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PubMedDate not supplied

Adoptive cellular therapy with tumor vaccine draining lymph node lymphocytes after vaccination with HLA-B7/beta2-microglobulin gene-modified autologous tumor cells.

Adoptive immunotherapy with anti-CD3-expanded lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors. This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-expanded tumor vaccine draining lymph node lymphocytes (TVDLN) in patients with metastatic melanoma and renal cell cancer (RCC). To facilitate the generation of tumor-specific lymphocytes in the TVDLN, autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7, a modification that has the potential to enhance the immunogenicity of the tumor cells. After vaccination with gene-modified tumor cells, patients' lymph nodes were harvested; TVDLN lymphocytes were activated and expanded ex vivo with anti-CD3 and interleukin-2 (IL-2), and adoptively transferred to patients in combination with systemic IL-2. Twenty patients, nine with melanoma and 11 with RCC were treated. Tumor was harvested successfully in all 20 patients. Ex vivo gene transfer was performed using lipofection with a lipid: DNA plasmid complex containing the genes for HLA-B7 and beta2-microglobulin. The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53% (range 0.3%-12.1%). Lymph nodes were harvested from all 20 patients with a mean of 53 x 107 and 60 x 107 cells obtained from the gene-modified and unmodified tumor vaccine sites, respectively. Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines. No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes. Typical IL-2-related toxicities were observed in all patients. No objective tumor regressions were observed. MHC class I restricted, tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients.

Adult↗
PubMed1996

Spatial localization with modified Fourier series windows. Application to the transmural 13C-nuclear magnetic resonance analysis of the in vivo myocardium.

RATIONALE AND OBJECTIVES: A modified Fourier Series Window (FSW) method is introduced that provides a simple, reasonably accurate, solution to spatial localization for layers in nuclear magnetic resonance (NMR) spectroscopy. This method was developed because signal originating from spins immediately adjacent to the coil plane can leak into standard FSW localized spectra obtained from more distal layers. METHODS: The B1 profile of the surface coil and a priori sample knowledge were used to generate modified FSW coefficients that largely compensate for contamination from proximal layers. These modified coefficients were used to acquire spatially localized spectra from a three-layered phantom containing inorganic phosphate, phosphocreatine, and pyrophosphate. Spatially localized spectra also were obtained from the open-chest canine myocardium. RESULTS: The modified Fourier Series Window approach was validated using a quality assurance phantom. This method was then applied to the transmural analysis of 13C-containing metabolites in the in vivo canine myocardium during 3-(13)C sodium pyruvate infusion (n = 10). In vivo NMR spectra were characterized by resonances corresponding to the C2, C3, and C4 carbons of glutamic acid and to endogenous triacyglycerides and surface lipids. A transmural trend in metabolites could be observed under these conditions. This trend, however, was likely to result from the interference of surface lipids in the epicardial layer. CONCLUSIONS: The authors demonstrate that the modified Fourier Series Window method can be applied in situations where signal-to-noise considerations limit the applicability of more sophisticated spatial localization methods. In addition, the authors report a slight gradient in the endogenous triacylglyceride resonance, which is likely to originate from the presence of surface lipids.

Animals↗
PubMed1997

Modified cow's milk formula with reduced renal acid load preventing incipient late metabolic acidosis in premature infants.

BACKGROUND: Premature infants receiving alimentation with cow's milk formulas are at a considerably high risk of developing incipient late metabolic acidosis, an early stage in the development of manifest late metabolic acidosis. Is it possible to reduce this risk by modification of the composition of a standard formula? METHODS: The mineral composition of a cow's milk preterm formula A was modified (formula B) with the aim of reducing the alimentary load to that of human milk. 160 premature infants were fed either mother's milk (n = 50) or the modified formula B (enriched with sodium and potassium) (n = 110), and their urine pH was tested twice a week. Randomly collected subgroups of infants were studied in detail for nutrient balances. The results were compared with earlier observations of 282 premature infants fed either mother's milk (n = 28) or the standard formula A (n = 254). RESULTS: Incipient late metabolic acidosis was observed in nine of 78 premature infants receiving mother's milk, 53 of 254 premature infants receiving the standard formula A, and only one of 110 premature infants fed the modified formula B. Net acid excretion was 0.58 mmol/kg/day in 11 premature infants receiving alimentation with the modified formula B compared with 1.73 mmol/kg/day in 23 premature infants fed formula A. This reduction was mainly due to an increased alkali excess (sodium + potassium-chloride) in intake and urine. CONCLUSIONS: Reduction of renal acid load with the modified formula B had a preventive effect on the rate of development of incipient late metabolic acidosis in premature infants.

