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Sensitivity and tolerance to tartrazine in aspirin-sensitive asthmatics.

The occurrence of sensitivity to tartrazine was examined in 51 patients with asthma and aspirin sensitivity. All patients underwent oral challenge tests with aspirin and tartrazine. Sensitivity to tartrazine was found in 16 i.e. 31.4% of tested asthmatics. The symptoms of sensitivity to tartrazine were similar to those of aspirin. Tolerance to tartrazine was induced in 5 aspirin and tartrazine sensitive asthmatics. Sensitivity to both substances was manifested in these 5 persons as dyspnea but 2 of them had additional extrabronchial symptoms. A good tolerance of 40 mg tartrazine was achieved in all the challenged patients who did not refer any dyspnea and extrabronchial symptoms. It was also proven that, being in the aspirin tolerance state the patients could be given tartrazine with no sensitivity symptoms. The authors think that the possibility of inducing tartrazine and aspirin tolerance, as well as the course of sensitivity reaction to both substances, both point to a similar pathogenetic background.

Adult↗

Conformational change accompanying transition of ADP-sensitive phosphoenzyme to potassium-sensitive phosphoenzyme of (Na+,K+)-ATPase modified with N-[p-(2-benzimidazolyl)phenyl]maleimide.

The addition of Mg2+ or ATP to (Na+,K+)-ATPase (EC 3.6.1.3) of pig kidney modified with a sulfhydryl fluorescent reagent N-[p-(2-benzimidazolyl)phenyl]maleimide simply reduced fluorescence in the presence of Na+; however, the addition of both ligands to the enzyme induced a reversible dynamic change. The direction of the change was dependent on the concentration of Na+ present. These dynamic changes in fluorescence intensity both in the presence of low and high concentrations of Na+ can be repeated by the re-addition of ATP but not by ADP. Addition of ouabain under the former condition stabilized the fluorescence at the highest level, but the addition of ouabain under the latter condition increased the fluorescence from the lowest to the highest level. The phosphoenzyme formed under the former condition was sensitive to K+ and insensitive to ADP while the phosphoenzyme formed under the latter condition was sensitive to ADP and insensitive to K+. The data indicate that the positive and negative fluorescence changes were induced by the formation of K+-sensitive phosphoenzyme and ADP-sensitive phosphoenzyme, respectively. N-Ethylmaleimide treatment partially inhibited the positive change without affecting the negative change. These data also indicate that the transition of ADP-sensitive phosphoenzyme to K+-sensitive phosphoenzyme accompanied the largest fluorescence intensity change which was examined during the hydrolysis of ATP. The data obtained from the tryptophan fluorescence of both the native and the modified enzyme suggest that the micro-environments of the tryptophan and the sulfhydryl residues are similar in the state of K+-sensitive phosphoenzyme but different in the state of ADP-sensitive phosphoenzyme.

Adenosine Diphosphate↗

Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

Animals↗

Adoptive cell transfer of contact sensitivity-initiation mediated by nonimmune cells sensitized with monoclonal IgE antibodies. Dependence on host skin mast cells.

A role for mast cell release of serotonin (5-HT), via Ag-specific factors derived from Thy-1+ B220+ lymphoid cells in the initiation of murine contact sensitivity (CS) has been suggested. However, because CS in mast cell-deficient mice was intact, a role for mast cells in CS initiation was unclear. Therefore, we examined whether CS could be initiated by i.v. injection of nonimmune mixed lymphoid cells that were sensitized in vitro with IgE. When naive mice received IgE-sensitized nonimmune spleen or lymph node cells, or IgE-sensitized purified mast cells, together with immune CS-effector B220- T cells, which therefore were depleted of CS-initiating, Thy-1+, B220+ cells, which could not transfer CS, then reconstitution of CS occurred. Mast cell-deficient W/Wv mice could not elicit this IgE-dependent CS ear swelling, but when mast cell deficiency was reversed by ear injection of normal bone marrow-derived cultured mast cells, then CS was restored. In vitro pretreatment with irrelevant monoclonal anti-OVA IgE prevented CS initiation mediated by Ag-specific, IgE mAb-sensitized cells, presumably by blocking sensitization with IgE. Thus Fc epsilon R on the normal lymphoid cells were involved. When ketanserin, a 5-HT2 receptor antagonist, was injected i.v. before cell transfer, CS initiation via IgE-sensitized cells and CS were no longer elicited. Thus, in this system, IgE Abs bound to circulating IgE Fc epsilon R bearing lymphoid cells sensitized in vitro (most likely basophils), probably mediated early activation of these circulating basophils to release mediators, causing 5-HT release from cutaneous mast cells, to mediate CS initiation.

