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Biomedical subjects

D Schulz

Publications and source records attributed to D Schulz.

At least 19 recordsLinked to original sources

Water maze performance, exploratory activity, inhibitory avoidance and hippocampal plasticity in aged superior and inferior learners.

In 28- to 30-month-old rats, in vitro short-term and long-term potentiation (STP and LTP) were measured in area CA1 of the hippocampus in seven superior and seven inferior learners, that were selected from a pool of 40 rats based on water maze escape performance over a period of 9 days. The aim was to examine whether levels of STP and LTP could account for group differences in learning of water maze escape, spatial preference and wall (thigmotaxis)-avoidance and in short-term retention of an inhibitory avoidance task. There was no significant group difference in open-field exploration, i.e. the number of rearings. In contrast to expectation, the superior and inferior learners did not differ significantly from each other in levels of STP and LTP. However, variability in escape and spatial learning, but not thigmotaxis-avoidance learning, was significantly predicted by variability in STP and LTP in the superior group. Also, open-field exploratory rearings were significantly correlated with STP and LTP as well as with maze escape learning in the superior group. The results show that, in the aged superior group, levels of CA1 STP and LTP coincided with residual water maze escape and spatial preference learning as well as open-field exploration, i.e. behavioural expressions known to be related to hippocampal functioning, but not with learning to avoid thigmotaxis in the maze. The lack of such correlations in the inferior group may be due to the severe impairment in escape and spatial preference learning and/or the influence of yet unknown third variables on these relationships.

Action Potentials↗

Characterization of the antibody response to pneumococcal glycoconjugates and the effect of heat-labile enterotoxin on IGg subclasses after intranasal immunization.

The antibody response to pneumococcal glycoconjugate (Pnc) was characterized by analyzing pneumococcal polysaccharide (PPS)-- and protein carrier-specific IgG subclass profiles and their relationship. Mice were immunized intranasally (inl) or subcutaneously (sc) with Pnc with mutants of Escherichia coli heat-labile enterotoxin, LT-R72 and LT-K63, as mucosal adjuvants. Subcutaneous immunization with Pnc alone induced predominantly IgG1, whereas native PPS administered sc induced very low IgG titers that were exclusively of the IgG3 subclass. Compared with sc immunization with Pnc alone, inl immunization with Pnc and LT mutants induced significantly higher systemic IgG2a, IgG3, and IgA antibodies to both PPS and the carrier, whereas the IgG1 titers were comparable. There also was a significant correlation between PPS- and protein carrier--specific antibody responses for all IgG subclasses. This demonstrates that LT mutants can be used to both enhance and modulate the antibody response to the PS moiety of glycoconjugate vaccines.

Adjuvants, Immunologic↗

Effect of additives on the flow-analysis determination of weak-acid-dissociable and total cyanide.

The effect of reductants, complexants, and nitrite eliminators on the flow-analysis determination of weak-acid-dissociable and total cyanide has been studied for: 1. cyanide recovery from copper, nickel, and iron complexes; 2. cyanide generation from the reagents in the presence of common interferents; and 3. cyanide consumption by the reagents in the presence of those interferents. In the absence of additives the UV-assisted recovery of (total) cyanide from the iron complexes (using a succinate buffer) was insufficient. Arsenite and hypophosphite had no measurable effect on the recovery, ascorbic acid resulted in total recovery but under these conditions nitrite and sulfite seemed to destroy cyanide. Phenanthroline promoted the recovery of cyanide from iron complexes but led to formation of cyanide from thiocyanate. Citrate resulted in good recovery but in the presence of nitrite cyanide was formed; the recovery with EDTA was also good. It proved necessary to destroy nitrite by use of sulfamic acid. If a combination of EDTA, citrate, and sulfamic acid is used rather high concentrations of thiocyanate, nitrite, thiosulfate, and sulfite can be tolerated in the samples. It is strongly advisable to test modifications of the cyanide determination comprehensively, because some surprising results have been obtained.

Acids↗

Activity and cross-reactivity of antibodies induced in mice by immunization with a group B meningococcal conjugate.

The capsular polysaccharide of group B Neisseria meningitidis is composed of a linear homopolymer of alpha(2-8) N-acetyl neuraminic acid or polysialic acid (PSA) that is also carried by isoforms of the mammalian neural cell adhesion molecule (NCAM), which is especially expressed on brain cells during development. Here we analyzed the ability of antibodies induced by the candidate vaccine N-propionyl polysaccharide tetanus toxoid conjugate to recognize PSA-NCAM. We hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin G monoclonal antibodies and evaluated their self-reactivity profile by using a battery of tests (immunoprecipitation, immunoblotting, and immunofluorescence detection on live cells and human tissue sections) chosen for their sensitivity and specificity to detect PSA-NCAM in various environments. We also searched for the effects of the vaccine-induced antibodies in two functional assays involving cell lysis or cell migration. Although they were highly bactericidal, all the antibodies tested showed very low or no recognition of PSA-NCAM, in contrast to PSA-specific monoclonal antibodies used as controls. Different patterns of cross-reactions were revealed by the tests used, likely due to affinity and specificity differences among the populations of induced antibodies. Furthermore, neither cell lysis nor perturbation of migration was observed in the presence of the tested antibodies. Importantly, we showed that whereas enzymatic removal of PSA groups from the surfaces of live cells perturbed their migration, blocking them with PSA-specific antibodies was not functionally detrimental. Taken together, our data indicated that this candidate vaccine induced antibodies that could not demonstrate an immunopathologic effect.

