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Biomedical subjects

J W Lammers

Publications and source records attributed to J W Lammers.

At least 91 records · Page 5Linked to original sources
PubMed1996

Screening for bronchiectasis. A comparative study between chest radiography and high-resolution CT.

STUDY OBJECTIVE: The aim of our study was to investigate whether in the search for bronchiectasis a correlation exists between abnormalities on the chest radiograph and high-resolution CT (HRCT), and if HRCT has an additional value when the chest radiography is normal. SUBJECTS AND METHODS: In a prospective study, chest radiographs were compared with HRCT in 84 patients. Analysis of presence and extent of bronchiectasis were made for each bronchopulmonary lobe. RESULTS: Thirty-seven patients had a normal radiograph, from whom 32 had a normal HRCT. The other 5 had a low HRCT severity score with a mild cylindrical bronchiectasis. From the 47 patients with an abnormal radiograph, 36 had signs of bronchiectasis at HRCT; 11 patients, however, had a normal HRCT. The sensitivity for chest radiography to detect bronchiectasis appeared to be 87.8% with a specificity of 74.4%. We found a significant linear relationship between the severity of bronchiectasis at HRCT and abnormalities as seen on the chest radiograph (r=0.62, p=0.0001). CONCLUSION: A normal chest radiograph almost always excludes relevant bronchiectasis and no further investigation seems necessary. There is a significant linear relationship between the severity of bronchiectasis at HRCT and abnormalities as seen on the chest radiograph.

Adult↗
PubMed1996

Eosinophil priming by cytokines: from cellular signal to in vivo modulation.

Eosinophils play an important role in the effector phase of allergic inflammation. This review will focus on the conversion of the unprimed eosinophil phenotype in the peripheral blood of normal individuals to the primed phenotype found in the peripheral blood and tissues of allergic patients, a phenomenon called priming. Recent data on the signals initiated after cytokine receptor activation on eosinophils will be reviewed.

Calcium↗
PubMed1995

Activation of the STAT3/acute phase response factor transcription factor by interleukin-5.

The receptor for interleukin-5 (IL-5R) is composed of a unique alpha chain (IL-5R alpha) expressed on eosinophils and basophils, associated with a beta c subunit, which is shared by the receptors for IL-3 and granulocyte macrophage-colony stimulating factor. One of the molecular events activated via the IL-5R is the JAK/STAT signaling pathway. Recent reports have shown that IL-5 induces tyrosine phosphorylation of JAK2 followed by the subsequent cell type-specific activation of either STAT1 alpha or STAT5. To identify additional STAT proteins activated by IL-5, we co-transfected the IL-5R with STAT cDNAs in COS cells. We found that IL-5 induces binding of STAT3 to the intercellular adhesion molecule-1 pIRE, and activates STAT3-dependent transcription. Moreover, endogenous STAT3 was tyrosine phosphorylated and activated in human IL-5-stimulated BaF3 cells ectopically expressing the human IL-5R (BaF3/IL5R). These data imply that multiple STAT proteins are involved in gene regulation by IL-5 in a cell type-specific manner. We further demonstrate using C-terminal truncations of the alpha and beta c subunits of the IL-5R that the membrane-proximal STAT activation. Interestingly, a beta c receptor mutant lacking intracellular tyrosine residues is able to mediate STAT3 activation, suggesting that tyrosine phosphorylation of the beta c receptor is not essential for STAT3 activation.

Acute-Phase Reaction↗
PubMed1995

Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha.

Signaling by a wide variety of cytokines, including interferons, interleukins, and growth factors, involves activation of JAK kinases and Stat (Signal transducers and activators of transcription) proteins. At present, not much is known about the molecular mechanisms by which interleukin-5 (IL-5) exerts its diverse biologic effects. Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell. IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. Moreover, IL-5 induced at least two DNA-binding complexes, using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter (ICAM-1 pIRE) in an electromobility shift assay. From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha, probably as a homodimer. Both DNA-binding complexes were inhibited by a phosphotyrosine antibody (4G10), suggesting that tyrosine phosphorylation is required for complex formation. IL-3 and granulocyte-macrophage colony-stimulating factor induced, similar to IL-5, two DNA-binding complexes in human eosinophils, including Stat1 alpha. These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family.

Base Sequence↗
PubMed1995

[Muscle weakness as initial symptom of bronchial carcinoma].

Lambert-Eaton myasthenic syndrome was diagnosed in three patients, two men aged 55 and 57 and one woman aged 66 years. After a variable time interval a small cell carcinoma of the lung was detected in all three patients. Two already had metastases outside the thorax and died, the other patient was doing well after treatment with chemotherapy and radiotherapy. The short survival of patients with a small cell carcinoma requires early diagnosis, and paraneoplastic phenomena such as the Lambert-Eaton myasthenic syndrome can be the earliest presenting sign. The syndrome can be diagnosed by electromyography.

