PubMed Health⌕ Search

Biomedical subjects

T Rubio

Publications and source records attributed to T Rubio.

At least 19 recordsLinked to original sources

Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.

UNLABELLED: We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. STUDY DESIGN: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. RESULTS: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. CONCLUSION: We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

Adolescent↗

Restoration of wild-type virus by double recombination of tombusvirus mutants with a host transgene.

Nicotiana benthamiana plants transformed with the coat protein gene of tomato bushy stunt virus (TBSV) failed to elicit effective virus resistance when inoculated with wildtype virus. Subsequently, R1 and R2 progeny from 13 transgenic lines were inoculated with a TBSV mutant containing a defective coat protein gene. Mild symptoms typical of those elicited in nontransformed plants infected with the TBSV mutant initially appeared. However, within 2 to 4 weeks, up to 20% of the transgenic plants sporadically began to develop the lethal syndrome characteristic of wild-type virus infections. RNA hybridization and immunoblot analyses of these plants and nontransformed N. benthamiana inoculated with virus from the transgenic lines indicated that wild-type virus had been regenerated by a double recombination event between the defective virus and the coat protein transgene. Similar results were obtained with a TBSV deletion mutant containing a nucleotide sequence marker, and with a chimeric cucumber necrosis virus (CNV) containing the defective TBSV coat protein gene. In both cases, purified virions contained wild-type TBSV RNA or CNV chimeric RNA derived by recombination with the transgenic coat protein mRNA. These results thus demonstrate that recombinant tombus-viruses can arise frequently from viral genes expressed in transgenic plants.

Capsid↗

Broad-spectrum protection against tombusviruses elicited by defective interfering RNAs in transgenic plants.

We have designed a DNA cassette to transcribe defective interfering (DI) RNAs of tomato bushy stunt virus (TBSV) and have investigated their potential to protect transgenic Nicotiana benthamiana plants from tombusvirus infections. To produce RNAs with authentic 5' and 3' termini identical to those of the native B10 DI RNA, the DI RNA sequences were flanked by ribozymes (RzDI). When RzDI RNAs transcribed in vitro were mixed with parental TBSV transcripts and inoculated into protoplasts or plants, they became amplified, reduced the accumulation of the parental RNA, and mediated attenuation of the lethal syndrome characteristic of TBSV infections. Analysis of F1 and F2 RzDI transformants indicated that uninfected plants expressed the DI RNAs in low abundance, but these RNAs were amplified to very high levels during TBSV infection. By two weeks postinoculation with TBSV, all untransformed N. benthamiana plants and transformed negative controls died. Although infection of transgenic RzDI plants initially induced moderate to severe symptoms, these plants subsequently recovered, flowered, and set seed. Plants from the same transgenic lines also exhibited broad-spectrum protection against related tombusviruses but remained susceptible to a distantly related tombus-like virus and to unrelated viruses.

Defective Viruses↗

A tandem array of Sp-1 sites and a reverse initiator element are both required for synergistic transcriptional activation of the T-cell-specific MAL gene.

We have characterized the three cis elements responsible for promoter strength present in the 5'-flanking proximal region of MAL, a human T-cell-specific gene encoding a proteolipid protein present in detergent-insoluble complexes of high molecular weight. The first element consisted of an initiator sequence that, curiously, was present in reverse orientation compared to that of the standard initiator elements. The other two elements were contained in a region of 126 bp upstream of the mRNA initiation site, and consisted of a tandem array of one GC box and one GA box. The GC box corresponds to a consensus site for the nuclear factor Sp1, whereas the GA box deviates from this consensus, although it was able to compete for the binding of Sp1 in vitro and to respond to trans-activation by Sp1 in vivo. This simple promoter lacks an apparent TATA box and lost more than 99% of its activity when a fragment of 60 bp containing the GC and GA boxes was deleted. A synergistic effect on transcriptional activation was observed in the presence, but not in the absence, of the initiator element when both GC and GA boxes were present.

Base Sequence↗

Alternative splicing of human T-cell-specific MAL mRNA and its correlation with the exon/intron organization of the gene.

Sequence analysis of the T-cell-specific MAL gene revealed four exons, each encoding a hydrophobic, presumably membrane-associated, segment and its adjacent hydrophilic sequence. Amplification by the polymerase chain reaction of cDNA from different T-cell samples indicated the existence of four different forms of MAL mRNA, termed MAL-a, -b, -c, and -d, that arise from differential usage of exons II and/or III. As the three introns were located between complete codons, the reading frame was maintained in all the transcripts. A model resembling the structures postulated for different proteolipid proteins is proposed for the protein encoded by each alternative mRNA species.

Alternative Splicing↗

Genomic structure and subcellular localization of MAL, a human T-cell-specific proteolipid protein.

Genomic DNA clones containing the T-cell-specific human MAL gene were isolated. Restriction and sequence analysis revealed four exons and three introns. Each hydrophobic segment of MAL together with its adjacent hydrophilic sequence correlates closely with one exon of the gene. RNase protection analysis revealed that the previously described MAL mRNA, which contains the sequences present in the four exons, is the mRNA species predominant in T-cells. A remarkable similarity was found between the hydrophobicity pattern of MAL and those of the peripheral membrane protein 22 (PMP-22) and the 16-kDa proteolipid of vacuolar H(+)-ATPase. Direct evidence supporting that MAL is a proteolipid was obtained by extracting bacterial lysates expressing recombinant MAL protein with lipophilic solvents used to extract lipids. The use of two different antibodies raised against distinct peptides from the MAL molecule has allowed the localization of MAL in the endoplasmic reticulum of T-cells. This subcellular localization is in agreement with the presence of a RWKSS motif in the COOH-terminal tail of MAL, next to its last putative transmembrane domain, that fits with one of the consensus sequences (RXKXX) for residency in the endoplasmic reticulum for transmembrane proteins. A possible function for MAL protein in T-cells is discussed based on its subcellular localization and the unique lipid-like properties of the proteolipid proteins.