Animals↗

A simple corneal perfusion chamber for drug penetration and toxicity studies.

AIMS: Corneal perfusion chambers are important tools in the development and assessment of ophthalmic drugs. The aim of this study was to design and test a modified perfusion chamber suitable for topical application of drugs to isolated corneoscleral preparations, and which allowed continuous monitoring of endothelial cell function. METHODS: A polycarbonate and stainless steel perfusion chamber was designed to clamp corneas in a horizontal plane suitable for topical drug delivery. Endothelial cell function was assessed by ultrasonic pachymetry and specular microscopy during perfusion. Epithelial barrier function was assessed by penetration of fluorescein. Leakage was examined by measuring penetration of a large protein, IgG. Tissue architecture after perfusion was examined by conventional histology. RESULTS: Corneas maintained a functionally and morphologically intact endothelial monolayer during perfusion periods of up to 14 hours. The epithelial barrier function was well preserved. The tissue clamp sealed the preparation effectively against leakage of macromolecules. CONCLUSION: The new chamber device forms a reliable tool for in vitro drug penetration and toxicity studies in isolated perfused corneoscleral tissue.

Animals↗

Lesion of the bed nucleus of the stria terminalis enhances learned despair.

The bed nucleus of the stria terminalis (BNST) was lesioned in adult male Wistar rats (n = 9) and its involvement in coping behavior during forced swim stress examined. Rats remain immobile longer in the second of two swim tests, a phenomenon known as learned despair. Results revealed that, compared to sham-operated controls (n = 8), BNST-lesioned animals displayed immobility significantly earlier and for longer durations in the second swim test. Rats with BNST lesions also showed significantly reduced escape behavior in the form of fewer numbers of jumps and dives compared to controls. Mobility deficits were not due to general motor impairment as revealed by an open field test. Results suggest that the BNST may modulate coping behavior especially during uncontrollable stress.

Adaptation, Psychological↗

Tolcapone increases maximum concentration of levodopa.

No significant increase of the maximum concentration (Cmax) of levodopa after addition of catechol-O-methyltransferase inhibitor tolcapone occurred in previous pharmacokinetic studies predominantly on healthy volunteers. We compared pharmacokinetics of levodopa in plasma before and after addition of tolcapone in 13 treated parkinsonian subjects under standardized conditions. We found a significant increase of Cmax of levodopa after the addition of tolcapone. This may represent one cause for the occurrence of dyskinesia previously early in the course of treatment with tolcapone.

Aged↗

Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma.

BACKGROUND: The expression of RET/PTC chimeras was demonstrated in 10% to 20% of sporadic papillary thyroid carcinomas (PTCs), whereas rearrangements of NTRK1 were detected less frequently. Some investigators have hypothesized that RET/PTC activation is preferentially associated with slow-growing tumors of low malignancy in elderly patients; other studies support the contrary. METHODS: Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction in tumor tissues from 119 patients with PTC. Samples with suspected rearrangements were further analyzed for the expression of the hybrid messenger RNAs RET/PTC 1 to RET/PTC 7 and for known NTRK1 chimeras, respectively. RESULTS: Seventeen of 119 tumors (14.3%) revealed somatic rearrangements of RET; NTRK1-derived hybrids were demonstrated in 15 cases (12.6%). In patients with RET/PTC chimeras, a statistically not significant tendency towards younger age, lower recurrence rate, and improved survival was observed, despite increased incidence of lymph node metastasis. Cumulative survival analysis of NTRK1 rearrangement-positive individuals demonstrated a worse outcome when compared with patients with expression of RET hybrids (P =.055). CONCLUSIONS: The high incidence of yet uncharacterized NTRK1 hybrid mRNAs in our patient cohort leads to the speculation that activating chromosomal rearrangements of several tyrosine kinase receptors may be a common feature of PTCs and that the expression of distinct chimeras may potentially be of prognostic significance.

Carcinoma, Papillary↗

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

Adjuvants, Immunologic↗

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Administration, Intranasal↗

[Primary orbital implant dislocation. A retrospective study].

