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Biomedical subjects

J D Campbell

Publications and source records attributed to J D Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Genotypic analysis of invasive Streptococcus pneumoniae from Mali, Africa, by semiautomated repetitive-element PCR and pulsed-field gel electrophoresis.

As part of a large, ongoing study of invasive infections in pediatric patients in Bamako, Mali, 106 cases of invasive pneumococcal disease were identified from June 2002 to July 2003 (J. D. Campbell et al., Pediatr. Infect. Dis. J. 23:642-649, 2004). Of the 12 serotypes present, the majority of isolates were not contained in PCV7 (the 7-valent pneumococcal conjugate vaccine), including 1 isolate that was serotype 1, 12 isolates that were serotype 2, 58 isolates that were serotype 5, 7 isolates that were serotype 7F, and 1 isolate that was serotype 12F. To determine whether clonal dissemination of the predominant serotypes had taken place, genotyping was performed on 100 S. pneumoniae isolates by using two methods: pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA, and the Bacterial Barcodes repetitive-element PCR (rep-PCR) method. Criteria for delineating rep-PCR genotypes were established such that isolates of different serotypes were generally not grouped together. The two methods were equally discriminatory within a given pneumococcal serotype. PFGE separated the isolates into 15 genotypes and 7 subtypes; rep-PCR separated isolates into 15 genotypes and 6 subtypes. Using either method, isolates within serotypes 2, 5, and 7 formed three large, separate clusters containing 1 genotype each. Both methods further distinguished related subtypes within serotypes 2 and 5. Interestingly, one of the PFGE subtypes of serotype 5 is indistinguishable from the Columbia(5)-19 clone circulating in Latin America since 1994. The data support that serotypes 2 and 5 were likely to be the result of dissemination of particular clones, some of which are responsible for invasive disease over a broad population range.

Adolescent↗
PubMed2001

Suppression of IL-2-induced T cell proliferation and phosphorylation of STAT3 and STAT5 by tumor-derived TGF beta is reversed by IL-15.

IL-2 responses are susceptible to suppression by TGFbeta, a cytokine widely implicated in suppression of inflammatory responses and secreted by many different tumor cell types. There have been conflicting reports regarding inhibition of IL-2-induced STAT3 and STAT5 phosphorylation by TGFbeta and subsequent suppression of immune responses. Using TGFbeta-producing multiple myeloma tumor cells we demonstrate that tumor-derived TGFbeta can block IL-2-induced proliferation and STAT3 and STAT5 phosphorylation in T cells. High affinity IL-2R expression was required for the suppression of IL-2 responses as a novel CD25(-) T cell line proliferated and phosphorylated STAT3 when cultured with tumor cells or rTGFbeta1. Activating T cells with IL-15, which does not use the high affinity IL-2R, completely restored the ability of T cells to phosphorylate STAT3 and STAT5 when cultured with tumor cells. IL-15-treated T cells proliferated normally when cocultured with tumor cells or rTGFbeta1, whereas IL-2 responses were consistently inhibited. Preincubation with IL-15 also restored the ability of T cells to respond to IL-2 by phosphorylating STAT3 and STAT5, and proliferating normally in the presence of tumor cells. IL-2 pretreatment did not restore T cell function. IL-15 also restored T cell responses by T cells from multiple myeloma patients, and against freshly isolated bone marrow tumor samples. Thus, activation of T cells by IL-15 renders T cells resistant to suppression by TGFbeta1-producing tumor cells and rTGFbeta1. This finding may be exploited in the design of new immunotherapy approaches that will rely on T cells avoiding tumor-induced suppression.

Cells, Cultured↗
PubMed2001

Proinflammatory cytokine expression by Theileria annulata infected cell lines correlates with the pathology they cause in vivo.