Animals↗

Neural sensitization and physiological markers in multiple chemical sensitivity.

This paper summarizes the key features of the olfactory-limbic, neural sensitization model for multiple chemical sensitivity (MCS) and presents relevant data on chemically intolerant human subjects from laboratory studies using quantitative electroencephalography, polysomnography, neuropsychological tests, cardiovascular measurements, and blood markers. MCS is a poorly understood chronic, polysymptomatic condition in which some prior controlled research studies have failed to find evidence to differentiate active from placebo tests. Closer examination of past MCS research, however, reveals that studies have failed to incorporate the design and methodological approaches necessary to test for nonimmunological sensitization. Time-dependent sensitization (TDS) is a well-documented phenomenon in the pharmacology literature involving the progressive increase in a given response by the passage of time between the initial and subsequent exposures to a substance or a stressor. As in MCS, multiple, chemically unrelated agents can trigger TDS. Females time-sensitize more readily than do males. Pharmacological and nonpharmacological (stress) stimuli can cross-sensitize. Dopaminergic pathways in the brain and the hypothalamic-pituitary-adrenal axis are likely involved in TDS. Data on the symptomatology of MCS point to central nervous system involvement, including limbic regions that receive input from both olfactory (odor) and trigeminal (irritant) pathways. Limbic and mesolimbic brain regions are among the most sensitizable to repeated, intermittent environmental stimuli. Sensitizable individuals can show no difference or lesser responses to a test substance on initial exposure, but later exhibit much greater increases in responsivity on the next exposure after a period of days. For future research, it is essential to distinguish chemical intolerance symptoms such as derealization, sudden mood changes, musculoskeletal pain, menstrual dysfunction, and uncontrollable sleepiness from chemical phobia and avoidance behaviors. This model permits hypothesis-driven research on MCS and has major implications for interpretation of apparently positive and negative tests for "true" as opposed to "perceived" sensitivity to low levels of environmental chemicals.

Humans↗

Does chromatic sensitivity develop more slowly than luminance sensitivity?

Chromatic sensitivity is very low in humans during the first few months of life. We examined whether low chromatic sensitivity reflects a deficiency among chromatic mechanisms or whether it is simply a manifestation of poor visual sensitivity in general. The sweep VEP was used to measure contrast sensitivity to gratings varying in the mixture of red and green components. For infants from 2 to 8 weeks of age, sensitivity to all mixtures was lower than color-normal adults' sensitivity, but infant and adult ratios of luminance/chromatic sensitivity were similar. This finding is consistent with the hypothesis that infants have functional MWS and LWS cones and the requisite post-receptor chromatic mechanisms to compare their signals.

Age Factors↗

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: II. Factors affecting detection sensitivity in a population with circulating wild poliovirus.

A basic framework for describing sensitivity of surveillance to detect poliovirus is extended from individuals to general populations (population sensitivity). Using the mathematical formulations for population sensitivity, the theoretical behavior of surveillance sensitivity under various conditions is analyzed. As a region nears the elimination of poliovirus, population sensitivity falls to a value lower than the case-to-infection ratio, regardless of the system proficiency. Also, a second stool specimen makes a substantial contribution to population sensitivity only in regions with relatively low specimen sensitivity and then only over a narrow range of population infection incidence. Estimates of the mean numbers of infected and uninfected acute flaccid paralysis cases investigated in a season are derived. These may serve as additional indicators of system operation but require the collection of 2 specimens per case.

Feces↗

Anxiety sensitivity in African-American adolescents: evidence of symptom specificity of anxiety sensitivity components.

OBJECTIVE: To examine the specificity of components of anxiety sensitivity (phrenophobia, fear of cardiovascular sensations, and fear of unsteadiness) to anxiety and depression in a sample of African-American adolescents. METHOD: Participants were 527 African-American adolescents (238 females, mean age 13.8 years) who were originally recruited as first graders in 1993 to 1994 for participation in the second-generation Johns Hopkins Prevention Intervention Research Center trials. Youths completed measures of anxiety sensitivity and anxious and depressive symptoms in the spring of 2001. Associations between anxiety sensitivity and depression and anxiety were examined using hierarchical linear regressions. RESULTS: Anxiety sensitivity as a unitary construct was positively associated with symptoms of anxiety after adjusting for symptoms of depression. Fear of unsteadiness showed specificity to anxiety after adjusting for depression and phrenophobia. Phrenophobia was positively associated with anxiety and depression, after adjusting for the other symptom and fears of physical sensations. CONCLUSIONS: Specificity of anxiety sensitivity to anxiety in a sample of African-American adolescents furthers understanding of the nature of anxiety sensitivity in this group and the potential roles of components of anxiety sensitivity in the development of psychopathology in general.

