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PubMed1990

Discontinuous polyacrylamide gel-agarose gel immunoelectrophoresis for analysis of plasma lipoproteins.

A modification of crossed immunoelectrophoresis for the analysis of plasma lipoproteins is described and is called polyacrylamide gel-crossed immunoelectrophoresis. The incorporation of albumin in the first-dimensional gel facilitates the transfer of the larger lipoproteins containing apolipoprotein B from the first-dimensional gel to the second dimension. Furthermore, under this condition the quantitation of total apolipoprotein B by polyacrylamide gel-crossed immunoelectrophoresis is in good agreement with the results obtained by rocket immunoelectrophoresis or nephelometry. The correlation between polyacrylamide gel-crossed immunoelectrophoresis and rocket immunoelectrophoresis is good for total apolipoprotein B (p greater than 0.001) and apolipoprotein A-I (p greater than 0.001). Polyacrylamide gel-crossed immunoelectrophoresis also offers interesting aspects to study the plasma lipoprotein classes and subclasses in different cases: normal plasma, current and complex dyslipoproteinemias in the presence or absence of lipoprotein small a. In a case of dyslipoproteinemia of Fredrickson's Type V polyacrylamide gel-crossed immunoelectrophoresis demonstrates the presence of a small-sized Lp (a) major peak in the low density lipoprotein (LDL) zone and of a large-sized Lp (a) minor peak in the very low density lipoprotein (VLDL) zone.

Electrophoresis↗
PubMed1995

Determination of optimally resolving gel concentration and migration time (path) in gel electrophoresis.

The notion of a mathematically defined optimally resolving gel concentration for components of a pair of molecular species of any given size was developed by Rodbard et al. (Electrophoresis and Isoelectric Focusing on Polyacrylamide Gel, pp. 28-62, de Gruyter, Berlin, 1974) 21 years ago. The mathematical treatment was incorporated into a computer program (T-OPT) for mainframe computers which upon input of the slope and intercept on the mobility axis of the Ferguson plots of the two components, electrophoresis time and temperature, yielded plots of resolution vs gel concentration. The same algorithms were later incorporated into the program ELPHOFIT for personal computers. Ideality of diffusion spreading and zero initial zone width were assumed along with a Gaussian peak distribution and an equal area for both components. Moreover, these programs failed to respond to the practical question of the migration time (or path) required for the resolution at the optimal gel concentration, although an independent program predicting the course of resolution under the assumption of free diffusion band spreading in gels (DAR-001) had been devised by Rodbard for application in preparative elution-PAGE. The present work advances the technology for predicting resolving conditions by presenting a computer program which allows the user (i) to predict the gel concentration which is optimal for obtaining the desired degree of resolution at any migration time, (ii) to prescribe the minimal degree of resolution between two band distributions one wishes to achieve, and (iii) to predict the migration time (or path) required at the optimal gel concentration for the resolution of the two components. The program is written in MATLAB and can be used by any computer that supports MATLAB language.

Algorithms↗
PubMed1996

SYPRO orange and SYPRO red protein gel stains: one-step fluorescent staining of denaturing gels for detection of nanogram levels of protein.

We have developed two new fluorescent dyes, SYPRO Orange protein gel stain and SYPRO Red protein gel stain, to detect proteins in electrophoretic gels. Stained protein bands can be excited by ultraviolet light at approximately 300 nm, or at visible wavelengths, with excitation maxima of 472 nm for the Orange stain and 547 nm for the Red stain. Detection can be documented with sensitivity similar to that achieved with silver stain, using standard UV transilluminators and Polaroid 667 black and white film, CCD cameras, or commercially available laser scanners. Staining with these dyes is noncovalent and is accomplished using a one-step procedure. Protein gels do not require fixation steps prior to incubation with the dyes. Staining is complete 30 to 60 min following electrophoresis, with no destaining required. Staining can also be accomplished by including dye in the running buffer; in this case a brief one-step destaining procedure follows electrophoresis. The dyes appear to bind to the detergent coat surrounding proteins in sodium dodecyl sulfate (SDS) denaturing gels; thus, staining in such gels is not strongly selective for particular polypeptides. Fluorescent signals are relatively photostable, allowing multiple photographs of gels to be taken without significant signal reduction.

