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Anxiety sensitivity and depression in multiple chemical sensitivities and asthma.

Patients with sensitivities to multiple chemicals report symptoms of cognitive dysfunction, respiratory distress, and mood disturbance. Lifetime and current psychiatric disorders, personality traits associated with symptom reporting, and tests of cognitive function were compared between 30 subjects with Multiple Chemical Sensitivities (MCS), 19 asthmatics, and 31 healthy controls. Relative to asthmatics and controls, more MCS subjects met criteria for current depression and somatization disorder. MCS subjects and asthmatics scored significantly higher than controls on scales of chemical odor intolerance and anxiety sensitivity, both of which were significant predictors of physical symptoms. Few differences on objective neuropsychological tests were noted. However, MCS subjects with comorbid depression performed significantly worse on a verbal memory test relative to asthmatics but not to controls. Anxiety and depression are significant contributors to the physical and cognitive symptoms of MCS subjects.

Adult↗

Sensitivity of conformation sensitive gel electrophoresis in detecting mutations in Marfan syndrome and related conditions.

OBJECTIVE: It has been firmly established that mutations in the gene for fibrillin 1, FBN1, cause Marfan syndrome (MFS). FBN1 mutations can also cause other phenotypes, such as ectopia lentis (EL) and familial isolated thoracic aortic aneurysm and dissection (FAA). When the clinical presentation is typical, diagnosis of MFS is usually easy to make. However, there can be a marked phenotypic variation between affected subjects even in one family, and making the diagnosis can be challenging, especially in childhood. The objective of this study was to test the sensitivity of conformation sensitive gel electrophoresis (CSGE) for detecting mutations in FBN1 in MFS and related phenotypes. DESIGN: Setting up CSGE analysis for the FBN1 gene and testing the method first by screening coded samples from 17 MFS patients with previously detected FBN1 mutations. We then used a test set consisting of 46 coded samples representing MFS, related phenotypes, and controls. RESULTS: Sixteen of the 17 known mutations were detected. Altogether 23 mutations were detected in a test set consisting of 46 coded samples representing MFS, related phenotypes, and controls. Nineteen of the mutations were novel. The mutation was detected in 18 of the 20 MFS patients and in one patient with familial EL, but not in a patient with sporadic MASS syndrome, any of the five sporadic annuloaortic ectasia (AAE) patients, or any of the 15 controls. A FBN1 mutation was detected in four members of a multigeneration family with AAE, however. CONCLUSIONS: These results indicate that CSGE is highly sensitive for the detection of mutations in FBN1, and that molecular diagnostics is a useful means of confirming clinical diagnoses of MFS and related disorders. Further careful investigations are needed, however, in order to correlate the interfamilial and intrafamilial clinical variabilities of fibrillinopathies and mutations in FBN1.

Adolescent↗

Effect of inhaled budesonide on seasonal changes in sensitivity and maximal response to methacholine in pollen-sensitive asthmatic subjects.

The aim of this study was to investigate the effect of inhaled budesonide on modifications of the provocative concentration of agonist causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) and maximal response plateau to inhaled methacholine during the pollen season in pollen-sensitive subjects with mild asthma. The effects of inhaled budesonide (800 micrograms.day-1) on the threshold value (PC20) and maximal response plateau to inhaled methacholine were studied in 28 pollen-sensitive subjects with mild asthma during a pollen season in a randomized, double-blind, placebo-controlled parallel fashion. They were challenged with methacholine (up to 200 mg.ml-1) in February (preseasonal assessment) and during the middle of the pollen season (in May and again in June). Subjects treated with budesonide (n = 13) were protected from the decrease in PC20 seen in the placebo (n = 15) group (geometric mean PC20 placebo group: preseasonal = 8.51, May = 2.19 and June = 1.78 mg.ml-1; budesonide group: preseasonal = 3.71, May = 3.23 and June = 2.40 mg.ml-1; intergroup differences in doubling concentrations, p < 0.05). Among 10 subjects in the placebo group who reached plateau during the preseasonal assessment, seven lost the plateau in May and six in June. In the budesonide group, among seven subjects who reached plateau during the preseasonal assessment, three lost the plateau in May and four in June. Between-group differences were not significant. We conclude that in pollen-sensitive subjects with mild asthma, inhaled budesonide blocks the effects of natural allergen exposure on the methacholine threshold value.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Sensitive assay for hormone-sensitive lipase using NBD-labeled monoacylglycerol to detect low activities in rat adipocytes.