Adolescent↗

The effect of urine testing in evaluations of the sensitivity of the Gen-Probe Aptima Combo 2 assay on endocervical swabs for Chlamydia trachomatis and neisseria gonorrhoeae: the infected patient standard reduces sensitivity of single site evaluation.

BACKGROUND: The Gen-Probe APTIMA Combo 2 (AC2) assay is a second-generation transcription-mediated amplification assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). GOAL: The goal of this study was to evaluate AC2 performance of endocervical (cx) swabs for the detection of CT and NG using either a specimen or an infected patient standard. STUDY DESIGN: In a multicenter clinical study, we compared AC2 with Abbott's ligase chain reaction (LCR) and Roche's polymerase chain reaction (PCR; Amplicor or COBAS) for CT, and we compared AC2 with Abbott's LCR and culture for NG. A total of 1569 females were enrolled in the study; we collected cx and first-catch urine (FCU) specimens. RESULTS: CT prevalence was 13.3% for cx specimens and 13.7% for FCU specimens. NG prevalence was 8.7% and 7.9% for cx and FCU specimens, respectively. When based only on cx specimens, AC2, LCR, and PCR sensitivities for CT were 99.4%, 95.6%, and 95.6%, respectively. However, cx sensitivity for CT was reduced to 92.1%, 86.6%, and 87.1% for each respective assay when based on both cx and FCU specimen results (infected patient standard). NG sensitivities for AC2, LCR, and culture based solely on cx specimen results were 99.2%, 96.1%, and 85.9%, respectively. Based on infected patient standard, the sensitivities of each respective assay were 98.5%, 93.9%, and 84.0%. CONCLUSIONS: The infected patient standard reduces the sensitivity of the endocervical evaluation because some infected patients are positive only with FCU. The reduction in sensitivity is greater when testing for CT. Specificities improved slightly, because some unique cx positives, initially classified as false-positive were confirmed by a positive FCU result. Sensitivity of AC2 was higher than LCR, PCR, and culture. Specificity was slightly lower, but discrepant analysis (using alternate TMA targets) of apparent AC2 false-positives showed that 75% to 80% were true-positives.

Chlamydia Infections↗

Contrast sensitivity and glare sensitivity changes with three types of cataract morphology: are these techniques necessary in a clinical evaluation of cataract?

LogMAR visual acuity, contrast sensitivity and glare sensitivity measurements were made on 39 eyes of 18 cataractous subjects and compared against normative data. Only cataracts of one of the main three morphological cataract types were used--cortical, nuclear and posterior subcapsular. Results indicate that contrast sensitivity decline with cataract is an intermediate and high spatial frequency loss. For nuclear and cortical cataracts with a LogMAR visual acuity of less than 0.5 (Snellen equivalent better than 6/18), there was no loss of contrast sensitivity at the lowest spatial frequency (1 c/deg). For posterior subcapsular cataracts, low spatial frequency contrast sensitivity loss did occur but was unrelated to visual acuity. Glare sensitivity increased for all cataract types. This was related to visual acuity for both cortical and nuclear cataracts but was not for the posterior subcapsular type. It was concluded that contrast and glare sensitivity measurements are a useful part of the assessment of visual function in patients with posterior subcapsular cataract.

Aged↗

Frequency of seeing characteristics of the short wavelength sensitive visual pathway in clinically normal subjects and diabetic patients with focal sensitivity loss.

AIMS: To define the frequency of seeing (FOS) characteristics of the short wavelength (SW) sensitive visual pathway in clinically normal subjects and in diabetic patients with focal SW sensitivity loss. METHODS: For clinically normal subjects, FOS was assessed at two retinal locations (4.24 degrees and 9.90 degrees eccentricity) for both white on white (WW) and SW stimulus parameters. Inter-examination variability was quantified for the clinically normal subjects only. For patients with diabetes, FOS was assessed inside an area of focal SW sensitivity loss, and at the same eccentricity in the quadrant diametrically opposite, using SW stimulus parameters only. RESULTS: For clinically normal subjects, the group mean SW FOS slope was significantly flatter (p<0.0001) than that of WW at both locations. The coefficient of repeatability for SW FOS slope was+/-41.55 dB(-1) (relative to a group mean sensitivity of 23.98 dB(-1)) and+/-19.98 dB(-1) (group mean sensitivity 16.15 dB(-1)) for 4.24 degrees and 9.90 degrees , respectively. For the patients with diabetes, the group mean SW FOS slope was significantly flatter (p=0.020), and group mean SW threshold significantly higher (p=0.007) in the area of focal SW sensitivity loss than in that of the non-focal sensitivity loss. CONCLUSIONS: The results of this study suggest that the clinical utility of SW automated perimetry will be limited by a greater magnitude of measurement variability, as indicated by a flatter FOS slope, compared to conventional automated perimetry.