Animals↗
PubMed1992

In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis.

We examined the different steps necessary for the enzymatic digestion of proteins in the polyacrylamide matrix after gel electrophoresis. As a result, we developed an improved method for obtaining peptides for internal sequence analysis from 1-2 micrograms of in-gel-digested proteins. The long washing-lyophilization-equilibration steps necessary to eliminate the dye, sodium dodecyl sulfate, and other gel-associated contaminants that perturb protein digestion in Coomassie blue-stained gels have been replaced by washing for 40 min with 50% acetonitrile, drying for 10 min at room temperature, and then rehydrating with a protease solution. The washing and drying steps result in a substantial reduction of the gel slice volume that, when next swollen in the protease solution, readily absorbs the enzyme, facilitating digestion. The Coomassie blue staining procedure has also been modified by reducing acetic acid and methanol concentrations in the staining solution and by eliminating acetic acid in the destaining solution. The peptides resulting from the in-gel digestion are easily recovered by passive elution, in excellent yields for structural characterization. This simple and rapid method has been successfully applied for the internal sequence analysis of membrane proteins from the rat mitochondria resolved in preparative two-dimensional gel electrophoresis.

Amino Acid Sequence↗
PubMed2001

Towards global analysis of mammalian proteomes using sample prefractionation prior to narrow pH range two-dimensional gels and using one-dimensional gels for insoluble and large proteins.

The number of unique protein species in proteomes from a single mammalian cell type is not well defined but is likely to be at least 10000-20000. Since standard-size two-dimensional gels typically resolve only about 1500 to 3000 spots, they merely analyze a small portion of these proteomes. In addition, all insoluble proteins and typically proteins > 100 kDa are seldom resolved on two-dimensional (2-D) gels. The current study demonstrates the feasibility of an overall strategy for more comprehensive quantitative comparisons of complex proteomes derived from physiological fluids or mammalian cell extracts. A key feature of this approach is to prefractionate samples into a few well-resolved fractions based on the proteins' isoelectric points (pIs) using microscale solution isoelectric focusing. These fractions are then separated on narrow pH range two-dimensional gels approximately +/- 0.1 pH unit wider than the prefractionated pool. When this prefractionation approach is applied to complex mammalian proteomes, it improves resolution and spot recovery at high protein loads compared with use of parallel narrow pH range gels without prefractionation. The minimal cross-contamination between fractions allows quantitative comparisons in contrast to most alternative prefractionation methods. In addition, complementary data can be obtained by parallel analysis of the solubilized fraction on high-resolution large-pore-gradient one-dimensional gels followed by mass spectrometric identification to analyze proteins between 100 and approximately 500 kDa. Similarly, insoluble proteins can be analyzed using large-pore gels for large proteins and 10-12% one-dimensional sodium dodecyl sulfate (SDS) gels for smaller proteins. Together, these strategies should permit more reliable quantitative comparisons of complex mammalian proteomes where detection of at least 10000 protein spots is needed in order to analyze the majority of the unique protein species.

Animals↗
PubMed1979

Effect of interaction of aluminum hydroxycarbonate gel and magnesium hydroxide gel on acid neutralization.

Acid neutralization by mixtures of aluminum hydroxycarbonate gel and magnesium hydroxide gel differs from the sum of the acid neutralization of each gel. Acid neutralization by magnesium hydroxide gel in the mixture is not observed until after a substantial portion of the aluminum hydroxycarbonate gel has reacted with acid, even though magnesium hydroxide gel is the faster reacting of the two gels. It is hypothesized that amorphous aluminum hydroxycarbonate forms a coating on the crystalline magnesium hydroxide particles due to electrostatic attraction. This coating prevents protons from reaching the highly reactive magnesium hydroxide until the coating is dissolved by the acid neutralization of aluminum hydroxycarbonate.

Acids↗
PubMed2003

A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard.

