-term treatment or who are receiving antifungal prophylaxis, and there is growing awareness of shifts of flora to more-resistant species. The frequency, interpretation, and, in particular, mechanism of resistance to current classes of antifungal agents, particularly the azoles (where resistance has climbed most prominently) are discussed in this review.

Muellerian aplasia associated with ring chromosome 8p12q12 mosaicism.

We report on a woman with Muellerian aplasia, renal and skeletal anomalies, and minor dysmorphic signs. Conventional cytogenetic analysis revealed mosaicism for a small supernumerary, undefinable ring chromosome. Chromosome microdissection and reverse painting demonstrated that this marker contained pericentric material from chromosome 8 (8p12q12).

Synergistic lethal effect of a combination of phage lytic enzymes with different activities on penicillin-sensitive and -resistant Streptococcus pneumoniae strains.

Pal and Cpl-1, two purified bacteriophage lytic enzymes, were tested for their in vitro activity, alone and in combination, against several serotypes of Streptococcus pneumoniae, including penicillin-resistant strains. The enzymes demonstrated synergism in their ability to cleave the bacterial peptidoglycan and thus may be more efficient for the prevention and elimination of pneumococcal colonization.

In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience.

Purpose: To determine if 3-T magnetic resonance (MR) spectroscopy allows accurate distinction of recurrent tumor from radiation effects in patients with gliomas of grade II or higher.

Materials And Methods: This blinded prospective study included 14 patients who underwent in vivo 3-T MR spectroscopy prior to stereotactic biopsy. All patients received a previous diagnosis of glioma (grade II or higher) and high-dose radiation therapy (>54 Gy).

Quantification of T-cell receptor excision circle DNA using fluorescence resonance energy transfer and the LightCycler system.

T-cell receptor excision circles (TRECs) are circular, stable extrachromosomal DNA fragments and are generated during V(D)J gene recombination, a process responsible for diversity of the T-cell receptor repertoire. Here we describe a sensitive, rapid and easy to perform real-time PCR assay based on the LightCycler technique for the quantification of TRECs among peripheral blood cells and a comparison of this assay with conventional PCR-ELISA. By LightCycler, a sensitivity of 20 copies of plasmid deltaRec-psiJalpha Signal Joint TREC DNA was achieved whereas by PCR-ELISA, a detection limit of 2 copies was demonstrated.

Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies.

Invasive aspergillosis has become a major cause of infection-related mortality in nonneutropenic patients after allogeneic stem cell transplantation (SCT). To assess the potential role of Aspergillus-specific T-cell responses for the successful control of invasive aspergillosis, lymphoproliferative responses to Aspergillus fumigatus antigens were studied in healthy individuals, patients with evidence of invasive aspergillosis, and patients late after allogeneic SCT. In healthy individuals, a positive lymphoproliferative response was documented to cellular extracts of A fumigatus (14 of 16), the 88-kDa dipeptidylpeptidase (4 of 16), and the 90-kDa catalase (8 of 11).

Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by the selective degeneration of upper and lower motor neurons. The lack of a molecular diagnostic marker is of increasing concern in view of the therapeutic strategies in development. Using an unbiased subtractive suppressive hybridization screen we have identified a clone encoding the neurite outgrowth inhibitor Nogo and shown that its isoforms display a characteristic altered expression in ALS.

Molecular prenatal diagnosis of Smith-Lemli-Opitz syndrome is reliable and efficient.

Smith-Lemli-Opitz (RSH) syndrome (SLOS, OMIM 270400) is a relatively common, autosomal recessive disorder of cholesterol biosynthesis with a broad spectrum of phenotypic abnormalities caused by mutations of the 7-dehydrocholesterol reductase gene (DHCR7) on chromosome 11. Prenatal diagnosis can be established by detection of elevated 7-dehydrocholesterol or of SLOS-causing mutations in the DHCR7 gene. We report here our experience with molecular prenatal diagnosis of SLOS.

Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation.

