bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Embolism in the Elderly: Clinical, Instrumental and Laboratory Aspects
Authors: Masotti Luca , Ceccarelli Elena , Cappelli Roberto , Guerrini Maurizio , Forconi Sandro 
Published: April 2003

<i>Objective: </i>To focus on diagnostic and therapeutic problems of pulmonary embolism in the elderly. <i>Methods: </i>Retrospective analysis of 5 years of clinical, instrumental, and laboratory data (collected at the time of hospital admission) for patients 65 years and older with pulmonary embolism proven by a high-probability scintigraphic lung scan or necropsy. Sixty-eight patients, 46 females and 22 males, 78.61 ± (SD) 7.71 years old, were enrolled in the study. <i>Results: </i>Dyspnea, chest pain, tachycardia, and tachypnea were the most common symptoms and signs; they were present alone or in combination in all patients. Bed rest over 4 days was found in 65% of the patients and deep vein thrombosis in the leg in 35%. Only 7 patients were on anticoagulant therapy which was likely to reduce the incidence of pulmonary embolism. The mortality was 29.5%. Major bleeding due to anticoagulant therapy was observed in 4.4% of the patients; 1 case was fatal. Sinus tachycardia, ST segment and T wave abnormalities in anterior leads, and incomplete bundle branch block were the most frequent electrocardiographic findings. Chest X-ray was normal in 19.5% of the patients and compatible with pulmonary embolism in 10%. A transthoracic two-dimensional echocardiogram was abnormal in 74% of the cases, with involvement of the right ventricle in the majority of them. Many patients had laboratory parameters within the normal range. The value of the latex agglutination <i>D</i>-dimer assay was less than the cutoff value of 500 µg/l in 16% of the patients. Hypoxemia and a high alveolar-arterial oxygen gradient were the most frequent aspects of the arterial blood gas analysis. Respiratory alkalosis was observed in only one third of the patients. <i>Conclusions: </i>Pulmonary embolism is often underdiagnosed in the elderly. Clinical, instrumental, and laboratory findings are nonspecific. Only acute suspicion can increase the number of diagnoses, reduce the time to diagnosis, and improve the prognosis.
The Effect of Antigen Stimulation on α<sub>4</sub>, β<sub>1</sub> and β<sub>7</sub> Chain Integrin Expression and Function in CD4+ Cells
Authors: Tarkowski Maciej , Pacheco Karin A. , Rosenwasser Lanny J. 
Published: April 2003

<i>Background:</i> The α<sub>4</sub> integrin, as α<sub>4</sub>β<sub>1</sub> (VLA-4) or α<sub>4</sub>β<sub>7</sub>, is critical for T cell migration and proliferation, although its functional modulation remains poorly understood. We hypothesized that increased receptor density, based on new receptor chain synthesis, was one such mechanism. We examined the surface receptor density of the α<sub>4</sub> and β<sub>1</sub> chains on CD4+CD45RO+ cells, and the mRNA expression of these and the β<sub>7</sub> chain in response to allergen and nonallergen antigen stimulation. <i>Methods:</i> Flow-cytometric analyses for CD49d, CD29, and CD45RO were performed on T cell lines specific for timothy, tetanus, and <i>Candida</i> from atopic and nonatopic donors. RNA was extracted from cells sorted to select CD4+/CD49d-positive cells before and after stimulation. Equivalent amounts of cDNA for β-actin, α<sub>4</sub>, β<sub>1</sub> and β<sub>7</sub> were used in PCR, and the products were quantified using phosphoimaging. <i>Results:</i> CD49d expression is heterogeneous on T cell lines and is upregulated by antigen stimulation on CD4+ T cells. The surface expression on CD4+CD45RO+ timothy allergen or tetanus toxoid T cell lines is at least double that found on CD45RO– cells. Antigen stimulation upregulated CD49d expression on the CD4+CD45RO+ subpopulation of both cell lines although it was not as significant as in the case of all CD4+ T cells. CD29 surface expression behaves similarly. <i>Candida</i> had no effect on CD49d or CD29. Messenger RNA expression for the α<sub>4</sub> chain (CD49d) is significantly upregulated 48 h following the addition of timothy or tetanus. β<sub>7</sub> chain expression also rises significantly on both cell lines. β<sub>1</sub> chain expression increases, but not significantly. <i>Conclusions:</i> The surface expression of the CD49d is heterogeneous and much higher on CD4+CD45RO+ cells than on CD4+RO– T cells. The CD49d integrin chain on CD4+ T cells is upregulated following antigen exposure. However, the CD4+CD45RO+ subpopulation is only partially responsible for this increase suggesting other T cells to have this receptor expression upregulated. CD29 expression behaves similarly. Messenger RNA expression increases coordinately for α<sub>4</sub>, β<sub>7</sub>, and not significantly for β<sub>1</sub> in these cells. These observations provide a potential mechanism for the selective accumulation of T cells at sites of inflammation, and suggest an important point of intervention for allergic and inflammatory disease.
Activation-Induced Apoptosis in T Cells from Young and Old Fischer 344 Rats
Authors: Pahlavani Mohammad A. , Vargas Danial A. 
Published: April 2003

