The urinary excretion of the N-oxide and the glucuronides of five C-monohydroxy metabolizes of methaqualone has been studied in a group of young women aged 24-34 years and in a group of elderly women aged 85-87 years. The rate of appearance of the metabolites in the urine was slower in the elderly group but the relative importance of the six metabolites was the same in the two groups. There were differences in some metabolite ratios between the two groups, but only one difference approached statistical significance. The metabolite excretion in a 80 year old woman who had received methaqualone daily for over ten years was consistent with that of the elderly group. The results indicate that the ageing process per se and chronic weak hepatic enzyme induction in the elderly are not accompanied by changes in the relative importance of competitive metabolic pathways.

Adult↗

PubMedDate not supplied

Deletion of the NF2 region in both meningioma and juxtaposed meningioangiomatosis: case report supporting a neoplastic relationship.

We report a case of juxtaposed atypical meningioma and meningioangiomatosis (MA) in an 8-year-old boy with no clinical stigmata or family history of neurofibromatosis. We studied the proliferative activity and genetic changes in the two lesions in an attempt to define their biologic and pathogenetic relationships. The MIB-1 index was 11% in the meningioma and <1% in the MA, indicating increased proliferative activity in the meningioma. Fluorescence in situ hybridization was done for two chromosomal regions commonly deleted in meningiomas. There was loss of the neurofibromatosis 2 locus (22q12) in both the meningioma and MA. Conversely, the region of 1p32 was not deleted. Our results indicate that both the meningioma and MA arose from the same clonal process, with the meningioma probably undergoing additional, but undefined, genetic alterations that confer upon it a more proliferative potential. This loss of 22q12 in the MA raises doubt about the presumed hamartomatous nature of MA.

Antigens, Nuclear↗

PubMedDate not supplied

Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.

Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial.

Ascites↗

PubMedDate not supplied

Contributions of hydrogen bonds of Thr 157 to the thermodynamic stability of phage T4 lysozyme.

Measurements of changes in structure and stability caused by 13 different substitutions for threonine 157 in phage T4 lysozyme show that the most stable lysozyme variants contain hydrogen bonds analogous to those in the wild-type enzyme and that structural adjustments allow the protein to be surprisingly tolerant of amino-acid substitutions.

Computer Simulation↗