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R Lagos

Publications and source records attributed to R Lagos.

54 records · Page 3Linked to original sources
PubMed1993

[Tolerance and immunogenicity of an oral dose of CVD 103-HgR, a live attenuated Vibrio cholerae 01 strain: a double-blind study of Chilean adults].

CVD 103-HgR is an attenuated, AB+, live, recombinant vaccine strain, developed by deletion of the toxA gen in a virulent Vibrio cholerae 01, Inada classical strain (569B). In phase II studies conducted to date, CVD 103-HgR has been well tolerated and immunogenic in volunteers from both industrialized countries and cholera-endemic areas. In this study of safety, immunogenicity and excretion, 81 Chilean adults were randomly allocated to receive, in a double blind fashion, a single oral dose of 5 x 10(9) FU of CVD 103-HgR or placebo, (5 x 10(9) heat-killed E. Coli K12 organisms), in 100 ml of buffered water. Side effects were assessed by daily visits to the participants. Immunogenicity, (vibriocidal seroconversion), was investigated in blood drawn before and on days 8 and 28 after immunization, while stool cultures to assess excretion of the vaccine strain were performed on specimens obtained on days 1 and 7. None of the participants, (40 vaccinees and 41 placebo recipients), experienced untoward effects during 30 minutes of close surveillance after ingestion of the preparation; upon follow up, neither adverse events were more frequently reported by the vaccinees. 34/40 vaccinees, and 2/41 participants receiving placebo had a significant raise, (> = fourfold), in their vibriocidal titers; (85 vs 2%, p < 0.001). The peak postimmunization geometric mean titer, (222), was ten fold higher than the baseline vibriocidal titer. The vaccine strain was recovered in stool cultures from 8 participants, one of them excreted the strain in both specimens. We conclude that CVD-103-HgR is safe and immunogenic in Chilean adults.

Administration, Oral↗
PubMed1992

Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru.

We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity.

Bacterial Proteins↗
PubMed1991

Molecular epidemiology of Haemophilus influenzae within families in Santiago, Chile.

Thirty-six consecutive patients with invasive Haemophilus influenzae type b (Hib) infections at Roberto del Rio Children's Hospital, Santiago, Chile, were enrolled in a prospective study. Throat cultures were obtained from household contacts of each index case, adjacent neighbors, and matched community control households. Colonization rates for H. influenzae were comparable among groups; however, among household contacts 18% of colonizing isolates were Hib, compared with 2% and 3% among neighbor and community controls. When selected isolates were evaluated further by outer membrane protein (OMP) profiles and multilocus enzyme electrophoresis, only one of the four Hib isolates from household members matched the corresponding index case isolate. One serologically nontypeable isolate from a household contact had an OMP profile and electrophoretic type identical to that of the corresponding Hib index case isolate; hybridization studies with a 9-kb capsular gene probe showed a profile consistent with a capsule-deficient mutant. Hib strains were isolated more frequently from household contacts than from control persons living in Santiago, but colonizing Hib strains were often unrelated to the index case strain.

Bacterial Outer Membrane Proteins↗
PubMed1991

Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model.

Citrobacter diversus is a cause of devastating neonatal meningitis, with illness characterized by formation of multiple brain abscesses. We developed an infant mouse intracranial inoculation model to evaluate the pathophysiology of C. diversus neonatal infections. Eighteen of 26 strains inoculated intracranially at a dose of ca. 3.3 x 10(3) CFU caused greater than 50% mortality in 2-day-old mice. No correlation was seen between the epidemiologic characteristics of a strain and its rate of mortality. When seven C. diversus isolates (four isolates from patients with meningitis, three from non-central nervous system [CNS] sites) were further evaluated, mortality was significantly correlated with bacteremia. The initial lesion in the CNS was a suppurative ventriculitis beginning 1 to 2 days postinoculation. Subsequent ventriculomegaly was associated with ventriculitis and periventricular abscessation. Brain lesions were seen with all strains, although strains of low virulence (as measured by having no bacteremia and low mortality) caused less-severe damage. An age-related susceptibility to C. diversus brain lesions was demonstrated, with 5-day-old mice showing a significant reduction in, and 8-day-old mice being apparently resistant to, infection and CNS damage. Our data indicate that C. diversus has a propensity to cause abscess formation in the neonatal mouse brain, with characteristic pathologic findings; however, the factors that determine whether a strain will cause meningitis in a human infant remain to be identified.

