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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
PubMed1999

Requirement for CD40 ligand, CD4(+) T cells, and B cells in an infectious mononucleosis-like syndrome.

Respiratory challenge with the murine gammaherpesvirus 68 (gammaHV-68) results in productive infection of the lung, the establishment of latency in B lymphocytes and other cell types, transient splenomegaly, and prolonged clonal expansion of activated CD8(+) CD62L(lo) T cells, particularly a Vbeta4(+) CD8(+) population that is found in mice with different major histocompatibility complex (MHC) haplotypes. Aspects of the CD8(+)-T-cell response are substantially modified in mice that lack B cells, CD4(+) T cells, or the CD40 ligand (CD40L). The B-cell-deficient mice show no increase in Vbeta4(+) CD8(+) T cells. Similar abrogation of the Vbeta4(+) CD8(+) response is seen following antibody-mediated depletion of the CD4(+) subset, through the numbers of CD8(+) CD62L(lo) cells are still significantly elevated. Virus-specific CD4(+)-T-cell frequencies are minimal in the CD40L(-/-) mice, and the Vbeta4(+) CD8(+) population remains unexpanded. Apparently B-cell-CD4(+)-T-cell interactions play a part in the gammaHV-68 induction of both splenomegaly and non-MHC-restricted Vbeta4(+) CD8(+)-T-cell expansion.

Animals↗
PubMed1998

Pathogenesis of murine gammaherpesvirus-68 infection in interleukin-6-deficient mice.

Murine gammaherpesvirus-68 (MHV-68) induces high levels of interleukin (IL)-6 production in both naive and primed lymphocyte populations. Mice that are homozygous (-/-) for deletion of the IL-6 gene were used to investigate the role of this cytokine in MHV-68 infection. The results showed that IL-6 is not essential for clearance of infectious MHV-68 from the lung or for the establishment, or control, of viral latency. Both IL-6 +/+ and -/- mice eliminated replicating virus from the respiratory tract within 15 days of infection, and their lungs remained clear of infectious virus for >/=150 days. Interestingly, the IL-6 -/- mice had both increased numbers of natural killer (NK)1.1+ cells and higher levels of NK cell activity than the +/+ controls at 10-15 days after infection. However, there was no difference in the cytotoxic T cell activity between the two groups of mice. Levels of latent virus were comparable in IL-6 +/+ and -/- mice over the time course studied. Furthermore, analysis of the numbers, types, and activation status of the various leukocyte subsets (other than NK cells) in the bronchoalveolar lavage population, lymph nodes, and spleens of +/+ and -/- mice revealed no striking differences. Apart from the expected lack of IL-6, cytokine profiles were not dramatically altered in IL-6 -/- mice. Thus, there is no evidence for an obligatory role for IL-6 in T cell activation during infection with MHV-68.

Animals↗
PubMed1998

Abdominal apoplexy.

We describe the case of a patient with abdominal apoplexy, the spontaneous rupture of a visceral vessel. Laparotomy revealed a hematoma arising from a ruptured gastroepiploic artery. We report the usefulness of preoperative abdominal computed tomography and transgastric ultrasonography and discuss the condition of abdominal apoplexy. An increased awareness of the condition is perhaps the most valuable aspect of the early preoperative diagnosis of this potentially fatal condition.

Aged↗
PubMed1997

Consequences of viral infections for lymphocyte compartmentalization and homeostasis.

The immune system has evolved to deal with pathogens. Analysing what happens during the course of infectious processes provides insights into the limits of lymphocyte homeostasis. Virus infections greatly alter normal T- and B-cell prevalence and localization patterns. Any mechanism that 'counts' T cells and B cells seems to be disrupted, at least while antigen persists. There is no simple 'dumping' process that controls numbers in the blood. Though the cell-surface 'language' that determines lymphocyte trafficking patterns must be central to modulating the consequences of infectious diseases, it is far from clear how such interactions maintain the system in reasonable balance.

Animals↗
PubMed1997

Immunological control of murine gammaherpesvirus infection is independent of perforin.

Perforin-mediated cytotoxic T cell killing has been suggested to be of importance in the control of noncytopathic virus infections, based on studies with lymphocytic choriomeningitis virus (LCMV). We examined the role of perforin in a mouse model of gammaherpesvirus infection using transgenic perforin-deficient mice. Previous work from this laboratory has shown that CD8 T cells are essential for the resolution of the acute lung infection and control of latently infected B cells in murine gamma-herpesvirus 68 infection. The absence of perforin did not significantly affect the kinetics of either the lytic lung infection or the latent spleen infection. Lymphocytes from both perforin-deficient and control mice secreted comparable levels of IFN-gamma, IL-10 and IL-6. In addition, lymphocytes from both strains had similar levels of CD3epsilon-dependent cytotoxic activity in the spleen, draining lymph nodes and bronchoalveolar lavage. These data indicate that the lack of perforin has little affect on the ability of mice to control an experimental gammaherpesvirus infection.

Animals↗
PubMed1997

Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections.

