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At least 631 records · Page 35Linked to original sources
PubMed1987

Analysis of visual modulation sensitivity. III. Meridional variations in peripheral flicker sensitivity.

Critical flicker frequency (CFF) and modulation sensitivity were measured throughout the visual field as a function of meridian, eccentricity, and luminance. The stimulus conditions were designed to excite preferentially the long-wavelength-sensitive (R) cones in equal numbers at each retinal location. Temporal-frequency responses under these conditions can be partitioned into two components by following the analysis of Kelly [J. Opt. Soc. Am. 51, 422 (1961)]: a high-frequency linear component unaffected by the mean luminance level and a nonlinear adaptive component that conforms to Weber's law of proportionality to luminance. The results suggest that the time constant of the linear component varies to some extent with meridian at a constant eccentricity, in addition to the substantial increase with eccentricity along all meridians. Retinal variations in sensitivity of the nonlinear, adaptive aspect of the visual response were small when equal numbers of cones were stimulated, and the variations did not account for the changes in CFF with either eccentricity or meridian.

Humans↗
PubMed2006

Highly sensitive long-period fiber-grating strain sensor with low temperature sensitivity.

A long-period fiber-grating sensor with a high strain sensitivity of -7.6 pm/microepsilon and a low temperature sensitivity of 3.91 pm/ degrees C is fabricated by use of focused CO(2) laser beam to carve periodic grooves on a large- mode-area photonic crystal fiber. Such a strain sensor can effectively reduce the cross-sensitivity between strain and temperature, and the temperature-induced strain error obtained is only 0.5 microepsilon/ degrees C without using temperature compensation.

Journal Article↗
PubMedDate not supplied

Photochemical behavior and Na+,K+-ATPase sensitivity of voltage-sensitive styrylpyridinium fluorescent membrane probes.

RH421 is a widely used voltage-sensitive fluorescent membrane probe. Its exposure to continuous illumination with 577 nm light from an Hg lamp leads, however, to an increase in its steady-state fluorescence level when bound to lipid membranes. The increase occurs on the second time scale at typical light intensities and was found to be due to a single-photon excited-state isomerization. Modifications to the dye structure are, therefore, necessary to increase photochemical stability and allow wider application of such dyes in kinetic studies of ion-transporting membrane proteins. The related probe ANNINE 5, which has a rigid polycyclic structure, shows no observable photochemical reaction when bound to DMPC vesicles on irradiation with 436 nm light. The voltage sensitivity of ANNINE 5 was tested with the use of Na+,K+-ATPase membrane fragments. As long as ANNINE 5 is excited on the far red edge of its visible absorption band, it shows a similar sensitivity to RH421 in detecting charge-translocating reactions triggered by ATP phosphorylation. Unfortunately the wavelengths necessary for ANNINE 5 excitation are in a region where the Hg lamps routinely used in stopped-flow apparatus have no significant lines available for excitation.

Journal Article↗
PubMed2001

Sensitization to the cytotoxicity of melphalan by ethacrynic acid and hyperthermia in drug-sensitive and multidrug-resistant Chinese hamster ovary cells.

The ability of physical and pharmacological modulators to increase the cytotoxicity of melphalan was investigated in Chinese hamster ovary cells using a clonogenic cell survival assay. Hyperthermia has potential for use in cancer treatment, particularly as an adjuvant to chemotherapy or radiotherapy. Ethacrynic acid is a glutathione S-transferase inhibitor and also undergoes conjugation with glutathione. Interactions between hyperthermia (41-43 degrees C), ethacrynic acid and melphalan were evaluated in multidrug-resistant (CH(R)C5) cells with overexpression of P-glycoprotein (33.69-fold), and in drug-sensitive (AuxB1) cells. GST alpha was expressed at a higher level (3.65-fold) in CH(R)C5 cells than in sensitive cells, whereas levels of isoforms pi and mu were the same. GST pi was the most highly expressed isoform in the two cell populations. Ethacrynic acid was cytotoxic at elevated temperatures, while it caused little or no cytotoxicity at 37 degrees C. This effect occurred in drug-resistant and drug-sensitive cells, and attributes thermosensitizing properties to ethacrynic acid. Ethacrynic acid (20 microM) alone did not alter the cytotoxicity of melphalan at 37 degrees C. Hyperthermia potentiated drug cytotoxicity in cells, both with and without ethacrynic acid treatment. Ethacrynic acid could be useful in cancer treatment by acting as a thermosensitizer when combined with heat and by enhancing the cytotoxicity of melphalan at elevated temperatures. A major advantage arising from the use of regional hyperthermia is the ability to target drug cytotoxicity to the tumor volume. A useful finding is that ethacrynic acid, heat and/or melphalan are also effective against multidrug-resistant cells with overexpression of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Impaired glucose sensitivity of ATP-sensitive K+ channels in pancreatic beta-cells in streptozotocin-induced NIDDM rats.