<i>Background:</i> Activation-induced apoptosis is believed to limit cell proliferation and eliminate the high number of activated cells during an immune response. <i>Methods:</i> Activation-induced apoptosis was investigated in splenic T cells isolated from young (6 months) and old (24 months) male Fischer 344 rats. The cells were incubated with anti-CD3, concanavalin A or staphylococcal enterotoxin B (primary stimulus) for 72 h, followed by restimulation with anti-CD3 or concanavalin A (secondary stimulus). Apoptosis was assessed by DNA fragmentation assay and DNA gel electrophoresis. The expression of the apoptotic marker CD95 was analyzed by flow cytometry and the relative levels of CD95 ligand, Bcl-2 and Bax protein were measured by immunoblotting. <i>Results:</i> It was shown that DNA fragmentation was very low in the unstimulated T cells from both young and old rats. However, the level of DNA fragmentation was 45–55% greater in the activated T cells from old rats than in the activated T cells from young rats. The increase in DNA fragmentation was paralleled by an increase in the proportion of cells expressing the CD95 molecule. The proportion of CD95+ cells was approximately 40% higher in T cells from old rats than in T cells from young rats. In addition, it was found that the expression of CD95 ligand and Bax increased and Bcl-2 decreased in the activated T cells from old rats compared to the activated T cells from young rats. <i>Conclusion:</i> Our data suggest that the increase in sensitivity of T cells to apoptosis with age may contribute to age-associated immune dysfunction and disorders.
Eosinophil Activation Status and Corticosteroid Responsiveness in Severe Asthma
Authors: Bossé M. , Audette M. , Laflamme G. , Ferland C. , Boulet L.P. , Laviolette M. 
Published: April 2003

<i>Background:</i> Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma. <i>Methods:</i> Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (ΔFEV<sub>1</sub>) ≥ 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (ΔFEV<sub>1</sub> ≤ 15%, n = 9) and dependent (≥ 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. <i>Results:</i> Calcium ionophore-induced leukotriene (LT) C<sub>4</sub> release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC<sub>4</sub> release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p ≤ 0.02) and decreased GM-CSF-enhanced LTC<sub>4</sub> release in CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily dose of oral CS (35 ± 8 mg), blood counts of eosinophils from CS-dependent subjects were higher (p = 0.03) and GM-CSF enhancement of LTC<sub>4</sub> release was greater (2.8-fold) than in CS-sensitive (2.1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM-CSF enhancement of LTC<sub>4</sub> release by eosinophils of CS-sensitive asthmatics (p = 0.001). <i>Conclusions:</i> Eosinophils from CS-dependent asthmatics have an impaired response to CS, whereas serum from CS-resistant subjects contains an inhibitor of eosinophil response to GM-CSF.
Herpes simplex Virus Type 1 DNase: Functional Analysis of the Enzyme Expressed by Recombinant Baculovirus
Authors: Kehm Elke , Göksu Mehmet-Ali , Bayer Stefanie , Knopf Charles W. 
Published: April 2003

Herpes simplex virus type 1 DNase (HSV-1 DNase) was expressed in insect cells by recombinant baculovirus (NPVUL12) and purified by a combination of anionic exchanger chromatography and gel filtration. Two polypeptides of 85 and 75 kD, whose ratio varied during purification, were induced 24 h after infection. The 75-kD protein was isolated and shown to possess catalytic activity. Gel filtration analysis indicated that the active form of the enzyme at an ionic strength of I = 0.3 is a dimeric protein with an apparent molecular weight of 130,000. The recombinant enzyme exhibited the overall characteristics of the native enzyme such as 5′-3′ exonuclease and endonuclease activities with a preferred degradation of DNA. In the absence of extraneously added Mg<sup>2+</sup>, the enzyme was capable of removing mononucleotides from 5′-end-labeled DNA, but not from RNA and 3′-end-labeled DNA. The peculiar mechanism of double-strand DNA degradation suggests a specific role of HSV-1 DNase in DNA recombination processes during viral replication.
A Precipitation Reaction Found in Patients with Hepatitis C as a Marker for the Purification of Virus-Like Particles
Authors: Kim Chung Yong , Yoon Jung-Hwan , Kim Joo Sung , Kim Yong Tae , Jung Hyun Chae , Lee Hyo-Suk , Yoon Yong Bum , Song In Sung 
Published: April 2003

