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Biomedical subjects

J W Brooks

Publications and source records attributed to J W Brooks.

At least 19 recordsLinked to original sources

Cytokine production in the immune response to murine gammaherpesvirus 68.

Cytokine profiles were determined following intranasal infection of C57BL/6J mice with murine gammaherpesvirus 68 (MHV-68). Spleen, mediastinal, and cervical lymph node cells from infected mice produced high levels of interleukin 6 (IL-6) and gamma interferon (IFN-gamma) and lower levels of IL-2 and IL-10 following in vitro restimulation. Little or no IL-4 or IL-5 was detected. Cytokine production was generally maximal at 10 days after infection, correlating with viral clearance from the lung, although significant levels were seen as early as 3 days after administration of the virus. In vitro infection of naive splenocytes induced B-cell- dependent secretion of IL-6 and IL-10, whereas IFN-gamma and IL-2 were produced only by cells that had been primed in vivo. Depletion of B lymphocytes from primed splenocyte populations did not, however, abrogate IL-6 and IL-10 production. Highly purified immune T cells made IL-6, IL-10. and IFN-gamma following in vitro restimulation with MHV-68. Thus, IL-6 and IL-10 are components of both the acquired and the innate host response. These cytokines have potential roles in the establishment and maintenance of persistent infection.

Animals

Interleukin 1 activation of the AP-1 transcription complex in murine T cells is regulated at the level of Jun B protein accumulation.

We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorbol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL4 6.1 C 10. IL-1 synergistically enhances the stimulatory effect of TPA on AP-1-mediated gene expression in this cell line. To elucidate the mechanism(s) by which IL-1 enhances AP-1-mediated gene expression, we examined the effect of IL-1 on the synthesis and turnover of Jun B, the member of the jun gene family that is present in AP-1 complexes in EL4 cells. We found that IL-1 + TPA-treated cells contain significantly higher Jun B protein levels than cells treated with TPA alone. IL-1 promotes the prolonged accumulation of Jun B, whereas the cellular content of Jun B decreases dramatically after 6 hr in cells treated with only TPA. IL-1 enhancement of Jun B protein levels is not the result of a change in the turnover rate of the Jun B protein, but rather results from the maintenance of sufficient jun B mRNA to support continued accumulation of newly synthesized protein. In addition to Jun B, we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Jun B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumulation that, in turn, facilitates Jun B heterodimerization with TPA-induced Fra-1 protein, thereby forming an active AP-1 complex.

Animals

Induction of AP-1 transcription factor components during T-cell activation by interleukin 1 and phorbol esters.

We have examined the effect of interleukin 1 (IL-1) and phorbol esters [12-O-tetradecanoylphorbol-13-acetate (TPA)] on the expression of various components of the AP-1 transcription factor complex during T-cell activation. We previously found that a chloramphenicol acetyltransferase reporter gene driven by the collagenase TPA responsive element was expressed upon stimulation of T-cells by TPA and that this expression was enhanced when IL-1 was added as a costimulant; IL-1 alone had no effect on TPA responsive element-chloramphenicol acetyltransferase expression. In this study, we have found that stimulation of T-cells by IL-1 and TPA is accompanied by activation of a subset of immediate early genes that comprise the AP-1 transcription factor complex. junB and fosB were rapidly induced following stimulation with TPA. Although the levels of other fos-related mRNAs were also elevated, their maximal induction was delayed by approximately 5 h. IL-1 alone had little or no effect, but enhanced TPA induced transcription and steady-state levels of these mRNAs. The expression of fos and jun during T-cell activation was accompanied by increased specific binding of JunB, FosB, and fos-related antigen containing complexes to the TPA responsive element. These findings indicate that the synergistic effect of IL-1 and TPA on AP-1 mediated gene expression is due, in part, to the ability of IL-1 to enhance the expression of genes encoding specific AP-1 transcription factor components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Activation of AP-1 by IL-1 and phorbol esters in T cells. Role of protein kinase A and protein phosphatases.

