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J Schwarze

Publications and source records attributed to J Schwarze.

34 records · Page 2Linked to original sources
PubMed1999

Development of eosinophilic airway inflammation and airway hyperresponsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes.

We previously defined a role for B cells and allergen-specific immunoglobulins in the development of allergic sensitization, airway inflammation, and airway hyperresponsiveness (AHR), using a 10-d protocol in which allergen exposure occurred exclusively via the airways, without adjuvant. In the present protocol, normal and B-cell-deficient (microMt(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and challenged with OVA via the airways in order to examine the requirements for AHR with this protocol. T-cell activation (antigen-specific proliferative responses and Th2-type cytokine production) and eosinophil infiltration in the peribronchial regions of the airways, with signs of eosinophil activation and degranulation, occurred in both experimental groups. In contrast to the 10-d protocol, increased in vivo airway responsiveness to methacholine and in vitro tracheal smooth-muscle responses to electrical field stimulation were observed in both normal and B-cell-deficient mice, and these responses were inhibited by anti-interleukin (IL)-5 administration before airway challenge. These data show that IL-5, but not B cells or allergen-specific IgE, are required for eosinophil airway infiltration and the development of AHR following allergen/alum sensitization and repeated airway challenge with allergen. These results emphasize that the use of different sensitization and challenge protocols can influence the requirements for development of AHR.

Allergens↗
PubMed1999

The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration.

Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.

Administration, Inhalation↗
PubMed1998

Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice.

We have used a mouse model of allergen-induced airway hyperresponsiveness to demonstrate that immunostimulatory DNA sequences (ISS) containing a CpG DNA motif significantly inhibit airway eosinophilia and reduce responsiveness to inhaled methacholine. ISS not only inhibited eosinophilia of the airway (by 93%) and lung parenchyma (91%), but also significantly inhibited blood eosinophilia (86%), suggesting that ISS was exerting a significant effect on the bone marrow production of eosinophils. The inhibition of the bone marrow production of eosinophils by 58% was associated with a significant inhibition of T cell-derived cytokine generation (IL-5, granulocyte-macrophage CSF, and IL-3). ISS exerted this inhibitory effect on T cell cytokine production indirectly by stimulating monocytes/macrophages and NK cells to generate IL-12 and IFNs. The onset of the ISS effect on reducing the number of tissue eosinophils was both immediate (within 1 day of administration) and sustained (lasted 6 days), and was not due to ISS directly inducing eosinophil apoptosis. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (i.p.), or mucosally (i.e., intranasally or intratracheally). Interestingly, a single dose of ISS inhibited airway eosinophilia as effectively as daily injections of corticosteroids for 7 days. Moreover, while both ISS and corticosteroids inhibited IL-5 generation, only ISS was able to induce allergen-specific IFN-gamma production and redirect the immune system toward a Th1 response. Thus, systemic or mucosal administration of ISS before allergen exposure could provide a novel form of active immunotherapy in allergic diseases.

Adjuvants, Immunologic↗
PubMed1998

Changes of circadian blood pressure patterns are associated with the occurence of lucunar infarction.

BACKGROUND: The occurrence of lacunar infarction is closely related to arterial hypertension. However, there is only limited and partly controversial knowledge regarding the possible pathogenetic role of circadian blood pressure changes. OBJECTIVE: To evaluate the relationship between circadian blood pressure rhythm, occurrence, and extent of lacunar infarction. METHODS: We analyzed circadian blood pressure patterns, other cardiovascular risk factors, and occurrence of lacunar infarction in 118 hospitalized patients older than 55 years. Noninvasive 24-hour blood pressure measurements and magnetic resonance or computed tomographic brain imaging were performed in 61 patients with lacunar infarction and in 57 control patients. Daytime blood pressure variability was defined as the within-subject SD of all systolic and diastolic blood pressure readings during the daytime measurement period. Circadian blood pressure variation was defined as the average percentage change of nighttime blood pressure values compared with the daytime blood pressure values. RESULTS: Patients with lacunar infarction were significantly older and showed more often a history of arterial hypertension, elevated average daytime blood pressure values, an increased systolic daytime blood pressure variability, and a reduced circadian blood pressure variation due to an increased incidence of a pathologic nighttime blood pressure increase. No significant correlation was found between these parameters and the number of lacunae. A logistic regression analysis revealed that a reduced systolic circadian blood pressure variation, age, systolic average daytime blood pressure, and a history of arterial hypertension were best correlated with the occurrence of lacunar infarction. CONCLUSION: Reduced nighttime decline in systolic blood pressure may be an important risk factor for the development of lacunar infarction in addition to the absolute level of blood pressure and age.