Even after the molecular cloning of the hepatitis C virus (HCV), an HCV-specific precipitation reaction has not yet been identified. We attempted to develop a precipitation system exclusively for anti-HCV-positive sera as a first step in finding an HCV-specific antigen and HCV-associated particles. In some patients being in a final stage of different liver diseases, we found sera (179/132,761; designated ‘a-CK’) which specifically precipitated with anti-HCV- and HCV-RNA-positive sera (designated ‘CK’). When CK-positive sera were searched for in patients with various liver diseases using standard a-CK-positive plasma, CK was detected in 420 (57.9%) of 726 anti-HCV-positive sera and in none of the 1,630 anti-HCV-negative ones. The nature of CK and a-CK has not been fully clarified yet; CK demonstrated inter-βγ mobility, whereas a-CK showed β-globulin mobility; CK was not detected in cryoprecipitate, but HCV RNA was present in precipitates of CK-positive plasma incubated with one that was a-CK positive. Transmission electron microscopy revealed two size ranges of particles in the precipitate of CK- and a-CK-positive plasmas, 23–38 nm and 48–65 nm. We have found a novel precipitation system which is exclusive to anti-HCV-positive sera and which specifically precipitates an HCV-RNA-containing serum fraction and particles. This system can be useful for the purification and characterization of the circulating particles. Furthermore, it may be a new approach to the nature of HCV-RNA-carrying material.
Respiratory Burst by Dengue-Virus-Induced Cytotoxic Factor
Authors: Misra Anita , Mukerjee Ruma , Chaturvedi U.C. 
Published: April 2003

<b>Objective:</b> This study investigates the induction and release of the superoxide anion (O<sup>–</sup><sub>2</sub>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by mouse spleen cells on stimulation with dengue type 2 virus (DV) and a DV-induced cytokine, the cytotoxic factor (mCF). <b>Methods:</b> Normal mice or their spleen cell cultures were inoculated with DV or mCF. At different time periods, the spleen cell supernatants were assayed for the production of O<sup>–</sup><sub>2</sub> and H<sub>2</sub>O<sub>2</sub>. <b>Results:</b> Inoculation of DV in spleen cell cultures resulted in peak production of O<sup>–</sup><sub>2</sub> and H<sub>2</sub>O<sub>2</sub> at 48 and 72 h, respectively, while in DV-infected mouse spleen, the maximum production was on days 7 and 8, which correlated with the appearance of mCF in the milieu. Maximum O<sup>–</sup><sub>2</sub> and H<sub>2</sub>O<sub>2</sub> production occurred at 45 min and 1 h after inoculation of 5 µg of mCF. Pretreatment of mCF with anti-mCF-antiserum inhibited O<sup>–</sup><sub>2</sub> and H<sub>2</sub>O<sub>2</sub> release indicating the specificity of the induction by mCF. The enriched subpopulations of macrophages and T cells produced O<sup>–</sup><sub>2</sub> and H<sub>2</sub>O<sub>2</sub> and not B cells. Treatment of the cells with superoxide dismutase increased H<sub>2</sub>O<sub>2</sub> release but inhibited O<sup>–</sup><sub>2</sub> release and the cytotoxicity in a dose-dependent manner. <b>Conclusion:</b> This showed that O<sup>–</sup><sub>2</sub> is responsible for the cytotoxic activity of mCF and not H<sub>2</sub>O<sub>2</sub>. In conjunction with our earlier findings that pretreatment with N<sup>G</sup>-monomethyl-<i>L</i>-arginine inhibited mCF-induced production of NO and the cytotoxicity, it is concluded that the presence of both O<sup>–</sup><sub>2</sub> and NO is required for the cytotoxic activity of mCF, thereby indicating a possible role of peroxynitrite.
Severe Fatal Group B Streptococcal Sepsis in an Adult
Authors: Habib A.G. , Al-Anazi A.R. , Mobeireek A. , Yousif A.I. , Azeem A.R. 
Published: April 2003