Control of Theileria annulata is currently best achieved by the use of live attenuated cell line vaccines. However, the mechanisms underlying attenuation are unclear and there is a need to rapidly produce new cell line vaccines, which could safely and effectively vaccinate cattle against tropical theileriosis. There is increasing evidence to suggest that proinflammatory cytokines produced by T. annulata infected cells play a central role in both pathology and immune evasion. This study aimed to test this hypothesis and to evaluate cytokine expression as a marker of virulence. The pathogenicity and protective efficacy of cloned T. annulata cell lines that expressed different levels of proinflammatory cytokines were compared. In two independent trials using different stocks of T. annulata, cell lines that expressed higher levels of proinflammatory cytokines induced severe reactions, and in some cases death, when used to vaccinate groups of cattle. In contrast, low cytokine expressing lines induced low post-vaccinal reactions. The results clearly demonstrated that cytokine expression by T. annulata infected cells could be used as a marker of virulence and provided strong evidence to support a role for cytokines in the induction of pathology. Both high and low cytokine expressing cell lines protected cattle against heterologous challenge infection, offering the possibility of using cytokine expression to rapidly select new safe, potent vaccines against tropical theileriosis without the need for culture attenuation.

Animals↗
PubMed2001

Comparison of chemiluminescent assays and colorimetric ELISAs for quantification of murine IL-12, human IL-4 and murine IL-4: chemiluminescent substrates provide markedly enhanced sensitivity.

Many available ELISAs lack the sensitivity required to reliably quantify levels of cytokines released in response to antigenic stimulation. In an effort to increase sensitivity of these assays, we compare the sensitivity of standard colorimetric ELISAs and corresponding chemiluminescent assays for three cytokines which are usually produced in very low quantities: mouse IL-12 p70, human IL-4 and mouse IL-4. Use of a chemiluminescent substrate enhanced the sensitivity of these assays 12-29-fold as compared to current colorimetric ELISAs. Accompanying this increase in sensitivity was an increase in dynamic range, a decrease in the time required to obtain maximum sensitivity and a decrease in the concentration of reagents required. These findings are of particular interest to those wanting to quantitate levels of any cytokine which is typically produced in low levels.

Animals↗
PubMed2001

The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors.

The lymphatic vessels (lymphatics) play an important role in channeling fluid and leukocytes from the tissues to the secondary lymphoid organs. In addition to driving leukocyte egress from blood, chemokines have been suggested to contribute to leukocyte recirculation via the lymphatics. Previously, we have demonstrated that binding sites for several pro-inflammatory beta-chemokines are found on the endothelial cells (ECs) of lymphatics in human dermis. Here, using the MIP-1alpha isoform MIP-1alphaP, we have extended these studies to further support the contention that the in situ chemokine binding to afferent lymphatics exhibits specificity akin to that observed in vitro with the promiscuous beta-chemokine receptor D6. We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6 probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive lymphatics were also abundant in mucosa and submucosa of small and large intestine and appendix, but not observed in several other organs tested. In lymph nodes, D6 immunoreactivity was present on the afferent lymphatics and also in subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6-positive. Peripheral blood cells and the ECs of blood vessels and high endothelial venules were consistently nonreactive with anti-D6 antibodies. Additionally, we have demonstrated that D6 immunoreactivity is detectable in some malignant vascular tumors suggesting they may be derived from, or phenotypically similar to, lymphatic ECs. This is the first demonstration of chemokine receptor expression by lymphatic ECs, and suggests that D6 may influence the chemokine-driven recirculation of leukocytes through the lymphatics and modify the putative chemokine effects on the development and growth of vascular tumors.

Adult↗
PubMed2001

In vivo stability of human chemokine and chemokine receptor expression.

Cross-sectional analyses of human PBMC, plasma, and tissue have reported altered chemokine and/or chemokine receptor expression in several inflammatory diseases. Interpretation of such studies is difficult without data on the in vivo stability of such parameters. Using four color flow cytometry, we longitudinally followed CXCR3, CCR5 (Th1-associated), and CCR3 (Th2-associated) expression within CD4+/CD45RO+ and CD8+/CD45RO+ T cell populations in peripheral blood of healthy individuals over a 21 day period. In parallel, we quantified plasma levels of IP-10, Mig, eotaxin and TARC. Chemokine and receptor expression differed markedly between subjects but was highly stable, varying by <5% within individuals. Differences in chemokine receptor expression between subjects were markedly altered when quantified as absolute cell numbers rather than frequencies. Finally, CCR3 expression by CD4+/CD45RO+ T cells was positively correlated with plasma levels of its ligand, eotaxin, whereas strong negative correlations were evident between CXCR3 expression and IP-10 or Mig. These data demonstrate longitudinal stability of chemokine receptor and ligand expression among healthy individuals; reveal that both frequency and absolute cell count analysis is essential for accurate assessment of chemokine receptor expression; and identify inverse relationships between type 1 and type 2 immunity-associated receptors and their ligands in vivo.

