Angiomyolipomas (AMLs) are renal tumors that occur both sporadically and in association with tuberous sclerosis (TSC). TSC is an autosomal dominant disorder characterized by hamartomatous lesions in multiple organs. Two TSC loci are recognized: TSC1 on 9q34 and TSC2 on 16p13. Loss of heterozygosity (LOH) at the TSC1 and TSC2 loci in lesions from TSC patients has recently been reported. Lesions that are not associated with TSC have not been previously examined for LOH at the TSC loci. We analyzed 29 renal angiomyolipomas from patients without a history of TSC. Three tumors demonstrated LOH on 16p13. This is the first report indicating that mutations in TSC2 occur in tumors of patients who do not have TSC. We also found LOH on 16p13 in 5 of 8 TSC-associated AMLs. Two of these tumors were from a single patient and demonstrated different regions of LOH. These findings support the hypothesis that the TSC2 gene functions as a tumor suppressor.
Recent research using rodent models of central nervous system gliomas indicates that a combination of gene transfer and drug treatment may be successful in killing tumor cells. In the present study, a mouse fibroblast-derived packaging cell line, psi 2, which releases a replication-defective retrovirus vector bearing the herpes simplex virus type 1 (HSV)-thymidine kinase (TK) gene, was grown with rat C6 tumor cells in the presence and absence of wild type Moloney murine leukemia virus (MoMLV). Consequently, tumor cells became sensitive to ganciclovir, which is selectively converted to a toxic nucleotide analog by HSV-TK. This killing effect was more effective in the presence than in the absence of wild type retrovirus both in culture and in subcutaneous tumors in nude mice. Tumors regressed in vivo and failed to regrow over a subsequent 10-day observation period after combined treatment with packaging cells, wild type MoMLV, and ganciclovir. This killing effect may be augmented by the ability of the helper retrovirus to package the vector in tumor cells and thus extend delivery of the HSV-TK gene to more tumor cells. This represents significant improvement in tumor therapy in this model system as compared with helper-free systems previously reported by the authors and others. Although additional improvements in the therapy can be envisioned, this approach may prove useful in combination with current modes of therapy for these insidious and lethal tumors.
The current COVID-19 pandemic has led to a dramatic shortage of masks and other personal protective equipment (PPE) in hospitals around the globe [1]. One component of PPE that is in particular demand are disposable N95 face masks. To alleviate this, many methods of N95 mask sterilization have been studied and proposed with the hope of being able to safely reuse masks [2]. Two major considerations must be made when re-sterilizing masks: (1) the sterilization method effectively kills pathogens, penetrating into the fibers of the mask, and (2) the method does not degrade the operational integrity of the N95 filters.We studied Cobalt-60 ( 60 Co) gamma irradiation as a method of effective sterilization without inducing mask degradation. Significant literature exists supporting the use of gamma radiation as a sterilization method, with viral inactivation of SARS-CoV reported at doses of at most 10 kGy [3], with other studies supporting 5 kGy for many types of viruses [4]. However, concerns have been raised about the radiation damaging the fiber material within the mask, specifically by causing cross-linking of polymers, leading to cracking and degradation during fitting and/or deployment [5,6].A set of 3M 8210 and 9105 masks were irradiated using MIT's 60 Co irradiator. Three masks of each type received 0 kiloGray (kGy), 10 kGy and 50 kGy of approximately 1.3 MeV gamma radiation from the circular cobalt sources, at a dose rate of 2.2kGy per hour.Following this sterilization procedure, the irradiated masks passed a OSHA Gerson Qualitative Fit Test QLFT 50 (saccharin apparatus) [7] when donned correctly, performed at the Brigham and Women's Hospital, in a blinded study repeated in triplicate. However, the masks' filtration of 0.3 µm particles was significantly degraded, even at 10 kGy.These results suggest against gamma, and possibly all ionizing radiation, as a method of disposable N95 sterilization. Even more importantly, they argue against using the qualitative fit test alone to assess mask integrity.
Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome in which patients develop hamartomatous lesions in the nervous system and a host of other organs. While considerable experience has been gained in defining the clinical spectrum of TSC, a number of nosological questions remain. Neuropathological studies have continued to refine our knowledge of the nervous system abnormalities that characterize TSC. Molecular genetic studies have implicated two chromosomal regions in the genesis of TSC, one on chromosome 9q and the other on chromosome 16p. The chromosome 16p gene, designated TSC2, has been cloned, although its function remains speculative. The identification of the TSC1 gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC.
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