Adult↗

[Radiation sensitizers: with special reference to hypoxic cell sensitizers].

Recent advances in radiation chemistry and radiation biology have led to the combined use of radiosensitizing agents with radiation in the treatment of radioresistant tumors. Various chemicals, including cancerocidal drugs, are used, although radiation sensitizers are defined as drugs which can increase cellular radiosensitivity but have no direct cancerocidal effect. At least four classes of agents, pyrimidine analogues, hypoxic cell sensitizers, PLDR inhibitors and thiol-depleting agents, can modify radiosensitivity and have potential for differential sensitization. Pyrimidine analogues are incorporated into DNA in replicating tumor cells, and can sensitize these cells to radiation up to a factor of 3. Results of clinical trials of intra-arterial infusion of BUdR have not proved satisfactory, especially with regard to long-term survival, possibly because of the existence of non-replicating cells in the tumor. The latter two are still in the experimental stage of study. The radioresistance of hypoxic cells in tumor has been regarded as one of the limiting factors in the local control of cancer by radiation. Attempts to improve the situation involve high-LET radiation and combined use of chemicals, such as oxygen, prefluorochemicals and electron-affinic compounds, with low-LET radiation. Although some clinical trials in head and neck cancer and in cervical cancer have yielded positive results in patients treated using hyperbaric oxygen, attempts have been made to devise other methods, such as those using perfluorochemicals with normobaric oxygen, because of the technical difficulty involved with the former method. A more promising and easier method is the combined use of electron-affinic chemicals, which like oxygen can sensitize the hypoxic cells. Misonidazole (alpha 2-nitroimidazole derivative) was found to be an excellent sensitizer of this kind in cultured mammalian cells and in some rodent tumors. Several randomized clinical trials to determine its efficacy have been carried out on a word-wide scale, but most of them failed to demonstrate any beneficial effect, mainly because of the drug's neurotoxicity which limits its dose. After misonidazole, many researchers have made every effort to develop more efficient hypoxic cell sensitizers. The present state and future prospects of study were reviewed with special reference to studies currently being undertaken in Japan.

Animals↗

[Clinical evaluation of force-sensitive probe in the examination of tooth sensitivity].

Two methods were tested for measuring the sensitivity of dentin to mechanical (force-sensitive probe) and cold air stimuli. Of the 212 sensitive teeth in 71 patients, 94.8% were sensitive to probe, with a mean threshold of 22.79g; 89.6% were sensitive to cold air. These two methods were significantly correlated (P < 0.001). The occlusal sites were less sensitive than the buccal sites measured by probe and cold air. It suggests that force-sensitive probe is a simple, quantitative method of measuring tooth hypersensitivity.

Adult↗

Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients.

The sensitivity and specificity of two sensitive thyrotropin assays were compared with those of other standard thyroid function tests in 544 ambulatory subjects who were clinically euthyroid, thyrotoxic, or hypothyroid. Both sensitive thyrotropin assays had the highest sensitivity and specificity (95%/89% and 92%/95%), following by estimated free thyroxine (T4) level (82% and 94%), calculated free T4 index (78% and 93%), and free triiodothyronine index (86% and 88%). Sensitivity of the two thyrotropin assay kits in the diagnosis of thyrotoxicosis was 86% and 95%, and that in the diagnosis of hypothyroidism was 92% and 94%. Other tests were nearly as sensitive in the diagnosis of thyrotoxicosis but not hypothyroidism. A cost analysis of a testing strategy that used either total T4, free T4 index, or sensitive thyrotropin assay alone as the first-line thyroid test disclosed that to establish the patient's thyroid metabolic status would have cost $11,093, $14,536, and $24,902, respectively, using each test first. We suggest that, at current prices, routine use of the thyrotropin assay as a first-line test in ambulatory patients is not as cost-effective as the free T4 index.

Adult↗

Sensitization to cisplatin action by step-down heating in cDDP-sensitive and -resistant cells.