We have examined the regulation of the AP-1 transcription complex in the IL-1-responsive murine T cell thymoma cell line EL-4 6.1 C10. Our results demonstrate that AP-1-mediated gene expression in T cells may be regulated by several signaling pathways and factors, including IL-1, protein kinase C, protein kinase A (PKA), and one or more serine/threonine-specific protein phosphatases. The activation of protein kinase C results in an increase in nuclear AP-1 DNA binding activity, as well as enhanced gene expression. IL-1 and agents that elevate intracellular cAMP levels do not, by themselves, induce AP-1 activation, but they synergize with phorbol esters. IL-1 and forskolin may enhance AP-1 function by different mechanisms, because forskolin enhanced gene expression without producing an increase in nuclear AP-1 DNA binding, whereas IL-1 increased AP-1-binding activity and gene expression. These observations, in conjunction with the lack of a demonstrable effect of IL-1 on cAMP production in EL-4 cells, are consistent with the view that IL-1 enhances AP-1 activation by a pathway that does not directly involve cAMP and PKA. However, the induction of AP-1 activity by IL-1 and phorbol esters is dependent upon the presence of PKA, as evidenced by the loss of AP-1 inducibility in cells transfected with a cDNA encoding protein kinase inhibitor, a specific inhibitor of PKA. The effect of protein kinase inhibitor on AP-1 activation in response to IL-1 and tetradecanoyl-phorbol-13-acetate was reversed in the presence of the serine/threonine protein phosphatase inhibitor okadaic acid. Thus, the level of AP-1 activity in T cells may be determined by the balance between the activities of several serine/threonine protein kinases and phosphatases.

1-Methyl-3-isobutylxanthine

Fine-needle aspiration cytology of an unusual primary lung tumor, chondrosarcoma: case report.

A case of primary chondrosarcoma of the lung diagnosed by fine-needle aspiration biopsy (FNAB) cytology in a 78-yr-old male is presented. A mass detected on chest x-ray and defined by CT scan was subjected to a preoperative percutaneous fine-needle aspiration under fluoroscopic guidance. The distinctive cytologic features of pleomorphic cells nestled in lacunae surrounded by a chondromyxoid background resulted in a diagnosis of chondrosarcoma. The left upper lobectomy specimen confirmed the FNAB diagnosis and identified the tumor as arising from the left upper lobe bronchus.

Aged

A study of the relationship among pulpal response, microbial microleakage, and particle heterogeneity in a glass-ionomer-base material.

This investigation was designed to study the pulpal responses to glass-ionomer base materials that differ in particle size distribution. The study was carried out according to the BSI (1980) recommendations for testing restorative materials in vivo. The base materials caused more pulpal inflammation than the control material, Kalzinol, although by an indirect mechanism. A significant association was demonstrated in the statistical model between bacterial presence within the experimental cavity and pulpal inflammation. The type of restorative material has no direct association with the degree of inflammation, although the model suggests that it exerts an indirect influence via its antibacterial properties, and hence its influence on microbial microleakage. The base material, with a heterogeneous particle distribution, was associated with greater bacterial microleakage. Particle size distribution, therefore, has some effect upon bacterial microleakage, but, because of its complex effect upon several physical properties of materials, further studies are indicated.

Animals

High anti-phosphorylcholine antibody levels and mortality associated with pneumonia.

Phosphorylcholine is an immunodominant determinant of pneumococcal teichoic acids. Antibodies to phosphorylcholine are naturally occurring in man and decline in amount with age. Since antibodies to phosphorylcholine are markers of the immune responsiveness to polysaccharides and since anti-polysaccharide antibodies are highly protective against most bacterial pneumonia we expected a higher rate of pneumonia in elderly individuals with low levels of antibodies to phosphorylcholine. The relationship between the levels of antibodies to phosphorylcholine and mortality was analyzed prospectively in a representative sample of elderly individuals. A significant anti-phosphorylcholine antibody response occurred in a subgroup of the probands. There was a strong association (p less than 0.0001) between high levels of antibodies to phosphorylcholine in the serum at 70 years of age and pneumonia related death up to 14 years later. A similarly strong association was not observed between mortality and the antibody titer to another naturally occurring polysaccharide antigen: the blood group B antigen. Furthermore, there was no association between mortality due to diseases other than pneumonia and the levels of antibodies to phosphorylcholine. The association between antibody levels and subsequent fatal pneumonia provides a means of detecting individuals at risk for pneumonia-related death.