The comparison of two-dimensional (2-D) gel images from different samples is an established method used to study differences in protein expression. Conventional methods rely on comparing images from at least 2 different gels. Due to the high variation between gels, detection and quantification of protein differences can be problematic. Two-dimensional difference gel electrophoresis (Ettan trade mark DIGE) is an emerging technique for comparative proteomics, which improves the reproducibility and reliability of differential protein expression analysis between samples. In the application of DIGE different samples are labelled with mass and charge matched spectrally resolvable fluorescent dyes and are then separated on the same 2-D gel. Using an Escherichia coli lysate "spiked" with varying amounts of four different known proteins, we have tested a novel experimental design that exploits the sample multiplexing capabilities of DIGE, by including a standard sample in each gel. The standard sample comprises equal amounts of each sample to be compared and was found to improve the accuracy of protein quantification between samples from different gels allowing accurate detection of small differences in protein levels between samples.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2006

Miconazole gel compared with Zataria multiflora Boiss. gel in the treatment of denture stomatitis.

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a miconazole 2% gel compared with Zataria multiflora 0.1% gel applied four times daily for 2 weeks, in the treatment of Candida-associated denture stomatitis. Twenty four patients were included in the study. The efficacy variables were the colony count of Candida from the palatal mucosa and the denture surface and the erythema surface of the palatal mucosa on days 0, 7, 14, 21 and 28 after commencement of therapy. Twelve patients received miconazole gel and twelve Z. multiflora gel. The erythema surface was significantly reduced by both gels. No significant difference was seen between the two groups (p < 0.05). There was a significant reduction in the colony count of the palatal mucosa in both groups (except on days 21 and 28 in the Zataria group p = 0.07 and 0.08). Miconazole treatment reduced the number of denture colonies more efficiently than Z. multiflora except for day 21 when the efficacy of both groups was similar (p = 0.17). The results indicate that Z. multiflora gel reduced the surface erythema of the palate more efficiently than miconazole gel but did not reduce the colony count of the denture surface as efficiently as miconazole.

Aged↗
PubMed1994

Electrophoresis of proteins and protein-protein complexes in native polyacrylamide gels using a horizontal gel apparatus.

Electrophoresis of proteins and protein-protein complexes in polyacrylamide gels under native conditions using a horizontal gel apparatus is described. The advantage of this system is that it permits the detection of both negatively and positively charged proteins as well as protein-protein complexes in the same gel. During electrophoresis, a continuous gel sandwiched between two glass plates is placed horizontally on the platform and submerged in a reservoir buffer. The sample wells are made along the center of the gel, allowing positively and negatively charged proteins to migrate toward the cathode and anode, respectively. Several proteins with varying molecular weights and isoelectric point (pI) values and pairs of proteins capable of forming protein-protein complexes were chosen as model systems to illustrate the methodology. The effects of several parameters on the performance of the gel system including protein molecular weight, pI, and gel concentration were also examined and the results obtained by this method are comparable to those obtained by the vertical system. Following electrophoresis, both negatively and positively charged proteins as well as protein-protein complexes can be transferred by electroblotting onto polyvinylidene difluoride membranes for further analyses.

Electrophoresis, Polyacrylamide Gel↗
PubMed1997

Polyacrylamide gel electrophoresis in discontinuous transverse urea-gradient gels.

Polyacrylamide gel electrophoresis in transverse urea-gradient gels is widely used for the study of changes in conformation and quaternary structure of proteins induced by increasing concentrations of urea. However, possible uncertainties regarding the effective concentration of urea at any given point across the gel must be considered when this technique is used for quantitative purposes. We describe here a simple, practical procedure for preparing urea-gradient gels discontinuously, by stacking various layers of acrylamide solution with increasing urea concentrations. We show that the urea concentration in different lanes of discontinuous gradient gels prepared in this way can be predetermined accurately enough for quantitative purposes and provide as an example the study of the dissociation of thyroglobulin in urea. Various levels of resolution can be attained by this technique. The use of discontinuous gradient gels may extend the usefulness of urea gel electrophoresis in relation with the quantitative aspects of the study of protein conformation.

Electrophoresis, Polyacrylamide Gel↗
PubMed2005

Sustained delivery of bioactive cytokine using a dense collagen gel vehicle collagen gel delivery of bioactive cytokine.

