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Biomedical subjects

R Kradin

Publications and source records attributed to R Kradin.

At least 19 recordsLinked to original sources
PubMed2001

Epinephrine yields translocation of lymphocytes to the lung.

Previous studies have demonstrated that acute stress leads to the appearance of T-lymphocytes in skin and bone marrow. In order to examine the effects of adrenergic stimulation on the traffic of immune lymphocytes to the lung, C57BL/6 mice were injected with epinephrine subcutaneously, and changes in lymphocyte representation in lung, hilar lymph node, spleen, and blood were examined at 30 min. Cytofluorimetric lymphocyte subset analysis showed that epinephrine increased "memory" CD4+ lymphocytes in enzymatic digests of lung but decreased their representation in spleen. NK1.1+ lymphocytes were concomitantly increased in lung and decreased in spleen. Next, lymphocytes in spleen or popliteal lymph nodes were labeled with the Hoechst lipophilic red dye PKH26 in vivo 48 h prior to epinephrine injection. PKH26+ lymphocytes were identified in lung tissue at 30 min postepinephrine but not in controls. Lymphocyte traffic was inhibited by propanolol. We conclude that epinephrine promotes rapid shifts in immune lymphocytes from lymphoid tissues into lung and blood. Directed traffic of immune lymphocytes may be a feature of the adaptive immune response to stress at mucosal barrier surfaces.

Adrenergic Agonists↗
PubMed2000

The pathogenesis of beryllium-induced pulmonary granulomatosis. A scanning secondary ion analytical microscopy study.

Chronic granulomatous pneumonitis was induced in rats with beryllium to study the pathogenesis of that disease, by identifying and localizing the beryllium in histological sections of the pulmonary tissues. This was done with scanning secondary ion mass spectrometry (SIMS). Thus, our observations suggest that the route of the Be from the site of injection into the lung, passes first by the blood, through the vascular wall and into the surrounding pulmonary tissues where Be was phagocytized by macrophages. There resulted in acute vasculitis throughout the lung. It was noted that the granuloma were focal inflammatory sites, solely observed within the vascular wall, distributed along the course of the affected vessel. These findings raise the question as to whether pulmonary granulomatous lesions of other origins are also localized within the vascular wall.

Animals↗
PubMed1999

Anxiety in patients with pulmonary disease: comorbidity and treatment.

Anxiety is a common and sometimes disabling symptom among patients with respiratory disease. Anxiety disorders appear to be the most prevalent psychiatric disorders in clinical samples of patients with pulmonary disease. Recognition that the differential diagnosis of dyspnea and anxiety includes both pulmonary and psychiatric conditions can be crucial to appropriate medical management and minimizing iatrogenic harm. This article reviews the epidemiology, comorbidity, diagnosis, and treatment of anxiety syndromes in patients with pulmonary disease. Successful treatment of anxiety disorders can substantially improve quality of life and a variety of treatment options are available. Safe and effective pharmacotherapy requires attention to potential adverse drug effects on pulmonary function and drug-to-drug interactions. Nonpharmacological treatments such as cognitive/behavioral therapies offer effective treatment without the risk of medication side effects.

Antidepressive Agents↗
PubMed1999

Generosity: a psychological and interpersonal motivational factor of therapeutic relevance.

This paper examines the role of generosity in analysis. Generosity represents a complex constellation of cognitions and affects that is antithetical to those states of super-ego harshness that characterize many forms of human psychopathology. In development, generosity is evoked by idealization, and a dynamic axis of idealization-generosity promotes relational proximity between the child and its caretakers, and eventually fosters separation and individuation. Generosity is highly sensitive to adverse conditions, and requires environmental conditions that are conducive to psychosomatic well-being. The imaginal basis of generosity is rooted in the myth of the 'hero and the return', which is the mythic foundation of the analyst's role as psychopomp. It is argued that the generosity of the analyst is a cardinal therapeutic factor in treatment.