The recent finding that p-nitrobenzofurazan (NBD)-FA is incorporated into and released from the acylglycerols of isolated rat adipocytes in an insulin-sensitive manner [G. Muller, H. Jordan, C. Jung, H. Kleine, and S. Petry. 2003. Biochimie. 85: 1245-1246] suggests that NBD-FA-labeled acylglycerols are cleaved by rat adipocyte hormone-sensitive lipase (HSL) in vivo. In the present study, we developed a continuous, sensitive in vitro lipase assay using a monoacylglycerol (MAG) containing NBD (NBD-MAG). NBD-MAG was found to provide an efficient substrate for rat adipocyte and human recombinant HSL. Ultrasonic treatment applied in the presence of phospholipids leads to the incorporation of NBD-MAG into the phospholipid liposomes and to a concomitant change of its spectrophotometric properties. The enzymatic release of NBD-FA and its dissociation from the carrier liposomes is accompanied by the recovery of the original spectrophotometric characteristics. The rate of lipolysis was monitored by measuring the increase in optical density at 481 nm, which was found to be linear with time and linearly proportional to the amount of lipase added. To assess the specific activity of recombinant HSL, we determined the molar extinction coefficient of NBD-FA under the assay conditions. This convenient assay procedure based on NBD-MAG should facilitate the search for small molecule HSL inhibitors.

Adipocytes↗

Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach-Zehnder configuration.

A high-sensitivity surface plasmon resonance (SPR) biosensor based on the Mach-Zehnder interferometer design is presented. The novel feature of the new design is the use of a Wollaston prism through which the phase quantities of the p and s polarizations are interrogated simultaneously. Since SPR affects only the p polarization, the signal due to the s polarization can be used as the reference. Consequently, the differential phase between the two polarizations allows us to eliminate all common-path phase noise while keeping the phase change caused by the SPR effect. Experimental results obtained from glycerin-water mixtures indicate that the sensitivity limit of our scheme is 5.5 x 10(-8) refractive-index units per 0.01 degrees phase change. To our knowledge, this is a significant improvement over previously obtained results when gold was used as the sensor surface. Such an improvement in the sensitivity limit should allow SPR biosensors to become a possible replacement for conventional biosensing techniques based on fluorescence. Monitoring of the bovine serum albumin (BSA) binding reaction with BSA antibodies is also demonstrated.

Antigen-Antibody Complex↗

Multiple chemical sensitivities--chemical sensitivity as a symptom of airway inflammation.

The term multiple chemical sensitivity confuses etiology with diagnosis. Chemical sensitivity is a symptom expressed by patients. The symptoms complex is also expressed by the majority of patients with asthma reactive airway dysfunction syndrome or rhinitis following a single acute exposure, called reactive upper airway dysfunction syndrome. The chemically sensitivity patient merits evaluation for upper airway and bronchial reactivity that may cause extra-airway symptomatology.

Humans↗

Plasma membrane properties regulating the sensitivity of leukemia, lymphoma, and solid tumor cells to merocyanine 540-sensitized photoirradiation.

Merocyanine 540 (MC 540) is a photosensitizing dye that has been used in a phase I clinical trial for the purging of leukemia and lymphoma cells from autologous bone marrow grafts. In this paper we examine the role of plasma membrane negative charge, plasma membrane fluidity, and plasma membrane hydrophobicity in the regulation of a cell's susceptibility to MC 540-sensitized photoirradiation. Among solid tumor cells, we found an inverse correlation between surface electronegativity, affinity for dye molecules, and susceptibility to MC 540-sensitized photoinactivation. That is, the least electronegative cells bound the highest amount of dye and were the most susceptible to dye-sensitized photoirradiation. By contrast, no such correlations were found among leukemia/lymphoma cells. This suggested that dye binding and susceptibility to MC 540-mediated photodynamic damages are regulated differently in hematopoietic/lymphopoietic and solid tumor cells.

Bone Marrow↗

Antibiotic sensitivity of enterobacteriaceae by disc diffusion and rapid fermentation sensitivity test methods.