Age Factors

Cricoid split for subglottic stenosis in infancy.

Historically, tracheostomy has been used for infants with airway obstruction caused by congenital or acquired subglottic stenosis. Postoperative morbidity and mortality with this provisional operation led Cotton, in 1980, to substitute anterior cricoid split as the primary definitive procedure. Within the past three years, anterior cricoid split has been performed in 4 infants, aged 3 to 9 months, with acquired (3 patients) or congenital (1 patient) subglottic stenosis requiring ventilation through an endotracheal tube. Following cricoid split, the trachea is stented for 12 to 14 days by a nasotracheal tube, with extubation and rigid bronchoscopy in the operating room with the patient under anesthesia to confirm healing and patency. During an 18- to 24-month follow-up in these 4 patients, morbidity has been minimal, patency has persisted, and stridor has not recurred. Accordingly, a conclusive operation, cricoid split, rather than a temporizing tracheostomy may be employed for certain obstructive tracheal lesions early in life.

Cricoid Cartilage

Pneumoperitoneum resulting from tracheal rupture following blunt chest trauma.

Pneumoperitoneum usually implies perforation of the gastrointestinal tract, although the tracheobronchial tree has been recognized as a source for free intraperitoneal air. We report a case of pneumoperitoneum resulting from tracheobronchial rupture following blunt chest trauma, which was successfully treated by surgical repair.

Accidents, Traffic

Extraction of large tracheal foreign bodies through a tracheostoma under bronchoscopic control.

Despite various technical manipulations through contemporary endoscopic equipment, large tracheal foreign bodies may be lost during bronchoscopic extraction, with a 1 to 2% in-hospital mortality. Recently, emergency tracheostomy was performed during bronchoscopy after a tracheal foreign body had become dislodged in the subglottic region causing blockage of the airway, and the results of this procedure provoked its deliberate application in a second patient. In 3 additional infants, aspirated tracheal T tubes (Montgomery tubes), which were producing acute respiratory distress, were brought from the carina to the performed tracheostoma under bronchoscopic manipulation and were withdrawn. Elective application of this simultaneous approach--tracheostomy with bronchoscopy--may decrease morbidity and mortality from large tracheal foreign bodies.

Airway Obstruction

Round (helical) atelectasis.

Round (helical) atelectasis is a little-known form of pulmonary collapse. It is thought to occur secondary to lung compression from pleural effusion or following therapeutic pneumothorax. Its occurrence is favoured in patients with exudative pleural effusions and extensive pleural thickening. It presents radiographically as a pulmonary pseudotumour, and experience with this entity and its pathogenesis are discussed.

Humans

Blunt traumatic rupture of the diaphragm.

Blunt traumatic rupture of the diaphragm must be suspected in all patients with massive trauma and especially in those whose chest roentgenogram reveals an abnormal or obscured diaphragmatic shadow. Regular reevaluation is most important. A diagnostic pneumoperitoneum is the most accurate preoperative test available. Transthoracic approach is the operation of choice.

Child, Preschool

Penumopericardium due to transdiaphragmatic perforation of a gastric ulcer.

A 65-year-old man presented with cardiogenic shock and massive pneumopericardium. A gastropericardial fistula due to transdiaphragmatic penetration of a large fundal ulcer was documented radiographically and confirmed at autopsy. Previously recorded cases of penumopericardium complicating gastric ulcers or other diseases of the digestive tract are briefly reviewed.

Aged