Adult↗
PubMed2001

Evolution of bone marrow transplantation--the original immunotherapy.

Allogeneic bone-marrow transplantation (BMT) has provided a curative treatment option for chronic myeloid leukaemia (CML) over the past 20-30 years. New drugs - signal transduction inhibitors - that target the bcr-abl oncogene have the potential to render such transplantation procedures obsolete and provide hope for those without a suitable donor ( approximately 60% of patients). Here, we discuss how new drug and immune-based approaches could be combined to enhance treatment of this already 'curable' malignancy.

Bone Marrow Transplantation↗
PubMed2001

Lifestyle, minerals and health.

This paper proposes that most poor health and behavioral conditions are related to a deficiency of essential minerals or an excess of toxic ones. Clients requesting a hair mineral analysis were required to complete a questionnaire including lifestyle, health status and diet. Most prevalent health conditions in order of frequency were: depression, allergies, low back pain, arthritis, cardiovascular disease and poor digestion. Most deficient minerals were chromium, magnesium, zinc and calcium. Aluminum was the most frequent toxic mineral. it is proposed that such mineral abnormalities were caused by an over consumption of nutrient-poor, highly processed foods such as white flour, sugar and harmful fats. Such a diet promotes poor lifestyles such as smoking, drug abuse, alcoholism and criminal activity. Poor diets and dangerous lifestyles precedes the development of most prevalent diseases. The most common one is cardiovascular disease which increased at an alarming rate in the last century.

Deficiency Diseases↗
PubMed2001

Introducing telemedicine technology to rural physicians and settings.

OBJECTIVE: The researchers investigated rural health providers' perceptions of telemedicine, developed a framework for assessing their readiness to adopt this type of technology, and offered a guide for its implementation. STUDY DESIGN: Qualitative data were collected from semistructured interviews with thematic analysis. POPULATION: The study population included physicians, nurses, and administrative personnel located in 10 health care practices in 4 communities in 3 rural Missouri counties. OUTCOMES MEASURED: The researchers measured how often health providers used telemedicine technology and their perceptions of the advantages, disadvantages, barriers, and facilitators involved in adopting it. RESULTS: Participants varied widely in their perceptions of telemedicine. Providers in practices affiliated with the university's tertiary center were more likely to use it than were those in private practice. Interviews and other data yielded 6 themes related to a provider's receptivity to technological change: These themes were turf, efficacy, practice context, apprehension, time to learn, and ownership. Each theme applies to the computer and videoconferencing components of telemedicine, and each may operate as a perceived barrier or facilitator of change. CONCLUSIONS: Care providers and administrators consider a range of factors, including economic ramifications, efficacy, social pressure, and apprehension, when deciding whether and how fast to adopt telemedicine. Since adopting this technology can be a major change, agencies trying to introduce it into rural areas should take all these factors into account in their approach to health care providers, staff, and communities.

Adult↗
PubMed2000

Experimental approaches to analysis of immune dysregulation in human allergic disease.

Over the last 40 years, much attention has been directed towards identification of the immunologic, genetic and environmental factors that predispose towards development of allergic disease. An implicit assumption in many such studies is that clinical tolerance reflects from immunologic tolerance. Here we critically review the conceptual background and experimental data arguing for the alternative hypothesis that failure to develop atopic disease reflects the success of type 1 dominated immunity that constitutively impedes development of type 2 responses to environmental antigens, hence, clinical immediate hypersensitivity. We report that endogenous production of type 1 chemokines such as IP-10 by non-atopic individuals may play a substantive role in maintaining this putatively protective type 1 bias in non-atopic subjects. Polyclonal activators (superantigen TSST-1, anti-CD3, PHA) were used to activate distinct intracellular signaling pathways, inducing quantitatively different IFNgamma:IL-4 ratios in primary culture of human PBMC. In parallel, physiologic stimuli such as grass pollen or cat antigen were used to evaluate the impact of IP-10 on CD4 T cell dependant, chloroquine-sensitive cytokine synthesis. IFNgamma responses by non-atopic subjects were markedly increased in the presence of nM concentrations of rhIP-10 while type 2 cytokine synthesis remained unaffected. Optimal rIP-10 concentrations for promoting expression and maintenance of type 1 cytokine synthesis in vitro (0.1 to 10 ng/ml) were at or well below those generally used for chemotaxis (5 to 100 ng/ml). Collectively, our findings suggest a potential role for this T cell focused chemokine in maintaining the default type 1 responses usually caused to environmental antigens in non-atopic subjects. These may play a role in determining the relative susceptibility of individuals to develop atopic disease. Taken together with recent reports of other roles played by chemokines in shaping the nature of immune responses, the data suggest that constitutive, endogenous type 1 chemokine synthesis may play a homeostatic role in inhibiting development of atopic disease.

