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Biomedical subjects

G Carlone

Publications and source records attributed to G Carlone.

11 recordsLinked to original sources

Small angle x-ray scattering from lipid-bound myelin basic protein in solution.

The structure of myelin basic protein (MBP), purified from the myelin sheath in both lipid-free (LF-MBP) and lipid-bound (LB-MBP) forms, was investigated in solution by small angle x-ray scattering. The water-soluble LF-MBP, extracted at pH < 3.0 from defatted brain, is the classical preparation of MBP, commonly regarded as an intrinsically unfolded protein. LB-MBP is a lipoprotein-detergent complex extracted from myelin with its native lipidic environment at pH > 7.0. Under all conditions, the scattering from the two protein forms was different, indicating different molecular shapes. For the LB-MBP, well-defined scattering curves were obtained, suggesting that the protein had a unique, compact (but not globular) structure. Furthermore, these data were compatible with earlier results from molecular modeling calculations on the MBP structure which have been refined by us. In contrast, the LF-MBP data were in accordance with the expected open-coil conformation. The results represent the first direct structural information from x-ray scattering measurements on MBP in its native lipidic environment in solution.

Computer Simulation↗

Immunologic memory 5 years after meningococcal A/C conjugate vaccination in infancy.

Infant vaccination with meningococcal conjugates may provide long-term protection against disease. Antibody levels and immunologic memory were assessed in 5-year-old Gambian children who received meningococcal A/C conjugate vaccination (MenA/C) in infancy. At 2 years, they were randomized to receive a booster of MenA/C (conjugate group), meningococcal A/C polysaccharide (MPS group), or inactivated polio vaccine (IPV group). All groups were revaccinated with 10 microg MPS at 5 years of age, as were 39 previously unvaccinated age-matched control subjects. Before revaccination, titers were higher in the conjugate and MPS groups than in control subjects (P<.001); titers for the IPV group were similar to those for control subjects. Ten days after revaccination, the conjugate and IPV groups had similar serogroup C serum bactericidal antibody titers (3421 vs. 2790, respectively). These levels were significantly higher than those in the MPS (426) and control (485) groups (P<.001). Thus, immunologic memory was sustained for > or =5 years; however, MPS challenge at 2 years interfered with a subsequent memory response.

Adult↗

Safety and immunogenicity of three doses of a Neisseria meningitidis A + C diphtheria conjugate vaccine in infants from Niger.

BACKGROUND: High rates of endemic disease and recurrent epidemics of serogroup A and C meningococcal meningitis continue to occur in sub-Saharan Africa. A meningococcal A + C polysaccharide diphtheria-toxoid-conjugated vaccine may address this issue. METHODS: In Niger three doses of a bivalent meningococcal A + C diphtheria-toxoid-conjugated vaccine (MenD), containing 1, 4 or 16 microg of each polysaccharide per dose, administered at 6, 10 and 14 weeks of age, were compared with Haemophilus influenzae type b-tetanus toxoid-conjugated (PRP-T) vaccine given with the same schedule or with a meningococcal A + C polysaccharide vaccine (MenPS) given at 10 and 14 weeks of age. One blood sample was taken at the time of enrollment (6 weeks of age) and another was taken 4 weeks after the primary series. RESULTS: All doses of MenD were well-tolerated. After the primary series a higher proportion of infants had detectable serum bactericidal activity against serogroup A for each dose of MenD (from 94% to 100%) than for MenPS (31%) or H. influenzae type b-tetanus toxoid-conjugated vaccine (18.9%); P < or = 0.05. Significant differences were also observed for serogroup C MenD 4 microg or MenD 16 microg (100%) vs. MenPS (69.7%) or Haemophilus influenzae type b-tetanus toxoid-conjugated vaccine (24.3%); P < or = 0.05. When MenPS vaccine was given to 11-month-old children, the immune response measured by both enzyme-linked immunosorbent assay and serum bactericidal assay was greater in those previously immunized with MenD than in those immunized with MenPS vaccine. CONCLUSION: MenD was safe among infants in Niger, and immunization led to significantly greater functional antibody activity than with MenPS. The 4-microg dose of MenD for both the A and C serogroups has been selected for further studies.

