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J Figueroa

Publications and source records attributed to J Figueroa.

At least 55 records · Page 3Linked to original sources
PubMed1993

Vaccination with SPf66, a chemically synthesised vaccine, against Plasmodium falciparum malaria in Colombia.

Preclinical and clinical studies have established the safety and immunogenicity of the chemically synthesised SPf66 malaria vaccine. The present study is a phase III randomised, double-blind, placebo-controlled, efficacy trial completed in La Tola, Colombia. 1548 volunteers over one year of age received three doses of either the vaccine (n = 738) or placebo (n = 810). Active and passive case detection methods were used to document clinical episodes of malaria among the study population. The follow-up period began one month after the third dose and lasted for one year. 168 and 297 episodes of Plasmodium falciparum malaria were documented in the SPf66 group and the placebo group, respectively; this corresponds to a crude protective efficacy of 38.8%. Incidence rates for first or only P falciparum malarial episodes were 22.3% per annum among the vaccinee group and 33.5% among the placebo group (RR = 1.5; 95% Cl 1.23, 1.84). Therefore, the protective efficacy of SPf66 against first or only episodes was 33.6% (95% Cl 18.8, 45.7), being highest in children aged 1-4 years (77%) and adults older than 45 years (67%). The estimated protective efficacy against second episodes was 50.5% (95% Cl 12.9-71.9). Our study shows that the chemically synthesised SPf66 malaria vaccine is safe, immunogenic, and protective against P falciparum malaria in semi-immune populations subject to natural challenge.

Adolescent↗
PubMed1993

Complement deficiency states and meningococcal disease.

Analysis of complement deficiency states has supported the role of complement in host defense and elucidated diseases associated with defective complement function. Although neisserial infection plays a prominent role in these deficiency states, examination of individuals with late complement component deficiency (LCCD) reveals a particular propensity for recurrent meningococcal disease and provides important clues to the role of complement in neisserial infections. In response to meningococcal disease, LCCD individuals produce significantly greater amounts of antilipooligosaccharide (LOS) antibody which can kill group B meningococcus in a complement-sufficient in vitro system. Further studies of antibody cross-reactivity to other meningococci has led to a clearer understanding of its epitopic specificity. Nevertheless, epidemiologic evidence is consistent with the relative absence of protective immunity in LCCD persons following an episode of infection and supported by quantitation of antibody to capsular polysaccharide. However, compared to anti-LOS antibodies, anticapsular antibodies can offer immune protection to LCCD individuals via complement-dependent opsonophagocytosis--the only form of complement-mediated killing available to these persons. Thus vaccination of LCCD persons with capsular antigens is considered an important means of protecting these high-risk individuals against meningococcal disease.

Complement System Proteins↗
PubMed1993

Oral administration of insulin in winter-acclimatized carp (Cyprinus carpio) induces hepatic ultrastructural changes.

1. The intestinal absorption of insulin in carps was assessed examining the transepithelial passage of ingested gold-labeled hormone by electron microscopy. Insulin transfer occurred mainly through the intercellular spaces between the enterocytes. 2. When reaching the lamina propria, the gold-labeled hormone gathered predominantly around the granules of the granular cells, and therefore can enter the circulatory system via the blood capillaries which are found in close contact with these cells. 3. Winter-acclimatized carp were also capable of internalizing the hormone when fed with insulin. 4. Furthermore, the absorbed hormone revealed full activity in regard to the observed changes in the ultrastructure of the liver cells of the treated cold-adapted fish. 5. The fish ingesting the hormone underwent the same type of hepatic ultrastructure reprogramming observed when winter-acclimatized carps are injected intraperitoneally with insulin, i.e. conversion to a phenotype corresponding to hepatocytes from summer-adapted carp. 6. The oral absorption of insulin by winter-acclimatized fish and its effect in reversing the cold-adaptive state might be useful for the fish culturing industry.

