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At least 757 records · Page 42Linked to original sources
PubMed1995

Regulatory mechanisms of antitumor T cell responses in the tumor-bearing state.

Tumor-bearing hosts develop antitumor immune responses. However, a number of immunosuppressive mechanisms come into operation with the progression of tumor growth. This article will review the observations regarding the modulation of antitumor immune responses in the tumor-bearing state, and consider the mechanisms underlying tumor-induced immune defects, especially in the light of the induction of an abnormal cytokine network. We will also describe the restoration of suppressed antitumor immune responses by administration of a particular cytokine, interleukin-12.

Animals↗
PubMed1982

Repair capability and the cellular age response for killing and mutation induction after UV.

The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D0 of 0.3 as compared to 3.2 J/m2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. A variation in the ability of this repair process to act in eliminating potentially lethal and mutagenic lesions (either due to a variation in repair enzyme activities through the cell cycle, or in the time available for repair) would account for most of the age response which is seen in the wild-type for killing and mutation induction by ultraviolet light.

Animals↗
PubMedDate not supplied

Comparative studies on photoreactivation of ultraviolet light-induced T4 endonuclease susceptible sites and sister-chromatid exchanges in Potorous cells.

Photoreactivation (PR) of T4 endonuclease-susceptible sites (ESS) and sister-chromatid exchanges induced by ultraviolet light was investigated in Potorous tridactylis Pt K2 cells, using monochromatic light from a grating monochromator. Both ESS and SCE showed maximum PR at 350 nm and the action spectra of PR essentially overlapped between ESS and SCE at 350, 400 and 450 nm. Exposure to 325-nm light after UV irradiation induced additional ESS and SCE, but reduction of ESS was shown by increasing exposure to 325-nm light, and further induction of SCE was observed by the same treatment. A possible difference in mechanisms between induction of ESS and SCE is suggested at 325 nm, while similar causes for ESS and SCE, presumably pyrimidine dimers, are suggested by UV (254-nm) irradiation.

Animals↗
PubMed1993

Induced contrast from radial patterns.

The perceived color of a region of visual space depends both on the spectral composition of the light incident from it and the light incident from surrounding regions. We studied the induced effect of combinations of colors surrounding a central test disk. Surround colors varied in a radially sinusoidal fashion around the perimeter of the test. Using a modulation nulling technique we show that when DC adaptation is controlled, the combined effect of such surrounds is equal to the sum of contrasts induced by individual elements of the surround. This result holds for both lightness and chromatic induction.

Color Perception↗
PubMed2005

Expression of transgenic stilbene synthases in wheat causes the accumulation of unknown stilbene derivatives with antifungal activity.

The expression of foreign phytoalexins in a new host is thought to increase fungal resistance, since host-specific pathogens have not experienced selection for detoxifying or metabolising the novel antifungal compounds. Two resveratrol synthase genes vst1 and vst2 from grapevine (Vitis vinifera L.) and the pinosylvin synthase gene pss from pine (Pinus sylvestris L.) were stably transformed into bread wheat. The expression of the target genes is regulated by stress-inducible grapevine promoters. The vst1 and vst2 promoters were functional in wheat and retained their expression profiles described for grapevine. ALL vst and pss transgenic lines accumulated stilbene derivatives upon induction by UV light. The detected stilbenes showed a remarkable similarity to resveratrol and pinosylvin, however were found to be more hydrophilic than resveratrol and pinosylvin. Upon inoculation with the biotrophic pathogen Puccinia recondita f.sp. tritici several vst expressing wheat lines showed a significant reduction of disease symptoms (19 +/- 9% to 27 +/- 8%) compared to wild-type plants. The reduction of disease symptoms was even more obvious after inoculation with the facultative biotrophic pathogen Septoria nodorum Berk. and ranged from 42 +/- 13% to 71 +/- 4%. None of the four tested pss expressing lines showed a reduction in disease incidence.

Acyltransferases↗
PubMed2004

Therapeutic monitoring of cyclosporine in kidney transplantation: the Halifax experience.

Appropriate dosing of an immunosuppressive agent is critical to its efficacy and tolerability. Finding a simple and effective method of monitoring cyclosporine (CsA/CyA) has been formidable despite a long history of widespread usage. Earlier reports linked CsA dosing to trough levels (C0), whereas later more elaborate systems have evaluated efficacy linked to 12-hour area-under-the-curve (AUC(0-12)) as a measure of total drug exposure. Recent work done at our center and elsewhere has shown that the 2-hour postdose concentration (C2) to be simple and more effective than the C0 or the AUC. With C2 monitoring as a guide to CsA dosing, acute rejection (AR) and nephrotoxicity (NT) can be effectively reduced. Furthermore, absorption profile as per C2 levels further emphasizes the importance of achieving the targeted peak concentration in the first week of transplantation. The C2 concentration strategy is discussed in light of newer induction agents and other immunosuppression.