ATP-sensitive K+ channels (KATP channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic beta cells. In order to examine the possible impairment of KATP channel function in non-insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the KATP channels in single beta cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic beta-cells was virtually identical to that in control beta cells and there was no difference in the sensitivity to ATP and glibenclamide of KATP channels between the NIDDM and control groups. In response to glucose, the activity of the KATP channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the KATP channels in beta-cells of NSZ rats was significantly less than that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single KATP channels were consistently observed in cell-attached patch membranes of diabetic, but not control, beta-cells. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells in NSZ rats is associated with a reduced sensitivity of the KATP channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism.

Adenosine Triphosphate↗
PubMedDate not supplied

Heat sensitivity of bleomycin-sensitive CHO derivatives is not due to improper initialization of heat shock response.

We have investigated whether differences in the heat shock response exist between CHO and three bleomycin-sensitive, heat-sensitive CHO derivatives. The binding of heat shock factor (HSF) in response to heat and varying concentrations of bleomycin in the four cell lines was examined using a gel shift assay and a synthetic heat shock element (HSE). Heat (45 degrees C, 10 min) and exposure to 1 micrograms/ml bleomycin for 1 h at 37 degrees C induced similar levels of HSF binding in all four cell lines. We also examined if bleomycin dose and the length of recovery from bleomycin treatment affected the induction of HSF binding. The level of activated HSF binding to HSE was higher in cells treated with low doses (1 ng/ml) of bleomycin than in cells treated with 1 or 25 micrograms/ml bleomycin. The amount of activated HSF was directly proportional to the time elapsed since bleomycin treatment. Our results therefore indicate no difference between CHO and its bleomycin-sensitive derivatives in the ability to initiate the heat shock response as determined by the production of activated HSF in response to either heat or bleomycin. We conclude that the intrinsic thermosensitivity of these cell lines is not related to the early response to heat shock, but either occurs later in the pathway or is unrelated to events after heating.

Animals↗
PubMed1991

Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity.

Non-acetylated salicylates have been recommended for use as alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) in aspirin and/or tartrazine-sensitive patients. We experienced a case of an aspirin-sensitive asthmatic patient who developed a broncho-obstructive reaction after taking 100 mg of sodium salicylate. The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients.

Aspirin↗
PubMed2002

Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine.

Methylphenidate (MP) (ritalin) is widely used in the treatment of children and adolescents with attention deficit hyperactivity disorder, but little is known about therapeutic mechanisms or about possible consequences of long-term exposure. To more closely simulate the clinical use of the drug, we orally administered MP to adolescent rats during the dark-active phase of the circadian cycle at doses (0.75-3.0 mg/kg) below threshold for locomotor activation. We found that doses in this range increased extracellular norepinephrine in hippocampus without affecting dopamine in nucleus accumbens. These results suggest that norepinephrine systems may play an important role in the therapeutic action of this drug. To examine one potential consequence of long-term exposure to MP, i.e., the development of locomotor sensitization, an adaptational change that has been implicated in drug abuse liability, animals received three daily oral administrations of these doses of MP for up to 4 weeks through adolescence. The animals were then challenged with methamphetamine (0.5 mg/kg). We found that the behavioral response to MP did not change during the course of chronic treatment and that MP-pretreated animals did not exhibit a sensitized locomotor response to the methamphetamine challenge. We propose that, to the extent that this treatment protocol more closely reflects clinical exposure patterns, the relative insensitivity of accumbens dopamine to the acute administration of these MP doses, and the corresponding absence of evidence for the development of locomotor sensitization, supports one clinical view that there is little abuse liability associated with low dose, long-term MP treatment.