Acidosis, Renal Tubular↗
PubMed2004

Mini-intervention for subacute low back pain: two-year follow-up and modifiers of effectiveness.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To Investigate the long-term effectiveness, costs, and effect modifiers of a mini-intervention, provided in addition to the usual care, and the incremental effect of a worksite visit for patients with subacute disabling low back pain (LBP). SUMMARY OF BACKGROUND DATA: A mini-intervention was earlier proved to be an effective treatment for subacute LBP. Whether the beneficial effect is sustained is not known. Furthermore, modifiers of a treatment effect are largely unknown. METHODS: A total of 164 patients with subacute LBP randomized into a mini-intervention (A, n = 56), a mini-intervention plus a worksite visit (B, n = 51), or the usual care (C, n = 57). Mini-intervention consisted of a detailed assessment of the patients' history, beliefs, and physical findings by a physician and a physiotherapist, followed by recommendations and advice. The usual care patients received the conventional care. Pain, disability, health-related quality of life, satisfaction with care, days on sick leave, and health care consumption and costs were measured during a 24-month follow-up. Thirteen candidate modifiers were tested for each outcome. RESULTS: There were no differences between the three treatment arms regarding the intensity of pain, the perceived disability, or the health-related quality of life. However, mini-intervention decreased occurrence of daily (A vs., C, P = 0.01) and bothersome (A vs. C, P < 0.05) pain and increased treatment satisfaction. Costs resulting from LBP were lower in the intervention groups (A 4670 Euros, B 5990 Euros) than in C (C 9510 Euros) (A vs. C, P = 0.04; and B vs. C, not significant). The average number of days on sick leave was 30 in A, 45 in B, and 62 in C (A vs. C, P = 0.03; B vs. C, not significant). The perceived risk for not recovering was the strongest modifier of treatment effect. Mental and mental-physical workers in A and B were less often on sick leave than those in C. CONCLUSIONS: Mini-intervention is an effective treatment for subacute LBP. Despite lack of a significant effect on intensity of low back pain and perceived disability, mini-intervention, including proper recommendations and advice, according to the "active approach," is able to reduce LBP-related costs. The perceived risk of not recovering was the strongest modifier of treatment effect. In alleviating pain, the intervention was most effective among the patients with a high perceived risk of not recovering.

Absenteeism↗
PubMed1998

New modified fluorescence polarization immunoassay does not falsely elevate vancomycin concentrations in patients with end-stage renal disease.

Recent literature has urged caution in the interpretation of vancomycin serum concentrations in patients with end-stage renal disease (ESRD), because falsely elevated levels in excess of 70% have been reported with the most commonly used fluorescence polarization immunoassay (FPIA). The purpose of this study was to evaluate the performance of a recently modified FPIA assay for use in patients with ESRD, in comparison to high-performance liquid chromatography (HPLC) and an enzyme-mediated immunoassay technique (EMIT). Serum vancomycin samples were prospectively collected from adults with ESRD undergoing chronic hemodialysis. Each sample was stored at -70 degrees C until analyzed in duplicate by FPIA, EMIT, and HPLC. In an in vitro experiment, blank serum samples with 15 microg/ml vancomycin were spiked with increasing amounts of CDP and analyzed in duplicate with the modified FPIA assay. When compared to HPLC, no statistically significant difference was found in patients with ESRD with the use of the modified FPIA assay (mean concentrations, HPLC 14.92 microg/ml, FPIA 15.96 microg/ml), with FPIA exhibiting a positive bias of 0.64 microg/ml and a precision of +/-3.49 microg/ml (n = 18, p = 0.44). The mean EMIT concentration was 18.34 microg/ml, with a positive bias of 3.43 microg/ml and a precision of +/-5.17 microg/ml (p < 0.01). The addition of increasing amounts of CDP to vancomycin in vitro resulted in concentrations similar to those expected in the absence of significant cross-reactivity with the modified FPIA assay. The modified FPIA assay is a satisfactory tool for monitoring vancomycin serum concentrations in patients with ESRD undergoing hemodialysis. Results obtained with EMIT were not as precise as with FPIA.