Adult↗
PubMed1998

Respiratory syncytial virus-associated infections in adult recipients of solid organ transplants.

BACKGROUND: Although respiratory syncytial virus (RSV) infection is known to cause severe pulmonary infections in bone marrow transplant recipients, less is known concerning its clinical course, diagnosis, and treatment in solid organ transplant recipients. METHODS: We have conducted a retrospective review of seven cases of RSV infection in adult recipients of solid organ transplants. Four patients received lungs, two received kidneys, and one received a heart. RESULTS: The most common presenting complaints were dyspnea (100%), cough (86%), and purulent sputum (57%). Physical findings included fever (43%), rales (100%), and wheezing (29%). Admission studies were significant for leukocytosis (29%), a left shift in the white blood cell differential (86%), and hypoxemia (mean PaO2 = 64). Chest radiographs were unchanged in 29% and showed infiltrates that were bilateral in 43% and unilateral in 29%. Pulmonary function tests in lung transplant recipients showed a mean fall in forced expiratory volume in 1 second of 26% and a fall in diffusion capacity for carbon monoxide of 24%. Five patients were treated with aerosolized ribavirin. Adverse events associated with treatment included wheezing (80%) and mild dyspnea (20%). The conditions of three of five treated patients were believed by their physicians to have improved 7 days after the initiation of therapy. One of the five treated patients died, and both untreated patients survived. CONCLUSIONS: RSV infection in this population has an extremely variable severity and clinical course, usually dominated by lower respiratory symptoms and obstructive airway disease. Ribavirin therapy is well tolerated, but its efficacy remains unknown.

Adult↗
PubMed1997

Expression of inducible nitric oxide synthase by macrophages in rat lung.

Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary macrophages (Mø). An inducible isoform of NO synthase (iNOS) catalyses the production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1 cytokines, including interferon-gamma and TNF-alpha. In the present study, iNOS+ interstitial cells were demonstrated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1+ interstitial Mø (IM) were iNOS+ and secreted modest amounts of NO without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS- and showed no basal NO secretion. When incubated with heat-killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM. Recombinant murine GM-CSF stimulated production of NO by AM but not by IM. However, when IM were costimulated with GM-CSF and IFN-gamma, they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by IM. We conclude that iNOS+ IM are present in normal rat lung, where they regulate the pulmonary cell-mediated immune response to antigen.

Animals↗
PubMed1997

Pulmonary response to inhaled antigen: neuroimmune interactions promote the recruitment of dendritic cells to the lung and the cellular immune response to inhaled antigen.

Dendritic cells (DCs) play a critical role in capturing and presenting inhaled antigens to T lymphocytes. We report that pulmonary DCs in the Lewis rat are normally located in the lung in immediate proximity to nerve fibers that contain immunoreactive substance P (SP). Functionally, pulmonary DCs bound 125I-SP and displayed increased motility in vitro in response to graded concentrations of SP. However, SP had no effect on the accessory cell activities of DCs. To examine the role of neural influences on the pulmonary immune response to inhaled antigen, Lewis rats were pretreated with capsaicin (CAP), which damages small nerves and depletes neuropeptide stores, and then challenged intratracheally (i.t.) with hen egg lysozyme (HEL). The number and antigen-presenting cell activities of pulmonary DCs in the CAP-treated rats were comparable to those of controls up to day 14. T lymphocytes harvested from the regional lymph nodes draining the lung were effectively sensitized to HEL in both groups. However, when CAP-treated rats sensitized to HEL i.t. at day 0 were rechallenged with HEL i.t. at day 14, the lungs showed decreased numbers of OX-6+ DCs and diminished pulmonary lymphoid infiltrates compared with controls. We suggest that CAP interferes with a neural-mediated response that contributes to the accumulation of inflammatory cells during the efferent limb of the pulmonary-cell-mediated immune response in vivo.

Administration, Inhalation↗
PubMed1996

Prevalence of panic in patients referred for pulmonary function testing at a major medical center.