Acclimatization↗
PubMed1993

Suppression of synthesis of natural antibodies by mycophenolate mofetil (RS-61443). Its potential use in discordant xenografting.

One of the major barriers to successful transplantation of immediately vascularized organs between discordant species is the presence of natural antibodies (NA) in the recipient. While natural antibodies can be depleted by plasmapheresis and/or organ absorption, they rapidly return to the circulation after such procedures. It will be desirable to suppress NA for longer periods of time. Since NA appear to be produced at least in part by CD5+ B cells, it was important to evaluate whether mycophenolate mofetil (RS-61443), a novel immunosuppressant that has been shown to suppress normally elicited antibody synthesis, would also be able to suppress NA. Adult rats were splenectomized, and 2 days later, 9 plasma exchanges, each of 4 ml, were performed. One group of rats received RS-61443 at 40 mg/kg/day (the dose described as efficacious for suppressing elicited antibodies in rats) starting immediately after the last exchange for 7 days, and then 20 mg/kg/day for an additional 7 days; no drug was given to the control group. NA levels were measured at various times by ELISA, using guinea pig platelets extracts as the target. Splenectomy alone led to a significant decrease from the control levels of NA; titers were further reduced by the plasma exchanges. In the absence of RS-61443, NA titers rose steadily, starting at 24 hr after the last plasma exchange. In contrast, administration of RS-61443 resulted in levels of NA on day 7 not significantly different from those after plasma exchange, reducing the dose of RS-61443 to the 20 mg/kg/day level during week 2 allowed the gradual return of NA. Administration of RS-61443 at the 40 mg/kg/day dose to rats after splenectomy alone led to a clear and significant further decrease in NA levels over the first week. It has been shown that RS-61443 can be administered for longer periods. The data presented suggest that use of this drug, perhaps with more conventional agents, may allow suppression of NA for a significant period after transplantation.

Animals↗
PubMed1993

In vivo depletion of xenoreactive natural antibodies with an anti-mu monoclonal antibody.

Hyperacute rejection of vascularized discordant xenografts, such as pig-to-primate kidney or heart xenotransplants, is thought to be mediated by xenoreactive natural antibodies (XNA) of the IgM isotype and the activation of the classic pathway of complement. Using the guinea pig-to-rat discordant xenograft model, we have developed a potential therapeutic protocol leading to long-term depletion of circulating IgM in adult animals. This protocol consists of the injection into adult LOU/C rats of an antirat IgM MAb (MARM-7) after splenectomy, plasma exchange, and the administration of an anti-B cell immunosuppressant, mycophenylate mofetil (RS61443). Splectomized plasma exchanged adult rats receiving RS61443 showed strongly decreased IgG and IgM serum concentrations for a relatively short period during which these isotypes remained nevertheless detectable by a sensitive ELISA technique. In contrast to IgM, IgG in serum returned, shortly after the end of this treatment, to normal concentrations. Splenectomy alone was able to significantly decrease, for a long period (more than 70 days), IgM but not IgG serum concentrations in these rats. During this treatment, IgM XNA concentration mirrored total IgM. The injection of MARM-7 MAb to adult LOU/C rats was able to deplete circulating IgM and IgM XNA for a period of several weeks during which IgM was undetectable by a sensitive ELISA technique. Depletion time was dose-dependent--the higher the dose of injected MARM-7, the longer the period for which IgM and IgM XNA remained undetectable. Moreover depletion of circulating IgM was correlated with the detection in the serum of these rats of noncomplexed, free MARM-7. Finally, MARM-7 administration was significantly more efficacious in rats that had decreased levels of circulating IgM after splenectomy, plasma exchange, and administration of RS61443. These experiments suggest that the anti-mu approach may allow depletion of IgM XNA for a sufficiently long period to test the hypothesis of "accommodation" in other xenograft models such as the pig-to-primate xenograft or even in ABO-incompatible allografts.

Animals↗
PubMed1993

Reprogramming of nucleolar gene expression during the acclimatization of the carp.