Administration, Oral↗
PubMed2002

Interference of an apcA insertion with complementary chromatic adaptation in the diazotrophic Synechocystis sp. strain BO 8402.

Complementary chromatic adaptation was studied in two unicellular diazotrophic Synechocystis-type cyanobacteria, strains BO 8402 and BO 9201. Strain BO 8402 was isolated from Lake Constance as a mutant lacking phycobilisomes due to an insertion sequence element in the gene apcA, encoding alpha-allophycocyanin. Strain BO 9201 recovered the ability to assemble functional phycobilisomes after a spontaneous excision of the insertion sequence element in apcA. Simultaneously, the strain became able to perform group II complementary chromatic adaptation by regulating the synthesis of phycoerythrin. The two strains had identical phycoerythrin operons, cpeBA, and similar-sized transcripts were formed upon induction by green light. However, in strain BO 8402 the cpeBA transcript level was approx. 20-fold lower than in strain BO 9201. Because strain BO 8402 cannot synthesize allophycocyanin and phycocyanin is sequestered in paracrystalline inclusion bodies, non-assembled phycoerythrin may accumulate inside the cells. It was examined whether non-assembled phycoerythrin or other effects caused by the absence of phycobilisomes, such as a permanently oxidized redox status of the photosynthetic electron transport chain or a distorted ratio of C and N assimilation mediated the repression of cpeBA transcription in strain BO 8402. No such links could be established. We therefore concluded that in these diazotrophic Synechocystis-type cyanobacteria the green light-induced transcription of the cpe operon directly required a functional apc operon.

Bacterial Proteins↗
PubMed1978

Relative rates of repair of single-strand breaks and postirradiation DNA degradation in normal and induced cells of Escherichia coli.

Labeled DNA from irradiated Excherichia coli cells has been studied on an alkaline sucrose gradient without acid precipitation of the DNA. This enables the observation of both DNA repair and DNA degradation. The use of a predose of ultraviolet light (UV) causes induction of an inhibitor of postirradiation DNA degradation in lex+ strains. The effect of this induction on both the repair of single-strand breaks and DNA degradation has been followed in strains WU3610 (uvr+) and WU3610-89 (uvr-). The repair process is more rapid than the degradation, and when degradation is inhibited more repair is apparent. Cells that are lex- (Bs-1 and AB2474) cannot be induced for inhibition of degradation. Nevertheless, by observation at short times repair can be seen clearly. This repaired DNA is degraded, suggesting that the signal for DNA degradation is not a single-strand break.

Centrifugation, Density Gradient↗
PubMed2002

Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. John's wort).

Hypericum perforatum L. (St. John's wort) is an herbal remedy widely used in the treatment of mild to moderate depression. Hypericin, a photosensitive napthodianthrone, is believed to be the compound responsible for reversing the depression symptoms. In this study, novel in vitro cell culture systems of H. perforatum were used to monitor the effect of elicitation on cell growth and production of hypericin. A dramatic increase in cell growth and hypericin production was observed after exposure to jasmonic acid (JA). However, other elicitors such as salicylic acid (SA) and fungal cell wall elicitors failed to show any stimulatory effect on either cell growth or hypericin production. Cell cultures treated with JA and incubated in the dark showed increased growth and hypericin production as compared to the cultures grown under light conditions. Jasmonate induction in dark conditions played an important role in growth and hypericin production in cell suspension cultures, to our knowledge an undocumented observation.

Anthracenes↗
PubMed2000

NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Bypass of a site-specific cis-Syn thymine dimer in an SV40 vector during in vitro replication by HeLa and XPV cell-free extracts.

The key step in skin cancer induction by UV light is thought to be the mutagenic DNA synthesis past a DNA photoproduct in a proto-oncogene or tumor suppressor gene. To investigate this critical step, we have constructed an SV40 vector containing a cis-syn thymine dimer, the major DNA photoproduct induced by UVB light, within an AseI site at a location that would initially be replicated by leading strand synthesis. When the dimer-containing SV40 vector was incubated with cell-free HeLa extracts in the presence of TAg, and then digested with AseI, a 2325 bp fragment corresponding to inhibition of cleavage at the dimer site was observed, suggesting that the dimer had terminated synthesis and/or had been bypassed. When the reaction was limited to one round of replication and the products of restriction enzyme digestion were examined by denaturing gel electrophoresis, bands corresponding to both termination and bypass were observed in roughly a one-to-one ratio. Whereas increasing the dNTP concentration from 10 microM to 1 mM increased the ratio of bypass to termination from 0.6 to 2.6, it had no effect on the site of termination, which occurred exclusively one nucleotide before the dimer. Experiments in which dGTP was held constant at 25 microM and various combinations of the remaining nucleotides were raised from 25 microM to 1 mM showed substantial increases in the bypass-to-termination ratio, with the greatest effect seen for raising all three nucleotides to 1 mM. Replication by primary fibroblast XPV extracts was also investigated and found to be greatly stimulated by rhRPA, whereas the stimulatory effect for HeLa cell extracts was variable. In the presence of rhRPA, the XPV extracts were also found to bypass the cis-syn dimer, which contrasts with a recent report that could not detect dimer bypass in SV40 transformed XPV extracts in the absence of added replication factors [Cordeiro-Stone, M., et al. (1997) J. Biol. Chem. 272, 13945-13954].