Administration, Oral↗
PubMed1999

Induced production of nitric oxide and sensitivity of alveolar macrophages derived from mice with different sensitivity to Coxiella burnetii.

We compared in vitro sensitivities to Coxiella burnetii of alveolar macrophages, derived from mice sensitive and resistant to C. burnetii, respectively, and examined the role of nitric oxide (NO) in the C. burnetii infection. Alveolar macrophages of sensitive A/J mice showed a larger population of C. burnetii antigen-positive cells than those of resistant C57BL/6 mice. C. burnetii induced NO production in alveolar macrophages, but N-methyl-L-arginine and sodium nitroprusside (SNP), NO inhibitor and donor, respectively, did not inhibit the infection. Thus the NO induction seems to be independent of the cell defense mechanism against the C. burnetii infection.

Animals↗
PubMedDate not supplied

The safety of calcitriol 3 microg/g ointment. Evaluation of cutaneous contact sensitization, cumulative irritancy, photoallergic contact sensitization and phototoxicity.

Vitamin D analogues are widely used for the treatment of psoriasis. A new topical formulation of calcitriol (3 microg/g ointment) has been shown to be effective in the treatment of stable plaque-type psoriasis. This paper reports the results of four separate studies designed to evaluate specific local-safety parameters: cumulative irritancy, cutaneous contact sensitization, potential photoallergic contact sensitization and phototoxicity. Calcitriol 3 microg/g ointment was classified as non-irritant when compared to calcipotriol, tacalcitol and white petrolatum. Petrolatum and tacalcitol were slightly irritant and calcipotriol moderately irritant. No sensitization was observed with calcitriol 3 microg/g ointment. With regard to phototoxic potential, sites treated with calcitriol 3 microg/g ointment or vehicle ointment were less irritated than those treated with white petrolatum or those that were untreated. Using standard photoallergenicity testing methodology, there were no skin reactions of a photoallergic nature to the study material. These studies showed that calcitriol 3 microg/g ointment is a well-tolerated treatment for stable plaque-type psoriasis.

Administration, Topical↗
PubMed1992

Oligomycin sensitivity-conferring protein (OSCP) of mitochondrial ATP synthase. The carboxyl-terminal region of OSCP is essential for the reconstitution of oligomycin-sensitive H(+)-ATPase.

Studies to establish the structure/function relationships of oligomycin sensitivity-conferring protein (OSCP) of mitochondrial ATP synthase were carried out using genetic engineering and biochemical approaches. A full-length cDNA clone encoding OSCP was isolated from a bovine heart cDNA library, and the mature form of OSCP was expressed in Escherichia coli using plasmid expression vector pKP1500. Recombinant OSCP was found to accumulate in the cytoplasmic inclusion bodies, by virtue of which the recombinant protein could be purified to greater than 85% purity by simple low speed centrifugation of cell lysates. Recombinant OSCP was found to be indistinguishable from OSCP isolated from mitochondria with respect to (i) apparent molecular mass on sodium dodecyl sulfate gel electrophoresis, (ii) immunological reactivity to anti-OSCP serum, (iii) biological activity in restoring oligomycin-sensitive ATPase and Pi-ATP exchange activities to OSCP-depleted ATP synthase complexes, and (iv) insensitivity of the biological activity to sulfhydryl-directed alkylating reagents. The amino-terminal sequence of the recombinant protein revealed that the initiating methionine was not removed by E. coli, although that apparently did not affect protein folding or its biological activity. Data on nested deletion mutations starting from the carboxyl terminus in OSCP demonstrated that, in each instance, the mutant form was expressed and the protein product was sequestered in cytoplasmic inclusion bodies, similar to the wild-type form. However, none of the variants, including the one in which only the last 10 residues were deleted, was able to restore cold-stable oligomycin-sensitive ATPase or Pi-ATP exchange activity in OSCP-depleted complexes. Taken together, these data suggest that amino acid residues 181-190 (or some of the residues in this region) in the OSCP sequence may be important for OSCP-F1 interactions.

