RESUMEN
OBJECTIVE: This multicenter randomized controlled clinical trial aimed to compare the outcomes of stepwise excavation (SW) and partial caries removal (PCR) regarding the maintenance of pulp vitality in deep caries lesions over 5 years. METHODS: At baseline, 299 permanent molars with deep caries lesions were randomly assigned to control or test groups. The control group received the stepwise excavation treatment (SW), while the test group received partial caries removal from the pulpal wall followed by restoration in a single session (PCR). Treatments were conducted in two centers located in the cities of Porto Alegre (South Brazil) and Brasília (Midwest Brazil). Survival analysis was performed to compare PCR and SW over time (Weibull regression models). The primary outcome of this study was pulp vitality, determined by the combination of the following characteristics: positive response to cold test, negative response to percussion, absence of spontaneous pain, and absence of periapical lesion (radiographic examination). RESULTS: This 5-year study includes data pertaining to 229 teeth: 121 teeth actually examined at the 5-year appointment, and 108 teeth contributed with data collected in previous follow-ups (18 months or 3 years). Survival analysis showed success rates of 80% in PCR group and 56% in SW group (p < 0.001). Failure was significantly associated with treatment [PCR, HR=0.38; 95%CI=0.23-0.63)] and region [South, HR=2.22; 95%CI=1.21-4.08]. CONCLUSION: PCR significantly reduced the occurrence of pulp necrosis when compared with SW. CLINICAL RELEVANCE: This study supports the PCR as a single-visit technique to manage deep caries lesions in permanent teeth.
Asunto(s)
Caries Dental/terapia , Necrosis de la Pulpa Dental/prevención & control , Restauración Dental Permanente/métodos , Adolescente , Adulto , Dentición Permanente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diente Molar , Resultado del TratamientoRESUMEN
Surviving during times of mergers and acquisitions is difficult but possible. Following is a case study of how one service managed not only to survive, but to thrive, during consolidation.
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Centros Médicos Académicos/organización & administración , Instituciones Asociadas de Salud/organización & administración , Perfil Laboral , Liderazgo , Supervisión de Enfermería/organización & administración , Servicio de Psiquiatría en Hospital/organización & administración , Comunicación , Humanos , Relaciones Interprofesionales , Missouri , Estudios de Casos Organizacionales , Innovación OrganizacionalAsunto(s)
Infección Hospitalaria/diagnóstico , Hepatitis C/diagnóstico , Sobreinfección/diagnóstico , Infección Hospitalaria/prevención & control , Infección Hospitalaria/transmisión , Hepacivirus/clasificación , Hepacivirus/patogenicidad , Hepatitis C/prevención & control , Hepatitis C/transmisión , Humanos , Sobreinfección/prevención & control , Sobreinfección/transmisiónRESUMEN
Immune evasion by the human immunodeficiency virus (HIV) is unexplained but may involve the mutation of viral antigens. When cytotoxic T lymphocytes engaged CD4-positive cells that were acutely infected with HIV bearing natural variant epitopes in reverse transcriptase, substantial inhibition of specific antiviral lysis was observed. Mutant viruses capable of these transactive effects could facilitate the persistence of a broad range of HIV variants in the face of an active and specific immune response.
Asunto(s)
Citotoxicidad Inmunológica , Antígenos VIH/inmunología , VIH-1/inmunología , Tolerancia Inmunológica , ADN Polimerasa Dirigida por ARN/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Variación Antigénica , Secuencia de Bases , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Línea Celular , Epítopos/genética , Antígenos VIH/genética , Transcriptasa Inversa del VIH , VIH-1/enzimología , VIH-1/genética , Antígeno HLA-B8/inmunología , Humanos , Datos de Secuencia Molecular , ADN Polimerasa Dirigida por ARN/genética , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
A typical protein antigen contains several epitopes that can be recognized by cytotoxic T lymphocytes (CTL), but in a characteristic antiviral immune response in vivo, CTL recognize only a small number of these potential epitopes, sometimes only one, this phenomenon is known as immunodominance. Antigenic variation within CTL epitopes has been demonstrated for the human immunodeficiency virus HIV-1 (ref. 11) and other viruses and such 'antigenic escape' may be responsible for viral persistence. Here we develop a new mathematical model that deals with the interaction between CTL and multiple epitopes of a genetically variable pathogen, and show that the nonlinear competition among CTL responses against different epitopes can explain immunodominance. This model suggests that an antigenically homogeneous pathogen population tends to induce a dominant response against a single epitope, whereas a heterogeneous pathogen population can stimulate complicated fluctuating responses against multiple epitopes. Antigenic variation in the immunodominant epitope can shift responses to weaker epitopes and thereby reduce immunological control of the pathogen population. These ideas are consistent with detailed longitudinal studies of CTL responses in HIV-1 infected patients. For vaccine design, the model suggests that the major response should be directed against conserved epitopes even if they are subdominant.
Asunto(s)
Variación Antigénica , Antígenos VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Epítopos Inmunodominantes/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , Infecciones por VIH/complicaciones , Antígeno HLA-B27/inmunología , Antígeno HLA-B8/inmunología , Hemofilia A/complicaciones , Hemofilia A/inmunología , Humanos , Modelos Inmunológicos , Datos de Secuencia MolecularRESUMEN
Most asymptomatic individuals infected with HIV-1 have a cytotoxic T lymphocyte (CTL) response to the virus Gag proteins which can be demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and p24-13) and -B27 (p24-14). Viruses isolated from patients who make CTL responses to these peptides vary within the genetic sequences encoding these epitopes and some mutations lead to reduction in killing activity in vitro. This was attributed to either failure of the variant epitope to bind major histocompatibility complex class I or failure of T-cell receptors to bind the presented peptide. But peptide variants of class I-restricted epitopes cause 'antagonism', that is, the presence of a variant epitope (in the form of peptide) inhibits normal lysis of targets presenting the original epitope. This mirrors similar findings in class II-restricted systems. Here we report that naturally occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL lines derived from the same individuals. The effect is present if the epitopes are derived from synthetic peptides and when they are processed from full-length proteins expressed by either recombinant vaccinia constructs or replicating HIV.