Allergens↗
PubMed2000

C-C chemokine receptor 3 antagonism by the beta-chemokine macrophage inflammatory protein 4, a property strongly enhanced by an amino-terminal alanine-methionine swap.

Allergic reactions are characterized by the infiltration of tissues by activated eosinophils, Th2 lymphocytes, and basophils. The beta-chemokine receptor CCR3, which recognizes the ligands eotaxin, eotaxin-2, monocyte chemotactic protein (MCP) 3, MCP4, and RANTES, plays a central role in this process, and antagonists to this receptor could have potential therapeutic use in the treatment of allergy. We describe here a potent and specific CCR3 antagonist, called Met-chemokine beta 7 (Ckbeta7), that prevents signaling through this receptor and, at concentrations as low as 1 nM, can block eosinophil chemotaxis induced by the most potent CCR3 ligands. Met-Ckbeta7 is a more potent CCR3 antagonist than Met- and aminooxypentane (AOP)-RANTES and, unlike these proteins, exhibits no partial agonist activity and is highly specific for CCR3. Thus, this antagonist may be of use in ameliorating leukocyte infiltration associated with allergic inflammation. Met-Ckbeta7 is a modified form of the beta-chemokine macrophage inflammatory protein (MIP) 4 (alternatively called pulmonary and activation-regulated chemokine (PARC), alternative macrophage activation-associated C-C chemokine (AMAC) 1, or dendritic cell-derived C-C chemokine (DCCK) 1). Surprisingly, the unmodified MIP4 protein, which is known to act as a T cell chemoattractant, also exhibits this CCR3 antagonistic activity, although to a lesser extent than Met-Ckbeta7, but to a level that may be of physiological relevance. MIP4 may therefore use chemokine receptor agonism and antagonism to control leukocyte movement in vivo. The enhanced activity of Met-Ckbeta7 is due to the alteration of the extreme N-terminal residue from an alanine to a methionine.

Adjuvants, Immunologic↗
PubMed2000

The Th1-Th2 classification of cellular immune responses: concepts, current thinking and applications in haematological malignancy.

The finding that T cell immune responses could be divided into those promoting cell mediated immunity (Th1) and humoral responses (Th2) has had a profound effect on the understanding of immune response generation over the last 15 years. With ever increasing knowledge of the immune system, the model has come under criticism, as not all responses easily fit the classification. Nonetheless, the model still provides a valuable framework on which to base immunological research. In this review we update the model with current thinking regarding the generation and maintenance of immune responses. We then examine how the Th1-Th2 paradigm may be applied in developing new understanding of several topical issues in haematological malignancy-control of graft-versus-host disease; cytokine control of proliferating clones in B and T cell diseases; and suppression of T cell responses in multiple myeloma.

Cytotoxicity, Immunologic↗
PubMed2000

The no-show rate in a high-risk obstetric clinic.

We wished to determine the reasons for an average missed appointment rate of 28% in a high-risk pregnancy clinic. Only 41% of the 261 women in the study group could be reached by telephone. The reasons included not having a phone, the phone had been disconnected, incorrect phone number on the chart, the patient had moved, and the patient did not respond to the answering machine message. The reasons for missing the appointment included lack of transportation, scheduling problems, overslept or forgot, presence of a sick child or relative, and lack of child care. The response of patients to assessing prenatal care may reflect their priority of medical care relative to other priorities associated with day-to-day existence. There may be a baseline missed appointment rate for prenatal care in lower socioeconomic populations of women. The commitment of personnel time and energy to attempt to modify the no-show rate should be reexamined.

Appointments and Schedules↗
PubMed2000

Why geriatrics? Academic geriatricians' perceptions of the positive, attractive aspects of geriatrics.

