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Biomedical subjects

K J Flynn

Publications and source records attributed to K J Flynn.

At least 19 recordsLinked to original sources
PubMed2000

Effect of Staphylococcus enterotoxin B on the concurrent CD8(+) T cell response to influenza virus infection.

Bacterial superantigens have potent in vivo effects. Respiratory viral infections are often associated with secondary bacterial infections, raising the likelihood of exposure to bacterial superantigens after the initiation of the anti-viral immune response. In this study, the general and V beta-specific effects of exposure to Staphylococcal enterotoxin B (SEB) during influenza virus infection on both the ongoing acute and the subsequent recall CD8(+) T cell responses were analyzed, using the well-characterized murine influenza model system and tetrameric MHC/peptide reagents to directly identify virus-specific T cells. The results show that although superantigen exposure during the primary viral infection caused delayed viral clearance, there was remarkably little effect of SEB on the magnitude or TCR repertoire of the ongoing cytolytic T cell response or on the recall response elicited by secondary viral infection. Thus, despite the well-characterized immunomodulatory effects of SEB, there was surprisingly little interference with concurrent anti-viral immunity.

Acute Disease↗
PubMed2000

The relationship between the dissolved inorganic carbon concentration and growth rate in marine phytoplankton.

A range of marine phytoplankton was grown in closed systems in order to investigate the kinetics of dissolved inorganic carbon (DIC) use and the influence of the nitrogen source under conditions of constant pH. The kinetics of DIC use could be described by a rectangular hyperbolic curve, yielding estimations of KG(DIC) (the half saturation constant for carbon-specific growth, i.e. C mu) and mu max (the theoretical maximum C mu). All species attained a KG(DIC) within the range of 30-750 microM DIC. For most species, NH4+ use enabled growth with a lower KG(DIC) and/or, for two species, an increase in mu max. At DIC concentrations of > 1.6 mM, C mu was > 90% saturated for all species relative to the rate at the natural seawater DIC concentration of 2.0 mM. The results suggest that neither the rate nor the extent of primary productivity will be significantly limited by the DIC in the quasi-steady-state conditions associated with oligotrophic oceans. The method needs to be applied in the conditions associated with dynamic coastal (eutrophic) systems for clarification of a potential DIC rate limitation where cells may grow to higher densities and under variable pH and nitrogen supply.

Carbon↗
PubMed1999

In vivo proliferation of naïve and memory influenza-specific CD8(+) T cells.

The virus-specific CD8(+) T cell response has been analyzed through the development, effector, and recovery phases of primary and secondary influenza pneumonia. Apparently, most, if not all, memory T cells expressing clonotypic receptors that bind a tetrameric complex of influenza nucleoprotein (NP)(366-374) peptide+H-2D(b) (NPP) are induced to divide during the course of this localized respiratory infection. The replicative phase of the recall response ends about the time that virus can no longer be recovered from the lung, whereas some primary CD8(+)NPP(+) T cells may proliferate for a few more days. The greatly expanded population of CD8(+)NPP(+) memory T cells in the lymphoid tissue of secondarily challenged mice declines progressively in mean prevalence over the ensuing 100 days, despite the fact that at least some of these lymphocytes continue to cycle. The recall of cell-mediated immunity thus is characterized by massive proliferation of the antigen-specific CD8(+) set, whereas the extent of lymphocyte turnover in the absence of cognate peptide is variable, at a low level, and can be influenced by intercurrent infection.

Animals↗
PubMed1999

Virus-specific immunity after gene therapy in a murine model of severe combined immunodeficiency.

Human severe combined immunodeficiency (SCID) can be caused by defects in Janus kinase 3 (JAK3)-dependent cytokine signaling pathways. As a result, patients are at high risk of life-threatening infection. A JAK3 -/- SCID mouse model for the human disease has been used to test whether transplant with retrovirally transduced bone marrow (BM) cells (JAK3 BMT) could restore immunity to an influenza A virus. The immune responses also were compared directly with those for mice transplanted with wild-type BM (+/+ BMT). After infection, approximately 90% of the JAK3 BMT or +/+ BMT mice survived, whereas all of the JAK3 -/- mice died within 29 days. Normal levels of influenza-specific IgG were present in plasma from JAK3 BMT mice at 14 days after respiratory challenge, indicating restoration of B cell function. Influenza-specific CD4(+) and CD8(+) T cells were detected in the spleen and lymph nodes, and virus-specific CD8(+) effectors localized to the lungs of the JAK3 BMT mice. The kinetics of the specific host response correlated with complete clearance of the virus within 2 weeks of the initial exposure. By contrast, the JAK3 -/- mice did not show any evidence of viral immunity and were unable to control this viral pneumonia. Retroviral-mediated JAK3 gene transfer thus restores diverse aspects of cellular and humoral immunity and has obvious potential for human autologous BMT.

Animals↗
PubMed1999

Protection against a lethal avian influenza A virus in a mammalian system.

The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from birds. Little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza A viruses using contemporary immunology techniques. Such experiments with the H5N1 viruses are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-expressing (Ig+/+) and Ig-/- mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8(+) T-cell memory in the Ig-/- mice provided some small measure of resistance to a low-dose H3N8 challenge. The H3N8 virus also replicated in the respiratory tracts of the H3N2-primed Ig+/+ mice, generating secondary CD8(+) and CD4(+) T-cell responses that may contribute to recovery. The results indicate that the various components of immune memory operate together to provide optimal protection, and they support the idea that related viruses of nonhuman origin can be used as vaccines.