Antibodies, Bacterial↗

Immune response to revaccination with meningococcal A and C polysaccharides in Gambian children following repeated immunisation during early childhood.

Forty-two Gambian children randomised to receive two doses of meningococcal A/C polysaccharide vaccine (MPS) in infancy and either MPS (n = 15), meningococcal A/C conjugate (n = 13) or inactivated polio vaccine (IPV n = 14) at 2 years, were revaccinated with MPS at 5 years of age along with 39 matched control children. Meningococcal A and C polysaccharide antibodies were analysed by ELISA and bactericidal assay (SBA) in sera taken before and 10 days after revaccination. The geometric mean group SBA titre in the MPS group following revaccination was about half that of the unvaccinated controls (0.51 95%CI: 0.28, 0.90) for group A and less than half that of the controls for group C (0.41, 95%CI: 0.16, 1.03 P = 0.06). The group C SBA response in the conjugate group was 14-fold higher than in the MPS group (P < 0.001). Multiple doses of meningococcal polysaccharide in childhood may therefore attenuate the SBA response to both group A and group C polysaccharides. In contrast, vaccination with meningococcal A/C conjugate after MPS in infancy gives immunological memory to N. meningitidis group C.

Antibodies, Bacterial↗

Safety of revaccination with pneumococcal polysaccharide vaccine.

CONTEXT: Revaccination of healthy adults with pneumococcal polysaccharide vaccine (PPV) within several years of first vaccination has been associated with a higher than expected frequency and severity of local injection site reactions. The risk of adverse events associated with revaccination of elderly and chronically ill persons 5 or more years after first vaccination, as is currently recommended, has not been well defined. OBJECTIVE: To determine whether revaccination with PPV at least 5 years after first vaccination is associated with more frequent or more serious adverse events than those following first vaccination. DESIGN: Comparative intervention study conducted between April 1996 and August 1997. PARTICIPANTS: Persons aged 50 to 74 years either who had never been vaccinated with PPV (n = 901) or who had been vaccinated once at least 5 years prior to enrollment (n = 513). INTERVENTION: PPV vaccination. MAIN OUTCOME MEASURES: Postvaccination local injection site reactions and prevaccination concentrations of type-specific antibodies. RESULTS: Those who were revaccinated were more likely than those who received their first vaccinations to report a local injection site reaction of at least 10.2 cm (4 in) in diameter within 2 days of vaccination: 11% (55/513) vs 3% (29/901) (relative risk [RR], 3.3; 95% confidence interval [CI], 2.1-5.1). These reactions resolved by a median of 3 days following vaccination. The highest rate was among revaccinated patients who were immunocompetent and did not have chronic illness: 15% (33/228) compared with 3% (10/337) among comparable patients receiving their first vaccinations (RR, 4.9; 95% CI, 2.4-9.7). The risk of these local reactions was significantly correlated with prevaccination geometric mean antibody concentrations. CONCLUSIONS: Physicians and patients should be aware that self-limited local injection site reactions occur more frequently following revaccination compared with first vaccination; however, this risk does not represent a contraindication to revaccination with PPV for recommended groups.

Aged↗

Relationship between cell surface carbohydrates and intrastrain variation on opsonophagocytosis of Streptococcus pneumoniae.