Adolescent↗
PubMed2004

The modified sting procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter.

PURPOSE: With the advent of tissue bulking agents, in particular dextranomer/hyaluronic acid copolymer (Dx/HA), for endoscopic implantation for vesicoureteral reflux (VUR), there has been a major shift in the surgical paradigm throughout Europe, and more recently, in the United States. We describe a modification of the technique used for implantation that has significantly improved our results. MATERIALS AND METHODS: Between October 2001 and October 2003, 285 children 7 months to 15 years old (mean age 4.6 years) underwent endoscopic implantation of Dx/HA for VUR at our institutions. A modified STING (subureteral transurethral injection) procedure (implantation submucosally within the intramural ureter) was introduced during the last year of the study. The average volume of injected material was measured for each ureter. Renal sonography was performed to determine if hydronephrosis was present. At 3 months flouroscopic voiding cystourethrograms were used to evaluate for the presence of VUR. A subset of 122 patients treated with STING (52) were compared to those treated with modified STING (70). RESULTS: A total of 459 ureters in 231 girls and 54 boys were treated (174 bilateral cases). Mean maximum grade per patient was 2.5/5. Mean injected volume was 0.9 cc ureter. There were 181 patients with at least 3 months of followup. After 1 treatment 76% (137 of 181) of cases were cured (grade 0 reflux), while 54% (24 of 44) of the failures were improved. The overall cure rate was 94% for grade I, 85% for grade II, 78% for grade III and 71% for grade IV reflux. The patients treated with STING had a mean age of 4.8 years, mean maximum reflux grade was 2.5 and success rate was 71% (37 of 52; 86% grade I, 89% grade II, 70% grade III and 63% grade IV reflux). The patients treated with a modified STING had a mean age of 5.5 years, mean maximum grade was 2.8 and a success rate was 89% (62 of 70; 100% grade I, 92% grade II, 91% grade III and 90% grade IV reflux). Ureteral success rates were significantly (p <0.01) greater for the modified STING (92%) vs the standard STING (79%). There were no cases of hydronephrosis at 3 months postoperatively. CONCLUSIONS: The majority of patients undergoing minimally invasive therapy for VUR with Dx/HA are cured after 1 treatment. The modified STING is our preferred method of implant injection for the correction of VUR and in our hands produces a resolution rate of 89% (92% of ureters). The technique optimizes ureteral coaptation, is easy to perform and is not associated with any significant short-term complications. Persistence of VUR in a minority of patients continues to be the only significant adverse effect of endoscopic implantation.

Adolescent↗
PubMed2006

Does patient-perceived handicap correspond to the modified clinical test for the sensory interaction on balance?

OBJECTIVE: To determine whether patient self-reported handicap correlates with scores obtained from the modified Clinical Test for the Sensory Interaction on Balance as assessed by the Neurocom VSR Balance Master platform. STUDY DESIGN: Prospective observational. SETTING: Balance clinic in tertiary referral center. PATIENTS: Patients referred with dizziness or imbalance as their primary complaint. OUTCOME MEASURES: The modified Clinical Test for the Sensory Interaction on Balance scores as assessed by the Neurocom VSR Balance Master platform, the Dizziness Handicap Inventory, and the Health Utilities Index Marks 2 and 3. RESULTS: One hundred fifty-nine patients were entered into the study. The mean age of participants was 54.5 years, with a female-to-male ratio of 2.1:1. The scores for the Dizziness Handicap Inventory and Health Utilities Index are similar between sexes, and although the Dizziness Handicap Inventory score did not correlate with age, Health Utilities Index 2 and 3 scores did show a negative correlation with increasing age. There are weak, positive correlations between the Dizziness Handicap Inventory and the firm surface conditions of the modified Clinical Test for the Sensory Interaction on Balance but no useful correlation with the foam conditions. Similar weak negative correlations were found between the Health Utilities Index 2 and 3 and the modified Clinical Test for the Sensory Interaction on Balance scores. CONCLUSION: Patient-perceived handicap of imbalance appears to correlate poorly with assessment of postural stability using the modified Clinical Test for the Sensory Interaction on Balance.