<i>Objective:</i> Group B <i>Streptococcus</i> (GBS) sepsis is largely a disease seen in neonates and infants. It is uncommon in adults except during pregnancy and puerperium. We hereby present an adult diabetic patient with severe fatal GBS sepsis with a view to increasing clinical awareness of this bacterial infection among adult patients. <i>Clinical Presentation:</i> A 56-year-old male from Saudi Arabia presented initially with features of pyelonephritis. He discharged himself against medical advice after 1 day but returned to the hospital 24 h later, with symptoms of headache, neck stiffness, confusion and left flank tenderness. Clinical and laboratory evaluation, including analysis of cerebrospinal fluid, confirmed sepsis (urosepsis, bacteraemia and meningitis) with GBS spp. <i>Intervention:</i> The patient was managed with intravenous ceftriaxone, vancomycin and later penicillin G and supportive ICU care. The patient required intubation initially. He expired from marked irreversible anoxic brain damage resulting from the sepsis. <i>Conclusion:</i> The case is presented to help in increasing the awareness of clinicians to GBS as a potential cause of morbidity and mortality in adults, particularly in those with chronic comorbid states.
Modifiable Stroke Risk Factors in Volunteers Willing to Participate in a Prevention Program
Authors: Sitzer Matthias , Skutta Michael , Siebler Mario , Sitzer Gerhard , Siegrist Johannes , Steinmetz Helmuth 
Published: April 2003

The current trends in stroke incidence require continued efforts to improve primary prevention. Compared to large-scale public health approaches, more limited programs targeting volunteers may offer some advantages. We invited all 12,824 members of a health insurance company program who lived within 50 km from one of two study sites to participate in a vascular screening program aimed at reducing modifiable risk factors. 1,837 persons registered and participated (14.3%, mean age 53 ± 12 years, 50% men). Using the Framingham stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke events can be predicted for this age group within 10 years. The majority of these 97 events will occur in those with mean resting blood pressure values ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic; 420 persons, mean age 64 ± 7 years, 60 expected events), or with a particularly high age- and sex-adjusted risk (288 persons, mean age 68 ± 7 years, 60 expected events). Our pilot study provides an estimate of the prevalence of modifiable vascular risk factors among volunteer participants of a prevention program. Possible benefits of this approach will be investigated in a second step using a randomized intervention.
The Restraint Stress-Induced Elevation in Plasma Interleukin-6 Negatively Regulates the Plasma TNF-α Level
Authors: Nukina Hideyuki , Sudo Nobuyuki , Komaki Gen , Yu Xiao-Nian , Mine Kazunori , Kubo Chiharu 
Published: April 2003

Although a considerable amount of evidence has shown that physical and psychological stress elevates the plasma interleukin 6 (IL-6) levels, the physiological significance of such an elevation remains to be elucidated. In this study, in order to determine whether the restraint stress-induced elevation of plasma IL-6 contributes to the activation of the hypothalamic-pituitary-adrenal axis, and whether or not such elevation can affect the inflammatory processes, the plasma levels of ACTH, corticosterone, interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) in mice pretreated with anti-IL-6 antibody (MP5-20F3 monoclonal antibody) were compared with those in mice pretreated with rat IgG (control antibody) both during and after stress. Both the anti-IL-6-antibody- and control-antibody-pretreated mice showed the same extent of plasma ACTH and corticosterone increases during stress, and no significant difference was found between the two groups of animals. On the other hand, the level of plasma TNF-α in the anti-IL-6-treated animals was also significantly higher than that in the control animals both immediately after cessation of stress and 60 min after the cessation of the 120-min period of restraint. Plasma IL-1 activity, however, did not reach a detectable level in either group of animals at any time point examined. These results thus indicate that the restraint-stress-induced elevation of plasma IL-6 negatively regulates the plasma TNF-α levels and may thus contribute to the maintenance of homeostasis.
Effects of Cholinergic Agonists and Antagonists on Interleukin-2-Induced Corticotropin-Releasing Hormone Release from the Mediobasal Hypothalamus
Authors: Karanth Sharada , Lyson Krzysztof , McCann S.M. 
Published: April 2003