Asunto(s)
Productos del Gen gag/inmunología , VIH-1/inmunología , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Linfocitos T Citotóxicos/inmunología , Proteínas Virales , Secuencia de Aminoácidos , Línea Celular , Epítopos/genética , Epítopos/inmunología , Productos del Gen gag/genética , Variación Genética , Antígenos VIH/genética , Antígenos VIH/inmunología , Proteína p24 del Núcleo del VIH/genética , Proteína p24 del Núcleo del VIH/inmunología , Antígeno HLA-B8/inmunología , Humanos , Datos de Secuencia Molecular , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Virus Vaccinia/genética , Productos del Gen gag del Virus de la Inmunodeficiencia HumanaRESUMEN
The mouse mammary tumor virus gag-pro transframe protein (p30) contains the nucleocapsid protein domain derived from the 3' end of gag, fused to 154 residues encoded by the 5' region of the pro open reading frame. The DNA coding for p30 was cloned into the plasmid pALTER-1, and an additional nucleotide was inserted by site-directed mutagenesis to allow the read-through from the gag into the pro open reading frame. The obtained insert was then cloned into pGEX-2T, a plasmid containing the glutathione S-transferase gene of Schistosoma japonicum and a nucleotide sequence encoding for a thrombin cleavage site. The chimeric protein (GST-p30) was isolated by affinity chromatography on a glutathione-Sepharose 4B column, and after thrombin treatment, the excised p30 was further purified on a single-stranded DNA-agarose column. This protein showed dUTPase activity, with only negligible cleavage of dATP, dGTP, dCTP, dTTP, or UTP. Its apparent Km for dUTP was 28 microM. The enzyme was inhibited by EDTA, but its effect could be reversed by Mg2+ and other divalent cations. dUTPase activity was also detected in purified mouse mammary tumor virus, and p30 was the only protein recognized by antibodies directed towards the carboxyl-terminal sequence of the dUTPase coding region.
Asunto(s)
Virus del Tumor Mamario del Ratón/enzimología , Pirofosfatasas/metabolismo , Proteínas del Núcleo Viral/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cationes Bivalentes/farmacología , Quelantes/farmacología , Clonación Molecular , Escherichia coli/genética , Expresión Génica , Productos del Gen gag/genética , Productos del Gen gag/aislamiento & purificación , Productos del Gen gag/metabolismo , Productos del Gen pol/genética , Productos del Gen pol/aislamiento & purificación , Productos del Gen pol/metabolismo , Datos de Secuencia Molecular , Pirofosfatasas/efectos de los fármacos , Pirofosfatasas/genética , Pirofosfatasas/aislamiento & purificación , Sistemas de Lectura , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Análisis de Secuencia , Especificidad por Sustrato , Proteínas del Núcleo Viral/efectos de los fármacos , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/aislamiento & purificaciónRESUMEN
Polyclonal antisera, produced against whole cells of Thiobacillus thiooxidans, T. ferrooxidans and Leptospirillum ferrooxidans, gave highly specific reactions when cross-reacted with 23 strains of acidophilic bacteria using an immunofluorescence (IF) staining technique. Strains of identical serotype exhibited maximum cross-reaction whereas strains of different serotype reacted only weakly. Lipopolysaccharides (LPS) examined by SDS-PAGE showed different, serotype-specific migration patterns indicating their rough or smooth character. LPS patterns may therefore be used for serological classification of acidophilic bacteria. Surface antigens of four strains were identified by immunoblot staining; LPS and some proteins were antigenic determinants with LPS the most specific.
RESUMEN
In rats with normal renal function the intestinal absorption of aluminium appears to be partly vitamin D dependent. To further characterise the similarities between the absorption of aluminium and calcium we investigated the effects of dihydroxylated vitamin D metabolites, prednisolone, and chloroquine (CQ) in Sprague-Dawley rats with normal or reduced renal function. The latter agents interfere with lysosomal functions and have been reported to reduce the intestinal absorption of calcium, whereas vitamin D metabolites may stimulate the absorption of both aluminium and calcium. To assess the intestinal absorption of aluminium we monitored urinary aluminium excretion and serum aluminium concentrations following an oral load of 410 mumol aluminium. Calcium absorption was calculated from the differences between an orally administered dose of 45calcium and faecal excretion. In vitamin-D-deficient rats cholecalciferol and calcitriol augmented urinary aluminium excretion to a similar degree subsequent to an oral load whereas 24R,25(OH)2D3 was without an apparent effect. In vitamin-D-replete rats with normal renal function CQ (225 mg/kg i.p.; 3 days) as well as prednisolone (25 mg/kg; 7 days) significantly reduced calcium absorption (% dose) (CQ: 39 +/- 5%, prednisolone: 42 +/- 3%, control: 58 +/- 11%). In contrast neither drug reduced urinary aluminium excretion (CQ: 519 +/- 92, prednisolone: 494 +/- 137, control: 469 +/- 187 nmol/5 days) or the postload increase in serum aluminium following oral exposure. When aluminium was administered intravenously recovery of aluminium was comparable between treatment groups and controls.(ABSTRACT TRUNCATED AT 250 WORDS)