Cell Line↗
PubMed2002

Photobiology and genetics of malignant melanoma.

The current state of knowledge of melanoma genetics is reviewed. Mutations in the tumour suppressor gene CDKN2A and in the oncogenes N-ras and H-ras seem to play the most important roles in the development and progression of malignant melanoma. Experimental studies to determine the role of ultraviolet (UV) light in the induction of melanoma have been hampered by a lack of suitable animal models. The commonly used laboratory animals are not susceptible to the induction of melanoma upon exposure to UV radiation (UVR) alone. Recent observations with four different animals have suggested, however, that UVR may be involved in the induction of melanoma. The most recent model consists of human skin grafted onto immunodeficient mice. To date, using this model, only the combination of UVB (280-320 nm) exposure and topical promoter treatment has led to the development of malignant melanoma. The wavelength dependency of the induction of melanoma has been established in the fish model Xiphophorus. The application of such an action spectrum to humans looks possible.

Animals↗
PubMed1998

Defense activation and enhanced pathogen tolerance induced by H2O2 in transgenic tobacco.

Transgenic tobacco deficient in the H2O2-removing enzyme catalase (Cat1AS) was used as an inducible and noninvasive system to study the role of H2O2 as an activator of pathogenesis-related (PR) proteins in plants. Excess H2O2 in Cat1AS plants was generated by simply increasing light intensities. Sustained exposure of Cat1AS plants to excess H2O2 provoked tissue damage, stimulated salicylic acid and ethylene production, and induced the expression of acidic and basic PR proteins with a timing and magnitude similar to the hypersensitive response against pathogens. Salicylic acid production was biphasic, and the first peak of salicylic acid as well as the peak of ethylene occurred within the first hours of high light, which is long before the development of tissue necrosis. Under these conditions, accumulation of acidic PR proteins was also seen in upper leaves that were not exposed to high light, indicating systemic induction of expression. Short exposure of Cat1AS plants to excess H2O2 did not cause damage, induced local expression of acidic and basic PR proteins, and enhanced pathogen tolerance. However, the timing and magnitude of PR protein induction was in this case more similar to that in upper uninfected leaves than to that in hypersensitive-response leaves of pathogen-infected plants. Together, these data demonstrate that sublethal levels of H2O2 activate expression of acidic and basic PR proteins and lead to enhanced pathogen tolerance. However, rapid and strong activation of PR protein expression, as seen during the hypersensitive response, occurs only when excess H2O2 is accompanied by leaf necrosis.

Catalase↗
PubMed2006

Acute toxicity and bioaccumulation of tributyltin in tissues of Urolophus jamaicensis (yellow stingray).

Tributyltin oxide (TBTO) is the main constituent of tin-based antifouling marine paint used on the hulls of ships to prevent the growth of fouling organisms. TBTO was shown to be hazardous to nontarget organisms. The stingray, Urolophus jamaicensis, may represent the ideal study organism for the adverse effects of TBTO to elasmobranches. This study investigated the toxicity and accumulation of tin in the gill tissue of the stingray U. jamaicensis after acute exposure to TBTO. This work demonstrates the alterations in the morphological architecture of the gill using electron and light microscopy, the induction of stress proteins, and peroxidative damage in response to tributyltin (TBT) exposure. A captured population of U. jamaicencis was housed in isolated, static tank systems. After a minimum 30-d acclimation period, the animals were exposed to one of 5 experimental doses of TBTO (4 microg/L, 2 microg/L, 1 microg/L, 0.5 microg/L, or 0.05 microg/L). A sixth group served as a control population. At 3h following treatment, animals were sacrificed and gill tissue was extracted, processed, and stored for analysis. Results indicate that U. jamaicensis is hypersensitive to TBT exposure. The elasmobranch gill showed a distorted, swollen epithelium with exfoliation following acute exposure to as little as 0.05 microg/L TBTO for 3 h. Graphite furnace atomic absorption spectroscopy (GFAAS) results indicate that tissues of treated animals contained a significantly increased tin concentration as compared to controls. Western blot analysis demonstrated the induction of the stress proteins Hsp 70 and HO1. 4-Hydroxynonenol (4HNE) adduct formation determined by Western blot analysis provides further evidence that observed membrane degradation is a result of lipid peroxidation.