BACKGROUND: Recruitment of geriatrics trainees has been poor, and the current shortage of academic geriatricians is expected to worsen. Although barriers to entering geriatrics practice have been identified, a review of the literature found few studies about why people choose to enter geriatrics. METHODS: We used qualitative methods to investigate the positive, attractive aspects of geriatrics. Long interviews with six academic geriatricians were taped and transcribed. Transcripts were entered into a textual database computer program and reviewed independently by two investigators. RESULTS: Six themes emerged: 1) traditional learning experiences, 2) value on personal relationships, 3) a perception of distinctive differences, 4) a desire to feel needed personally and societally, 5) prefer democracy versus autocracy, and 6) desire intellectual challenges. Academic geriatrics, therefore, is particularly attractive to people who value enduring relationships, see challenges in complexity, practice social responsibility, prefer working within a multidisciplinary team, and derive satisfaction from making seemingly small but nonetheless important changes in peoples' lives. CONCLUSIONS: If further studies validate these findings, they could promote geriatrics as a career, by, for example, identifying students and family practice and internal medicine residents who share these values, beliefs, and attitudes and encouraging them to consider this important field.

Adult↗
PubMed2000

T cell chemokine receptor expression in human Th1- and Th2-associated diseases.

The interaction between chemokines and their receptors is an important step in the control of leukocyte migration into sites of inflammation. Chemokines also mediate a variety of effects independent of chemotaxis, including induction and enhancement of Th1- and Th2-associated cytokine responses. Recent studies have shown that human Th1 and Th2 clones, activated under polarizing conditions with polyclonal stimuli in vitro, display distinct patterns of chemokine receptor expression: Th1 clones preferentially express CCR5 and CXCR3, while many Th2 clones express CCR4, CCR8 and, to a lesser extent, CCR3. These differential patterns of chemokine receptor expression suggest a mechanism for selective induction of migration and activation of Th1- and Th2-type cells during inflammation and, perhaps, normal immune homoeostasis. Studies have begun to examine T cell chemokine receptor expression in vivo to determine the relevance of these in vitro observations to human Th1- and Th2-associated diseases. In this review, we critically examine recent reports of T cell chemokine receptor expression in human autoimmune disorders (multiple sclerosis and rheumatoid arthritis) and atopic disorders (allergic rhinitis and asthma) which are believed to arise from inappropriate Th1- and Th2-dominated responses, respectively.

Arthritis, Rheumatoid↗
PubMed1999

Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis.

This study was designed to examine the effect of ascorbic acid (vitamin C) on various death pathways of mouse T cells. Unlike humans, mice produce their own ascorbic acid and our study tested the effect of additional ascorbic acid on murine T cells. Our data show that three T cell death pathways (growth factor withdrawal-, spontaneous-, and steroid-induced death) were inhibited when T cells were incubated with ascorbic acid. The data show that both activated and resting T cells were responsive to ascorbic acid since both populations were resistant to death stimuli when treated with ascorbic acid. Additionally, effector T cells were more likely to enter S phase if treated with ascorbic acid. Our data implicate ascorbic acid as a potent inhibitor of various forms of T cell death and suggest that vitamin C may function as an immune booster through this mechanism.

Animals↗
PubMed1999

CD40 activation boosts T cell immunity in vivo by enhancing T cell clonal expansion and delaying peripheral T cell deletion.

In this report we show that activation of APC with an agonist anti-CD40 mAb profoundly alters the behavior of CD4 T cells in vivo. Stimulation of mice with anti-CD40 2 days before, but not 1 day after, administration of superantigen (SAg) enhanced CD4 and CD8 T cell clonal expansion by approximately threefold. Further, CD40 activation also delayed peripheral T cell deletion after activation. Dying, activated T cells were quantitated by detecting extracellular phosphatidylserine with concomitant staining for SAg-reactive T cells using a TCR Vbeta-specific mAb. Upon close examination, it was shown that CD40 activation delayed the death of the activated T cells. Additionally, it was found that enhanced survival of CD4 T cells was equally dependent on APC expression of B7-1 and B7-2. This is in contrast to CD8 T cells, which did not depend as much on B7-1 as B7-2. Thus, CD40 activation indirectly promotes T cell growth and delays the death of SAg-stimulated CD4 T cells in vivo. These data suggest that one way CD40 activation promotes a more robust immune response is by indirectly increasing the production of effector T cells and by keeping them alive for longer periods of time.

Animals↗