OBJECTIVE: The use of cytokines as localized therapeutic agents is limited by the lack of a satisfactory delivery system. The aim of the current investigation was to determine the release kinetics and bioactivity of a simplified cytokine/collagen gel system designed to achieve extended, local delivery of bioactive cytokines at sites of premature cranial suture fusion (craniosynostosis). DESIGN: Cytokine release was determined by ELISA measurements of Tgf-beta3 collected in media. Cytokine bioactivity was determined by measuring the effect of conditioned media, containing released Tgf-beta3, on mink lung epithelial cell proliferation and osteoblast alkaline phosphatase activity. Osteoblast response was evaluated by measuring proliferation of cells cultured on collagen gel containing Tgf-beta3 using an AlamarBlue assay. RESULTS: Gels loaded with 100 and 500 ng of Tgf-beta3 produced a sustained release over 14 days with a pattern of initial large release followed by a gradual reduction in the amount released over the time. The reduced release over time was correlated to the amount initially loaded. Mink lung epithelial cell assay results indicated that Tgf-beta3 released from the collagen gel retained its bioactivity following incorporation into the collagen gel and release into the media. This bioactivity was further illustrated by a decreased alkaline phosphatase activity measured in osteoblasts cultured on the gels loaded with Tgf-beta3. Osteoblast proliferation assays demonstrated that the collagen gel has an inherent inhibitory effect on osteoblast cell number. CONCLUSIONS: This collagen gel/cytokine delivery system can retain and release bioactive cytokine over a prolonged period. These results will allow for better optimization of future in vitro and in vivo studies directed at improving the treatment of craniosynostosis.

Alkaline Phosphatase↗
PubMed1998

Clinical efficacy of becaplermin (rhPDGF-BB) gel. Becaplermin Gel Studies Group.

The results of four multicenter, randomized, placebo-controlled, parallel group studies of the efficacy of becaplermin gel are reviewed here. The four studies included a total of 922 patients, all of whom received a standardized regimen of good ulcer care. Patients were randomized to receive placebo gel, 30 or 100 microg/g becaplermin gel, or good ulcer care alone. In Studies 1 and 2, the incidence of complete healing was significantly higher in patients receiving becaplermin gel (30 microg/g, Study 1; 100 microg/g, Study 2) compared with that in patients receiving placebo gel. In Study 3, which was not powered for statistical analysis, the incidence of complete healing in patients treated with 100 microg/g becaplermin gel was approximately twice that of patients treated with good ulcer care alone. In Study 4, there was no significant difference in the incidence of complete healing in patients treated with becaplermin gel versus good ulcer care alone.

Administration, Topical↗
PubMed2004

Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea.

Oral wide-spectrum antibiotics are the linchpin of rosacea treatment. Oral and topical metronidazole, topical tretinoin, and topical benzoyl peroxide may also be used in the treatment of rosacea. We aimed to show that benzoyl peroxide-erythromycin gel is efficient in the treatment of acne rosacea. Fifty-six patients with acne rosacea were enrolled in our study. We administered benzoyl peroxide-erythromycin gel to 27 patients and metronidazole gel to 29 patients. In all the patients, the intensities of erythema, telangiectasia, papules/pustules, and nodules were evaluated before, during and after the treatment. The positivity of Demodex folliculorum from skin scratches was compared between the two groups at each visit. At the end of the therapy on the third examination, in the benzoyl peroxide-erythromycin group, 91.7% of the patients showed marked clinical improvement, and 8.3% of them showed complete remission. In the metronidazole group, 73.3% showed marked clinical improvement, and 26.7% of them showed complete remission. Clinical improvement in the papular component was 65.2% for the benzoyl peroxide-erythromycin group, and 81.5% for metronidazole group. In the first examination, the clinical results of the agents were similar. Although both of the drugs were found to be effective in the second and third examinations, metronidazole gel was more effective than benzoyl peroxide-erythromycin. Both of the drugs were found to be significantly effective especially in treating the papular component of rosacea. Demodex folliculorum was found to be positive in 74.1% of the benzoyl peroxide-erythromycin group and in 62.1% of the metronidazole group at the beginning. In the benzoyl peroxide-erythromycin group, 40.7% of Demodex folliculorum positive patients, became negative by the first examination. This was 17.2% for the metronidazole group. In the benzoyl peroxide-erythromycin group, among the patients who were positive for Demodex folliculorum in the first examination, 37.5% of them became negative. This was 36.7% for the metronidazole group. Benzoyl peroxide-erythromycin gel was superior to metronidazole gel in decreasing Demodex folliculorum by the first examination, but the effect of the two drugs on Demodex folliculorum was similar by the second examination. As a result, topically applied combined benzoyl peroxide-erythromycin gel may be an alternative choice of treatment for acne rosacea.

