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D Schulz

Publications and source records attributed to D Schulz.

At least 19 recordsLinked to original sources

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

[Tolerance and immunogenicity of the capsular polyoside vaccine against Haemophilus influenzae type b. A study of 325 children 15 to 71 months of age].

The antigenic properties of the capsule polyoside (PRP) from Haemophilus influenzae type b (Hib) are adequate to form the basis for immunization designed to prevent the severe infections caused by this organism. The tolerance and immunogenicity of a vaccine containing either 12.5 or 25 micrograms PRP were studied in 325 healthy children aged 15 to 71 months after informed consent had been obtained from the parents. Each child was given one subcutaneous injection of 0.5 ml vaccine. Antibodies against Hib were assayed before and one month after the injection. Clinical tolerance was outstanding both locally (moderate and transient pain in 13% of cases) and systematically, with only eight (2.6%) febrile reactions in excess of 38.5 degrees C within 24 hours after the injection. A very significant rise in antibody titers was seen in all age groups, but a mean titer of 1 microgram/ml was achieved only in children aged 24 months or more. No significant difference was found between the two dosages. Individual analysis showed that following immunization antibody titers reached 0.15 micrograms/ml or more in 65% of infants aged 15 to 17 months, 71% of infants aged 18 to 23 months, 80% of infants aged 24 to 30 months and 95% of children older than 30 months. Despite the inadequate immune response evidenced in the younger age groups, our results confirm that Hib infections are preventable from the age of 2 years. Our results are consistent with those recorded with a similar vaccine in Finland.

Antibody Formation

Measurement of anti-Haemophilus influenzae type b capsular polysaccharide antibodies by ELISA.

Measurement of antibodies to the capsular polysaccharide polyribosylribitolphosphate (PRP) of Haemophilus influenzae type b by ELISA is made difficult by the poor binding of this antigen to the solid phase. Six coating conditions were compared using immune and non-immune human sera. Direct coating with PRP was inefficient. Precoating with protamine or poly-L-lysine (PLL) yielded irreproducible results and high background levels. Assays with PRP conjugated with PLL as coat were not sensitive enough. In addition, anti-PRP antibodies, especially those belonging to the IgM class, crossreacted with PLL. Coating with avidin or streptavidin followed by incubation with biotin-coupled PRP was not satisfactory either, due to binding of certain sera in the absence of PRP. Coating with PRP coupled to tyramine resulted in low backgrounds and acceptable specific binding levels. However, the finding that the binding of a few sera was only partially inhibited by soluble PRP led us to include an inhibition step in every experiment. Only optical densities inhibited by the antigen were taken into account. In view of the lack of parallelism of dilution curves from different sera, no attempt was made to express the results in weight units. They were expressed in arbitrary units calculated by comparison with internal standards. Under such conditions, the assay permitted a reproducible (interassay coefficients of variation around 10%) determination of PRP-Ab belonging to the various immunoglobulin classes and IgG subclasses and showed a good correlation with results obtained using the Farr assay.

Adult

Protective activity of Vi capsular polysaccharide vaccine against typhoid fever.

The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.

Adolescent

Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report.

We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

Adolescent

Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.

Serum IgG subclasses were measured by a competitive indirect immunoassay with monoclonal antibodies in 31 leukemic patients before and after bone marrow transplantation. Antibodies to Hemophilus influenzae type b (Hib) capsular polysaccharide were determined in 28 cases. Abnormally low or borderline subclass (mostly IgG2 and IgG4) levels were found late after transplant in 23 infected and noninfected patients. These levels persisted for as long as 25 months, in association with low or borderline IgA levels in 78% of the cases. IgG2, IgG4, and IgA often showed a parallel evolution, whereas IgG1, IgG3, and IgM often varied together in the opposite way. Class but not subclass deficiencies were more frequent in patients with graft-v-host disease (GVHD). Subclass abnormalities predominated in infected patients, with mean levels correlating with the severity of infections; however, the abnormalities are not clearly predictive of infections in individual cases. Most patients with Hib pneumonia showed virtually no IgG antibody response to Hib, and one-half of the patients had a moderate IgM and IgA response. In the whole series, many sera collected greater than 1 year after graft contained very low or undetectable antibodies. Correlation between anti-Hib antibody and IgG2 levels was significant but weak because of discrepancies that were only partially explained by the subclass distribution of the antibodies.

Antibodies, Bacterial

Reactions of OH radicals with poly(U) in deoxygenated solutions: sites of OH radical attack and the kinetics of base release.

Pulse radiolysis of N2O-saturated solutions of poly(U) in the presence of tetranitromethane showed that 81 per cent of the radicals formed are reducing in nature. Using data from other sources it has been estimated that 70 per cent of the OH radicals add to the base at C(5) and 23 per cent at C(6) while only 7 per cent abstract an H-atom from the sugar moiety. To a large extent the C(5) OH adduct radicals attack the sugar moiety of poly(U) thereby inducing strand breakage and base release. G (base release) = 2.9 can be subdivided into three components: (a) immediate (20 per cent), (b) fast (50 per cent) and (c) slow (30 per cent). The immediate base release must occur either during the free-radical stage or as a result of the rapid (t1/2 less than 4 min at 0 degree C) decomposition of a diamagnetic product. The fast and the slow processes are only readily observable at elevated temperatures, e.g. at 50 degrees C the half lives are 83 min and 26 h, respectively (Ea (fast) = 68 kJ mol-1, Ea (slow) = 89 kJ mol-1, A (fast) = 1.5 X 10(7) s-1, A (slow) = 1.9 X 10(9) s-1. It is concluded that there are three different types of sugar lesions giving rise to base release, structures for which are tentatively proposed.

DNA