Aged↗
PubMed1995

Sample sizes for comparative inhaled corticosteroid trials with emphasis on showing therapeutic equivalence.

In the near future it is to be expected that many new inhaled corticosteroids or formulations of these drugs will be compared with older ones, to discover whether they are therapeutically equivalent or not. The statistical evaluation of these trials differs from the classic methods. When two averages are similar or differ only slightly, power is very low. The regulatory bodies demand a power of at least 80%. This problem was initially solved by using the so-called power approach. Researchers included enough volunteers to enable them to detect a predefined difference, considered to be without any clinical significance, with a power of 80%. This approach, however, has been shown to be incorrect and has been replaced by the two one-sided tests procedure, where a new sample size equation is derived. Important elements of this new equation are the coefficient of variation of the parameter measured, the difference between the averages of the two groups and the equivalence limit (the difference between the means still tolerable). This equation was used in the present study to estimate the number of volunteers needed in a parallel inhaled corticosteroids equivalence trial. The end points chosen were the changes in FEV1 and PC20 due to the corticosteroid effect. Calculations were performed by extracting data from published placebo-controlled trials, and defining a range of equivalence limits and differences between the group averages. It was shown that a huge number of volunteers (500-1000) will be needed, as a result of the small corticosteroid effect and the high variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Pancuronium masks the prejunctional muscarinic autoreceptor in guinea pig tracheal smooth muscle.

The effect of pancuronium pretreatment on the function of the prejunctional muscarinic receptor in guinea-pig trachea was studied by using electrical field stimulation (EFS). The effects of cumulative doses of the muscarinic M2 receptor antagonist gallamine were investigated in tracheal smooth muscle strips from guinea-pigs after addition of pancuronium in vitro and in strips from guinea-pigs which had been pretreated with doses of pancuronium that caused 100% neuromuscular blockade. The results of both types of experiments were compared to those of control groups of the same size. In all strips a dose response curve with cumulative doses of methacholine was made before EFS was switched on. No differences were found between the mean pD2 value and slope of the concentration-response curves of untreated guinea-pigs and animals treated with anaesthetics and pancuronium. The animals showed variable responses to pancuronium. The bath concentration of pancuronium which decreased the EFS-induced contraction to half the original value varied between 14-61 microM. The intravenous dose necessary to paralyze the muscles, varied among the different guinea-pigs from 0.017-0.085 mg.kg-1. The EFS-induced contraction for the concentration range of gallamine 0.32 microM-0.32 mM was found to differ significantly between the strips treated with pancuronium in the organ bath and their control group. For the guinea-pigs anaesthetized and pretreated with pancuronium a significant difference with control was observed at gallamine concentrations ranging from 0.032-0.32 mM. These results show that pancuronium, added to the organ bath as well as administered intravenously to the guinea-pig, masked the inhibitory muscarinic receptor.

Animals↗
PubMed1995

The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis.

Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF.

Adolescent↗
PubMed1995

Screening family members of patients with hereditary hemorrhagic telangiectasia.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder which may give rise to arteriovenous malformations in lungs and brain. When left untreated, these may cause serious complications. We screened family members of HHT patients for presence of the disease and associated pulmonary or cerebral arteriovenous malformations. PATIENTS AND METHODS: We investigated 98 family members of HHT patients on an outpatient basis. A stepped screening protocol was used based on prevalence of different manifestations of HHT. RESULTS: Thirty-six cases of HHT were found in the 98 persons screened. Pulmonary arteriovenous malformations were found in 12 of the 36 patients (33%), and cerebral arteriovenous malformations in 4 (11%). Therapy was recommended in 9 patients with pulmonary arteriovenous malformations and in 2 with cerebral arteriovenous malformations. CONCLUSIONS: Family members of known HHT patients should be encouraged to engage in a screening program, since the prevalence of potentially serious localizations is higher than previously thought.

Arteriovenous Malformations↗
PubMed1995

Embolisation of pulmonary arteriovenous malformations: results and follow up in 32 patients.