Preemptive treatment based on the sensitive detection of CMV-DNA has helped to reduce HCMV-related mortality after allogeneic stem cell transplantation (SCT). Detection of active viral replication might help to better predict HCMV disease. In this study, 33 recipients at risk for HCMV infection after allogeneic SCT were prospectively monitored 1x/week for active HCMV infection by NASBA, whole blood DNA-PCR and virus culture assays.

Proton beam stereotactic radiosurgery of vestibular schwannomas.

Purpose: The proton beam's Bragg peak permits highly conformal radiation of skull base tumors. This study, prompted by reports of transient (30% each) and permanent (10% each) facial and trigeminal neuropathy after stereotactic radiosurgery of vestibular schwannomas with marginal doses of 16-20 Gy, assessed whether proton beam radiosurgery using a marginal dose of only 12 Gy could control vestibular schwannomas while causing less neuropathy.

Methods And Materials: Sixty-eight patients (mean age 67 years) were treated between 1992 and 1998.

Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: factors associated with seizure incidence and seizure outcomes.

Objective: Previous reports of seizure outcomes after arteriovenous malformation (AVM) treatment have involved single-treatment modality (surgery, radiosurgery, or embolization) series. Such series reflect only selected lesions, of certain sizes, locations, and other clinical and anatomic characteristics, that are amenable to the single therapy, limiting the analysis of those factors. We report the results of AVM treatment using a multimodality approach that we think encompasses a broader spectrum of treatable brain AVMs.

The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner.

Resistance to conventional adjuvant therapies (i.e., chemotherapy and radiation) has been well documented in malignant gliomas.

Novel mutation in the Delta-sterol reductase gene in three Lebanese sibs with Smith-Lemli-Opitz (RSH) syndrome.

The Smith-Lemli-Opitz syndrome (SLOS), or RSH syndrome, is a well-characterized multiple congenital anomalies/mental retardation syndrome. The phenotype has been redefined to include mildly affected individuals with minor anomalies and developmental delay, and severe malformations with pre- and perinatal mortality. The condition is due to the deficient activity of the enzyme 7-dehydrocholesterol (7-DHC) reductase [Shefer et al.

Brain metastases.

Brain metastases are an increasingly common complication in patients with systemic cancer. The optimal treatment for each patient depends on careful evaluation of several factors: the location, size, and number of brain metastases; the patient's age, general condition, and neurologic status; and the extent of systemic cancer to name a few. For patients with a single brain metastasis and limited systemic disease, the standard treatment is surgical resection followed by whole brain radiation therapy.

Enhancement of p53 activity and inhibition of neural cell proliferation by glucocorticoid receptor activation.

In analyzing the molecular mechanisms underlying glucocorticoid-induced apoptosis in neural cells, we observed that dexamethasone, by activating glucocorticoid receptors, causes arrest of HT-22 cells in the G1 phase of the cell cycle; upon withdrawal of the agonist, cells resume proliferation. Our investigations revealed that glucocorticoid treatment, although having no effects on endogenous p53 protein stability, induces rapid translocation of p53 to the nucleus and enhances its transcriptional activity. Consistently, transfection studies with p53-responsive promoters revealed a substantial stimulation of the trans-activation potential of exogenous p53 by dexamethasone.

Automated extraction of genomic DNA from medically important yeast species and filamentous fungi by using the MagNA Pure LC system.

A fully automated assay was established for the extraction of DNA from clinically important fungi by using the MagNA Pure LC instrument. The test was evaluated by DNA isolation from 23 species of yeast and filamentous fungi and by extractions (n = 28) of serially diluted Aspergillus fumigatus conidia (10(5) to 0 CFU/ml). Additionally, DNA from 67 clinical specimens was extracted and compared to the manual protocol.

Relative biological effectiveness (RBE) values for proton beam therapy.

Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs.

Gemcitabine-induced radiation recall.

Purpose: To study and report 6 patients with radiation recall in unique sites, secondary to gemcitabine chemotherapy.

Methods And Materials: The clinical presentations and outcomes of 6 patients with radiation recall secondary to gemcitabine chemotherapy were retrospectively analyzed over the course of a 1-year period.

Results: Radiation recall reactions were seen in the central nervous system, skin, gastrointestinal tract, and in the lymphatic and musculoskeletal systems.