Adenosine Triphosphatases↗
PubMedDate not supplied

Effect of the tiapamil analog RO11-2933 on cellular sensitivity to antitumor drugs in sensitive and multidrug resistant human ovarian cancer cells.

The ability of the Tiapamil analog N-(3,4 Dimethoxyphenyl)-N-methyl-2-(naphthyl)-m-dithiane-2-propylamine hydrocloride (RO11-2933) to influence the cytotoxic activity of Doxorubicin (DX) and seven other antitumor agents was evaluated in sensitive and treatment-induced multidrug resistant human ovarian cancer cells. In vitro treatment of A2780 sensitive cells with 1 microM RO11-2933 for 72hr potentiated by less than 3-fold the cytotoxic effects of each antitumor drug tested, with the exception of Cisplatin and Fluorouracil, which were potentiated by 7.2- and 5.0-fold, respectively. In A2780-DX3 resistant cells, RO11-2933 increased by a mean of 50-fold the cytotoxic effects of the anthracyclines and the Vinka alkaloids analyzed. A potentiation of Cisplatin activity was also observed (6.5-fold), whereas the Tiapamil analog did not significantly modify the antiproliferative activity of Bleomycin, Fluorouracil or Ara-C. Analysis of DX uptake and retention showed that in resistant cells RO11-2933 restored the intracellular DX content to levels comparable to those of sensitive A2780 cells, suggesting that the cytoplasmic membrane might represent a possible site of action of this compound. The results obtained indicate that RO11-2933 might represent an effective agent in combination with several anticancer drugs for the treatment of drug resistant ovarian carcinomas.

Antineoplastic Agents↗
PubMed1988

Comparison of radially sensitive and circumferentially sensitive microtransducer esophageal manometry probes in normal subjects.

Circumferentially sensitive microtransducer probes are commercially available for use in esophageal manometry, and may offer an advantage over radially sensitive microtransducer probes in sphincters with radial asymmetry. In order to compare performance of the two probes, we performed esophageal manometry in 30 healthy adult volunteers with both probes. In only three of 52 manometric parameters measured were differences between mean values for the two probes statistically significant. Intrasubject variability was significantly (p = less than 0.005) less with the circumferentially sensitive probe (coefficient of variation 37% vs. 53%).

Adult↗
PubMed1983

Studies on the mechanism of natural killer cytotoxicity. II. coculture of human PBL with NK-sensitive or resistant cell lines stimulates release of natural killer cytotoxic factors (NKCF) selectively cytotoxic to NK-sensitive target cells.

This investigation has employed the "innocent bystander" type of experimental design to determine whether soluble cytotoxic factor(s) are released during interactions between human peripheral blood lymphocytes (PBL) and NK-sensitive target cells. PBL cocultured with NK-sensitive Molt-4 or K562 target cells in the lower well of a miniaturized Marbrook culture released natural killer cytotoxic factors (NKCF), which diffused across a 0.2-mu Nucleopore membrane and lysed Molt-4 or K562 target cells cultured in the upper chamber. Coculture of PBL with the NK-resistant Raji or WI-L2 cell lines also induced release of NKCF. These factors were selectively cytotoxic to NK-sensitive targets and lysed Molt-4 and, to a lesser extent, K562 cells. However, Raji, WI-L2, and RPMI 1788 cells were all resistant to lysis. In addition, low density fractions from Percoll density gradients that were enriched for NK effector cells also released increased levels of NKCF during coculture with Molt-4 cells. Lysis of Molt-4 and K562 targets was observed after exposure to NKCF for 48 hr and 60 to 70 hr, respectively. Cellfree supernatants containing NKCF were obtained after a short time of incubation (i.e., within 5 hr of coculture of PBL with NK target cells). The factors were nondialyzable, stable at 56 degrees C for 3 hr, and showed partial loss of activity on storage at 4 degrees C or -20 degrees C for 7 days. These data suggest that NKCF may be involved in the lytic mechanism of human NK cell-mediated cytotoxicity.