BACKGROUND: Pulmonary arteriovenous malformations may cause a number of complications when left untreated. Embolisation of the feeding vessels is a relatively new approach and information concerning its efficacy and long term results is scarce. METHODS: Pulmonary arteriovenous malformations with feeding arteries of > 3 mm were treated by embolisation. Right to left shunt fraction and arterial oxygen pressure breathing air (PaO2) were measured before and after treatment. Six monthly measurement of shunt fraction was used for follow up. RESULTS: In 32 patients 92 pulmonary arteriovenous malformations were treated by coil embolisation. Mean shunt fraction decreased from 16.6% to 7.4% and PaO2 increased from 9.6 kPa to 11.5 kPa. Treatment was incomplete in two patients, one of whom was subsequently treated surgically. Serious complications occurred in one patient. Recanalisation of embolised vessels occurred in two cases after 22 and 28 months, respectively. Mean period of follow up was 25 months. CONCLUSIONS: Embolisation is a safe and efficacious treatment for most pulmonary arteriovenous malformations. Long term studies are necessary to determine the risk of recanalisation.

Adolescent↗
PubMed1995

Rigid external resistances cause effort dependent maximal expiratory and inspiratory flows.

A fixed orifice or a fixed upper airway obstruction (UAO) causes an expiratory and inspiratory plateau-shaped limitation on maximal flow-volume (MEFV, MIFV) curves and, according to the classic concept, a MEF50/MIF50 ratio of 0.9-1.1. However, since maximal expiratory static transrespiratory pressures (PEmax,stat) are clearly greater than the inspiratory ones (PImax,stat), the pressures applied during forced expiration also must be expected to be greater than inspiratory pressures; therefore, the MEF should be larger than the MIF because orifice flow is effort-dependent. We investigated this hypothesis in seven healthy, nonsmoking male volunteers (mean age +/- 1 SD: 34 +/- 10 yr, FVC: 5.9 +/- 1.0 L, PEmax,stat: 168 +/- 16 cm H2O, PImax,stat: 107 +/- 33 cm H2O). They performed MEFV curves and MIFV curves through four different added resistances placed in between the pneumotachograph and the mouth (the orifice diameters ranged between 7.8 mm and 2.8 mm). During these maneuvers dynamic mouth pressures were also measured (PE and PI). We found that the MEF50/MIF50 ratios were significantly increased (p < 0.05) from a control value of 1.1 +/- 0.4 up to 1.5 +/- 0.3 with the resistances. For each added resistance the PE/MEF ratios and (-)PI/MIF ratios were situated on a single line corresponding with the pressure-flow (P/V) characteristics of the resistance. We concluded that external resistances cause a MEF50/MIF50 ratio of clearly more than 1 and that this is determined by the PE/(-)PI ratio, which in healthy subjects is markedly larger than 1.

Adult↗
PubMed1995

Molecular and biological factors in the prognosis of non-small cell lung cancer.

For patients with non-small cell lung cancer the tumour/node/metastasis (TNM) staging system and other conventional prognostic factors fail to predict the outcome of treatment and survival accurately. New prognostic factors are urgently needed to improve understanding of the biological behaviour of the different subtypes of non-small cell lung cancer and to recognize patients with a good or poor prognosis. This review will focus on molecular and biological factors published in the English language literature between 1988 and 1994. To be included in this survey, the predictive value of a specific prognostic factor had to be confirmed by multivariate analysis in at least two different studies. Blood group antigen expression, ras oncogenes, microvessel density, and factors reflecting the proliferative state of the tumour may be important determinants of outcome of treatment. The search for new determinants of prognosis has provided insight in the complex tumour biology of non-small cell lung cancer and indicated possible targets for tumour therapy. Several promising prognostic factors have now been recognized. To validate these factors, prospective studies of a large patient population are needed. This ultimately serves the recognition of subsets of patients who may benefit from adjuvant therapy.

Biomarkers, Tumor↗
PubMed1995

Radiation exposure in standard and high-resolution chest CT scans.

It has been suggested that radiation doses due to high-resolution computed tomography (HRCT) of the chest are considerably higher than those from conventional CT. We compared the effective dose (E, mSv) in conventional chest CT (10-mm contiguous slices) and HRCT (1.5-mm slices, gap 10 mm). In our study, the effective dose from a HRCT (0.98 mSv) is about 6.5 times less than the effective dose from a standard CT scan (6.5 mSv), and only a factor 12 higher than from a conventional chest examination (0.085 mSv).

Humans↗
PubMed1995

Cognate interaction between human lymphocytes and eosinophils is mediated by beta 2-integrins and very late antigen-4.