In previous research we found that interleukin-2 (IL-2)-induced corticotropin-releasing hormone (CRH) release in vitro is mediated by cholinergic activation of nitric oxidergic (NOergic) neurons. The NOergic neurons release nitric oxide that stimulates CRH release. To further characterize the mechanism of IL-2-induced CRH release, the possible role of nicotinic as well as muscarinic receptors in IL-2-stimulated CRH release was evaluated. Medial hypothalamic (MH) explants from adult male rats were preincubated in Krebs-Ringer (KRB) buffer for 45 min followed by incubation for an additional 30 min in fresh KRB or KRB containing various compounds. As previously reported, acetylcholine (ACH) stimulated CRH release in a dose-related fashion. IL-2 (10<sup>–13</sup> <i>M</i>) stimulation of CRH release was unaffected by the lower concentration of ACH (10<sup>–9</sup> <i>M</i>), but surprisingly was inhibited by a 100-fold higher concentration. Atropine (ATR) (10<sup>–7</sup> <i>M</i>) blocked CRH release induced by ACH (10<sup>–7</sup> <i>M</i>) and the release of CRH induced by IL-2. The cholinergic agonist carbachol (CAR) (10<sup>–7</sup> <i>M</i>) also released CRH and this action was blocked by ATR (10<sup>–7</sup> <i>M</i>). CRH release in the presence of CAR was lowered below basal when the concentration of ATR was increased to 10<sup>–6</sup> <i>M</i>. In contrast to ACH, CAR had an additive effect to release CRH when combined with IL-2 (10<sup>–13</sup> <i>M</i>). Nicotine (10<sup>–7</sup> <i>M</i>) also stimulated CRH release and this stimulation was completely blocked by 10<sup>–6</sup> <i>M</i> but not by 10<sup>–7</sup> <i>M</i> of the nicotinic receptor blocker, hexamethonium (HEX). The lower concentration of HEX blocked the stimulatory effect of ACH (10<sup>–7</sup> <i>M</i>) and IL-2 on CRH release. Combined blockade with ATR plus HEX completely blocked the action of ACH and even reduced the CRH concentration to below basal values. Furthermore, combined blockade completely blocked the release of CRH induced by IL-2. We conclude that nicotinic as well as muscarinic receptors play an important role in CRH release, and that they both act to mediate IL-2-stimulated CRH release.
Adrenergic Modulation of Apoptosis in Splenocytes of <i>Xenopus laevis</i> in vitro
Authors: Haberfeld Meredith , Johnson Rachel O. , Ruben Laurens N. , Clothier Richard H. , Shiigi Stanley 
Published: April 2003

Impaired and healthy cells undergo suicide using an intrinsic genetic program. Exposure to stress-related α<sub>2</sub>- or β-adrenergics for 4 or 20 h in vitro had no effect on apoptosis in splenocytes of adult <i>Xenopus laevis</i>, while a 4-hour coincubation of clonidine, an α<sub>2</sub>-agonist, with a calcium ionophore (A23187) or a phorbol diester (PMA), <i>enhanced</i> apoptosis induced by each apoptogen alone. Clonidine did not affect apoptosis stimulated with dexamethasone (DEX), however. Comparable in vitro exposures to isoproterenol, a β-agonist, <i>reduced</i> apoptotic levels stimulated by all three apoptogens alone. Following 20 h coexposure, clonidine no longer affected A23187-induced apoptosis, but <i>reduced</i> PMA-induced apoptosis, while isoproterenol <i>enhanced</i> apoptosis stimulated with both. Neither agonist modulated apoptosis induced by 20 h of exposure to DEX. Thus, adrenergic agonists modulated apoptosis in cells coexposed to A23187 and PMA, in a time-dependent and adrenoceptor class-dependent fashion. These stress-induced products can affect concurrent apoptosis reversibly over time in vitro, and thus possibly in vivo.
Time-Dependent Effect of Cyclosporine on Mitogenic Responses and Lymphocyte Subset Populations in Rat Spleen and Submaxillary Lymph Nodes
Authors: Esquifino Ana I. , Arce Agustín , Selgas Laura , Cardinali Daniel P. 
Published: April 2003

Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation and T lymphocyte subsets were measured in spleen and submaxillary lymph nodes of male rats injected with cyclosporine (5 mg/kg s.c. for 5 days, at 12.00 or 24.00 h; animals kept under light from 08.00 to 20.00 h daily). One hour before the third injection, Freund’s complete adjuvant or its vehicle was administered. A suppressive effect of cyclosporine on the mitogenic action of LPS was seen in the spleen of rats injected with cyclosporine at noon whereas the effect of ConA remained unaffected. CD4+, CD8+ and CD4+-CD8+ cells decreased in spleen and lymph nodes of Freund’s adjuvant-injected rats only with cyclosporine given at noon. The results further support occurrence of time-of-day-dependent effects of cyclosporine on lymphocyte subsets and proliferation.