Adult↗
PubMed2006

The effects of unfractionated heparin, low molecular weight heparin and danaparoid on the thromboelastogram (TEG): an in-vitro comparison of standard and heparinase-modified TEGs with conventional coagulation assays.

To investigate the effects of unfractionated heparin (UFH), low molecular weight heparin (LMWH) and danaparoid (DPD) added to whole blood in vitro on standard and heparinase-modified thromboelastogram (TEG) parameters compared with conventional assays of coagulation. The effects of UFH, LMWH and DPD on standard TEG parameters were compared with the prothrombin time, activated partial thromboplastin time, thrombin time and anti-activated factor X (anti-FXa) activity, at concentrations of these anticoagulants ranging from 0.025 to 1 U/ml. In the second part of the study, the effects of very low concentrations (0.005-0.05 U/ml) of UFH, LMWH and DPD on the difference between standard and heparinase-modified TEG parameters were compared with the prothrombin time, activated partial thromboplastin time, thrombin time and anti-FXa activity. Standard TEG parameters were outside the reference range at lower concentrations of UFH, LMWH and DPD than most conventional coagulation assays were able to detect. Only anti-FXa activity was more sensitive to the presence of these anticoagulants than the standard TEG alone. The lowest concentration of UFH, LMWH and DPD used in this study (0.005 U/ml) caused significant differences between the standard and heparinase-modified alpha-angles of the TEG. In addition, the difference between standard and heparinase-modified TEG parameters distinguished between low concentrations (0.005-0.05 U/ml) of UFH with greater sensitivity than anti-FXa activity, but were less sensitive to LMWH and DPD. The standard TEG is more sensitive to UFH, LMWH and DPD than most conventional coagulation tests, with the exception of anti-FXa activity. Calculation of the difference between standard and heparinase-modified TEG parameters greatly increases the sensitivity of the assay for the effects of these anticoagulants, and is more sensitive to very low quantities of UFH than anti-FXa activity.

Adult↗
PubMed2004

Modified mattress suture technique to correct anterior septal deviation.

The purpose of this study was to evaluate the efficacy of a modified mattress suture technique in septal anterior deviation correction and to compare it with the Hinderer technique. This was a randomized, controlled, single-blind clinical trial. Fifty patients with anterior septal deviation were assigned to one of two surgery treatment groups: in group A, 25 patients underwent anterior septoplasty with modified mattress suture technique; and in group B, 25 patients underwent anterior septoplasty with the Hinderer technique. Subjective (oral respiration, epistaxis, rhinorrhea, and nasal obstruction) and objective (anterior rhinomanometry) parameters were analyzed and compared between groups. Better results in obstructive deflections were achieved with the modified mattress suture technique. Unilateral and total nasal resistances improved during the 6-month follow-up in patients who underwent anterior septoplasty with the modified mattress suture technique, and there was a significant difference in the values when compared with patients who underwent anterior septoplasty with rhinoplasty using the Hinderer technique (p = 0.003). The modified mattress suture technique had better subjective and objective results than rhinoplasty with the Hinderer technique and therefore could be considered as an alternative technique in anterior septal surgery.

Adolescent↗
PubMed2003

Modified rapid deployment hemostat bandage reduces blood loss and mortality in coagulopathic pigs with severe liver injury.