Administration, Cutaneous↗
PubMed2003

Determining optimal gel sensitivity in optical CT scanning of gel dosimeters.

A method for determining the gel sensitivity that is necessary for obtaining optimal image contrast in optical CT scanning of gel dosimeters is presented. The effective dynamic range of the OCTOPUS-ONE research scanner (MGS Research, Inc., Madison, CT) is analyzed. Optical density increments for selected straight-line paths across a gel cylinder to be scanned are calculated based on the optical properties of the polymer gel and the dose distribution from a commercial treatment planning system (Cadplan, Varian Corporation, Palo Alto, CA). Maximum optical density increment across the entire gel is obtained by searching the gel cylinder over a set of transverse planes at different rotational angles. The application of this quantity as a criterion for optimizing the quality of the optical CT scanning is demonstrated through dose verification of two representative treatment plans. When the MU dependence of the dose distribution for a treatment plan is linear, as is the case for static field irradiation, it is possible to scale the treatment plan such that the intensity variation of the signals received by the photodetector spans its entire dynamic range. For treatment plans that are possibly nonlinear, IMRT plans, for example, modification of the sensitivity of the gel material is necessary for the high-dose signals to be collected at a certain signal-to-noise ratio. Results obtained using the optimized CT scanning approach are compared with those from the treatment planning system and the film measurement.

Algorithms↗
PubMed1984

A comparative clinical study of Solcoseryl Eye-Gel and Cysteine Eye-Gel 2.4% in the treatment of foreign-body injuries of the cornea.

Solcoseryl, a protein-free haemodialysate, promotes tissue regeneration and improves utilization of oxygen in the cell. In a randomized, double-blind, clinical study, Solcoseryl Eye-Gel was compared with Cysteine Eye-Gel in the treatment of foreign-body injuries of the cornea in a total of 99 eyes. In order to facilitate objective evaluation of the effects of the treatment, the area of the lesion before the start of treatment and on the following day was determined by means of slit-lamp photographs. Healing of the lesion and relative reduction of the area of the wound were observed much more frequently in the group treated with Solcoseryl Eye-Gel than in the reference group. Maculae corneae after the end of the treatment were significantly less frequent under Solcoseryl Eye-Gel than under Cysteine Eye-Gel. Teh tolerability of the test preparation was good; an itching sensation was reported in only 2 cases. Under Cysteine Eye-Gel, on the other hand, a burning sensation was reported by a number of patients and very fine deposits in the epithelium were also observed in a few cases. Thus complete closure of the epithelium over the lesion after 1 day was observed much more frequently in the group of patients treated with Solcoseryl Eye-Gel than in the reference group (63 vs. 53%).

Actihaemyl↗
PubMed1995

The effect of molecular weight and gel preparation on humoral adjuvancy of silicone oils and silicone gels.