Animals↗
PubMed1997

The cost of selected tuberculosis control measures at hospitals with a history of Mycobacterium tuberculosis outbreaks.

OBJECTIVE: To determine the cost of nonrespirator-related tuberculosis (TB) control measures at several hospitals, following publication of the Centers for Disease Control and Prevention (CDC)'s revised TB infection control guidelines. DESIGN: Infection control (IC) and TB coordinators obtained cost information on tuberculin skin-test (TST) programs, addition of IC and employee health service (EHS) personnel, and the retrofit or new construction of environmental controls. SETTING: Four hospitals with, and one community hospital without, prior nosocomial multidrug-resistant TB transmission. RESULTS: During the study period, the TST program costs remained constant at four of five hospitals and increased at one hospital (median 1994 TST program cost: $5,568; range, $2,393-$44,902). Additional IC or EHS personnel were hired at four of five hospitals (median cost increase, $125,500; range, $63,000-$228,000). The median cost of new construction or new equipment purchases (ie, sputum induction booths, ultraviolet lights, or portable high-efficiency particulate air filters) at study hospitals was $163,000 (range, $45,000-$524,000) and $70,000 (range, $31,000-$93,000), respectively. CONCLUSIONS: Costs associated with implementing control measures similar to those recommended in the CDC TB IC guidelines varied widely by hospital. Engineering controls involved the largest capital outlay, but increases in personnel were the largest continuing cost. These costs represent improvements made to upgrade selected aspects of hospital TB control programs, not the cost of an optimal TB control program.

Cross Infection↗
PubMed1990

Effects of enflurane on visual evoked potentials in humans.

Effects of enflurane on visual evoked potentials (VEP) were studied in eight healthy female patients. Control VEP were recorded from the occipital electrode (OZ-CZ), and prominent negative (N70) and positive (P100) peaks were observed following flash light stimulation. After induction of anaesthesia with thiopentone, VEP were recorded at expired concentrations of 1.2, 1.8, 2.4 and 2.7% of enflurane in 100% oxygen. The amplitude of the P100 was decreased and the latency of the N70 was increased significantly from the control with all concentrations of enflurane. No significant difference was found between different concentrations of enflurane. The latency of the P100 was increased significantly only at concentrations above MAC and at 2.7% when it was significantly longer than those at 1.2 and 1.8%. We conclude that VEP are altered significantly with enflurane in clinically used concentrations.

Adult↗
PubMed2002

Stimulus-specific induction of an Egr-1 transgene in rat brain.

Regulated expression of Egr-1 (Zif268/NGFIA) in a variety of brain networks suggests a diversity of roles in neuronal plasticity. Here, we aimed to determine whether an egr-1 transgene would mediate transcriptional responses to different pharmacological and physiological stimuli in the brain of transgenic rats. Constitutive transgene expression was observed in the cortex, CA1 hippocampal area and pituitary, recapitulating expression of egr-1. Transgene induction was stimulus-specific. Metrazole induced widespread expression in the dentate gyrus, CA2 and CA3 areas, amygdala, and ventromedial nucleus. In contrast, induction following a light stimulus was restricted to the hypothalamic suprachiasmatic and periventricular nuclei. Our studies have provided novel insights into the differential regulation of egr-1, and facilitated approaches to the genetic manipulation of Egr-1-regulated neuronal systems.

Animals↗
PubMed1997

Pathogenetic mechanisms and treatment of cutaneous lupus erythematosus.

The mechanisms of cutaneous lupus erythematosus are under active investigation, and important advances have been made. Humoral mechanisms are likely important in subacute cutaneous lupus erythematosus, the cutaneous subset most associated with the Ro antibody. Many advances have been made in understanding the various Ro epitopes and the specificities of the Ro antibody response. Lupus mice experiments have provided insight into the contributing roles of various T-cell subsets. Variations in cytokine production related to genetic polymorphisms and induction by ultraviolet light combined with alterations in selectins and adhesion molecules contribute to the accumulation of inflammatory cells in cutaneous lupus erythematosus. It is important to institute aggressive systemic therapy when there is widespread scarring disease. Antimalarial agents continue to be first-line systemic drugs, and our understanding of the use of combination antimalarial agents and proper dosing limits problems with toxicity and improves efficacy. Other therapies, including thalidomide, are helpful for patients with resistant disease.

Animals↗