BACKGROUND: Hemostasis can be difficult to achieve after blunt abdominal trauma, especially if the patient is coagulopathic. The U.S. Food and Drug Administration has recently approved a hemostatic dressing for treating bleeding after extremity trauma (RDH bandage; Marine Polymer Technologies, Cambridge, MA). It has not been evaluated for internal bleeding after trauma. We redesigned this dressing for internal use, and then tested whether this modified bandage (Miami-modified Rapid Deployment Hemostat) could achieve hemostasis when used as an adjunct to standard laparotomy pad packing in a pig model of severe liver injury with coagulopathy. METHODS: Anesthetized swine (35-45 kg) received an isovolemic 45% blood volume replacement with refrigerated Hextend (6% hetastarch). Core body temperature was maintained at 33-34 degrees C with intra-abdominal ice packs. A coagulopathic condition was documented by thromboelastography. At this point a severe liver injury was induced by the avulsion of the left lateral hepatic lobe, then the pigs were randomized to treatment with either standard abdominal packing (control) or packing plus Miami-modified Rapid Deployment Hemostat. Two series of experiments were conducted. In series one (n = 14), the abdomen was closed and the animals were observed with no resuscitation. After one hour, the abdomen was opened, the packing was removed and the presence of bleeding was noted. In series two (n = 10), the abdomen was closed and the animal resuscitated with one unit of blood plus as much lactated Ringers intravenous fluid (IVF) as required to maintain a mean arterial pressure (MAP) > 70 mm Hg. After one hour, the packing was removed, the abdomen closed, and data were collected for an additional two hours. RESULTS: Series one: 6/7 animals in the control group had continued bleeding at one hour; 1/7 animals in the treatment group had active bleeding (p = 0.0291). Series two: With control vs. Miami-modified Rapid Deployment Hemostat, the three-hour survival was zero vs. 80% (p = 0.0476). The total blood loss was 1.2 +/- 0.1 vs. 0.3 +/- 0.1 mL/kg/min (p = 0.001) and the IVF requirement was 1.6 +/- 0.3 vs. 0.6 +/- 0.3 mL/kg/min (p = 0.026). CONCLUSIONS: The Miami-modified Rapid Deployment Hemostat bandage significantly reduced mortality, blood loss, and fluid requirements when used as an adjunct to standard abdominal packing following severe liver injury in coagulopathic pigs [corrected].

Animals↗
PubMed1985

Abnormal processing of the modified oligosaccharide side chains of phytohemagglutinin in the presence of swainsonine and deoxynojirimycin.

Phytohemagglutinin, the glycoprotein lectin of the common bean, Phaseolus vulgaris, has both high-mannose (Man(8-9)GlcNAc(2)) and modified oligosaccharide side chains. The modified side chains have glucosamine, mannose, fucose, and xylose in the molar ratios 2:3.8:0.6:0.5, and are resistant to hydrolysis by endoglycosidase H. Synthesis and processing of side chains in the presence of 1-deoxynojirimycin, an inhibitor of alpha-glucosidase, results in the formation of chains which are all alike. They are sensitive to endoglycosidase H, do not contain fucose, and are largely resistant to alpha-mannosidase. This indicates that they are probably high-mannose chains blocked by terminal glucose residues. Synthesis and processing of side chains in the presence of swainsonine, an inhibitor of alpha-mannosidase II, results in the formation of normal high-mannose chains, and of modified chains which contain fucose residues, are resistant to endoglycosidase H, and can be distinguished from normal modified chains only by the presence of extra mannose residues.Processing of the phytohemagglutinin modified chains of PHA under normal conditions involves the attachment of peripheral N-acetylglucosamine residues in the Golgi complex and their subsequent removal in the protein bodies. The attachment of the N-acetylglucosamine residues is largely inhibited by deoxynojirimycin but still occurs in the presence of swainsonine. The results presented in this work show that processing of the asparagine-linked oligosaccharides is under the control of several glycosidases and glycosyltransferases and involves the formation of intermediate products.

Journal Article↗
PubMed1992

Involvement of calcium in germination of coat-modified spores of Bacillus cereus T.

The effect of calcium on germination of coat-modified Bacillus cereus T spores was investigated. Coat-modified spores produced either by chemical extraction (SDS-DTT-treated spores) or by mutagenesis (10LD mutant spores) were unable to germinate in response to inosine. While SDS-DTT-treated spores could germinate slowly in the presence of L-alanine, 10LD mutant spores could not germinate at all. The lost or reduced germinability of coat-modified spores was restored when exogenous Ca2+ was supplemented to the germination media. The calcium requirement of coat-modified spores for germination was fairly specific. The simultaneous presence of germinant with Ca2+ was also required for germination of coat-modified spores. The optimal recovery of germinability was observed in the presence of 1.0 mM of calcium acetate. The calcium requirement itself was remarkably diminished under the condition in which L-alanine and a certain purine nucleoside analog, adenosine or inosine, coexisted. The lost or diminished germinability observed in SDS-DTT-treated spores or 10LD mutant spores may be attributed to the loss of calcium associated with the spore integuments.