Cell Line↗
PubMed1983

Visual fields described by contrast sensitivity, by acuity, and by relative sensitivity to different orientations.

Sinewave grating contrast sensitivity was measured as a function of eccentricity and azimuthal angle for four orientations of gratings whose spatial frequencies ranged from 2 to 20 c/deg. Visual fields for cutoff spatial frequency were also mapped. Log contrast sensitivity fell off approximately linearly with eccentricity for all azimuths. Orientational differences in contrast sensitivity varied irregularly over the visual field and, though small for central vision, could reach as high as 25 dB in localized patches at eccentricities greater than about 12 degrees.

Adult↗
PubMed1980

Distribution of immunogenic cells after painting with the contact sensitizers fluorescein isothiocyanate and oxazolone. Different sensitizers form immunogenic complexes with different cell populations.

The distribution of fluorescent cells in the draining lymph nodes of mice painted with the contact sensitizing agent fluorescein isothiocyanate (FITC) was investigated using a fluorescence-activated cell sorter. Up to 30% of the cells were fluorescent after 18 h and this decreased thereafter becoming undetectable after 4-5 days. Most of the fluorescent cells were morphologically lymphocytes, theta - ve and adherent to nylon wool. Immunogenicity of these cells was tested by injecting them into the footpads of normal mice and measuring contact sensitivity after 6 days. This was restricted to large cells which represented less than 5% of the white cell population and nearly all of which became fluorescent after skin painting. The large fluorescent cells were a mixture of monocytes and lymphocytes. Most of the lymphocytes had surface immunoglobulin. The immunogenicity was reduced by nylon filtration but was not affected by silica and anti-theta. These results showed that the immunogenicity is not associated with T cells. In contrast, similar immunogenic activity in the draining lymph nodes of mice painted with oxazolone is associated with T cells. The results therefore showed that different sensitizers form immunogenic complexes with different cell populations, perhaps in this case becuase of the different water solubilities of FITC and oxazolone. They also suggested that this may cause important differences in antigen presentation, for example in their association with different MHC products.

Animals↗
PubMed1981

Lymphocyte sensitization detected by the macrophage electrophoretic mobility assay in patients with renal cell carcinoma: Theophylline increases the sensitivity of the assay.

An antigen-induced release of a macrophage slowing factor (MSF) by peripheral blood lymphocytes was used to evaluate lymphocyte sensitization to various antigens in 30 patients with renal cell carcinoma (RCC) and in 14 normal individuals. Twenty-three of 30 (77%) patients with RCC, but no healthy controls were found to be sensitized to a soluble antigen prepared from an allogeneic kidney tumor by 3 M potassium chloride extraction. Peripheral blood lymphocytes from some patients with RCC displayed sensitization to protein isolated from fetal kidney (6 of 24; 25%), control "normal" kidney (6 of 30; 20%) and urinary bladder carcinoma (3 of 21; 14%) tissues. It has been suggested that cyclic adenosine 3' ,5'-monophosphate (cyclic AMP) could play a role in the mechanism of the MSF action (24). In agreement with this idea, the presence of 10-4 M theophylline enhanced the macrophage electrophoretic mobility (MEM) reduction caused by MSF. Furthermore, the DNA synthesis in lymphocytes (monitored by measuring the uptake of tritiated thymidine) on contact with phytohemagglutinin (PHA) was depressed in 9 of 21 (43%) patients with RCC as compared with healthy controls.

Adenocarcinoma↗
PubMed1981

Effects of adult thymectomy on the contact sensitivity skin reaction and the unresponsiveness caused by feeding contact sensitizing agents.

Unresponsiveness was produced in mice by three feeds of high doses of oxazolone or picryl chloride. The mice were then sensitized and contact sensitivity assessed by ear swelling. Adult thymectomy prevented the unresponsiveness caused by feeding. In some but not all experiments adult thymectomy also increased the response to a single skin paint. This effect of thymectomy was apparent at 1 week and reached a plateau at 2-3 weeks. The effect of adult thymectomy, on unresponsiveness caused by feeding and its ability to increase the contact sensitivity skin reaction, was reversed by treatment with crude thymosin fraction V.

Animals↗