A total of 400 strains of Gram negative bacilli were examined both by conventional disc diffusion (DD) and by rapid fermentation sensitivity test (RFST) methods. Various strains which were examined included Esch. coli Kleb. aerogenes, Kleb. pneumoniae, Prot. vulgaris, Prot. mirabilis, Prot. morgani, Prot. rittgeri and Providencia. The antibiotics used were streptomycin, chloramphenicol, kanamycin, gentamycin and ampicillin. The correlation between the two methods was found to vary from 75 to 98 per cent. By RFST method the results are obtained within six hours. The limitations of this method are (i) it cannot be used for Pseudomonas aeruginosa as it does not ferment glucose, (ii) it cannot be used for antibiotics active only at acidic pH like tetracycline and (iii) partial or intermediate sensitivity cannot be tested by this method. On the other hand, it is a simple, inexpensive, rapid and reliable method feasible in small laboratories also. The results are not affected by the size of inoculum or quality of medium (agar) used. Thus, it is very helpful especially when immediate antibiotic sensitivity is required.

Diffusion↗

Drug sensitization, substance abuse, and chemical sensitivity.

Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. Much has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper.

Adaptation, Physiological↗

A unique and sensitive ELISA technique for typing ABH antigens in bloodstains using UEA-I lectin--the removal of detergent with a Sephadex G-25 mini-column improves sensitivity.

A unique sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of ABH antigens in bloodstains has been developed. Human anti-A and -B antisera and Ulex europaeus anti-H lectin were coated on the inner surface of microplate wells. The sample antigens from bloodstains, solubilized with n-octyl-beta-D-glucopyranoside which was then removed by passing through a Sephadex G-25 (G-25) mini-column, were placed in the wells. After washing the wells repeatedly, peroxidase-conjugated Ulex europaeus lectin I was added and incubated. Antigen activities were determined by the development of colors using o-phenylenediamine/H2O2. This technique permitted clear detection of all ABH antigens corresponding to the antisera and lectin with high sensitivities. The A and B antigens were solubilized as aggregates with H antigen from the erythrocyte membrane. Excess detergent remaining in the sample reduced the sensitivity and accuracy of this ELISA, probably due to the removal of antibody from the wells by the effect of the surfactant. The treatment of solubilized antigens with G-25, an indispensable step, eliminated the adverse effect of the detergent on the ELISA. The ELISA method reported here was proved to be easy, economical and sensitive, and this technique should be useful in the forensic practice.

ABO Blood-Group System↗

Olfactory sensitivity, nasal resistance, and autonomic function in patients with multiple chemical sensitivities.

A frequent, if not predominant, complaint of persons reporting symptoms of multiple chemical sensitivities (MCS) is that of heightened sensitivity to smells. In this study odor detection thresholds for phenyl ethyl alcohol (a major component of rose oil) and methyl ethyl ketone (a common solvent) were measured in 18 persons exhibiting symptoms of MCS and in 18 matched normal controls. In addition, nasal resistance, blood pressure, heart rate, and respiration rate were determined before and after the olfactory tests. Scores on the Beck Depression Inventory were obtained prior to testing. Although olfactory thresholds were equivalent in the two study groups, the MCS group evidenced significantly higher nasal resistances, respiration rates and Beck Depression Inventory scores. Decreases in systolic blood pressure and pulse were noted in both groups across the test sessions. These results do not support the hypothesis that MCS is associated with greater olfactory threshold sensitivity (at least to the two target chemicals), but do suggest that MCS is associated with depression, increased respiration rate, and decreased nasal airway patency.

Adult↗

Sensitivity of cultured cells to gamma radiation in a patient exhibiting marked in vivo radiation sensitivity.

An apparently normal 13-year-old girl developed multiple severe complications over several years after radiation therapy for Stage IIB Hodgkin's disease, including hypothyroidism, esophageal stenosis, restrictive lung and pericardial disease, extrahepatic biliary fibrosis, and sudden death presumed secondary to a myocardial infarction. Cultured skin fibroblast cells from the patient exhibited marked sensitivity to gamma radiation in vitro. The D0 of the radiation survival curve (the inverse of the straight line portion of the curve and that dose of radiation which theoretically leads to one lethal hit per cell) was 89 cGy, compared to a mean D0 for nine normal individuals of 155 cGy, and 85 cGy for two patients with the radiation sensitive disease ataxia-telangiectasia (AT). Profound clinical heterogeneity in response to cancer therapeutic agents may exist, with some individuals who show no signs or symptoms of DNA repair deficiency (for example, as is manifested by individuals with AT) exhibiting marked in vivo and in vitro sensitivity to certain DNA-damaging agents.