Alanine↗
PubMed1990

Detection of proteins that recognize platinum-modified DNA using gel mobility shift assay.

Using a gel mobility shift assay, we have identified proteins, in the nuclear extracts of a human lung cancer cell line, that recognize cis-diamminedichloroplatinum(II) (cis-DDP, CDDP)-modified DNA. A 158-base-pair double-stranded DNA fragment, derived from pBR322 plasmid DNA, was modified by either CDDP, tetrachloro(dl-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) or trans-DDP (the stereoisomer of CDDP and clinically ineffective). These platinum drug-modified probes were incubated with nuclear extracts and analyzed by gel mobility shift assay. Proteins in the extracts selectively recognized the clinically active platinum-modified DNA fragment. No binding to the trans-DDP-modified DNA fragment was observed. These proteins may play a role in the cytotoxicity or in a DNA repair process.

Cisplatin↗
PubMed2004

Biological characterization of glutaraldehyde-modified Parietaria judaica pollen extracts.

BACKGROUND: Allergoids are widely used in specific immunotherapy (SIT) for the treatment of IgE-mediated allergic diseases, but all techniques for standardization of conventional allergic extracts may not be appropriate for standardization of a glutaraldehyde (GA)-modified extract because of the unique characteristics of these extracts. OBJECTIVE: To assess an accurate methodology for standardization of chemically modified extracts. METHODS: GA-modified extracts from Parietaria judaica pollen were purified by diafiltration. Biochemical properties were investigated by determination of amino groups, chromatography, and SDS-PAGE. The IgE-binding activity was determined by skin prick test, enzyme allergosorbent test inhibition, basophil activation, and histamine release tests. Peripheral blood mononuclear cells (PBMCs) from P. judaica pollen-allergic subjects were stimulated with either native or allergoid extracts, and proliferation was measured. RESULTS: Biochemical data indicated a high degree of allergen polymerization resulting in extract components higher than 100 kDa. IgE-binding activity, both in vivo and in vitro, was reduced by more than 99.8%. Both allergen and allergoid induced PBMC proliferation and synthesis of blocking IgG antibodies at similar rates. Moreover, no evidence of introduction of new determinants by chemical modification was found. CONCLUSIONS: The preparation of GA-modified extracts by diafiltration is faster and more reliable than previous chromatographic methods. These modified extracts have drastically reduced their allergenicity while maintaining their immunogenicity, and therefore they can be used in safer and shortened schedules of SIT.

Adolescent↗
PubMed2005

Double-blind study of tolerability and antibody production of unmodified and chemically modified allergen vaccines of Phleum pratense.

BACKGROUND: The physicochemical modification of allergen extracts provides a chance for administering higher doses of allergen vaccines. OBJECTIVE: To evaluate the safety of a chemically modified (depigmented-glutaraldehyde polymerized) therapeutic vaccine of Phleum pratense administered at doses that are 10 times higher than those used in clinical practice, in comparison with conventional doses of the corresponding non-modified alum-adsorbed vaccine. MATERIALS AND METHODS: The design of the study was randomized, double-blind, parallel and included two groups of patients. Twenty-three patients were treated weekly during nine visits for the build-up phase, followed by two weekly maintenance doses (a total of 11 injections per patient). Twelve patients received a vaccine containing the standardized unmodified extract, at a maximum concentration of 308.5 mcg of freeze dried material/mL (Group A). Eleven patients received a standardized modified allergen extract (Group B). The maximum dose used was 2400 mcg/mL. Safety was evaluated recording all adverse events. Skin test results and specific antibody levels were evaluated at the beginning and at the end of the study. RESULTS: Group A patients experienced three local immediate (two clinically irrelevant and one with a diameter>5 cm) and 18 delayed reactions (15 irrelevant and three with a diameter>10 cm), while Group B experienced six local immediate and 12 delayed reactions (all clinically irrelevant). Nine Group A patients experienced 12 systemic reactions (one immediate of grade 1, one of grade 2; and one delayed of grade 1; four of grade 2 and three of grade 3), while Group B patients experienced one immediate systemic reaction of grades 1, and 1 delayed reaction of grade 1. CONCLUSIONS: The modified extract of P. pratense is safe to treat sensitive patients, even at concentrations that are 10 times higher than those regularly administered in clinical practice. The majority of the local reactions were clinically irrelevant. No systemic reactions of grade 2, 3 or 4 were reported using the modified extract.