Amino Acid Sequence↗

Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis.

We sought to define objective indicators of the resolution of Pseudomonas aeruginosa endobronchial infection in patients with cystic fibrosis. We prospectively studied 75 patients admitted for treatment of a pulmonary exacerbation and quantitated sputum bacterial density, DNA content, and the concentration of albumin and total protein in sputum, and compared these values with clinical evaluation. Eleven of the 75 patients had systemic signs, fever, and leukocytosis, which we arbitrarily defined as due to endobronchial infection. At the end of hospitalization, these 11 patients were afebrile, had peripheral leukocyte counts in the normal range, and were judged improved. Sputum P. aeruginosa density, DNA content, and total protein content on admission were similar in the two illness groups. Hospitalization and parenteral antibiotic administration for an average of 14.6 days were associated with improved pulmonary function in all 75 subjects (P values for forced vital capacity, forced expiratory volume at 1 second, and peak expiratory flow rate were all less than 0.001). With improvement, there was a decrease in sputum P. aeruginosa density (mean of both groups decreased from 10(7.80) CFU/g on admission to 10(5.96) CFU/g; P less than 0.001), and a decreased DNA concentration (overall mean 4.73 +/- 4.75 on admission to 2.76 +/- 2.49 mg/g; P less than 0.002). The decrease in sputum total protein concentration for both groups was not significant (overall mean 60.5 +/- 48.4 to 43.9 +/- 38.2 mg/g; P = 0.06). Sputum albumin concentrations did not change in either group. We conclude that in cystic fibrosis subjects with a pulmonary exacerbation, bacterial density, sputum DNA and protein content decrease with hospitalization and parenteral antibiotic therapy. At the end of treatment, these indices of sputum infection and inflammation correlate with improved pulmonary function and clinical improvement. These changes are independent of the presence or absence of fever on admission.

Adolescent↗

A controlled study of the nephrotoxicity of mezlocillin and amikacin in the neonate.

The nephrotoxicity of the aminoglycoside amikacin sulfate was evaluated in an open, controlled study of newborns with presumed neonatal sepsis. One hundred twelve neonates were randomly allocated to receive either amikacin-ampicillin or mezlocillin, a semisynthetic penicillin. Neonates receiving amikacin, in contrast to those receiving mezlocillin, showed significant nephrotoxicity as evidenced by a delayed postnatal fall in mean serum creatinine level (82 to 80 mumol/L [0.93 to 0.90 mg/dL] vs 84 to 72 mumol/L [0.95 to 0.82 mg/dL]) and a delayed postnatal rise in mean creatinine clearance per kilogram of body weight (12% vs 38%). Furthermore, 40% of neonates receiving amikacin-ampicillin compared with 19% of neonates receiving mezlocillin had a decline in creatinine clearance (greater than 25%). There was no relationship between amikacin nephrotoxicity and either peak or trough amikacin levels. In summary, in a controlled study of the use of amikacin and mezlocillin in neonates, the combination of amikacin and ampicillin proved more nephrotoxic to the newborn kidney.

Amikacin↗

A controlled study of the nephrotoxicity of mezlocillin and gentamicin plus ampicillin in the neonate.

The nephrotoxicity of the aminoglycoside gentamicin was evaluated in an open, controlled study of newborn infants randomly allocated to receive either combination drug therapy with gentamicin and ampicillin or single drug therapy with mezlocillin for treatment of presumed neonatal sepsis. There were no significant differences in initial clinical characteristics between the groups. Neonates receiving gentamicin, in contrast to those receiving mezlocillin, had significant nephrotoxicity manifested by a smaller postnatal fall in mean serum creatinine concentration (-9%, P NS vs -21%, P less than 0.005, respectively) and a diminished postnatal rise in mean creatinine clearance (+ 21%, P NS vs + 51%, P less than 0.01, respectively). In neonates with a fall in creatinine clearance, the mean decline was significantly greater in those receiving gentamicin (44% vs 20%, P less than 0.01). There was no relationship between the incidence of gentamicin nephrotoxicity and either peak or trough gentamicin levels. For treatment of presumed neonatal sepsis, gentamicin proved more nephrotoxic than mezlocillin.

Ampicillin↗

Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission.

A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.

Chromosome Aberrations↗

Neck pain due to acute suppurative thyroiditis and thyroglossal duct abscess.

One case of acute suppurative thyroiditis and one case of thyroglossal duct abscess are presented and discussed. Although they may often present similar symptoms and signs, they need to be differentiated from each other and from other causes of painful thyroid-related neck masses to ensure appropriate therapeutic intervention. Techniques and new developments helpful in differential evaluation, including thyroid radioscintigraphy and ultrasonography, are discussed.

Abscess↗

Tuberculous otomastoiditis in children.

We report three cases of tuberculous otomastoiditis in children. Review of the literature, with particular emphasis on the ten other cases reported since 1960, discloses that this form of tuberculosis is most frequent in infants and young children. All too often, the diagnosis is made too late, with resulting complications such as irreversible hearing loss and facial nerve paralysis. Antituberculous medication and surgical drainage controlled the infection in all 13 cases diagnosed since 1960. Tests for tuberculosis in children with chronic ear infection should be mandatory, but periodic testing of all children is recommended.

Child↗