Are asthma and chronic obstructive pulmonary disease different diseases?--Con.
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Asthma↗
Biomedical subjects
W Timens
Publications and source records attributed to W Timens.
The use of the gastroepiploic artery for peripheral revascularisation. A study in pigs.
OBJECTIVES: To use the autologous gastroepiploic artery (GEA) as arterial bypass graft for peripheral revascularisation. We compared the development of intimal hyperplasia and nitric oxide (NO) capacity in GEA and internal jugular vein (IJV) implanted as peripheral grafts. MATERIALS AND METHODS: In pigs the GEA was implanted into the right peripheral circulation as a femoropopliteal bypass graft. In the left peripheral circulation the IJV was implanted as a femoropopliteal graft. After 21 days all grafts were harvested. Vascular rings of each graft before and after operation were studied for NO capacity. The distal half of each graft was prepared for histomorphometric studies. RESULTS: Administration of bradykinin to IJV and GEA induced relaxation. After implantation bradykinin resulted in contraction in IJV grafts, whereas in GEA grafts relaxation was reduced. In IJV grafts extensive intimal hyperplasia was formed, whereas in GEA grafts only small areas of intimal hyperplasia were formed. CONCLUSIONS: The functional studies lost NO capacity in IJV grafts, whereas NO capacity in GEA grafts remained intact. Intimal hyperplasia in IJV grafts was extensive, whereas GEA grafts demonstrated preservation of pre-existent intimal architecture. These results may encourage the application of the human GEA as bypass graft for reconstruction of arteries in the lower limb or foot.
Anastomosis, Surgical↗
Vascular adhesion molecules in nocturnal asthma: a possible role for VCAM-1 in ongoing airway wall inflammation.
BACKGROUND: Increased airway inflammation at night is thought to be one of the underlying mechanisms in nocturnal asthma. Vascular adhesion molecules may be important for the recruitment of inflammatory cells in the process of asthmatic airway inflammation. OBJECTIVE: To determine the possible role of vascular adhesion molecules in increased airway inflammation at night in subjects with nocturnal asthma. METHODS: Bronchial biopsies were obtained at 16.00 h and 04.00 h from 13 healthy controls, 15 asthmatic patients with PEF variation < or = 15% and 10 asthmatic patients with PEF variation > 15%. Biopsies were snap-frozen and double-immunostained for CD31 in combination with P-selectin, E-selectin, ICAM-1 or VCAM-1. RESULTS: No significant day-night differences in expression of adhesion molecules were found in any of the three groups. The percentage of VCAM-1 positive vessels in biopsies of asthmatic patients was higher than in biopsies of healthy controls: 5.8 vs 2.5% (P < 0.05) at 16.00h and 11 vs 0% (P<0.05) at 04.00 h. In asthma, VCAM-1 expression was correlated with the number of EG2 positive cells: at 16.00 h (rho = 0.57, P < 0.01) as well as at 04.00 h (rho = 0.64, P< 0.01). Moreover, VCAM-1 expression was correlated with the number of CD25 positive cells at 16.00 h (rho = 0.43, P < 0.05) and at 04.00 h (rho = 0.41, P < 0.05). CONCLUSION: Increased nocturnal airway obstruction in asthma is not associated with an increased nocturnal expression of vascular E-selectin, P-selectin, ICAM-1 or VCAM-1. The relationship between vascular VCAM-1 expression and sub-mucosal EG2 and CD25 positive cells, both at 16.00 h and 04.00 h, suggests a role for VCAM-1 in the ongoing airway wall inflammation of asthma.
Adult↗
Haemophilus influenzae in lung explants of patients with end-stage pulmonary disease.