Here the cognate interactions between human eosinophils and lymphocytes are studied. These interactions were measured in a double-colored FACS analysis by applying fluorescent red eosinophils (stained with hydroethidine, 40 mumol/L) and fluorescent green lymphocytes (stained with sulfidofluorescein diacetate, 100 mumol/L) in a ratio of 1:3. When normal eosinophils were mixed with a total lymphocyte preparation in stirred suspensions (37 degrees C), no physical interaction was present between both cell types. However, the addition of phytohemagglutinin and PMA resulted in a clear aggregation response between both cell types (up to 30% of the eosinophils interacted with lymphocytes after 15 minutes). CD8(+)- and CD4(+)-positive T cells contributed equally to the heterotypic aggregation response. It is interesting that when lymphocytes were pretreated with phytohemagglutinin or eosinophils with phorbol myristate acetate and subsequently washed, the cells still interacted with unstimulated counterparts. The heterotypic interaction between lymphocytes and eosinophils is blocked by monoclonal antibodies directed against the beta-chain of the beta 2-integrins (CLB LFA1/1; CD18) and the alpha-chain of very late antigen-4 (VLA-4) (HP2/1; CD49d), indicating that both the beta 2-integrins and VLA-4 contributed to this heterotypic interaction. When eosinophils bound to PHA-treated lymphocytes, the cells exhibited an activated phenotype that was characterized by an enhanced expression of CD66b and CD11b. The cells interacted with each other provided that an intact cellular metabolism was present--that is, no interaction was seen after treatment with the glycolysis inhibitor sodium mono-iodoacetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1994

Cooperation between Fc gamma receptor II and complement receptor type 3 during activation of platelet-activating factor release by cytokine-primed human eosinophils.

After priming with cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or IL-5, eosinophils are stimulated potently by opsonized particles like serum-treated zymosan (STZ), resulting in activation of the respiratory burst and production of lipid mediators, such as platelet-activating factor (PAF) and leukotriene C4 (LTC4). In the present study, the role of the opsonin receptors Fc gamma RII and CR3 during both STZ-induced activation of the respiratory burst and PAF release by human eosinophils was investigated. Inhibition studies with blocking mAbs (alpha hFc gamma RII: AT10, IV.3; alpha CR3: B2.12, 44a) showed that both Fc gamma RII and CR3 are important for STZ-induced PAF release by cytokine-primed eosinophils. In contrast, CR3 is involved in activation of the respiratory burst, whereas Fc gamma RII seems not to be important, because blocking anti-Fc gamma RII mAbs had no effect. Subsequently, experiments were performed with zymosan particles coated with IgG, iC3b, or a combination of both. IgG-coated particles poorly activated both responses in GM-CSF primed and unprimed cells. iC3b-Zymosan activated the respiratory burst as well as zymosan expressing both opsonins (IgG/iC3b-zymosan). In contrast, iC3b-zymosan induced significantly less PAF release by GM-CSF-primed eosinophils than did IgG/iC3b-zymosan, suggesting synergism between Fc gamma RII and CR3. This synergistic effect was not observed when IgG-zymosan and iC3b-zymosan were added simultaneously. Therefore, these data indicate that on human eosinophils, Fc gamma RII and CR3 act synergistically to activate PAF release, provided that their ligands are in close proximity.

Cytokines↗
PubMed1994

RANTES- and interleukin-8-induced responses in normal human eosinophils: effects of priming with interleukin-5.

We report that responses of normal human eosinophils toward the chemokines RANTES and interleukin-8 (IL-8) are modulated and upregulated by priming with IL-5. In a modified Boyden chamber assay, we studied migratory responses toward the members of the chemokine family RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) (C-C subfamily), and IL-8, platelet factor-4 (PF-4), and neutrophil-activating peptide-2 (NAP-2) (C-x-C subfamily). These chemokines were also studied in terms of actin polymerization and ([Ca2+]i)-mobilizing properties, intracellular signals that are thought to play a role during migratory responses. We found that eosinophils showed significant migratory responses toward RANTES and IL-8 at concentrations of 10(-9) to 10(-7) mol/L only after priming with IL-5 (10 pmol/L). At these concentrations, PF-4, NAP-2, MCP-1, and MIP-1 alpha induced no significant migratory responses after priming. Unprimed eosinophils only showed a significant migratory response toward RANTES (10(-6) mol/L). Changes in [Ca2+]i were found after addition of RANTES, MIP-1 alpha, and NAP-2 (10 nmol/L) to unprimed eosinophils. RANTES (10(-9) to 10(-7) mol/L) significantly induced actin polymerization both in primed and unprimed eosinophils, whereas IL-8 (10(-9) to 10(-8) mol/L) and MIP-1 alpha (10(-8) mol/L) only induced actin polymerization after priming with IL-5. NAP-2, PF-4, and MCP-1 did not affect actin polymerization. These findings are further evidence for the hypothesis that cytokines like IL-5 and locally secreted chemokines like RANTES and IL-8 are both at the basis of specific eosinophil influx into the allergic inflammatory locus.

Actins↗