Adolescent↗

Supramolecular photochirogenesis in sensitizing chiral nanopore: enantiodifferentiating photoisomerization of (Z)-cyclooctene included and sensitized by POST-1.

By using homochiral mesoporous POST-1 (Scheme 1) as an inherently chiral sensitizing host, supramolecular enantiodifferentiating photoisomerizations of (Z)-cyclooctene (1Z) were performed for the first time to examine the sensitizing ability of the chiral nanopores, walls of which are decorated with pyridine chromophore. The homochiral nanopores of POST-1 crystals were demonstrated to function as an effective chiral-sensitizing cavity to give the optically active (E)-isomer 1E in up to 5% enantiomeric excess (ee), thus expanding the scope of porous material-mediated chirogenesis to both ground and excited electronic states.

Journal Article↗

The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese.

BACKGROUND: Insulin sensitivity (SI), glucose sensitivity (SG), acute insulin response to glucose load (AIR), and obesity in adolescent type 2 diabetes patients (young diabetes, YDM) in Taiwan were studied. METHODS: Forty patients diagnosed at <22 years of age were enrolled and divided into non-obese (NOYDM, BMI < 27 kg/m(2)) and obese groups (OBYDM BMI > 27 kg/m(2)). Adult-onset type 2 diabetes patients (ADM) >40 years old (n = 41) and nondiabetic young adults (N) (n = 23) served as controls. Fasting plasma lipids, insulin, and glucose were measured. Homeostasis model assessment was calculated to estimate insulin sensitivity and beta-cell function. A frequent-sampled intravenous glucose tolerance test was performed to evaluate SI, SG, and AIR. RESULTS: SI and AIR were significantly lower in YDM and ADM than in N (0.92 +/- 0.13, 0.8 +/- 0.15 and 3.24 +/- 0.47 x 10(-4)/U/mL for SI; 40.3 +/- 20.3, 107.3 +/- 50.2, 1208 +/- 306.3 uU/min for AIR). SG of YDM and ADM were lower compared with N (0.014 +/- 0.00138, 0.0292 +/- 0.0058 vs 0.034 +/- 0.0086 min(-1) respectively). No difference was noted between YDM and ADM. SI and SG were not different in NOYDM and OBYDM. AIR was higher in OBYDM (83.6 +/- 34.3 vs -7.6 +/- 13.66 uU/min). CONCLUSIONS: YDM had defects in SI, SG, and AIR compared to N, which was similar to the pathophysiology of ADM. The results imply that YDM may be either a different subtype of diabetes or the same type of diabetes as ADM, with severe defects associated with earlier age of onset. OBYDM had higher AIR than NOYDM.

Adult↗

Differential sensitivity of multi-drug-resistant and -sensitive cells to resistance-modifying agents and the relation with reversal of anthracycline resistance.

Calcium channel blockers, calmodulin inhibitors, and some other classes of non-related compounds reverse multi-drug resistance. In the present study, we found that several resistance modifiers are more toxic for MDR cells than for the corresponding sensitive parent cells, whereas others show the opposite effect. Several calcium channel blockers including bepridil, diltiazem, nifedipine and verapamil, as well as the calmodulin inhibitor trifluoperazine, were more toxic for several MDR cell lines than for the parent cell lines. In contrast, cross-resistance for cyclosporin A and the verapamil analogue Ro II-2933/001 was observed in the MDR/sensitive cell couple CHRC5/AUXB1, probably due to a concentration-dependent stimulation of cell growth in the range of 0-4 microM cyclosporin A and of 1-4 microM Ro II-2933/001. In partially revertant CHRC5 cells, growth inhibition by Ro II-2933/001 at concentrations below I microM, as seen in CHRC5 cells, changed into growth stimulation, and the collateral sensitivity to verapamil and bepridil disappeared almost completely. In the MDR cells CHRC5, 2780AD and DC3F/DMXX, cross-resistance to another calcium channel blocking agent, Ro II-1781/001 (tiapamil), was observed as well. This compound showed exceptional behavior: it induced marked potentiation of Dx cytotoxicity as well as stimulation of Dx accumulation in AUXB1 cells, even at low tiapamil concentrations, but not in the CHRC5 cells, even at high concentrations. It is concluded that resistance modifiers can selectively influence growth of MDR cells via more than one process, and resulting in either strong growth inhibition in MDR cells relative to the effect on sensitive cells or in growth stimulation.