During seasonal acclimatization of eurythermal fish, the nucleolus of the hepatocyte undergoes ultrastructural reprogramming. In winter acclimatized carp, the nucleolar components are segregated, a condition that suggests a decreased transcription of rRNA. The same nucleolar reorganization was observed when pituitary cells from winter- and summer-acclimatized carp were examined. In situ analyses of nucleolar RNA revealed a marked lowering of RNA content in the segregated nucleoli. Accordingly, in vitro synthesis of RNA was shown to be significantly lower in pituitary tissue from cold-acclimatized fish where precursor accumulated. Conversely, in pituitary tissue from summer-adapted fish the rate and extent of synthesis and of rRNA processing was notably higher. The involvement of pre-rRNA processing events during seasonal acclimatization was corroborated by the strong differences of U3 RNA content detected by in situ hybridization in pituitary cells from summer- and winter-fish. When RNA polymerase I activity from both acclimatized states were assayed, no differences were detected. Thus, it appears that in fish RNA polymerase I itself does not play an important role in the control of nucleolar gene expression and the nucleolar gene expression reprogramming that the seasonal rearrangement represents might involve, among the many nucleolar-specific proteins, transcription factors.

Acclimatization↗
PubMed1992

Evidence that 15-deoxyspergualin inhibits natural antibody production but fails to prevent hyperacute rejection in a discordant xenograft model.

Preventing hyperacute rejection (HAR) is a difficult and unsolved problem in xenotransplantation. This may be due, in part, to a lack of therapies that can suppress production of natural antibodies (NA), which are thought to be critical mediators of HAR. This study examined the effect of 15-deoxyspergualin (DSPG) and splenectomy (Spx) on NA production and return of NA after plasma exchange (PE) in a discordant species combination (strain 2 guinea pig to Lewis rat). A dose of 5 mg/kg/day DSPG + Spx significantly reduced Lewis rat anti-guinea pig NA titer after one week of therapy. Antibody titer was not significantly reduced in rats treated with splenectomy alone. PE alone acutely depleted NA titers; however, complete rebound was seen in 48 hr. When PE was performed in rats treated with DSPG + Spx, an additional significant NA reduction occurred; no rebound 24-48 hr after PE was seen. Except for a 20% reduction in body weight, no serious complications occurred in DSPG + Spx recipients. Despite a profound NA titer reduction, treatment with DSPG, Spx, and PE did not prolong guinea pig cardiac xenograft survival in a clinically significant fashion. Immunopathological study of rejected cardiac xenografts revealed no antibody deposition but persistent complement deposition on vascular endothelium. We conclude that DSPG + Spx effectively inhibits synthesis of rat anti-guinea pig NA, that further NA titer reduction can be achieved with the addition of PE, and that DSPG + Spx prevents post-PE antibody rebound. We also conclude that the limited prolongation in cardiac xenograft survival achieved, despite marked suppression of NA, supports a complement-mediated mechanism of HAR in our animal model.

Animals↗
PubMed1991

Na+/Na+ exchange and Na+/H+ antiport in rabbit erythrocytes: two distinct transport systems.

