Earthquakes Cannot Be Predicted Geller, Robert J.; Jackson, David D.; Kagan, Yan Y. ...
Science (American Association for the Advancement of Science),
03/1997, Letnik:
275, Številka:
5306
Journal Article
Recenzirano
Research suggests that earthquakes cannot be predicted. Earthquakes result from sudden slips along geological faults, and they are notoriously intractable.
Hidradenitis suppurativa (HS) is a disease of the apocrine sweat glands resulting in chronic wounds with abscesses, sinuses, and fibrosis. Because many patients referred for treatment have both ...recurrent and progressive disability, we attempted to determine which factors have the greatest impact on outcome so we could develop an operative treatment algorithm.
We identified 57 patients with HS who underwent operative treatment for chronic recurrent HS from January 1994 through December 2003. Charts were reviewed for demographic, treatment, and outcome data.
The mean age at presentation was 34 years and the average duration of symptoms was 6.7 years. Two thirds of the patients had undergone 1 or more incision and drainage procedures and 90% had received long-term antibiotic therapy. Axillary involvement was present in 88% of women and was bilateral in half of all patients. Inguinoperineal involvement was present in 87% of men and was bilateral in 92% of all patients. An algorithm for operative treatment was developed based on the extent of involvement, chronicity, and comorbid conditions. Ninety-two operative procedures were performed, 50% involved the axilla, 36% involved the perineum, and 14% involved the inguinal region. Excision and primary closure was used for localized disease; wide excision with or without skin grafting was used for diffuse disease.
HS is a chronic relapsing disease that frequently causes disabling pain, diminished range of motion, and social isolation. Definitive treatment involves operative excision of the involved apocrine tissue and should be individualized based on the stage and location of the disease.
We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the ...clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14. 3. A portion of the DNA segment that spans this locus and is flanked by the microsatellite loci D13S153 and D13S163 was lost in 85% of the specimens with allele losses and was designated as a LOH cluster region (LCR). The LCR spans more than 6 Mbp of DNA. The results suggest that a TSG relevant for the development of prostate cancer is located telomeric to the RB locus. There was a significant correlation (P=0.0024) between chromosome 13q LOH and advanced metastatic disease, suggesting that loss of 13q14.3 region is associated with prostate cancer progression. However, further research must be conducted to establish the identity and function of this putative TSG.
Metallothionein (MT) is a low-molecular-weight cysteine-rich protein with extensive metal binding capacity and potential nonenzymatic antioxidant activity. Despite the sensitivity of vascular ...endothelium to either heavy metal toxicity or oxidative stress, little is known regarding the role of MT in endothelial cells. Accordingly, we determined the sensitivity of cultured sheep pulmonary artery endothelial cells (SPAEC) that overexpressed MT to tert-butyl hydroperoxide (t-BOOH), hyperoxia, or 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN; peroxyl radical generator). Nontoxic doses of 10 microM Cd increased MT levels from 0.21 +/- 0.03 to 2.07 +/- 0.24 microg/mg and resulted in resistance to t-BOOH and hyperoxia as determined by reduction of Alamar blue or 3Hserotonin transport, respectively. SPAEC stably transfected with plasmids containing either mouse or human cDNA for MT were resistant to both t-BOOH and hyperoxia. In addition, we examined transition metal-independent, noncytotoxic AMVN-induced lipid peroxidation after metabolic incorporation of the oxidant-sensitive fluorescent fatty acid cis-parinaric acid into phospholipids and high-performance liquid chromatography separation. SPAEC that overexpressed MT after gene transfer completely inhibited peroxyl oxidation of phosphatidylserine, phosphatidylcholine, and sphingomyelin (but not phosphatidylethanolamine) noted in wild-type SPAEC. These data show for the first time that MT can 1) protect pulmonary artery endothelium against a diverse array of prooxidant stimuli and 2) directly intercept peroxyl radicals in a metal-independent fashion, thereby preventing lipid peroxidation in intact cells.
Physicists are critical members of the radiation therapy team, and rightfully so. Therefore, it is not unreasonable that they be acquainted with the broader aspects of the management of patients who ...receive radiation treatments, as well as the roles played by surgeons, medical oncologists and other members of the treatment team. The spate of recent technical developments openly embraced by medical physicists, many of whom appear unconcerned by questionable benefits and very high costs, leads the authors to believe that this acquaintance is not as widespread as it should be. The present paper provides a brief review of clinical considerations in radiation oncology, statistics for the most prevalent cancers, and how those cancers that account for over 90% of mortality are currently treated. With these data as background, it then considers the extent to which one of the more widely promoted new technologies is likely to impact upon survival. By providing this modicum of perspective, physicists will be in a better position to evaluate these new technologies in more fundamental clinical terms, and thereby enhance their contributions to the overall care of the cancer patient.
Comparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and ...cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns.
Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results.
Qualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS.
Measures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG.
The requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.
To determine whether markers of T cell activation and maturation are independently predictive of the response to potent antiretroviral therapy, the Immunophenotypic Markers and Antiretroviral Therapy ...study applied a novel data-sharing strategy across 5 Adult AIDS Clinical Trial Group trials that counted naive and activated CD4+ and CD8+ T cells in 324 subjects. Regression models—adjustment for baseline CD4 cell count, human immunodeficiency virus (HIV) RNA, and study—revealed that high pretreatment CD8+ T cell activation predicted virologic failure ( P = .046). Additional models showed the greatest increase in CD4+ T cell counts in subjects with highest pretreatment naive CD4+ T cell counts ( P < .0001 ), which was enhanced by high CD4+ and low CD8+ T cell activation. Total lymphocyte count also predicted a subsequent CD4+ T cell change. These results document the utility of T cell markers in predicting treatment outcome and their potential value for the study and management of HIV-1 infection.
Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ...ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer’s, Huntington’s, and Parkinson’s diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
This Primer reviews the mechanisms, tools, and guidelines to study ferroptosis, a form of cell death that is emerging as a central player in several degenerative diseases.
PDF