In order to determine the presence and distribution of Haemophilus influenzae in lung tissue sections, we obtained lung explants from 49 lung transplant recipients with cystic fibrosis (CF) (n = 16), chronic obstructive pulmonary disease (COPD) including emphysema (n = 16), bronchiectasis (n = 5), pulmonary hypertension (n = 9), Langerhans cell histiocytosis (n = 1), and idiopathic pulmonary fibrosis (n = 2). Analysis was done by selective culturing, immunoperoxidase (IP) staining, and by polymerase chain reaction (PCR). H. influenzae was cultured from specimens of the lung explants from one CF and one COPD patient. IP staining of tissue sections was positive in 24 patients (10 CF patients, eight COPD patients, two bronchiectasis patients, and four patients with noninfectious pulmonary diseases). IP-positive tissue sections were PCR-positive, and IP-negative sections were PCR-negative. H. influenzae was more frequently detected in tissue sections of lung explants from CF and COPD patients than from patients with bronchiectasis or noninfectious pulmonary diseases. H. influenzae was diffusely present in the epithelium, the submucosa of the bronchi, the bronchioles, the interstitium, and the alveolar epithelium. H. influenzae was localized extracellularly alone and in bacterial clusters, and was also associated with macrophages in CF patients. The results of this study demonstrate that H. influenzae is often present in the lungs of patients with end-stage pulmonary disease, especially CF and COPD patients. H. influenzae is diffusely present in the respiratory epithelium and subepithelial layers of the lungs of these patients.
Adolescent↗
Specificity of antibodies to nitric oxide synthase isoforms in human, guinea pig, rat, and mouse tissues.
Ten commercially available rabbit polyclonal anti-NOS antibodies were tested for their immunohistological applicability in normal human, guinea pig, rat, and mouse organs. Most antibodies reacted as expected and described in the literature with various tissues of the investigated species. Several antibodies did not react with the expected cell populations in a certain species, or reacted in previously unknown patterns. In addition, different antibodies to the same isoform rarely detected identical cell populations, even within one species. Most of these unexpected immunoreactivities were observed in bronchial epithelial, glomerular epithelial, and vascular smooth muscle cells. These unexpected results usually occurred when the antibodies were tested in other organs or species than that to which they were originally raised. We therefore strongly recommend the use of anti-NOS antibodies only after careful immunohistological and biochemical analysis of their reactivity in the organ and species to be studied.
Animals↗
Increased peak expiratory flow variation in asthma: severe persistent increase but not nocturnal worsening of airway inflammation.
Asthma at night is characterized by a nocturnal increase in airway obstruction. It has been hypothesized that nocturnal asthma results from an increase in airway wall inflammation at night. However, studies on inflammatory cells in bronchoalveolar lavage (BAL) fluid and bronchial biopsies have produced conflicting data. This study assessed inflammatory cell numbers at 16:00 h and 04:00 h in bronchial biopsies of 13 healthy controls, 15 asthmatic patients with peak expiratory flow (PEF) variation < or =15% and 10 asthmatic patients with PEF variation >15%. There was no significant increase at night in the number of CD3, CD4, CD8, CD25, AAI (tryptase) and EG2-immunopositive cells in the submucosa in both groups. Numbers of EG2-positive cells in the two asthmatic groups were significantly higher than in healthy controls, both at 16:00 h (p<0.05) and 04:00 h (p<0.01). The number of EG2, CD4 and CD25-positive cells at 04:00 and 16:00 h tended to be higher in asthmatics with a PEF variation >15% than in asthmatics with PEF variation < or =15%. At 04:00 h the median numbers of EG2-positive cells (per mm basement membrane) in subjects with PEF variation >15% and < or =15% were 6 and 3 cells, respectively, and at 16:00 h 4 and 25 cells respectively. Increased nocturnal airway obstruction is not associated with increased numbers of inflammatory cells in the bronchial submucosa at night. Apparently, asthmatic patients with a peak expiratory flow variation >15% suffer from a higher overall severity of bronchial inflammation at night and during the day.
Adolescent↗
Techniques in human airway inflammation: quantity and morphology of bronchial biopsy specimens taken by forceps of three sizes.
