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Biomedical subjects

D L Stevens

Publications and source records attributed to D L Stevens.

At least 55 records · Page 3Linked to original sources
PubMed1998

Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation.

We have demonstrated chromosomal instability in the clonal descendants of hemopoietic stem cells after irradiating murine bone marrow with alpha-particles. However, because cells that are irradiated by alpha-particles are defined by a Poisson distribution of individual particle traversals, there is an inevitable proportion of unirradiated cells in the surviving population. The calculated expected proportions of irradiated and nonirradiated cells indicate that the number of clonogenic cells transmitting chromosomal instability is greater than the number expected to be hit and survive. To investigate further this discrepancy, we studied the effects of interposing a grid between the cells and the alpha-particle source so that the surviving population consists predominantly of untraversed stem cells. Comparison with the same irradiation conditions without the grid reveals that the same level of instability is induced. The data confirm that alpha-particles induce chromosomal instability but instability is demonstrated in the progeny of nonirradiated stem cells and must be due to unexpected interactions between irradiated and nonirradiated cells. This untargeted effect has important implications for mechanistic studies of radiation action and for assessment of radiation risk.

Abnormalities, Radiation-Induced↗
PubMed1998

Novel therapies in streptococcal toxic shock syndrome: attenuation of virulence factor expression and modulation of the host response.

The systemic manifestations of severe invasive group A streptococcal infections, such as streptococcal toxic shock syndrome, are mediated by an overwhelming inflammatory response induced by streptococcal superantigens and other virulence factors. The high mortality rates associated with streptococcal toxic shock syndrome demonstrate a need for better therapy in these diseases. Novel strategies to attenuate or prevent streptococcal toxic shock syndrome at different stages of illness have been proposed. The most promising therapies include agents that by various mechanisms attenuate the inflammatory response or the action of streptococcal toxins/superantigens, or both.

Journal Article↗
PubMed1998

In vitro antimicrobial effects of various combinations of penicillin and clindamycin against four strains of Streptococcus pyogenes.

Previous studies using mouse models of Streptococcus pyogenes necrotizing fasciitis demonstrated that clindamycin had greater efficacy than penicillin. Frequently both agents are used concurrently in the treatment of severe S. pyogenes infections. This study investigated interactions between penicillin and clindamycin. E-test and broth microdilution assays suggested additivity or indifference, while timed-killing assays demonstrated concentration-dependent variable effects. Timed-kill studies utilizing clinical concentrations suggest that there is no antagonism with the combination of drugs but that the combination does not have a bactericidal advantage over either penicillin or clindamycin alone.

Clindamycin↗
PubMed1998

Induction of DNA-protein crosslinks in Chinese hamster V79-4 cells exposed to high- and low-linear energy transfer radiation.

The induction of DNA-protein crosslinks (DPCs) in Chinese hamster V79-4 cells after irradiation under hypoxic and aerobic conditions at 277 K with 60Co gamma rays, 238Pu alpha particles and aluminum K (Al(K)) ultrasoft X rays has been determined using a nitrocellulose filter binding assay. The dose dependences for the induction of DPCs, which involves covalent linkage, are linear over the absorbed dose range used (0-400 Gy with alpha-particle and gamma radiation, 0-600 Gy with Al(K) X rays). The yield of DPCs induced under hypoxic conditions is 55, 51 and 25 DPCs per gray per cell for 60Co gamma rays, alpha particles and Al(K) X rays, respectively. The yield of DPCs is significantly reduced in the presence of oxygen by 20, 50 and 79% for 60Co gamma rays, alpha particles and Al(K) X rays, respectively. Since the mean size of the DNA attached to the protein is uniform for 60Co gamma rays and alpha particles, variations in the DNA size do not influence the yields of DPCs. Although a DPC may be considered as a complex lesion combining two macromolecules, the dependence of the yield of DPCs on LET does not reflect the ionizing density of the radiations used. Further, this dependence on LET and the effect of oxygen do not reflect the corresponding dependences determined for a variety of biological responses. From these findings and knowledge of the radiation tracks, it is proposed that DPCs induced particularly under aerobic conditions with 60Co gamma rays are formed mainly in the sparsely ionizing segments of the radiation track.

Animals↗
PubMed1997

Alpha toxin from Clostridium perfringens induces proinflammatory changes in endothelial cells.

Alpha toxin from Clostridium perfringens type A, a phospholipase C, has been implicated in many of the localized and systemic features of gas gangrene. We demonstrated that human endothelial cells synthesize two vasoactive lipids, platelet-activating factor (PAF) and prostacyclin, in response to alpha toxin treatment. The stimulated synthesis of PAF required the enzymatic activity of the toxin and subsequent protein kinase C activation. Alpha toxin-treated endothelial cells accumulated the products of the phospholipase C reaction, diacylglycerol and ceramide, and exhibited a decrease in the enzymatic precursors phosphatidylcholine and sphingomyelin. Furthermore, the temporal accumulation of PAF depended on the concentration of the toxin in the overlying medium and was blocked in the presence of a neutralizing antibody. The cultured endothelial cells also exhibited enhanced neutrophil adhesion in response to alpha toxin which was mediated through the PAF receptor and P-selectin. P-selectin expression by endothelial cells and extravascular neutrophil accumulation were also observed in tissue sections from alpha toxin-injected Sprague-Dawley rats. These endothelial cell-mediated processes are important in maintaining vascular homeostasis and, when activated in a dysregulated manner by C. perfringens alpha toxin, may contribute to localized and systemic manifestations of gas gangrene including enhanced vascular permeability, localized neutrophil accumulation, and myocardial dysfunction.