Animals↗
PubMed1987

Evolutionary relationship between plasmids and phages: phasmid P4 as a model.

Phasmid (phage-plasmid) P4 is capable of propagating as a temperate phage, lytic helper-dependent phage, and as a plasmid (pP4vir1). Alteration of cellular growth conditions can be used to manipulate the copy number (n) of pP4vir1 from low (n = 1-2) to high (n = 30-40). The levels of gene expression of P4 in the plasmid and phage states are radically different. While there is high expression of P4 proteins in the phage state, low levels of gene expression are found in the plasmid mode of propagation thereby allowing pP4vir1 to remain intracellularly without perturbing host homeostasis. Possible evolutionary origins of phasmid P4 are discussed.

Bacteriophage P2↗
PubMed1986

Rho-dependent transcription termination of a bacterial operon is antagonized by an extrachromosomal gene product.

The psu gene product of "phasmid" (phage-plasmid) P4 acts as a transcription antitermination factor in trans and in cis, respectively, within the morphogenic operons of its P2 phage helper during lytic viral development and on P4 itself during the establishment stage of its alternative mode of propagation as a plasmid. Here we show that psu also antagonizes activity of the Escherichia coli transcription termination factor rho at the terminator of the trp operon. Such a finding provides to our knowledge the first direct evidence for antitermination activity at a known rho-dependent site by the psu gene product. It also reveals an example of an extrachromosomal gene product that acts on specific sites of three different genomes to regulate expression of unlinked families of genes.

Coliphages↗
PubMed1984

Phasmid P4: manipulation of plasmid copy number and induction from the integrated state.

"Phasmid" P4 is unusual in that it is capable of (i) temperate, (ii) lytic, helper-dependent, and (iii) plasmid modes of propagation. In this report we characterize most of the known P4 genetic functions as to their essential or nonessential roles in the stable maintenance of plasmid P4 vir1 (pP4 vir1 (pP4 vir1). We also identify growth conditions that can be used to stably maintain pP4 vir1 at any one of several different copy number levels (n = 1 to 3, n = 10 to 15, or n = 30 to 40). Analyses of a temperature-sensitive alpha derivative of pP4 vir1 show that shifting the temperature from 37 to 42 degrees C allows this mutant to maintain an integrated copy of the plasmid, whereas replication of free copies is repressed because of the nonpermissive condition for their DNA synthesis. Conversely, a shift from 42 to 37 degrees C can be used to reinstate plasmid propagation. The utility of the inducible states of pP4 vir1 is discussed with respect to its attributes as a vector with the potential for cloning inserts of DNA up to 33,000 base pairs in a wide range of bacterial hosts.

Coliphages↗
PubMed1983

Characterization of the Ca2+- or Mg2+-ATPase of transverse tubule membranes isolated from rabbit skeletal muscle.

Transverse tubule membranes isolated from rabbit skeletal muscle have high levels of a Ca2+- or Mg2+-ATPase with Km values for Ca-ATP or Mg-ATP in the 0.2 mM range, but do not display detectable levels of ATPase activity activated by micromolar [Ca2+]. The transverse tubule enzyme is less temperature or pH dependent than the Ca2+-ATPase of sarcoplasmic reticulum and hydrolyzes equally well ATP, ITP, UTP, CTP, and GTP. Of several ionic, non-ionic, and zwitterionic detergents tested, only lysolecithin solubilizes the transverse tubule membrane while preserving ATPase activity. After extraction of about 50% of the transverse tubule proteins by solubilization with lysolecithin most of the ATPase activity remains membrane bound, indicating that the Ca2+- or Mg2+-ATPase is an intrinsic membrane enzyme. A second extraction of the remaining transverse tubule proteins with lysolecithin results in solubilization and partial purification of the enzyme. Sedimentation of the Ca2+- or Mg2+-ATPase, partially purified by lysolecithin solubilization, through a continuous sucrose gradient devoid of detergent leads to additional purification, with an overall 3- to 5-fold purification factor. The purified enzyme preparation contains two main protein components of molecular weights 107,000 and 30,000. Cholesterol, which is highly enriched in the transverse tubule membrane, copurifies with the enzyme. Transverse tubule membrane vesicles also display ATP-dependent calcium transport which is not affected by phosphate or oxalate. The possibility that the Ca2+- or Mg2+-ATPase is the enzyme responsible for the Ca2+ transport displayed by isolated transverse tubules is discussed.

