Biomedical subjects

William T Shearer

Publications and source records attributed to William T Shearer.

13 recordsLinked to original sources

PubMed2003

Trichosporon pullulans infection in 2 patients with chronic granulomatous disease: an emerging pathogen and review of the literature.

BACKGROUND: Chronic granulomatous disease is a genetically determined primary immunodeficiency disease in which phagocytic cells are unable to kill certain bacteria and fungi after ingestion. Manifestations include recurrent pyogenic infections caused by catalase-positive microbes. Trichosporon species are emerging as opportunistic agents that cause systemic disease in immunocompromised patients. Typically disease has been described in association with T beigelii in patients with secondary immunodeficiency, such as underlying malignancy. OBJECTIVE: The objective was to report the first 2 cases of T pullulans infection in 2 male children with chronic granulomatous disease. METHODS: The records of the 2 patients were reviewed. In addition, all cases of T pullulans infection reported in the English language literature are presented. RESULTS: This report brings to 7 the total number of cases of T pullulans reported and the first in patients with chronic granulomatous disease, one with invasive pneumonia and the other with an infected paronychium and localized cellulitis. In the 5 additional cases malignancy was the principal risk factor. CONCLUSION: T pullulans has rarely been reported as a fungal pathogen. The most prominent risk factor for the development of trichosporonosis is immunocompromise, most notably with neutropenia. Abnormally functioning neutrophils, such as with chronic granulomatous disease, may also predispose individuals to this opportunistic pathogen.

Child↗

PubMed2003

Basic and clinical immunology.

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

Animals↗

PubMed2003

Long-term assessment of T-cell populations in DiGeorge syndrome.

BACKGROUND: Patients with DiGeorge syndrome present with a broad range of T-cell deficiency. Partial DiGeorge syndrome (pDGS) is a preferred designation for patients with detectable T-cell function. Among immunology experts, there is no uniform opinion on the necessity of T-cell precautions for pDGS patients. Few studies have addressed the natural course of their immune function over time. OBJECTIVE: The objective of this study was to describe the natural history of immune parameters in pDGS. METHODS: We reviewed the medical records of 45 pDGS patients. Peripheral blood T-cell subsets counts and percentages were recorded at 1, 6, 12, 18, 24, 30, 48, 60, 72, 96, and 120 months of age, and the rates of change of T-cell measurements over the follow-up period (slopes) were calculated for each individual. Humoral immunity was evaluated by quantification of immunoglobulins and by testing antibody titers to recall antigens. RESULTS: T-cell subsets counts from pDGS patients were generally lower than those of age-matched normal populations but were not severely depressed (ie, CD4+ T-cell percentage less than 15%). The median of the slopes for CD3+, CD4+, and CD8+ T-cell percentages were -0.7%, -0.8%, and -0.1%/month, respectively, in the first year of age and 0.1%/month for each subpopulation from 12 to 120 months of age. Lymphoproliferative responses to phytohemagglutinin were adequate at all ages. Immunoglobulin deficiencies or inadequate production of specific antibodies were not detected. CONCLUSIONS: In our pDGS patient cohort, a significant deterioration of T-cell number or function did not occur over time. Clinical implications of this finding include the possibility of discontinuing T-cell deficiency precautions and frequency of reevaluations of pDGS patients with stable and adequate immune function.

CD3 Complex↗

PubMed2003

30. Defining the spectrum of clinical immunology.

Historically, in the development of the subspecialty of clinical immunology, loosely connected groups of transplanters, endocrinologists, gastroenterologists, and many others have existed, each practicing a special form of immunology pertinent to their area of interest. The diversity of interests and separation of efforts, and the absence of educational initiatives in this field, have conspired to prevent most clinical immunologists from receiving the education required and the recognition appropriate for this subspecialty of medicine. What is proposed here is an attempt to collect the wide spectrum and isolated components of clinical immunology-specific practices into a unifying concept centered around four themes that define the field of clinical immunology better than traditional organ or disease based specialties: (1) immunoregulation, (2) immunotherapy, (3) immunogenetics, and (4) immunodiagnostics. This definition of the themes of clinical immunology provides a cross-disciplinary approach to understanding the present spectrum of interests of clinical immunologists and easily incorporates new interests, such as host defense, as the practice of clinical immunology evolves. In the future, through the use of a thematic approach to the training of clinical immunologists, a new, more organized mechanism may evolve for defining this specialty, educating the members, and providing a common pathway of certification.