Animals↗
PubMed1997

Screening, prevention, counseling, and treatment for the complications of type II diabetes mellitus. Putting evidence into practice.

PURPOSE: To summarise current knowledge of interventions that should improve the care of patients with type II diabetes mellitus. Interventions lie within the realms of preventions, screening, and treatment, all of which are focused on office practice. METHODS: Review of the literature by a multidisciplinary team involved in the care of patients with diabetes, followed by synthesis of the literature into a clinical care guideline. Literature was identified through consultation with experts and a focused MEDLINE search. MAIN RESULTS: An algorithm-based guideline for screening and treatment of the complications of diabetes was developed. The emphasis is on prevention of atherosclerotic disease, and prevention, screening, and early treatment of microvascular disease. Implementation of these practices has the potential to significantly improve quality of life and increase life expectancy in patients with type II diabetes mellitus.

Algorithms↗
PubMed1997

Radiation-induced transformation of SV40-immortalized human thyroid epithelial cells by single exposure to plutonium alpha-particles in vitro.

Human thyroid carcinomas have been induced following exposure of SV40-immortalized human thyroid epithelial cells in vitro to single doses (0.14 Gy to 1.57 Gy) of 3.26 MeV alpha-particles from a plutonium 238 source. Tumours were detected between 50 and 160 days following subcutaneous transplantation of the irradiated cells in athymic mice. No tumours were observed following transplantation of unirradiated cells. The relative biological effectiveness (RBE) of the alpha-particles, estimated from cell survival curves, was 4.8 at 50% survival and 3.3 at 5% survival. A first estimate of the RBE at peak tumour induction was 3.8. This system provides a means of studying the mechanisms of tumourigenesis in human thyroid epithelial cells induced by ionizing radiations, including tumours induced by single alpha particles such as from environmental natural radon and polonium and artificial plutonium and americium, and those induced by beta- or Auger-emissions from particular iodine isotopes.

Alpha Particles↗
PubMed1997

Familial transmission of a serious disease--producing group A streptococcus clone: case reports and review.

Invasive group A streptococcus (GAS) infections are emerging diseases; however, person-to-person transmission of invasive GAS producing life-threatening infection has been observed rarely. We report a small intrafamilial cluster of life-threatening GAS infections. A previously healthy 47-year-old father developed necrotizing fasciitis of the neck. Two days later, his 16-year-old daughter developed streptococcal angina, pneumonia, and pleural empyema. Both patients had signs of streptococcal toxic shock syndrome. Pulsed field gel electrophoresis revealed that the M6 strains of GAS isolated from the father and daughter had identical patterns. Cases of person-to-person transmission of invasive GAS infection reported in the literature are also reviewed.

Adolescent↗
PubMed1997

Clostridial gas gangrene: evidence that alpha and theta toxins differentially modulate the immune response and induce acute tissue necrosis.

The rapid extension of necrosis and an absence of polymorphonuclear leukocytes (PMNL) at the site of infection are two hallmarks of Clostridium perfringens gas gangrene. While both alpha and theta toxins profoundly affect PMNL function and viability in vitro, their roles in muscle destruction and impairment of the inflammatory response in vivo have not been investigated. Comparative histopathologic examinations were performed on animals infected with either wild-type C. perfringens, or isogenic, toxin-deficient mutants of C. perfringens. Tissue destruction was modest in animals infected with the alpha toxin-deficient mutant; destruction was more pronounced in tissues infected with the theta toxin-deficient mutant or the wild-type strain. alpha and theta toxins also displayed differing abilities to modulate the inflammatory response. Histopathologic studies in which recombinant toxins were injected together with killed, washed C. perfringens further substantiated these tissue-destructive and differential antiinflammatory effects.

Animals↗
PubMed1997

Clostridium perfringens enterotoxin lacks superantigenic activity but induces an interleukin-6 response from human peripheral blood mononuclear cells.

We investigated the potential superantigenic properties of Clostridium perfringens enterotoxin (CPE) on human peripheral blood mononuclear cells (PBMC). In contrast to the findings of a previous report (P. Bowness, P. A. H. Moss, H. Tranter, J. I. Bell, and A. J. McMichael, J. Exp. Med. 176:893-896, 1992), two different, biologically active preparations of CPE had no mitogenic effects on PBMC. Furthermore, PBMC incubated with various concentrations of CPE did not elicit interleukin-1, interleukin-2, gamma interferon, or tumor necrosis factor alpha or beta, which are cytokines commonly associated with superantigenic stimulation. However, CPE did cause a dose-related release of interleukin-6 from PBMC cultures.

Clostridium perfringens↗