Rabbit erythrocytes are well known for possessing highly active Na+/Na- and Na+/H+ countertransport systems. Since these two transport systems share many similar properties, the possibility exists that they represent different transport modes of a single transport molecule. Therefore, we evaluated this hypothesis by measuring Na+ transport through these exchangers in acid-loaded cells. In addition, selective inhibitors of these transport systems such as ethylisopropyl-amiloride (EIPA) and N-ethymaleimide (NEM) were used. Na+/Na+ exchange activity, determined as the Na+o-dependent 22Na efflux or Na+i-induced 22Na entry was completely abolished by NEM. This inhibitor, however, did not affect the H+i-induced Na+ entry sensitive to amiloride (Na+/H+ exchange activity). Similarly, EIPA, a strong inhibitor of the Na+/H+ exchanger, did not inhibit Na+/Na- countertransport, suggesting the independent nature of both transport systems. The possibility that the NEM-sensitive Na+/Na+ exchanger could be involved in Na+/H+ countertransport was suggested by studies in which the net Na+ transport sensitive to NEM was determined. As expected, net Na+ transport through this transport system was zero at different [Na+]i/[Na+]o ratios when intracellular pH was 7.2. However, at pHi = 6.1, net Na+ influx occurred when [Na+]i was lower than 39 mM. Valinomycin, which at low [K+]o clamps the membrane potential close to the K+ equilibrium potential, did not affect the net NEM-sensitive Na+ entry but markedly stimulated the EIPA- and NEM-resistant Na+ uptake. This suggest that the net Na+ entry through the NEM-sensitive pathway at low pHi, is mediated by electroneutral process possibly involving Na+/H+ exchange. In contrast, the EIPA-sensitive Na+/H+ exchanger is not involved in Na+/Na+ countertransport, because Na+ transport through this mechanism is not affected by an increase in cell Na+ from 0.4 to 39 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1991

Production of species-specific murine monoclonal antibodies against Cryptococcus neoformans which recognize a noncapsular exoantigen.

Three monoclonal antibodies (MAbs), designated 7C5, 7C9, and 5G8, against a cytoplasmic antigen of Cryptococcus neoformans were produced. MAbs 7C5 and 7C9 recognize culture filtrate antigen (exoantigen) of both encapsulated and nonencapsulated isolates of this pathogen, which suggests that they do not recognize capsular polysaccharide material. This is supported by immunofluorescence data which show reactivity of all 3 MAbs to cytoplasm and cell membranes only. MAb 7C9 also recognized C. neoformans var. gattii antigens but no other fungal pathogens tested in an enzyme-linked immunosorbent assay, while 7C5 and 5G8 recognized antigens of the cross-reactive pathogen Trichosporon beigelii but did not recognize either C. neoformans var. gattii isolates or any other fungal antigens. By Western blot (immunoblot), 7C9 detected antigen at 110 to 120, 65 to 70, 45 to 50, and 36 to 38 kDa; in addition to the latter band, the other two MAbs recognized a band at approximately 30 kDa. All three MAbs were of the immunoglobulin G1 subclass. The two MAbs which are capable of reacting with noncapsular culture supernatant antigen have possible uses in serodiagnosis, particularly in AIDS patients infected with C. neoformans, since in this group the present latex agglutination test has some limitations.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Vasotocin genes of the teleost fish Catostomus commersoni: gene structure, exon-intron boundary, and hormone precursor organization.

cDNA clones encoding two members of the vasotocin hormone precursor gene family have been isolated from the white sucker Catostomus commersoni. The hormone is encoded by at least two distinct genes, both of which are expressed, as indicated by Northern blot analysis. Genomic DNA amplified by the polymerase chain reaction has been used to define exon-intron boundaries. Both vasotocin genes contain introns in positions corresponding to those found in the gene of their mammalian counterpart vasopressin. The predicted vasotocin precursors show a surprising degree of sequence divergence, amounting to 45% at the amino acid level, of which only approximately half can be accounted for by conservative amino acid changes. The precursors include a hormone moiety followed by a putative neurophysin sequence that is longer at the C-terminus by a tract of some 30 amino acids by comparison to their mammalian counterpart. Each of these sequences contains a leucine-rich core segment resembling that found in copeptin, a glycopeptide moiety present in mammalian vasopressin precursors.

Amino Acid Sequence↗
PubMed1990

A murine monoclonal antibody exhibiting high species specificity for Histoplasma capsulatum var. capsulatum.