Aged↗
PubMed1998

Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice.

BACKGROUND: Systemic administration of IL-12 can prevent airway hyperresponsiveness (AHR) in mice after sensitization and repeated allergen challenge. However, systemic IL-12 has been associated with severe adverse effects. OBJECTIVE: We determined whether IL-12 administration to the airways in a dose sufficiently low so as not to result in systemic effects can modify allergic inflammation and AHR after allergen challenge. METHODS: Mice were sensitized to ovalbumin by intraperitoneal injection and challenged with ovalbumin aerosol on 3 consecutive days. During the period of challenge, IL-12 was administered intranasally following 2 regimens, designated high (1500 ng) or low (150 ng). We monitored airway responsiveness to inhaled methacholine by barometric body plethysmography, lung inflammatory cells, local cytokine production, and, to assess systemic effects of IL-12 treatment, spleen weights and numbers of eosinophils in the bone marrow. RESULTS: Allergen challenge resulted in increases in airway responsiveness and in numbers of lung eosinophils. These increases were prevented by both high- and low-dose IL-12. Additionally, IL-12 administration resulted in enhanced local interferon-gamma production and prevented the increases in local IL-4 and IL-5 production after airway challenge. A high dose, but not a low dose, of IL-12 resulted in increased spleen weights and prevented the increase in numbers of bone marrow eosinophils after allergen challenge. CONCLUSION: These data indicate that local administration of IL-12 can prevent AHR and reduce lung eosinophilia after allergen challenge in sensitized mice without eliciting systemic adverse effects. IL-12 exerts these effects by inducing local T(H1)-type responses in the airways in a setting that is normally dominated by T(H2)-type responses.

Allergens↗
PubMed1998

Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice.

Aeroallergens such as Amb a I from short ragweed are important in the development of allergic airway disease. We tested the ability of a human monoclonal immunoglobulin-A (IgA) antibody specific for Amb a I (A-IgA) to modulate airway responsiveness and lung eosinophilia after airway challenge with nebulized Amb a I or ragweed extract in mice sensitized to Amb a I or ragweed extract, respectively. A-IgA or nonspecific IgA (C-IgA) were given intranasally up to 8 h before each challenge. Allergen challenge resulted in increases in airway responsiveness, in numbers of lung eosinophils, and in Amb a I-specific IgE levels. These were prevented by pretreatment with A-IgA but not with C-IgA. Decreases in IFN-gamma and increases in IL-4 and IL-5 production following challenge with Amb a I were also reduced by A-IgA treatment. In contrast, increases in total IgE and total IgG and in numbers of lung neutrophils after challenge were not significantly affected by A-IgA, which additionally induced increased levels of Amb a I-specific IgG2a antibodies. In mice sensitized and challenged with ovalbumin (OVA), A-IgA did not affect airway responsiveness, lung eosinophilia, cytokine production, or immunoglobulin levels. These data indicate that allergen-specific IgA can prevent airway hyperresponsiveness and reduce eosinophil influx into the lungs following allergen challenge via the airways in sensitized mice, and these effects are allergen-specific. Neutralization of allergen may contribute to the effects of IgA, but the induction of allergen-specific IgG2a in A-IgA-treated mice suggests an immunomodulatory action for A-IgA.

Animals↗
PubMed1997

Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.

Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.

Allergens↗
PubMed1997

Assessment of functional hemispheric asymmetry by bilateral simultaneous cerebral blood flow velocity monitoring.

