Search PubMed⌕ Search

Biomedical subjects

T Rouse

Publications and source records attributed to T Rouse.

9 recordsLinked to original sources

CD4+CD25+ regulatory cells in acquired MHC tolerance.

Tolerance to self-antigens is an ongoing process that begins centrally during T-cell maturation in the thymus and continues throughout the cell's life in the periphery by a network of regulated restraints. Remaining self-reactive T-cells that escape intrathymic deletion may be silenced within the peripheral immune system by specialized regulatory CD4+ cells. By analogy, regulatory CD4+ cells that control immunity to "acquired self" should arise in circumstances where the immune system acquires tolerance to foreign MHC, such as the tolerance that develops following the exposure to foreign MHC antigens during the neonatal period. We have used this classic model of neonatal tolerance to examine the role of regulatory CD4+ cells in acquired tolerance to disparate class I and class II MHC. Adoptive transfer of unfractionated but not CD4+-depleted spleen cells from neonatal tolerant mice into SCID recipients inhibited skin graft rejection by immunocompetent CD8+ T cells. Using 5-bromo-2'-deoxyuridine incorporation, standard cytotoxic T-lymphocyte assays, short-term interferon-gamma ELISPOT, and intracellular FACS analysis to study CD8+ T-cell effector function, we demonstrated that neonatal tolerant mice contain CD4+CD25+ cells that suppress the development of anti-donor CD8+ T-cell responses in vitro. We conclude that regulatory CD4+CD25+ cells initiate and/or maintain tolerance by preventing the development of CD8+ T-cell alloreactivity.

Animals↗

Is the grass greener? Early results of the Nuss procedure.

BACKGROUND/PURPOSE: Minimal access surgery (MIS, Nuss Procedure) is gaining acceptance rapidly as the preferred method for pectus excavatum repair. This shift in operative management has followed a single institution's evaluation of the procedure. This report describes an additional experience with the Nuss procedure. METHODS: Twenty-one patients with pectus excavatum underwent repair by the Nuss Procedure. The patients ranged in age from 5 to 15 years (average, 8.2 years). There were 19 boys and 2 girls. RESULTS: In 1 patient (age 5 years) the MIS procedure was aborted because of persistence of chest wall asymmetry. The other 20 patients had completion of their procedure without intraoperative complication. The operating times ranged from 45 to 90 minutes; however, there was an additional anesthetic set-up time (average, 45 minutes). All cases utilized a single support bar (11 to 17 inches). Patients underwent extubation in the operating room and were admitted to a ward bed with an epidural catheter in place for pain control and received intravenous analgesia. The hospital stay ranged from 4 to 11 days and averaged 4.9 days. Early postoperative complications included ileus (n = 1), bilateral pleural effusion (n = 2), atelectasis (n = 1), fungal dermatitis (n = 1), pneumothorax (n = 1), and flipped pectus bar (n = 2). Delayed complications included flipped pectus bar (n = 2), marked pectus carinatum requiring bar removal (n = 1), mild carinatum (n = 1), mild bar deviation (n = 1), progressive chest wall asymmetry (n = 3) with 1 requiring bar removal and open pectus repair, pleural effusion (n = 1), and chronic persistent pain requiring bar removal (n = 1). The length of follow-up is 3 to 20 months with an average of 12.3 months. CONCLUSIONS: The Nuss Procedure is quick, minimally invasive, and a technically easy method to learn; however, our data indicate there is a significant learning curve. Although previous reports suggest that few complications occur, we believe further assessment of patient selection regarding age, presence of connective tissue disorder, and severe chest wall asymmetry are still needed. Long-term follow-up also will be required to assure both health professionals and the public that this is the procedure of choice for patients with pectus excavatum.

Adolescent↗

Traumatic disruption of the thoracic aorta in children.

HYPOTHESIS: This study was undertaken to identify mechanisms of injury, diagnostic modalities, surgical management, and outcome in children with traumatic aortic disruptions. DESIGN: Retrospective study. SETTING: University-affiliated private hospital. PATIENTS: All patients younger than 17 years listed in the trauma registry. INTERVENTION: Operative repair of thoracic aortic injuries. MAIN OUTCOME MEASURES: There were 8 boys and 3 girls ranging in age from 12 to 17 years (mean, 14.8 years). Seven children were motor vehicle passengers; 3 were pedestrians struck by vehicles; and 1 was thrown from a bull. Aortic injuries were suspected on the basis of the mechanism of injury and abnormal chest x-ray films (mediastinal widening). Aortic injuries were confirmed in 9 patients by arch aortography and in 2 patients by computed tomography. The injuries involved the isthmus of the aorta in 9 patients (complete transections) and the aortic arch in 2 patients (avulsions of the great vessels). Isthmus injuries were repaired by means of left heart bypass with direct cannulation of the distal thoracic aorta in 8 patients and femoral venous to femoral arterial bypass in 1 patient. Arch injuries were repaired during hypothermic circulatory arrest. The injured aortic segments were replaced with interposition grafts. There were no direct complications of anticoagulation. Ten patients (91%) survived. The only death was caused by a severe closed head injury. There were no instances of paraplegia related to aortic repairs. CONCLUSION: Good outcomes resulted from early diagnosis based on mechanism of injury, prompt aortography, and computed tomography and operative management that included distal aortic perfusion with left heart bypass.