BACKGROUND: In recent years, fiberoptic bronchoscopy has been introduced successfully in the research of bronchial asthma. Bronchial biopsy specimens obtained by this procedure are small, and an optimal biopsy technique is necessary to obtain high-quality tissue samples, as sufficient length of intact basement membrane and sufficient depth of submucosal tissue are required. METHODS: We compared size and qualitative aspects of bronchial biopsy specimens from nonasthmatic subjects, obtained by forceps of three different sizes, types FB-19C, FB-21C, and FB-35C (Olympus; Tokyo, Japan). RESULTS AND CONCLUSIONS: We conclude from this study that the hypothesis that the bigger the biopsy forceps, the larger the biopsy specimen and the better the quality of the tissue does not hold. Bronchial biopsy specimens obtained with forceps type FB-35C and FB-21C were equal in size, but the FB-35C biopsy specimens showed more damage and crush artifacts, whereas biopsy specimens obtained with forceps type FB-21C had more intact basement membrane, more submucosal depth, and well-preserved morphology.
Biopsy↗
Submucosa 1.0 x 0.1 mm in size is sufficient to count inflammatory cell numbers in human airway biopsy specimens.
Counting of inflammatory cells in human airway biopsy specimens is difficult because immunopositive cells are present in varying density in lung tissue. The goal of our study was to assess the minimal amount of tissue that is necessary for the counting of constant cell numbers. In bronchial biopsy specimens from 5 healthy controls and 5 patients with asthma, we evaluated 20 successive areas of submucosa 0.1 x 0.1 mm in size. We recorded positive and negative changes of more than 10% in the counted numbers of CD4-, CD8-, and EG2-positive cells. We demonstrated that tissue 1.0 x 0.1 mm in size, along 1-mm basement membrane, is sufficient to obtain constant cell numbers.
Asthma↗
Biopsies: processing and assessment.
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Asthma↗
Macrophages in lung tissue from patients with pulmonary emphysema express both inducible and endothelial nitric oxide synthase.
To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema. We studied the presence of inducible and endothelial NO synthases (iNOS and eNOS, respectively) and determined nicotinamide diphosphate (NADPH) diaphorase activity. Patients with severe emphysema showed lower percentages of iNOS- and eNOS-positive alveolar macrophages in situ than did patients with mild emphysema. In patients with both iNOS and eNOS immunoreactivity in macrophages, the majority of the macrophages expressed either iNOS or eNOS, whereas only a minority of the macrophages showed iNOS and eNOS immunoreactivity simultaneously. Immunoreactivity for eNOS in endothelial and/or bronchiolar epithelial cells and NADPH diaphorase activity in macrophages and in endothelial, epithelial, and smooth muscle cells were similar in the three studied groups. The expression of eNOS in macrophages suggests that eNOS plays an additional role, besides iNOS, in the NO housekeeping in inflammatory processes in pulmonary tissue. We suggest that NO might have a protective role in maintenance of structural integrity of pulmonary tissue after smoke-induced damage.
Adolescent↗
Hemopoiesis in human fetal and embryonic liver.
In this review, we describe the topographic distribution of hemopoietic cells of the lymphoid, myeloid, and erythroid lineages in the human fetal and embryonic liver. The data are based on studies of frozen tissue, allowing the determination of a broad range of hemopoietic antigens, and studies on paraffin-embedded tissue, allowing the combination of optimal morphology and immunodetection of lineage-specific antigens. The different hemopoietic lineages each show their own immunophenotype and distribution; intercellular and microenvironmental relationships were easily determined. In a few cases, some scarce CD34-positive early progenitor cells were seen. The number of proliferating cells, identified by monoclonal antibody (MAb) Ki-67, varied from 350 to 2500 (median = 1,500) per square millimeter of tissue. Erythroid cells reacted with antisera to glycophorin A, CDw75, and CD43 and partly surround a central macrophage, whereas the myelomonocytic cells reacted with CD45, CD43, CD74, and antilysozyme serum, and with LN3 from 14 weeks onward. Myelopoietic (CD15 positive) cells were localized mainly around portal triad vessels and increased in number with gestational age. The lymphoid cells showed CD45, CD43, CD45RA/MT2, CD45RA/MB1, MB2, and CD74 reactivity. B cells and their precursors were scattered among the hepatocytes without any sign of focal development in the age range studied. We seldom found cells positive for delta-H chain or C3bR (CD35); C3dR (CD21)-positive cells were even more scarce. Cells reactive with MAb WT1 (CD7) were present in a scattered single pattern (< or = 20/mm2) among the parenchymal cells; cells expressing mature T-cell markers (CD2, CD3, CD5) were rare. Large (> 15 mu) CD43-positive hemopoietic cells in the fetal liver were distinguished that exclusively expressed CD43, probably representing early hemopoietic progenitor cells.