The aim of this study was to investigate side-to-side differences of simultaneously measured middle cerebral artery (MCA) blood flow velocities during various hemisphere-specific tasks. Using a transcranial Doppler device, flow velocity changes of 24 healthy, right-handed subjects were monitored simultaneously in the left and right MCA during different hemisphere-specific tasks. Mean flow velocity (MFV) curves were averaged for each individual subject and task. Simultaneously, heart rate, blood pressure and end-tidal carbon dioxide (CO2) were measured in a subgroup of six subjects. When compared with the resting state, all stimuli produced significant (p < 0.001) bilateral MFV increases, ranging from 2.5-9.2%. A lateralization of MFV increases with a significantly (p < 0.001) more pronounced increase in MFV in the hemisphere contralateral to the performing band was observed both during simple sequential finger movements and a complex spatial task. During the complex spatial task, consistently higher MFV increases were observed in the right MCA (p < 0.001), regardless of the side of task performance. Recognition of pictorial material presented as part of a memory task, also resulted in a side-to-side difference of respective MFV increases (right > left, p < 0.001), whereas memorization did not. Whereas bilateral MFV elevations observed during stimulation with white noise were only discrete and not lateralized, exposure to overt speech produced significantly higher (p < 0.001) MFV increases in the left MCA. The time course of the MFV reaction showed a rapid increase with an initial maximum after 4-5 s. Heart rate, blood pressure, and end-tidal CO2 showed only subtle changes during the stimulation periods. In conclusion, the observed side-to-side differences of MFV reaction in the left and right MCA concur with current functional imaging data. Bilateral simultaneous repetitive transcranial Doppler monitoring is a sensitive method to detect cerebral perfusion asymmetries caused by hemisphere-specific activation, and thus may be helpful for noninvasive assessment of hemispheric dominance for language.

Adult↗
PubMed1997

Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography.

To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta 2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.

Airway Resistance↗
PubMed1997

Allergen-specific IgE and IL-5 are essential for the development of airway hyperresponsiveness.

The mechanisms underlying the development of airway hyperresponsiveness are not fully delineated. We addressed this question by studying the effects of passive sensitization with anti-OVA IgE on the development of altered airway responsiveness (AR) following local challenge with OVA in normal and athymic mice. Both normal and athymic BALB/c mice developed allergen-specific immediate cutaneous hypersensitivity after passive sensitization with anti-OVA IgE. In contrast, the combination of local challenge with allergen via the airways and passive sensitization triggered the development of airway hyperresponsiveness only in normal but not in athymic mice. Treatment of athymic mice with IL-5 significantly increased eosinophil accumulation in the lungs after local challenge with OVA; increased airway reactivity was only observed in athymic mice which received anti-OVA IgE, not an unrelated IgE, plus IL-5 treatment and airway challenge with OVA. These findings identify the requirement for allergen-specific IgE and IL-5 for the development of airway hyperresponsiveness following allergen challenge via the airways.

Allergens↗
PubMed1996

Relationships between delayed ischemic dysfunctions and intracranial hemodynamics following subarachnoid hemorrhage.

Delayed ischemic dysfunctions (DID) are one of the main complications following subarachnoid hemorrhage. It was the aim of our study to analyse the possible prognostic value of different transcranial Doppler ultrasonography parameters and to elucidate the risk of developing DID with particular reference to the intracranial pressure. The relative change of mean blood flow velocity and of corresponding cerebral circulatory resistance index as well as the intracranial pressure were determined in 44 patients with spontaneous subarachnoid hemorrhage. No relationship was found between the occurrence and extent of DID and the relative change of mean flow velocity during the clinical course. In contrast, there was a significant correlation between the relative change of the cerebral circulatory resistance index and the occurrence of DID. While patients without or with reversible DID showed a decreased resistance index compared to the initial value (without DID: -17% +/- 15%; reversible DID: -3% +/- 14%), patients with irreversible DID had a significant increase of the resistance index (+14% +/- 9%). Accordingly, patients with irreversible DID showed a significant increase of intracranial pressure compared to the patients with reversible DID. We conclude that the evaluation of relative changes of the cerebral circulatory resistance index by bedside monitoring is a useful tool to predict the occurrence of subarachnoid hemorrhage-associated DID and has therapeutic impact.

Adolescent↗
PubMed1995

[The mobility of the anterior teeth after the direct bonding of lingual retainers. A comparison of in-vitro and in-vivo measurements].