BACKGROUND: To compensate the orbital volume deficit after enucleation orbital implants are used. METHOD: Between 1986 and 1996, 449 enucleations were performed. One hundred and fifty-five orbital implants were used: 96 hydroxylapatite-ceramic-silicon (HAK-silicon), 29 hydroxylapatite-ceramic (HAK), 26 Kiel bone chips, 3 Walser and 1 Bangerter implant. RESULTS: Ten orbital implants (6.45%) had to be explanted. Seven of the 96 HAK-silicon implants were explanted: four could be changed, two of them with a smaller and two with a same diameter. We observed a complication rate of 7.29% and a rate of total loss of 3.13%. One luxated HAK-implant could be refixated (3.45%), and one implant (3.85%) of the Kiel bone chip implants was explanted. CONCLUSION: Using different types of orbital implants after enucleation, we observed a complication rate of 7%. However, to avoid the post-enucleation-syndrome and to achieve better motility of the prosthesis, orbital implants should be used.

Adolescent↗

OH-radical formation by ultrasound in aqueous solution--Part II: Terephthalate and Fricke dosimetry and the influence of various conditions on the sonolytic yield.

Terephthalate and Fricke dosimetry have been carried out to determine the sonolytic energy yields of the OH free radical and of its recombination product H2O2 in aqueous solutions under various operating conditions (nature of operating gas, power, frequency, temperature). For example, in the sonolysis of Ar-saturated terephthalate solutions at room temperature, a frequency of 321 kHz, and a power of 170 W kg-1, the total yield [G(.OH) + 2 G(H2O2)], equals 16 x 10(-10) mol J-1. This represents the total of .OH that reach the liquid phase from gas phase of the cavitating bubble. The higher the solute concentration, the lower the H2O2 production as more of the OH free radicals are scavenged, in competition with their recombination. Fricke dosimetry, in the absence and presence of Cu2+ ions, shows that the yield of H atom reaching the liquid phase is much lower, with G(H.) of the order of 3 x 10(-10) mol J-1. These sonolytic yields are smaller in solutions that are at the point of gas saturation, and increase to an optimum as the initial sonication-induced degassing and effervescence subsides. The probing of the sonic field has shown that the rate of sonolytic free-radical formation may vary across the sonicated volume depending on frequency and power input.

Journal Article↗

Isotypes of human vaccinal antibodies to the Vi capsular polysaccharide of Salmonella typhi.

The immunoglobulin class and IgG subclass distribution of anti-Vi antibodies elicited by vaccination with a single injection of the purified polysaccharide or three injections of the inactivated whole cell typhoid vaccine was examined using an immunoenzymatic assay. The two vaccines induced antibody responses of similar magnitude and the predominant subclass of IgG antibodies was IgG1.

Adolescent↗

Properties of the polyalcohol prepared from the beta-D-glucan schizophyllan by periodate oxidation and borohydride reduction.

The structure of the title polyalcohol was confirmed by 13C-n.m.r. spectroscopy. The polyalcohol was more soluble in water than schizophyllan and the aqueous solutions were more viscous than those of schizophyllan. The viscosity slightly decreased during 1 h on heating at 121 degrees, was not influenced by high concentrations of salt, and was independent of pH in the range 3-11. However, the viscosity markedly declined on storage of an aqueous solution of the polyalcohol at pH 2 and 20 degrees for 100 h. The polyalcohol was more susceptible to hydrodynamic shear than schizophyllan and the proportion of glycerol released indicated that both the main and side chains in the polyalcohol were cleaved.

Borohydrides↗

Clinical and immunologic responses to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age.

The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving injections at 3, 5, 7, and 18 months of age. No serious local or systemic reactions were noted. After the first injection the geometric mean Hib antibody level rose to 0.55 micrograms/ml, and each subsequent injection elicited a statistically significant rise in the geometric mean. The percentage of vaccinees with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after the first, 97.4% after the second, and 100% after the third Hib-TT injection. This percentage fell to 90.9% at 18 months of age but rose again to 100% after the fourth injection. Control infants (n = 10) injected with diphtheria-tetanus toxoid-pertussis vaccine only had nondetectable levels after the second injection. Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater than IgM greater than IgA. Among IgG subclasses the highest increases were of IgG1. All vaccinated subjects had greater than 0.01 U/ml of TT antibody (estimated protective level) throughout the study. We conclude that Hib-TT, injected at 3, 5, 7, and 18 months, is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by Hib.

Antibodies, Bacterial↗

Molecular size characterization of bacterial capsular polysaccharide vaccines by high performance liquid chromatography.

Bacterial capsular polysaccharides are major virulence factors and some are used as vaccinal antigens. Their molecular size is an important physicochemical criterion which correlates with immunogenicity. This article describes a new application of high performance liquid chromatography (HPLC), based on molecular sieving, for such an evaluation. This HPLC method is rapid, accurate, reproducible, requires only very low amounts of product and presents good correlation with conventional gel permeation chromatography.

Bacterial Capsules↗