Antigens, CD↗
(A)symptomatic bronchial hyper-responsiveness and asthma.
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Adolescent↗
A new in vitro assay for quantitation of chemotherapy-induced mucositis.
Patients receiving high-dose chemotherapy (HD-CT) are at risk of severe mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this study was to develop an objective in vitro assay of chemotherapy-induced mucositis. Twelve patients with locally advanced breast carcinoma received HD-CT followed by peripheral stem cell reinfusion. Before and twice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity grading; furthermore, blood leucocyte levels were determined. For the oral washings, the percentage of viable epithelial cells was determined by trypan blue dye exclusion and leucocytes were counted by fluorescence microscopy after incubation with acridine orange. Maturity of buccal cells was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunteers served as controls. The mean percentage (+/- s.e.m.) of viable oral epithelial cells was stable in controls (44 +/- 2%). In patients, they increased after HD-CT, which was significant after day 7 compared with pretreatment (P < or = 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observed. Oral leucocyte levels were closely correlated with the blood leucocyte counts. The WHO score followed the results of these other evaluations with some delay. The viability of buccal cells obtained by oral washings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more immature cells. These data can be quantitated, and this assay may therefore be useful in studies aimed at prevention of mucositis.
Adult↗
Techniques in human airway inflammation: differences in plastic-embedded and snap-frozen sections for CD3, CD4, and CD8 immunostaining of bronchial biopsy specimens.
Today, the quantification of inflammatory cells in human airway biopsies might be facilitated by better morphologic resolution provided by special resin (plastic)-embedding techniques. The present study compares the numbers of CD3-, CD4-, and CD8-positive cells in glycolmethacrylate-embedded versus snap-frozen biopsy specimens of normal bronchial mucosa in 10 patients with various pulmonary diseases. In general, larger numbers of CD3-, CD4-, and CD8-positive cells were counted in snap-frozen specimens than in plastic-embedded ones. Loss of antigenic properties during storage of plastic-embedded tissue (blocks) might have contributed to the weak correlation between both methods. An additional study showed that the number of CD3-, CD4-, and CD8-positive cells decreased significantly within a few months after embedding in glycolmethacrylate. Therefore, we recommend processing glycolmethacrylate-embedded specimens as soon as possible. For standard evaluation of established inflammatory cell parameters such as CD3, CD4, CD8, and EG2, frozen tissue is preferable because of the ease of the method and its reliable cell counting. Because glycolmethacrylate-embedded tissue shows superior morphologic resolution, under strict rules, this method seems attractive for the study, in particular, of cell-cell and cell-matrix relationships.
Biopsy↗
The presence of cytokines in Langerhans' cell histiocytosis.
Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and pathogenesis of LCH are unknown; it is suggested that LCH is caused by an immunological dysregulation. Production of cytokines is a central feature of immunological regulation. LCH lesions and normal LCs were studied for the presence of cytokines known to influence the functioning of LCs: IL-1 alpha, IL-1 beta, IL-4, GM-CSF, IFN-gamma, TGF-alpha, TGF-beta, bFGF, and TNF-alpha. Cytokines were abundantly present within LCH lesions; LCH cells stained for IL-1 alpha, IL-1 beta, IL-4, GM-CSF, TGF-alpha, TGF-beta, TNF-alpha, and IFN-gamma. Macrophages, lymphocytes, eosinophil granulocytes, and, surprisingly, multinucleated giant cells were also sources of cytokines. These results suggest that cytokines play a prominent role in the pathogenesis of LCH and may explain phenomena that often occur in LCH, such as osteolysis and fibrosis and the recruitment of typical inflammatory infiltrates. The results also suggest that a 'down-regulatory' signal is lacking in LCH, resulting in an accumulation and/or proliferation of abnormal LCs.
Adolescent↗
Fc-receptor function after human splenic autotransplantation.
Mononuclear phagocytic function was studied using the Fc-receptor test in 24 patients who underwent splenectomy, ten of whom underwent splenic autotransplantation. All patients undergoing autotransplantation had mononuclear phagocyte system (MPS) activity at the transplantation sites. In eight of the 14 patients who did not undergo autotransplantation there was also scintigraphic MPS activity indicative of ectopic splenic tissue. Although the Fc-receptor test showed delayed and monoexponential blood clearance in all patients after splenectomy, there were no significant differences between the patient groups. Autotransplantation of small amounts of splenic tissue after splenectomy provides some MPS activity but is inadequate for blood clearance.
Adolescent↗
Lack of adhesion molecules in testicular diffuse centroblastic and immunoblastic B cell lymphomas as a contributory factor in malignant behaviour.
Diffuse large B-cell lymphoma of the testis is a rare tumour, often with disseminated disease. According to the Kiel Classification, these lymphomas are of centroblastic or immunoblastic type, corresponding in the Working Formulation to malignant lymphoma, large cell non-cleaved and large cell immunoblastic, respectively. Adhesive cell-cell and cell-matrix interactions are generally assumed to play an important part in the metastatic process, and to find clues to the highly malignant biological behaviour of this tumour we examined expression of integrins and other adhesion molecules on the tumour cells and the presence of matrix proteins. Few adhesion molecules appeared to be expressed. CD44 was expressed in 10/12 lymphomas, CD49f/VLA-6 was positive in 5/12 cases, and CD49d/VLA-4, CD54 and CD62L were detectable in a small number (2-3) of lymphomas. All other adhesion molecules were lacking. This expression pattern is suggestive of a high metastatic potential: the tumour cells seem to be poorly attached to the extracellular matrix, to each other and to other cells (CD54-, CD11a-, CD58-). The adhesion molecules expressed, CD44, CD49f/VLA-6 and CD49d/VLA-4, have been reported to play a part in dissemination, mediating intravasation (CD49f/VLA-6) and extravasation (CD44, CD49d/VLA-4). This profile of adhesion molecules may explain, at least in part, the specific biological behaviour of these lymphomas with early and rapid dissemination.
Cell Adhesion Molecules↗
Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells.
A functionally intact spleen with a marginal zone, containing B cells with high density of surface C3d-receptors (CD21), is essential for the ability to induce a primary immune response to thymus-independent type 2 (TI-2) antigens. Main representatives of natural TI-2 antigens are capsular pneumococcal polysaccharides (PPSs). In this study the localization of different types of PPS antigen is determined in human spleen tissue. Our findings indicate that a main type of TI-2 antigen, PPS, localizes preferentially in the marginal zone. PPSs show co-localization with C3, presumably C3d, at the surface of strongly CD21+ B cells equipped for rapid activation. This enables a rapid primary humoral response. The other main PPS localization at follicular dendritic cells in germinal centers, relevant for isotype switching of anti-PPS antibodies, does not seem to be dependent on the presence of specific immunoglobulin. This may explain the finding of specific IgG in an early stage after antigenic challenge. It seems likely that complement C3 fragments (likely C3d), bound to PPSs, enable PPS localization at B-cell and follicular dendritic cell surfaces by binding to CD21, the C3d receptor.
Adolescent↗