A monoclonal antibody (mAb) exhibiting a high degree of species specificity for the yeast phase of the dimorphic fungus Histoplasma capsulatum was produced by a modification of the standard mAb production protocol. The technique for generating mAbs involved the use of the immunosuppressive drug cyclophosphamide to diminish the response in mice to immunodominant cross-reactive epitopes. This mAb exhibited clear specificity and did not react by ELISA with the closely related genera Blastomyces, Paracoccidioides and Sporothrix. In Western blots it recognized a linear determinant on a 70-75 kDa molecule in H. capsulatum antigen, with an extremely faint reactivity to antigens of identical molecular mass derived from Sporothrix and Paracoccidioides, and no reactivity against Blastomyces antigen.

Animals↗
PubMed1990

Leprosy in Puerto Rico: a decade later.

A study to evaluate the changes in the incidence and prevalence of leprosy in Puerto Rico was done to include the years 1981-1989. During this period, 75 new cases were diagnosed with an average of 8.3 cases per year. The yearly incidence was 1.9 cases per million which is significantly lower to the 4.6 per million in the previous study. At the present moment 182 cases are been followed at the Tropical Diseases Clinic of the University of Puerto Rico School of Medicine with a prevalence of 5.4 per 100,000 inhabitants. It is important to notice that 16 percent of the patients at the clinic were foreigners, a significant increase from a previous study. The decrease in the incidence of leprosy may be due to advances in the treatment of the disease and the new approach to integrate the patient into the community.

Adolescent↗
PubMed1990

Evidence that the M antigen of Histoplasma capsulatum var. capsulatum is a catalase which exhibits cross-reactivity with other dimorphic fungi.

A panel of monoclonal antibodies (Mabs) was raised against histoplasmin, the antigen derived from the mycelial phase of Histoplasma capsulatum var. capsulatum which contains the diagnostically useful H and M antigens. A number of Mabs were obtained which recognized a 70-75 kD component of an antigenic preparation of H. capsulatum var. capsulatum by Western blotting. When reacted with histoplasmin by Western blotting the Mabs recognized a similar 70-75 kD band, together with a series of higher molecular mass bands at approximately 130, 190 and 230 kD, a pattern which correlates strongly with both the published relative molecular mass (Mr) of the M antigen and the known subunit structure of the enzyme catalase. These Mabs were also shown to recognize a commercial preparation of Aspergillus niger catalase by ELISA. Other dimorphic fungi were also reactive with these Mabs by Western blotting, indicating the presence of common epitopes on the catalase molecules of these species.

Antibodies, Monoclonal↗
PubMed1989

Presence of RNA in the sperm nucleus.

The RNase-colloidal gold procedure for the ultrastructural localization of RNA was used for rat testis. Along with other structures, it was found that the testicular sperm nucleus was well stained. Similar labelling was observed in the nucleus of rat epididymal sperm and human sperm. The RNA was extracted from sperm and analyzed by electrophoresis on 10% polyacrylamide gel and 7 M urea. The electrophoretic profile revealed a complex set of bands ranging in size from tRNA to high molecular weight components. On the average, a content of about 0.1 pg of RNA per rat or human sperm was found.

Animals↗
PubMed1989

Two isotocin genes are present in the white sucker Catostomus commersoni both lacking introns in their protein coding regions.

Two genes each encoding a distinct precursor protein to the hormone isotocin and a neurophysin-related protein are present in the teleost fish Catostomus commersoni. These precursors are referred to as isotocin 1 and 2. As shown by the polymerase chain reaction technique, both genes lack introns in their protein-coding sequences. Both genes are transcribed giving rise to mRNAs of 920 (isotocin 1) and 1020 (isotocin 2) bases, respectively. Based on the nucleotide sequences, the predicted isotocin precursors contain, besides the hormone moiety, a neurophysin-like protein that, in contrast to its mammalian counterpart, is extended at its C-terminus by a peptide which includes a leucine-rich core segment. This segment shows similarities to the copeptin of the mammalian vasopressin precursor that is known to possess prolactin-releasing activity. The data imply that the mammalian copeptin sequence was initially part of a larger ancestral neurophysin molecule.

Amino Acid Sequence↗