Hormone

Ohne Zusammenfassung     

Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbits inoculated. In competitive enzyme-linked immunosorbent assay, these antibodies reacted with high affinity to type Ia polysaccharide and with lower affinity to the structurally related GBS type Ib polysaccharide. Despite the lower binding affinity of the Ia-TT-induced antibodies for the type Ib polysaccharide, Ia-TT antiserum opsonized not only type Ia GBS but also type Ib GBS for killing by human blood leukocytes. Ia-TT antiserum was also evaluated in a mouse model designed to test the efficacy of maternal antibodies in protecting neonates against GBS infection. Pups born to dams that had received Ia-TT antiserum were protected against lethal challenge with either type Ia or Ib GBS. These studies using a polysaccharide-protein conjugate as an immunogen support the view that the carbohydrate immunodeterminant recognized on Ib strains by Ia antisera is a common epitope contained within the structurally related Ia and Ib capsular polysaccharides. Although antibodies elicited by Ia-TT had protective activity against both Ia and Ib strains, these antibodies reacted with lower affinity to Ib than to Ia polysaccharide.     

Dermatoglyphic peculiarities in patients with Williams-Beuren syndrome

The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams-Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C°); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th inter digital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a “Log.Score-Index,” provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A “phantom picture” for WBS was constructed, which can be used for its diagnosis. © 1994 Wiley-Liss, Inc.     

Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3:1:3 vaccine series

CONTEXT: The association between infant age at initiation of hepatitis B vaccination and completion of the 3-dose hepatitis B vaccination series is unclear. OBJECTIVE: To assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). DESIGN, SETTING, AND PARTICIPANTS: Analysis of data from the 1998 National Immunization Survey, a random-digit-dialing telephone survey (n = 34,480 completed interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. MAIN OUTCOME MEASURES: Percentage of infants who received at least 3 doses of hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by age at receipt of the first dose of hepatitis B vaccine. RESULTS: Overall, 86.9% of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose hepatitis B vaccine series among children who received the first dose at 8 to 41 days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95% CI, 7.0-13. 3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5), respectively; ORs for not completing the 4:3:1:3 vaccine series among these same groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0. 8-1.1), 1.7 (95% CI, 1.3-2.3), 3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively. CONCLUSION: Administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. JAMA. 2000;284:978-983     

Dopamine-antagonistic, anticholinergic, and GABAergic effects on declarative and procedural memory functions

Declarative and procedural memory functions are related to dissociable neuroanatomic substrates. In the present study differential effects of pharmacologically induced changes in dopaminergic, GABAergic, and cholinergic activity in the brain on declarative (object and face recognition, immediate and delayed word recall) and procedural memory processes (compensatory tracking) were investigated. In a double-blind design, either 3 mg of haloperidol, 11 mg of midazolam, 1 mg of scopolamine, or placebo were administered to 80 healthy volunteers randomly assigned to one of the four drug conditions. Although all three drugs produced a detrimental effect on immediate and delayed word recall, recall performance was substantially more impaired by the benzodiazepine midazolam than by either haloperidol or scopolamine. While recognition of faces was affected by neither of the drugs, performance on object recognition was significantly decreased by midazolam as compared to placebo. Procedural learning was markedly impaired by all drugs but, again, the observed effect was most pronounced with midazolam. Additional analyses of measures of subjective activation, cortical arousal, and psychomotor performance argued against the assumption that the observed memory-impairing effects were secondary to drug-induced sedation. The overall pattern of results revealed that memory processes are much more susceptible to changes in GABAergic than in dopaminergic or cholinergic neurotransmitter activity. Furthermore, the present findings point to the conclusion that the modulating effects of dopaminergic, GABAergic, and cholinergic neurotransmitter systems on declarative and procedural memory functions are less specific than suggested by neuropsychological studies in patients.     

Inhibition of CD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo.

The common acute lymphoblastic leukemia antigen [(CALLA) CD10, neutral endopeptidase 24.11 (NEP)] is a cell-surface zinc metalloprotease expressed by a subpopulation of early murine B-lymphoid progenitors and by bone marrow stromal cells that support the earliest stages of B lymphopoiesis. In previous in vitro studies in which uncommitted murine hematopoietic progenitors plated on a stromal cell layer differentiate into immature B cells, the inhibition of CD10/NEP increased early lymphoid colony numbers. To further characterize CD10/NEP function during lymphoid ontogeny in vivo, we utilized a Ly5 congenic mouse model in which the lymphoid differentiation of uncommitted hematopoietic progenitors from Ly5.1 donors was followed in sublethally irradiated Ly5.2 recipients treated with a specific long-acting CD10/NEP inhibitor (N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta- alanine (SCH32615)). The expression of Ly5.1, B220, and surface IgM (sIgM) was utilized to characterize donor-derived hematopoietic cells (Ly5.1+), B lymphocytes (B220+), and mature B cells (B220+ sIgM+) from the lymphoid organs of recipient animals treated with SCH32615 or vehicle alone. SCH32615-treated animals had higher percentages of Ly5.1+ donor splenocytes than animals treated with vehicle alone (16.9% vs. 10.4%, 63% increase, P = 0.013). Animals treated with the CD10/NEP inhibitor also had relatively more Ly5.1+ splenic B (B220+) cells than vehicle-treated animals (14.4% vs. 8.2%, 75% increase, P = 0.018). To more specifically characterize the effects of CD10/NEP inhibition on B-cell differentiation, Ly5.1+ splenocytes from animals treated with SCH32615 or vehicle alone were analyzed for coexpression of B220 and sIgM. Animals treated with the CD10/NEP inhibitor had a significantly higher percentage of mature donor B cells (Ly5.1+ B220+ sIgM+, 10.2% vs. 5.2%, 90% increase, P = 0.006) and a more modest relative increase in immature donor B cells (Ly5.1+ B220+ sIgM-, 4.7% vs. 3.4%, 38% increase, P = not significant). Taken together, these results suggest that CD10/NEP inhibition promotes the reconstitution and maturation of splenic B cells. Therefore, CD10/NEP may function to regulate B-cell ontogeny in vivo by hydrolyzing a peptide substrate that stimulates B-cell proliferation and/or differentiation.