OBJECTIVE: The authors examined the prevalence and correlates of panic disorder in a group of patients who were referred for pulmonary function testing. METHOD: Patients (N = 115) were screened for the presence of panic attacks and panic disorder with a self-report questionnaire; a subgroup (N = 25) received structured diagnostic assessment. RESULTS: Of the 115 patients, 41% (N = 47) reported panic attacks and 17% (N = 20) met screening criteria for panic disorder. From the confirmed rate of panic disorder among the subgroup who received structured diagnostic assessment, the overall prevalence rate of panic disorder was estimated to be 11% and included six of the nine patients (67%) who had a diagnosis of chronic obstructive pulmonary disease. There were no significant differences between patients with and without panic in the severity of pulmonary function abnormalities or in the response to bronchodilators. However, patients with panic attacks were significantly more likely to report dyspnea at rest and irritable bowel symptoms and tended to report difficulty swallowing. CONCLUSIONS: This study suggests that panic disorder and subsyndromal panic are relatively common and may be unrecognized and inadequately treated in patients who present with respiratory symptoms.

Airway Obstruction↗
PubMed1995

Reply to Tauber.

Explore the source record for details and available documents.

Immune System↗
PubMed1995

Gender differences in hostility among depressed and medical outpatients.

We assessed possible gender differences in state and trait hostility in a large sample of depressed outpatients and in a group of medical outpatients. We administered the Cook and Medley Hostility Scale, measuring trait hostility and aggressiveness, and the Symptom Questionnaire, including a state measure of irritability and hostility, to 218 depressed outpatients and 51 medical outpatients. There was a statistically significant positive correlation between severity of depression and our state measure of hostility, and a weak, although statistically significant, relationship between severity of depression and total score of our trait measure of hostility. Among depressed outpatients, trait hostility was greater in men than in women, while no significant gender difference was observed in state hostility. Among medical outpatients, the state hostility scale scores were significantly higher in men than in women. These gender differences in both groups remained significant even after adjusting for severity of depression. Thus, it appears that men with depression tend to have higher scores than women on state and trait measures of hostility, suggesting that men may be at greater risk than women of developing patterns of pathologic aggression and hostile behavior.

Adult↗
PubMed1994

The T cell antigen receptor CD3:CD4 molecular complex is diminished on the surface of pulmonary lymphocytes.

CD4, a 55-kd cell surface glycoprotein, binds to class II major histocompatibility complex (MHC) (Ia) antigens and functions as a coreceptor for the T cell antigen receptor (Ti alpha beta)-CD3 complex. We have observed that critical elements of the T cell antigen multireceptor complex, including Ti alpha beta, CD3, CD4, but not CD8, were diminished on CD45RO+ pulmonary T lymphocytes but not CD45RO+ peripheral blood T lymphocytes (PBL). Epitopes mapping from the first (D1) to the fourth (D4) extracytoplasmic Ig-like domains of CD4 were expressed to a lesser degree on pulmonary T cells than on PBL (P = 0.002). CD4 expression on pulmonary T cells did not increase after 72 hours of ex vivo culture in complete medium but was restored toward control levels by stimulation with phytohemagglutinin, anti-CD3, or interleukin-2. CD4 mRNA isolated from lung T cells and PBL co-migrated on Northern blots and the total levels of CD4 mRNA were comparable, suggesting that diminished CD4 expression by pulmonary T cells might reflect a posttranscriptional change. To determine whether CD4bright T cells convert with mitogen stimulation to CD4dim cells, PBLs were stimulated with immobilized anti-CD3, anti-CD4, or a molecularly engineered anti-CD3:CD4 bispecific monoclonal antibody and the ratio of the CD4:CD3 mean fluorescence staining intensities was calculated at days 3 and 13. The CD4:CD3 ratio decreased primarily for cells stimulated with anti-CD3:CD4, suggesting that co-ligation of CD3 and CD4 is required for the generation of CD4dim T cells. We conclude that diminished Ti alpha beta-CD3:CD4 expression is a characteristic of T cells in lung that is not shared by peripheral blood T cells in vivo, and speculate that this change reflects T cell activation in a millieu of limited interleukin-2 availability.