Adolescent↗

Evidence for excessive Th2 CD4+ subset activity in vivo.

Although distinct Th1 and Th2 CD4+ subsets are apparent in in vitro studies, controversy exists over whether these subsets occur functionally in vivo. We describe a patient whose presenting laboratory features of elevated IgG4 and IgE and eosinophilia suggested high levels of IL-4 and IL-5 and in vivo expansion of the CD4+ Th2 subset. Anti-CD3-activated patient PBL induced heightened levels of IgG4 and IgE from normal B cells, indicating that the patient's abnormal Ig isotypes were T cell driven. Stimulated PBL from the patient secreted more IL-4, compared with control PBL, but similar levels of IFN-gamma. Semiquantitative reverse polymerase chain reaction demonstrated that activated PBL from the patient produced higher IL-4 and IL-5, lower IL-2, and similar IFN-gamma mRNA levels, compared with controls. FACS analysis showed that the patient expressed an expanded population of CD4+Leu-8+CD45RA- cells, the memory-effector population, and RNA in situ hybridization confirmed that the CD4+Leu-8+CD45RA- population of the patient was enriched for IL-4-transcribing cells. Moreover, IL-4-transcribing cells outnumbered IFN-gamma-transcribing cells by 2:1 in the memory-effector CD4 population, confirming that Th2 cells exist in vivo within the expanded CD4+Leu-8+CD45RA- population. Taken together, these results provide evidence that Th2 cells exist in vivo and they suggest that the expanded Th2 population produces excessive cytokines that may contribute to the sinopulmonary pathology of the patient.

Base Sequence↗

Childhood injury: a current perspective.

The majority of childhood injuries requiring admission are due to traffic-related injury, falls, and burns. Many of these injuries are preventable. In the case of the unpreventable, unintentional injury, the natural history of the injury and outcome can be altered by adherence to established safety standards. New standards also need to be set. There is definitely room for improvement in vehicular restraint systems for the smaller and younger passengers. It is known that wearing bicycle helmets, using safety belts, securing firearms in the home, and controlling hot water heater temperature levels will prevent or lessen injury in children. This information is being promulgated to communities by activities such as the National SAFE KIDS Campaign, a program of Children's National Medical Center sponsored by Johnson & Johnson Family of Companies and the National Safety Council. This campaign emphasizes important aspects of childhood injury: scope, causes, and prevention. Questions about the most devastating of childhood injuries, child abuse and assault related to violent crime, are more complex and the answers elusive. The study of patterns of injury in children highlights the need to implement new strategies aimed at prevention. At the same time, valuable information is obtained about specific injuries and responses seen in children that set them apart from adults.

Abdominal Injuries↗

Effects of anti-IgM suppression on polyclonally activated murine B cells: analysis of immunoglobulin mRNA, gene specific nuclear factors and cell cycle distribution.

Polyclonal activation of murine B cells with bacterial lipopolysaccharide (LPS) and dextran sulfate (DxS) results in cell proliferation as well as increased immunoglobulin gene transcription and antibody secretion. When added to B cell cultures during mitogen activation, anti-mu antibody suppresses the rate of proliferation and immunoglobulin gene expression. Using this model system we show that co-cultures of B cells with LPS/DxS and anti-mu resulted in a decrease of both mu and kappa chain mRNA. Suppression did not prevent B cell entry into cycle nor a significant alteration in the distribution of cells in phases of cell cycle, although it did prolong the cycle transit time in a dose dependent fashion as determined by bromodeoxyuridine pulse labelling. Analysis of B cell specific nuclear binding factors, which previously have been shown to be important in regulating immunoglobulin gene transcription were examined. Results show that the kappa-specific enhancer binding activity of NF-kappa B was induced in activated as well as suppressed cultures. The lymphoid specific factor NF-A2, which recognizes the octamer sequence motif in the promoters of immunoglobulin genes, was induced by the polyclonal activation but was selectively lost in extracts from suppressed cells. Thus, specific regulation of the nuclear factor which plays a critical role in both heavy and light chain immunoglobulin gene expression may contribute to the transcriptional suppression observed in anti-mu treated B cells.

Animals↗

Isolated injury to the intestine from blunt abdominal injury.

Isolated injury to the intestine due to blunt abdominal trauma is an uncommon event. Since the haemodynamic disturbance which accompanies injury of the liver or spleen is absent the initial symptoms and signs may be very slight, or obscured by injuries of the abdominal wall, musculoskeletal or nervous systems. We present four cases which illustrate pitfalls in management. A high index of suspicion is essential if morbidity and mortality are to be reduced to a minimum. Abdominal radiography and peritoneal lavage are useful aids when diagnosis is in doubt.

Abdominal Injuries↗