Adult↗
PubMed1981

Changes in amount of hypo-modified tRNA having guanine in place of queuine during erythroid differentiation of murine erythroleukemia cells.

The amounts of hypo-modified tRNAs having guanine in place of queuine in murine erythroleukemic cells decreased markedly when the cells differentiated into mature erythroid cells. The amounts of these hypo-modified tRNAs can be determined easily by measuring incorporation of labeled guanine into tRNA with Escherichia coli tRNA--guanine transglycosylase. The decrease was detected at on early stage of erythroid differentiation: namely, before any detectable increase in the percentage of cells containing hemoglobin. The amount of guanine-accepting tRNA species was nearly proportional to the percentage of undifferentiated cells in the population, regardless of the type of inducer used. Decrease in the amounts of hypo-modified tRNAs in the cells was effectively blocked by 12-O-tetradecanoylphorbol 13-acetate, which inhibits differentiation of these cells. 8-Azaguanine, which is known to be substrate of tRNA--guanine transglycosylase, was incorporated almost exclusively into the first position of hypo-modified tRNA in murine erythroleukemic cells when they were pulse-labeled in culture with 8-azaguanine, suggesting strongly that tRNA-guanine transglycosylase in the cells is actually involved in incorporation of 8-azaguanine into tRNA in vivo. The amount of 8-azaguanine incorporated into tRNA in differentiated cells was one third of that in undifferentiated cells, the decrease being parallel with that in the amount of guanine-accepting tRNA in these cells. The results suggest that the appearance of hypo-modified tRNAs in the transformed cells was due to lack of substrate for queuosine biosynthesis in tRNA.

Animals↗
PubMed1991

Polyclonal antibodies elicited against trans-diamminedichloroplatinum(II)-modified DNA and their application in nonradioactive hybridization experiments.

Polyclonal antibodies that bind selectively to adducts formed with DNA by chemotherapeutically inactive trans-diamminedichloroplatinum (II) [trans-[Pt(NH3)2Cl2]) were produced by immunization with calf-thymus double-helical DNA modified by trans-[Pt(NH3)2Cl2] at a ratio of bound platinum/nucleotide (rb) of 0.1. High selectivity was obtained by separation of the antibodies from the antiserum with the aid of affinity chromatography on a Sepharose column. The antibodies were competitively inhibited in an ELISA assay by 25 pM trans-[Pt(NH3)2Cl2] bound to double-helical DNA and 2.5 pM trans-[Pt(NH3)2Cl2] bound to denatured DNA (rb = 0.1). The conversion of monofunctional adducts, formed on DNA at the early stage of its interaction with trans-[Pt(NH3)2Cl2], to bifunctional lesions, decreased the ability of the modified DNA to competitively inhibit these antibodies. They did not cross-react with unmodified, denatured DNA, but they reacted with diethylenetriamine-chloroplatinum(II)-chloride-modified double-helical DNA and with double-helical DNA treated with cis-diamminedichloroplatinum(II) for a short time (10 min). The results of this work best fit a model in which one of the major antigenic determinants of double-helical DNA modified by trans-[Pt(NH3)2Cl2] is the platinum atom coordinated in a monodentate or bidentate manner with non-paired nucleotide residues or perhaps a short segment of single-stranded DNA which occurs around the platination site. Nucleic acids modified by trans-[Pt(NH3)2Cl2] can be used as immuno-probes in hybridization experiments.

Animals↗
PubMed1993

Sulphhydryl-modifying reagents alter ototoxin block of muscarinic receptor-linked phosphoinositide turnover in the cochlea.

In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPs) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin-induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents N-ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPs in the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose-dependent way without altering the basal metabolism of IPs. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1-50 microM) does not alter carbachol-evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N-ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N-ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond-modifying agents do not alter the carbachol-enhanced metabolism of IPs. These results suggest that molecules having thiol-modifying properties inhibit the carbachol-induced turnover of IPs without acting at the muscarinic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