Allergy and Immunology↗

PubMed2002

Evaluation of coxsackievirus infection in children with human immunodeficiency virus type 1-associated cardiomyopathy.

In a matched case-control study of the association between coxsackieviruses and cardiac impairment, 24 human immunodeficiency virus (HIV) type 1-infected children with cardiac impairment were compared with 24 HIV-1-infected control subjects. Serologic evidence of coxsackievirus infection was present in all children, with no significant difference in geometric mean antibody titers between case patients and control subjects. Conditional logistic regression to test for an association between coxsackievirus antibody titer and the presence or absence of cardiac impairment, by any indicator, showed an odds ratio of 1.11 (95% confidence interval, 0.58-2.10; P=.75), indicating no association between coxsackievirus infection and cardiac impairment. Coxsackievirus antibody titers correlated positively with total IgG levels in nonrapid progressors but not in rapid progressors. Paired serum samples taken before and after diagnosis of cardiac impairment in 5 patients showed no evidence of intervening coxsackievirus infection. These results do not identify a causal role for coxsackieviruses for cardiomyopathy in HIV-1-infected children.

Cardiomyopathies↗

PubMed2002

SDF-1alpha regulates HIV-1-gp120-induced changes in CD79b surface expression and Ig production in activated human B cells.

Binding of HIV-1 glycoprotein (gp120) to activated B cells of HIV-infected and HIV-uninfected subjects induces increased cell proliferation, cAMP generation, immunoglobulin (Ig) production and downregulation of the invariant chain, CD79b, of the B-cell receptor. We present evidence that the stromal cell-derived factor-1alpha (SDF-1alpha), itself a B-cell stimulant, reversed gp120-driven downregulation of CD79b in CD40- and IL-4-activated purified HIV-1 seronegative human peripheral blood B cells. SDF-1alpha augmented gp120-induced Ig production, downregulated CXCR4 receptor expression, and alone, exerted no effect on CD79b surface expression, reversed the gp120-induced downregulation of CD79b. These SDF-1alpha-modulated B-cell responses were specifically abrogated by an anti-SDF-1alpha antibody. These data suggest that SDF-1alpha plays an important regulatory role in the altered B-cell responses seen in HIV-1 infection. Further, these findings may enhance the understanding of the pathophysiology of HIV-1 infection and suggest a strategy utilizing SDF-1alpha or related molecules as an anti-HIV therapy.

Anti-HIV Agents↗

PubMed2002

Immune function during space flight.

It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.

Aerospace Medicine↗

PubMed2002

Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter.

Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.

Antarctic Regions↗

PubMed2002

HIV: clinical manifestations.

HIV infection in the United States appeared early in the 1980s, when previously healthy homosexual men manifested opportunistic infections attributable to apparent underlying immunodeficiency. After these initial isolated reports, there appeared many other groups of patients at risk for development of this devastating disease. From these meager beginnings, the problem has escalated exponentially. HIV infection can affect every system in the human body. Since the era of highly active antiretroviral therapy, however, the prevalence of opportunistic infections and HIV-AIDS clinical manifestations has declined dramatically. In addition to antiretroviral therapy, management of HIV-infected persons requires knowledge of the extent of system involvement, as well as highly active antiretroviral therapy-related adverse effects, so as to recognize complications and initiate appropriate intervention. In the following review we will attempt to comprehensively summarize the clinical manifestations of HIV infection for both pediatric and adult populations.

AIDS-Related Opportunistic Infections↗

PubMed2002

Magnitude of IFN-gamma production in HIV-1-infected children is associated with virus suppression.