Hyperthermia treatment (> or = 43 degrees C) has been shown to be able to (partially) reverse acquired cDDP resistance. However, such heat treatment is difficult to achieve in the clinic. Short pre-treatment at a high temperature (> 42 degrees C), immediately before a treatment at a lower temperature (< 42 degrees C) can enhance the heat toxicity of the lower temperatures. This "step-down heating schedule" was explored for its possible drug-sensitizing potential in in vitro-cultured cDDP-sensitive and -resistant murine and human tumour cells. A 10-min pre-treatment at 44 degrees C enhanced the cytotoxicity of 41 degrees C hyperthermia alone. It also enhanced sensitivity to cDDP when given at 37 degrees C. However, it did not increase the 41 degrees C-induced cDDP sensitization. Thus, no correlation was found between heat kill and cDDP sensitization for step-down heating schedules. The observed effects of step-down heating were comparable in sensitive and in resistant cells, so the step-down heating schedule, unlike the 43 degrees C treatment, did not lead to a decrease of the cDDP-resistance factor. Yet the total cytotoxicity caused by this treatment protocol was 10-fold more than for cDDP with 41 degrees C alone, due to the extra hyperthermic cell killing and the cDDP-sensitizing effect of the pre-treatment. This treatment could have a substantial impact on cDDP efficacy in the clinic even when cDDP resistance has developed.

Animals↗

Structure of preschool phonological sensitivity: overlapping sensitivity to rhyme, words, syllables, and phonemes.

Phonological sensitivity is an important causal variable in reading acquisition; however, there is controversy concerning its nature. One view holds that sensitivity to various linguistic units reflects independent abilities, whereas another holds sensitivity to these units reflects one ability. We examined relations among sensitivity to words, syllables, rhymes, and phonemes in 149 older preschool children (4- and 5-year-olds) and 109 younger preschool children (2- and 3-year-olds) who completed eight measures of phonological sensitivity and measures of print knowledge. Confirmatory factor analyses of all combinations of word, syllable, rhyme, and phoneme factors found that a one-factor model best explained the data from both groups of children (CFIs >.98). Only variance common to all phonological sensitivity skills was related to print knowledge and rudimentary decoding. Findings support a developmental conceptualization of phonological sensitivity.

Awareness↗

Comparison of the pharmacologic effects of N-allylnormetazocine and phencyclidine: sensitization, cross-sensitization, and opioid antagonist activity.

The effects of phencyclidine (PCP) on locomotor activity were compared to those of the stereoisomers of N-allylnormetazocine (NAN) after acute administration to rats. PCP produced swaying and falling movements, increased sniffing behavior, and enhanced horizontal locomotor activity. d-NAN also induced swaying, falling, sniffing behavior and locomotion, and decreased rearing behavior. l-NAN decreased rearing activity, depressed locomotion, antagonized morphine antinociception and precipitated the morphine-withdrawal syndrome. Sensitization to drug-induced sniffing, rearing and locomotion developed after four daily injections of PCP, d-NAN or l-NAN in rats. Rats which were sensitized to PCP-induced locomotion, sniffing, and rearing were also cross-sensitized to both d-NAN and l-NAN. Animals sensitized to the effects of either d- or l-NAN exhibited cross-sensitization to PCP. There was little evidence that the cross-sensitization between the three agents was stereoselective. These data indicate that the acute effects of PCP are similar to those of d-NAN, but differ from l-NAN, the only agent of the three with opioid antagonist properties. The data further indicate that as sensitization to the motor effects develops during repeated administration of PCP, d-NAN or l-NAN, the differences among the three agents become less apparent.

Animals↗

Relationship of histidine sensitivity to DNA damage and stress induced responses in mutagen sensitive mutants of Neurospora crassa.

Previous work in other laboratories has shown that several mutagen sensitive mutants of Neurospora crassa are extremely sensitive to low levels of histidine in the culture medium. We have shown that wild type Neurospora accumulates nicks or breaks in the DNA in the presence of histidine. The number of nicks accumulating in histidine sensitive mutants is found to increase in relation to their sensitivity to histidine. Although these nicks can be repaired by both wild type and histidine sensitive mutants when histidine is removed from the medium, a steady state number of nicks exists as long as histidine is present. We suggest that the presence of these nicks or breaks induces an increase in recombination in these possibly recombination defective mutants and that this is the source of the high level of histidine sensitivity. We speculate on the mechanisms by which histidine induces this DNA damage. This report also shows that several polypeptides are induced by the wild type organism in the presence of histidine. Some of these polypeptides are also induced during other stress situations, such as heat shock and DNA damage due to ultraviolet irradiation. Two of the histidine induced proteins cannot be induced by any of the histidine sensitive mutants.

DNA Damage↗