Animals↗

Reduction of artifacts by optimization of the sensitivity map in sensitivity-encoded spectroscopic imaging.

Sensitivity-encoded spectroscopic imaging (SENSE-SI) reduces scanning time by using multiple coils for parallel signal acquisition. Significant artifacts could be induced by SENSE-SI, mainly due to the low-resolution nature of spectroscopic imaging. The present study introduces a novel method to reduce the artifacts. High-resolution sensitivity maps are used in low-resolution SENSE reconstruction. An intermediate unaliased image is obtained after SENSE reconstruction. Based on the intermediate image, the sensitivity maps are optimized and then the SENSE reconstruction is performed again. The final unaliased image has significantly reduced artifacts.

Algorithms↗

Nonspecific regulatory mechanism of contact sensitivity: nonspecific suppressor factor suppresses the antigen-presenting activity of dendritic cells to induce contact sensitivity.

Nonspecific suppressor factor (NSF), which inhibits the passive transfer of contact sensitivity (CS), is produced from macrophage-like cells induced by oxazolone-conjugated spleen cells. NSF binds selectively to Ia-positive, cyclophosphamide-sensitive, and plastic-adherent non-T cells (named intermediate cells) present in the spleen. NSF-treated intermediate cells acquire the ability to suppress the passive transfer of CS nonspecifically. Because the phenotype of the intermediate cells is similar to that of antigen-presenting cells (APC) of macrophage lineage, we examined the effect of NSF on APC. NSF suppressed the APC activity of draining lymph node cells from mice sensitized with fluorescein isothiocyanate or picryl chloride (FITC-LNC or TNP-LNC) to induce CS. Suppressor molecules which suppress the passive transfer of CS and the APC activity were recovered in the same fraction around 43 kDa by dye-affinity and gel chromatography purification. The results that the suppressor activity of NSF was absorbed with lymph node cells or FITC-LNC, but not 33D1 or anti-Ia monoclonal antibody plus complement-treated FITC-LNC indicated that NSF reacts directly with antigen-bearing dendritic cells in the draining lymph node. In contrast with spleen cells, lymph node cells did not have the intermediate function, i.e., NSF-treated LNC could not suppress the passive transfer of CS nor the ability of FITC-LNC to induce CS (APC activity). NSF still blocks the ability of FITC-LNC to induce CS after treatment with cyclophosphamide. Thus, the lymph node and spleen include distinct functional cell populations which express Ia antigen and interact with NSF. APC in the draining lymph node are downregulated directly by NSF and the intermediate cells in the spleen play a modulatory role in the suppressor pathway of NSF.

Absorption↗

Capsaicin sensitive nerves in the jejunum of Nippostrongylus brasiliensis-sensitized rats participate in a cardiovascular depressor reflex.

Superfusion of capsaicin onto the serosal surface of jejunum of Nippostrongylus brasiliensis-sensitized rats induces a short-lasting (1-3 min), dose-dependent (2 to 20 micrograms) decrease in blood pressure which ranges from -5.3 +/- 1.4% to -22.6 +/- 2.2%. The hypotension evoked by capsaicin was more marked in sensitized rats than in unsensitized animals, which responded only to the highest dose (20 mg) of capsaicin tested. The hypotensive effects of capsaicin were not affected by intravenous injections of mepyramine (10 mg/kg), a histamine receptor antagonist, or by the cyclooxygenase inhibitor indomethacin (10 mg/kg). However, an intravenous injection of a platelet-activating factor (PAF) antagonist, BN 52021 (20 mg/kg), or an intraperitoneal injection of guanethidine (8 mg/kg) 18 h prior to experimentation, to functionally impair the sympathetic nerves, abolished the capsaicin-induced drop in blood pressure. Treatment of neonatal rats with capsaicin reduced by 75% the hypotensive effects of capsaicin, whereas the capsaicin antagonist, ruthenium red, reduced non-significantly the hypotensive action of capsaicin. It is concluded that the activation of jejunal sensory nerves in N. brasiliensis-sensitized rats by capsaicin induced a reflex hypotension that is dependent upon PAF release from mast cells and functional sympathetic nerves. In addition, the afferent function of the sensory nerves are not totally blocked by ruthenium red as capsaicin elicits the reflex hypotension in the presence of this blocker of sensory nerve efferent function.

Anaphylaxis↗