Adenosine Triphosphatases↗
PubMed1981

Ontogeny of chick liver hexokinase isozymes.

Glucose phosphorylating activities were measured in liver extracts from chicks at several developmental stages. Enzyme activity levels in supernates were low (about 0.16 units/g liver) from day 10th of egg incubation until the 17th day, at which time a transient increase to 0.5 units/g was observed. At hatching, the levels were again low (0.15 units/g) compared to adult levels (0.9 units/g). Particulate hexokinase activity was rather constant from day 10th to adulthood (about 0.3 units/g). Chromatography of liver supernates in DEAE-cellulose columns revealed the presence of four hexokinases in embryos up to day 15th of incubation. From that day onwards, the least retained from (hexokinase 4) was no longer found. The most retained form (hexokinase 1) disappeared at hatching, at which time a pattern consisting of hexokinases 2 and 3 was found to be very similar to the adult profile. The four isozymes were characterized as low Km glucose hexokinase of broad sugar specificities and molecular weights of about 100,000. Particulate hexokinase activity of embryonic chick liver was found to be composed of the same isozymes observed in cytosolic extracts. Incubation of particles with glucose 6-P or ATP failed to release hexokinase activity.

Animals↗
PubMedDate not supplied

Safety and immunogenicity of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine administered in a dual-chamber syringe to infants in Belgium and Chile.

To document any unexpected differences in the immune response between study populations and to evaluate immunogenicity and safety of a simplified presentation (dual-chamber syringe) of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine, a multicentre, randomized, comparative study was conducted in Belgium and Chile. A total of 537 healthy infants, 270 in Chile and 267 in Belgium, received PRP-T and DTP vaccines combined in a dual-chamber syringe (D-Ch group, DTP/PRP-T, reconstituted by pressing the plunger of the syringe immediately before injection, n = 239) or combined in a single-chamber syringe (C-In group, DTP@PRP-T, reconstituted immediately before injection, n = 61) or in separate injections (S-In group, DTP + PRP-T, simultaneously injected at separate sites, n = 237) at 3, 4, and 5 months of age. Serum samples were collected before vaccination and at 6 months of age. In the D-Ch group, the incidence of adverse events was comparable to administration of DTP vaccine alone. Higher rates of local and systemic reactions were observed in the Chilean population, possibly due to differences in surveillance practice. The immune response to each vaccine component compared well to that of the separate administration of PRP-T and DTP vaccines, except for higher post-immunization anti-PRP geometric mean titre (GMT) values after separate injections (25.6 micrograms mL-1) than after combined injection with the dual-chamber syringe (17.6 micrograms mL-1) (p = 0.001). An unexpected 'syringe' effect was seen: a greater post-immunization anti-PRP GMT was observed in the D-Ch group (17.6 micrograms mL-1) than in the C-In group (7.7 micrograms mL-1) (p = 0.0001). Whereas pre-immunization GMTs of some antibodies were significantly lower in Chilean than in Belgian infants, the post-immunization GMTs of Chilean infants were two to three times greater for all of the antibodies studied (p < 0.005). Differences in reactogenicity and in the immune response between the study populations or the different vaccine presentations were striking, but are probably of no clinical relevance. The convenient dual-chamber syringe presentation of DTP and PRP-T vaccines is safe and highly immunogenic.

Antibodies, Bacterial↗
PubMedDate not supplied

[Urinary tract infections].

During the past ten years, new concepts on host-parasite interaction have allowed better understanding of the pathogenesis of urinary tract infections (UTI). In addition, significant progress has been achieved with the development of new methods for differentiating upper and lower UTI. This review is intended to discuss current information about virulence factors of Escherichia coli, host genetic risk markers associated to recurrence and complications, and new diagnostic tools for localizing the anatomic place of urinary tract infections.

Adolescent↗