Silicone gels from commercial breast implants have been shown previously by our laboratory to be potent humoral adjuvants, while the low molecular size 20 centistoke (cs) silicone oil (M.W. 1900) possesses no measurable adjuvant properties. It became necessary to shear the silicone gel during our previous experiments in order to facilitate injection through a syringe and needle, it is conceivable that shearing may reduce the molecular weight of the silicone gel used. This investigation was undertaken to determine whether humoral adjuvancy of silicone oils is dependent on molecular weight and whether the method of shearing the silicone gel affects its adjuvancy. Four Dow Corning 360 Medical silicone oils (100 cs, M.W. approximately 5,000; 350 cs, M.W. approximately 10,000; 1000 cs, M.W. approximately 16,500 and 12,500 cs, M.W. approximately 60,000) and Dow Corning octamethylcyclotetrasiloxane (D4, M.W. 296) were tested for their humoral adjuvancy by immunizing 64 Sprague Dawley rats with 50 micrograms of bovine serum albumin (BSA) mixed with each oil. The rats were periodically bled and the sera were analyzed for anti-BSA antibodies by ELISA. In a separate experiment, three silicone gel preparations with reproducible characteristics were prepared by using a tissue homogenizer and varying the applied shear force. Each of these preparations was tested for its humoral adjuvancy as previously described for silicone oils. Rats immunized with BSA mixed with the highest molecular size silicone oil tested (M.W. approximately 60,000) showed a significant increase in anti-BSA antibodies as compared to the lower molecular size oils. The three silicone gel preparations showed no difference in their adjuvancy effect. Thus, the humoral adjuvancy of silicone oil appears to be dependent on molecular weight. Differential shearing of the silicone gel does not alter its humoral adjuvancy.

Adjuvants, Immunologic↗
PubMed2006

Intrarectal administration of lidocaine gel versus plain lubricant gel for pain control during transrectal ultrasound-guided extensive 10-core prostate biopsy in Hong Kong Chinese population: prospective double-blind randomised controlled trial.

OBJECTIVE: To compare the level of pain experienced by patients during transrectal ultrasound-guided prostatic biopsy using intrarectal 2% lidocaine gel versus plain lubricant gel. DESIGN: Prospective double-blind randomised controlled trial. SETTING: Regional hospital, Hong Kong. PATIENTS: From March 2002 to December 2003, patients who underwent ultrasound-guided prostate biopsy at a Geriatric Urology Centre. MAIN OUTCOME MEASURES: Pain and discomfort scores measured by horizontal visual analogue scales. RESULTS: A total of 338 consecutive patients were randomised to lidocaine gel or plain lubricant gel groups. The two groups were statistically similar in demographic and disease characteristics. There were no significant statistical differences in pain or discomfort score in the lidocaine gel and plain lubricant groups--pain score: 1.75 versus 1.79 (P=0.66) on day 0 and 0.21 versus 0.15 (P=0.97) on day 1; discomfort score: 0.79 versus 0.77 (P=0.86) on day 0 and 0.12 versus 0.12 (P=0.76) on day 1. No major complications were recorded in this cohort. CONCLUSIONS: Transrectal ultrasound-guided trucut biopsy of the prostate can be safely performed with no anaesthesia in Chinese patients. Pain and discomfort are minimal. It was found that 2% lidocaine gel has no statistical therapeutic or analgesic benefit over plain lubricant gel.

Administration, Rectal↗
PubMed2006

The effect of simulated solar UV irradiation on tretinoin in tretinoin gel microsphere 0.1% and tretinoin gel 0.025%.

Topical tretinoin is highly effective and widely used in the treatment of acne vulgaris. Tretinoin gel microsphere 0.1% (TGM)--alone or in combination with erythromycin-benzoyl peroxide (EBP) or clindamycin-benzoyl peroxide (CBP) topical gels-and tretinoin gel 0.025% (TG)--alone or, combined with EBP-were exposed to simulated solar UV irradiation to determine the degree of tretinoin photodegradation/isomerization. The investigation revealed that 94% and 84% of the initial tretinoin in the TGM formulation remained stable after 2 and 6 hours, respectively, of simulated solar UV irradiation. When combined with EBP topical gel, 89% and 81% of the initial tretinoin remained stable after 2 and 6 hours, respectively, of exposure to simulated solar UV irradiation; 86% and 80% of the tretinoin remained stable after 2 and 6 hours, respectively, when combined with CBP topical gel. In contrast, only 19% and 10% of the tretinoin remained unchanged after 2 and 6 hours, respectively, of simulated solar UV irradiation of TG. Combined with the EBP topical gel, undegraded tretinoin quantities were further reduced to 7% and 0% at 2 and 6 hours, respectively, with TG. These data suggest that the TGM formulation offers marked protection against tretinoin photodegradation compared with TG, even in the presence of a topical gel containing a potent antibiotic or a strong oxidizing agent. Although simulated solar UV irradiation is not entirely reflective of actual conditions, the results appear to be substantial.

Anti-Bacterial Agents↗