The rules for T-cell-mediated control of viruses that infect via the respiratory mucosae show both common themes and differences, depending on the nature of the pathogen. Virus-specific CD8+ cytotoxic T lymphocytes (CTLs) are the key effectors of virus clearance in mice infected with both negative strand RNA viruses (influenza and Sendai) and a DNA virus, the murine gamma-herpesvirus-68 (MHV-68). Recently completed experiments establish that these activated CD8+ T cells indeed operate primarily via contact-dependent lysis. Perforin-mediated cytotoxicity seems to be the preferred mode, though a Fas-based mechanism can apparently serve as an alternative mechanism. Immune CD4+ T cells functioning in the absence of the CD8+ subset cannot eliminate MHV-68 from lung epithelial cells, are somewhat less efficient than the CD8+ CTLs at clearing the RNA viruses, and are generally ineffectual in mice that lack B lymphocytes. Though cytokine secretion by CD4+ and CD8+ T cells in the virus-infected lung may promote both T-cell extravasation and macrophage activation, such processes are not alone sufficient to deal consistently with any of these infections. However, CD4+ T help is mandatory for an effective B-cell response, and can operate to promote the clonal expansion of virus-specific CD8+ T cells in the lymph nodes and spleen. Furthermore, a concurrent CD4+ T-cell response seems to be essential for maintaining continued CD8+ T-cell surveillance and effector capacity through the persistent, latent phase of MHV-68 infection in B cells. Thus, the evidence to date supports a very traditional view; CD8+ T cells function mainly as killers and the CD4+ T cells as helpers in these respiratory virus infections.

Animals↗
PubMed1997

Gamma interferon is not essential for recovery from acute infection with murine gammaherpesvirus 68.

Murine gammaherpesvirus 68 (MHV-68) when administered intranasally induces high levels of gamma interferon (IFN-gamma) in the lymphoid tissues of infected mice. In order to investigate the role of this cytokine in the immune response to MHV-68, mice which were congenitally deficient in the IFN-gamma gene (IFN-gamma knockout mice) were infected with the virus. Comparison of the courses of the disease in wild-type control and IFN-gamma knockout mice revealed surprisingly little difference. Both groups of mice had cleared infectious virus from the lungs 15 days after infection, although there did appear to be a slight delay in viral clearance in the IFN-gamma knockout mice. In addition, after the initial phase of viral clearance, the lungs of both groups remained clear of replicating virus throughout the course of the experiment, which concluded 34 days after infection. Consistent with these observations, cytotoxic T-cell activities were similar in the two groups of mice. Levels of latent virus were comparable in wild-type and knockout mice over the time course studied. Furthermore, analysis of the numbers, types, and activation status of cells in the lungs, lymph nodes, and spleens of control and knockout mice revealed no striking difference. This suggests that IFN-gamma is not essential for regulating the cell recruitment or proliferation that normally occurs during this viral infection. Apart from the expected lack of IFN-gamma, cytokine profiles were not dramatically altered in IFN-gamma knockout mice, demonstrating that IFN-gamma did not suppress the proliferation or differentiation of Th2 cells during MHV-68 infection. These observations indicate that IFN-gamma plays a nonessential or redundant role in the control of acute infection with MHV-68.

3T3 Cells↗
PubMed1996

Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells.

A unique experimental model has been developed for dissecting the integrity of CD8+ T cell-mediated immunity to a persistent gammaherpesvirus under conditions of CD4+ T cell deficiency. Respiratory challenge of major histocompatibility complex class II -/- and +/+ C57BL/6J mice with the murine gammaherpesvirus 68 (MHV-68) leads to productive infection of both lung and adrenal epithelial cells. Virus titers peak within 5-10 d, and are no longer detected after day 15. Persistent, latent infection is established concurrently in splenic and lymph node B cells, with higher numbers of MHV-68+ lymphocytes being found in all lymphoid sites analyzed from the +/+ mice concurrent with the massive, but transient splenomegaly that occurred only in this group. From day 17, however, the numbers of infected B lymphocytes were consistently higher in the -/- group, while the frequency of this population diminished progressively in the +/+ controls. Infectious MHV-68 was again detected in the respiratory tract and the adrenals of the -/- (but not the +/+) mice from day 22 after infection. The titers in these sites rose progressively, with the majority of the -/- mice dying between days 120 and 133. Even so, some CD8+ effectors were still functioning as late as 100 d after infection. Depletion of CD8+ T cells at this stage led to higher virus titers in the -/- lung, and to the development of wasting in some of the -/- mice. Elimination of the CD8+ T cells from the +/+ group (day 80) increased the numbers of MHV-68+ cells in the spleen, but did not reactivate the infection in the respiratory tract. The results are consistent with the interpretation that CD8+ T cell-mediated control of this persistent gammaherpesvirus is progressively lost in the absence of the CD4+ T cell subset. This parallels what may be happening in AIDS patients who develop Kaposi's sarcoma and various Epstein Barr virus associated disease processes.

Animals↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1988

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↗