Antibodies, Bispecific↗
PubMed1990

Anti-RMA: a murine monoclonal antibody that activates rat macrophages. I. Distribution and characterization of the RMA antigen.

Activated macrophages participate in inflammation by eliminating foreign cells, promoting wound healing, and modulating the immune response. A murine monoclonal antibody, designated anti-rat macrophage activator (RMA), was raised against alveolar macrophages (AM) activated with interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA). The RMA antigen is expressed by resident macrophages but not by other cells. Binding to AM by anti-RMA is not competitively inhibited by the murine monoclonal antibodies MRC OX-41, OX-42, and OX-43. Surface membrane expression of RMA antigens is upregulated by lipopolysaccharide, PMA, and tumor necrosis factor-alpha but not by IFN-gamma. Stimulation of AM with anti-RMA yields distinct ultrastructural alterations, as well as de novo protein and DNA synthesis. Immunoprecipitation of [35S]methionine metabolically labeled AM yields a 120 kD protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that is not altered by chemical reduction. We conclude that the RMA antigen is macrophage specific and that binding of anti-RMA to AM promotes functional activities in a subset of these cells.

Animals↗
PubMed1990

Anti-RMA, a murine monoclonal antibody, activates rat macrophages: II. Induction of DNA synthesis and formation of multinucleated giant cells.

Anti-RMA is a murine anti-rat monoclonal antibody that binds to a 120-kD surface membrane antigen expressed primarily by alveolar macrophages. Saline-lavaged alveolar macrophages (AM) formed clusters after incubation with anti-RMA. Anti-RMA produced multinucleated giant cells (MGC) in approximately 15% of adherent AM, and the F (ab')2 fragment of anti-RMA yielded MGC in approximately 9% of AM. The Fab fragment of anti-RMA did not promote MGC formation, nor did the murine anti-rat monoclonal antibodies OX41 and W3/25 (anti-CD4). Although anti-RMA produced a tenfold increase in [3H]thymidine incorporation by AM, it yielded a minimal increase in the number of AM. Autoradiography of AM stimulated with anti-RMA showed heterogeneous labeling of nuclei in MGC, suggesting that 3H-labeled AM may fuse with AM that are not actively synthesizing DNA. These findings suggest that binding of anti-RMA to AM may activate DNA synthesis, and promote clustering and fusion of AM, leading to MGC formation.

Animals↗
PubMed1989

Adoptive immunotherapy with interleukin-2 (IL-2) results in diminished IL-2 production by stimulated peripheral blood lymphocytes.

We examined the responses of peripheral blood lymphocytes (PBL) to a panel of T-cell mitogens in patients receiving adoptive transfers of tumor-infiltrating lymphocytes and continuous infusions of interleukin-2 (IL-2) for treatment of advanced cancer. All patients showed diminished proliferative responses to soluble and alloantigens, lectins, anti-CD3, and IL-2 during therapy. The non-major histocompatibility complex (MHC)-restricted cytolytic activities of PBL were increased by treatment and were further augmented by IL-2 in vitro. The expression of approximately 55-kd low-affinity IL-2 receptors (IL-2R) by PBL increased during treatment but functional IL-2R were simultaneously down-regulated. Proliferative responses were partially restored to pretreatment levels when PBL were costimulated with recombinant IL-2 and mitogens. Lectin stimulation of PBL produced little IL-2 secretion during treatment, while IFN-gamma secretion persisted. We conclude that infusions of IL-2 down-regulate the expression of functional IL-2R, decrease the secretion of IL-2, and lead to decreased mitogen responses by PBL.

Antigens, Surface↗