BACKGROUND: Little is known about the cytokine production by peripheral blood cells of pediatric patients who have suppressed HIV-1 replication after highly active antiretroviral therapy (HAART). OBJECTIVE: We sought to determine the effect of HAART on the production of T(H)1 and T(H)2 cytokines by HIV-infected children who have suppressed HIV replication. METHODS: At 3- to 6-month intervals over a 5-year period, CD4(+) T cells were enumerated, plasma HIV-1 RNA was measured, and levels of cytokine production by whole blood cultures were determined in 21 HIV-1-infected children. RESULTS: Ten patients achieved an HIV-1 RNA level of less than 3000 copies/mL of plasma and maintained that level for at least 15 months (virus-suppressed [VS] group). Eleven patients had a mean HIV-1 RNA level of greater than 10(4) copies/mL of plasma and a mean CD4(+) T-cell count of less than 500/microL of blood (active infection group). The median levels of anti-CD3-induced IL-2, IFN-gamma, and IL-10 in the active infection group were significantly lower than those in the VS group after suppression of the virus. The median slope of IFN-gamma production by means of PHA-stimulated culture after achieving VS status (4.04) was significantly higher than the level before VS status (-1.31, P =.004). The difference in the median slopes for IL-10 production by anti-CD3-stimulated cultures before (0.21) and after (-0.16) achieving VS status was statistically different (P =.027). CONCLUSION: The immune restoration of HIV-1-infected children receiving HAART might be related to an increase in IFN-gamma production and a decrease in the rate of IL-10 production after virus suppression.

Antiretroviral Therapy, Highly Active↗

PubMed2002

Molecular virology and immunology of HIV infection.

Great progress has been made with respect to our understanding of the immunopathogenesis of AIDS and the infectious agent, HIV, that causes the disease. HIV, a human retrovirus with tropism for CD4(+) T cells and monocytes, induces a decrease of T-cell counts, T-cell dysfunction, and, ultimately, immunodeficiency. HIV also causes B-cell dysfunction characterized by polyclonal activation, hypergammaglobulinemia, and lack of specific antibody responses. Chemokine receptors-mainly CCR5 and CXCR4-have been found to be necessary for viral entry into the host cell, a step that can be inhibited by chemokine-related molecules that are ligands for those receptors. After HIV infection, a strong cellular immunity develops and partially controls viral replication. It can take several years for HIV infection to become clinically evident. Studies in long-term nonprogressors have shown the determinant roles of both helper and cytotoxic T cells in the control of HIV disease. Advances in HIV immunology research are currently being applied in the development of prophylactic and therapeutic vaccines.

AIDS Vaccines↗

PubMed2002

Recognition of clinical immunology as a distinct medical subspecialty: importance for the practice of allergy.

BACKGROUND: Although residents trained in accredited teaching programs in allergy and immunology are exposed to many areas of clinical immunology, the vast majority of these residents' subsequent practices are composed of caring for patients with allergic and asthmatic conditions. Except for rheumatologists, almost all other clinical immunologists appear to lack organized training programs, defined certification pathways, and clear career opportunities. OBJECTIVE: Recognition of clinical immunology as a distinct medical subspecialty with many areas of expertise will enhance the image of allergists and clinical immunologists, ensure subspecialty certification, and provide better career opportunities. METHODS: Documents, publications, and private opinions of individuals within professional allergy and clinical immunology organizations were evaluated for possible contribution to the subject content of this article. RESULTS: There is a need for defined residency programs, medical board certification, and professional organizations that speak for and provide postgraduate education for all clinical immunologists. Molecular and genetic discoveries are delineating the central role of fundamental immunology in all immune-mediated diseases and future therapy of allergic and immunologic diseases. CONCLUSIONS: Allergists of the 21st century should participate in the growing recognition of clinical immunology as an important medical subspecialty that can provide science-based therapies for allergic and immunologic disorders. The future practice of allergy depends largely on the molecular and genetic discoveries that serve to unite all practitioners of clinical immunology. Forging common alliances of education, certification, and career pathways with other clinical immunologists is the correct investment for a bright future for allergy.

Allergy and Immunology↗

PubMedDate not supplied

Effects of the space flight environment on the immune system.

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

Animals↗