Streptococcus pneumoniae undergoes spontaneous phase variation between a transparent and an opaque colony phenotype, the latter being more virulent in a murine model of sepsis. Opaque pneumococci have previously been shown to express lower amounts of C polysaccharide (cell wall teichoic acid) and in this study were shown to have a higher content of capsular polysaccharide by immunoelectron microscopy. This report then examined the relationship between expression of these two cell surface carbohydrate structures and their relative contribution to the increased virulence of opaque variants. Comparison of genetically related strains showed that the differential content of capsular polysaccharide did not affect the amount of teichoic acid as measured by a capture enzyme-linked immunosorbent assay (ELISA). In contrast, when the teichoic acid structure was altered by replacing choline in the growth medium with structural analogs, the quantity of capsular polysaccharide as measured by a capture ELISA was decreased, demonstrating a linkage in the expression of the two surface carbohydrate structures. A standardized assay was used to assess the relative contribution of cell surface carbohydrates to opsonophagocytosis. The opaque variants required 1.2- to 30-fold more immune human serum to achieve 50% opsonophagocytic killing than did related transparent variants (types 6B and 9V). The opsonophagocytic titer was proportional to the quantity of capsular polysaccharide rather than teichoic acid. The major factor in binding of the opsonin, C-reactive protein (CRP), was also the amount of capsular polysaccharide rather than the teichoic acid ligand. Only for the transparent variant (type 6B), which bound more CRP, was there enhanced opsonophagocytic killing in the presence of this serum protein. Increased expression of capsular polysaccharide, therefore, appeared to be the major factor in the decreased opsonophagocytic killing of opaque pneumococci.

Animals↗

Dermatoglyphics in von Recklinghausen neurofibromatosis.

We studied dermatoglyphic traits in 27 patients (12 males and 15 females) with neurofibromatosis type I (NF-1) to verify which characteristics may be considered typical of this disorder. The frequency of digital central pockets in the patients was significantly greater than in control individuals (P less than .005), but when we evaluated the sexes separately, the difference was significant only among females (P less than .002). The distribution of central pockets on the various fingers was significantly different in affected females, compared with normal controls, but only on fingers II (P less than .05), IV (P .002), and V (P less than .05). The quantitative finger tip pattern values and the total finger ridge count (TFRC) were always higher in the patients, as well as was the a-b ridge count. The latter was significantly increased only on the right hand in females (P less than .01). Among the patients, the atd angle values were increased on both hands of females and on the right hand in males, whereas both the ulnar index A'-d and the a-t' ridge counts were diminished. The frequency of high endings (5' or 5") of line A was increased in NF-1 patients on both hands. Like in previous investigations, our patients showed an increased number of secondary creases, limited to II degree according to Vormittag et al. [1986] (P less than .048). Our results only partially confirmed prior data. Therefore, we think that there is no typical dermatoglyphic pattern in NF-1 and that this parameter is not a diagnostic indicator in this disorder.

Adolescent↗

Enamel defects in a case of Menkes' syndrome.

A patient affected by Menkes' syndrome presents some dental abnormalities, such as enamel defects, delayed eruption and a biconically shaped incisor. The deficient action of a cuproenzyme in this syndrome leads us to hypothesize an explanation of defective enamel formation.

Brain Diseases, Metabolic↗

Extracorporeal photochemotherapy reduces the severity of Lewis rat experimental allergic encephalomyelitis through a modulation of the function of peripheral blood mononuclear cells.

Extra corporeal photochemotherapy (ECP) is an immunomodulating procedure used in several nonneurological diseases which, similarly to multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity and it is probable that ECP can modulate the normal activity of peripheral blood mononuclear cells (PBMC). Using the Lewis rat experimental allergic encephalomyelitis (EAE) model of human multiple sclerosis (MS) we examined the effect of extracorporeal UV-A irradiation on psoralen-activated PBMC. In our experiment the comparison between the two groups of animals (ECP or sham-treatment) evidenced that the ECP treatment reduced the severity of EAE on clinical grounds and this result was confirmed by the pathological examination. The changes in the titers of anti-myelin antigen antibodies typical of EAE were also modulated by the procedure. Ex vivo examination evidenced a significant reduction in tumor-necrosis factor-alpha (TNF-alpha) released by PBMC after lipopolysaccharides (LPS) stimulation in culture. We conclude that ECP modifies the normal activity of PBMC during the course of EAE and it is possible that one of the anti-inflammatory mechanisms of action of ECP is correlated to a down-regulation of T-helper 1 lymphocytes activity.

Animals↗