Animals↗
PubMed1998

Body images and obesity risk among black females: a review of the literature.

The prevalence of obesity among Black women has reached epidemic proportions. Some researchers have suggested that the body images of Black females may contribute to their high risk for obesity by inhibiting motivation for weight control. While a number of empirical studies have examined the body images of Black females, findings are complex and at times, inconsistent. For example, some studies show that Black females consider overweight bodies more attractive, while other studies show that Black females prefer normal-weight bodies. Divergent findings may be due, in part, to the multidimensional nature of body image. Inconsistencies may also be due to differences between the Black females sampled. Methodological problems, including the use of measures that have been validated among Black females, the use of various weight-for-height standards, and the inconsistent analyses of or lack of physiological data, also may contribute to conflicting results. This review addresses the complexity of body image findings among a heterogeneous Black female population and the relationship between their body images and obesity risk. Implications for effective obesity treatment programs and suggestions for improvements in future body image studies are also discussed.

Black or African American↗
PubMed1998

Virus-specific CD8+ T cells in primary and secondary influenza pneumonia.

Virus-specific CD8+ effector T cells (eCTL) are enriched in the lungs of mice with primary influenza pneumonia, though later detection of memory T cells (mCTL) in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining protocols is at the limits of flow cytometric analysis. Respiratory challenge with an H3N2 virus months after H1N1 priming induces a massive recall response, which reduces virus titers 2-3 days earlier than in nave controls. Influenza-specific mCTL produce interferon-gamma within 6 hr, but still take 4-5 days to localize to the infected respiratory tract. The delay reflects that the recall response develops first in the MLN, which contains relatively few mCTL. The response to a subdominant epitope is less obvious after secondary challenge.

Animals↗
PubMed1998

Thymic lymphoproliferative disease after successful correction of CD40 ligand deficiency by gene transfer in mice.

Inherited deficiency of the CD40 ligand (X-linked hyper-IgM syndrome) is characterized by failure of immunoglobulin isotype switching and severe defects of cell-mediated immunity. To test the potential for gene transfer therapy to correct this disorder, we transduced murine bone marrow or thymic cells with a retroviral vector containing the cDNA for the murine CD40 ligand (CD40L) and injected them into CD40L-/- mice. Even low-level, constitutive expression of the transgene stimulated humoral and cellular immune functions in these mice. With extended follow-up, however, 12 of 19 treated mice developed T-lymphoproliferative disorders, ranging from polyclonal increases of lymphoblasts to overt monoclonal T-lymphoblastic lymphomas that involved multiple organs. Our findings show that constitutive (rather than tightly regulated), low-level expression of CD40L can produce abnormal proliferative responses in developing T lymphocytes, apparently through aberrant interaction between CD40L+ and TCRalphabeta+CD40+ thymocytes. Current methods of gene therapy may prove inappropriate for disorders involving highly regulated genes in essential positions in proliferative cascades.

Animals↗
PubMed1997

Evidence for production of paralytic shellfish toxins by bacteria associated with Alexandrium spp. (Dinophyta) in culture.

A substantial proportion of bacteria from five Alexandrium cultures originally isolated from various countries produced sodium channel blocking (SCB) toxins, as ascertained by mouse neuroblastoma assay. The quantities of SCB toxins produced by bacteria and dinoflagellates were noted, and the limitations in comparing the toxicities of these two organisms are discussed. The chemical nature of the SCB toxins in selected bacterial isolates was determined as paralytic shellfish toxins by pre- and postcolumn high-performance liquid chromatography, capillary electrophoresis-mass spectrometry, and enzyme immunoassay.

Animals↗
PubMed1997

Malignant melanoma simulating a seborrheic keratosis: a case report.

This is a case report of malignant melanoma presenting with both clinical and histopathologic features of a seborrheic keratosis. Not a rare phenomenon, this report emphasizes the importance of biopsy to evaluate apparent seborrheic keratoses. We believe that this phenomenon is best considered a presentation of melanoma. Diminished routine histopathologic evaluation of apparent seborrheic keratoses may well increase the number of mistaken diagnoses in such cases.

Aged↗
PubMed1995

Subungual keratoacanthoma masquerading as a chronic paronychia.

Subungual keratoacanthoma is a rare, benign tumor of the digits. Patients present with progressive fusiform swelling, erythema, and tenderness, usually affecting a single digit on the radial side of the hand. A cup-shaped lytic lesion of the distal phalanx is a uniform finding on radiography. Delay in diagnosis and misdiagnosis are common because of the rarity of the lesion and difficulties with histological differentiation from subungual squamous cell carcinoma. Accurate diagnosis requires a high index of suspicion, a careful history, and histological evaluation. The natural progression of the disease appears to be continued growth with ongoing destruction of the distal phalanx. Proper treatment involves surgical removal of the mass by curettage and close follow-up for at least 2 years to monitor for local recurrence.

Curettage↗
PubMed1991

Maggot therapy revisited: a case study.

This article chronicles a personal experience with the care of a patient with chronic, recalcitrant stasis ulcers who presented with maggot infestation. A case study format is used. A brief history, technique, and benefits of maggot therapy are also included.

Aged↗