Lingual retainers are today widely used in the long-term stabilization of incisors. In that they are left in place for a period of years, the question arises to what extent lingual retainers allow sufficient physiological movement. To answer this question first an in-vitro study of the inflexibility of various retainers under horizontal and vertical load was carried out. Next the retainer which limited physiological movement to the least degree was studied in-vivo. Both dynamic and static mobility measurements of the lower jaw front teeth were carried out on 5 patients before and after bonding the retainers. A self developed measuring instrument was used to make the static measurements and a periotest device was employed in the dynamic measurements. The in-vitro tests indicated that, with the exception of the retainer made of multistranded 0.0155" wire or glass fiber, a significant reduction in tooth mobility can be expected with all the retainers. However, the static in-vivo measurement carried out with the 0.0155" wire resulted in a distinct reduction in tooth movement. The dynamic measurements using the periotest device confirmed this finding. With regard to clinical practice within the framework of long-term retention, highly flexible retainers appear to be the most suitable and are to be recommended.

Cuspid↗
PubMed1994

Influence of dexamethasone on lymphocyte proliferation in whole blood cultures of neonates.

The lymphocyte proliferative response to mitogen stimulation was measured in cord blood cultures of term and preterm neonates. The lymphocyte proliferative response increased 150- to 400-fold above baseline after stimulation with mitogens. Dexamethasone suppressed the lymphocyte proliferative response in a concentration-dependent manner with considerable suppression at concentrations applied during treatment of preterm neonates for bronchopulmonary dysplasia (BPD). Dexamethasone and other corticosteroids tested in equipotent glucocorticoid concentrations suppressed the lymphocyte proliferative response to the same extent. We conclude that dexamethasone treatment for BPD may well compromise immune functions of preterm neonates.

Adrenal Cortex Hormones↗
PubMed1994

[Migration from East to West Germany: intention and realization. A sequential probit model with unobserved heterogeneity controls].

"This study investigated migrations from eastern to western Germany. Using a sequential decision model we first examined which persons expressed the intention of wanting to move from eastern to western Germany. Then, using unobserved heterogeneity controls we determined at the same time which persons of those willing to move actually did so later.... Once the intention to move has been declared...those who are well-qualified, short-time workers and persons who feel threatened by unemployment as well as persons with relatives in western Germany more often than average do in fact realise this intention. Commuters also have a very high rate of realisation." (SUMMARY IN ENG AND FRE AND RUS)

Behavior↗
PubMed1992

Mechanical and biochemical effects of individual co-transmitters in rat tail arteries.

1. The effects of (1) nerve stimulation (NS, 0.5 ms, 1-16 Hz, supramaximal voltage, 20 s) upon vasoconstriction, as measured by changes in perfusion pressure and (2) exogenously added co-transmitters noradrenaline (NA) and alpha, beta,-methylene ATP (alpha, beta, MeATP) upon polyphosphoinositide (PPI) breakdown, and vasoconstriction, were studied in rat tail perfused arteries or arterial rings. The interaction between NA and ATP upon contraction of artery rings and inositol phosphate (IP) accumulation was also studied. 2. Nerve stimulation evoked vasoconstriction in rat tail arteries. These pressor responses were largely (approximately 80%) blocked by the alpha 1-adrenoceptor antagonist, prazosin (10(-6) M), but not significantly affected by desensitization of P2x-purinoceptors by prior, repeated (five times) addition of alpha, beta, MeATP (10(-6) M). 3. Noradrenaline evoked a prazosin (10(-6) M)-sensitive, concentration-dependent, increase in both perfusion pressure and total inositol phosphate (IP) accumulation over the same concentration range (10(-6)-10(-4) M). The amplitude of the pressor responses to NA were about 80% of those obtained to nerve stimulation (0.5 ms, 1-16HZ 20s supramaximal voltage). 4. alpha, beta,-methylene ATP (10(-7)-10(-5) M) evoked a concentration-dependent increase in perfusion pressure which, at maximum, was equivalent in amplitude to approximately 20% of that obtained to nerve stimulation. Concentrations of the nucleotide greater than 10(-5) M were required to stimulate total IP accumulation. 5. The effects of NA (10(-6) M) and alpha, beta, MeATP (10(-5) M) upon contraction of artery rings and IP accumulation were additive and no evidence of synergism between them, on either parameter, was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