Search PubMed⌕ Search

Biomedical subjects

W Timens

Publications and source records attributed to W Timens.

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

Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction: an ex vivo study.

1. Using a guinea-pig model of allergic asthma, we investigated the role of nitric oxide (NO) in allergen-induced airway hyperreactivity after the early asthmatic reaction, by examining the effects of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the responsiveness to methacholine and histamine of isolated perfused tracheae from unchallenged (control) animals and from animals 6 h after ovalbumin challenge. 2. All animals developed airway hyperreactivity to inhaled histamine at 6 h after ovalbumin challenge, with a mean 3.11 +/- 0.45 fold increase in sensitivity to the agonist (P < 0.001). 3. In perfused tracheal preparations from the ovalbumin-challenged guinea-pigs, the maximal responses (Emax) to methacholine and histamine were significantly enhanced compared to controls, both after intraluminal (IL) and extraluminal (EL) administration of the contractile agonists. In addition, a small but significant increase in the pD2 (-log10 EC50) for IL and EL methacholine and for IL histamine was observed. As a consequence, the delta pD2 (EL-IL) for histamine was slightly decreased from 1.67 +/- 0.13 to 1.23 +/- 0.14 (P < 0.05). However, the delta pD2 for methacholine was unchanged (1.85 +/- 0.11 and 1.77 +/- 0.12, respectively; NS). 4. Incubation of control tracheae with 100 microM L-NAME (IL) significantly enhanced the Emax for both IL and EL methacholine and histamine to approximately the same degree as observed after ovalbumin challenge, with no effect on the pD2 and delta pD2 for both agonists. On the contrary, L-NAME had no effect on Emax and pD2 values of tracheal preparations from ovalbumin-challenged guinea-pigs. 5. L-NAME (10 microM-1 mM) had no effect on methacholine-induced contraction of isolated tracheal strip preparations obtained from control animals, indicating that L-NAME has no antimuscarinic effect on tracheal smooth muscle. 6. Histological examination of the intact tracheal preparations indicated epithelial and subepithelial infiltration of eosinophils after ovalbumin challenge. However, no apparent damage of the airway epithelium was observed in these preparations. 7. The results indicate that a deficiency of NO contributes to allergen-induced airway hyperreactivity after the early asthmatic reaction and that this deficiency appears not to be due to epithelial shedding.

Allergens↗
PubMed1996

In vitro complement-dependent binding and in vivo kinetics of pneumococcal polysaccharide TI-2 antigens in the rat spleen marginal zone and follicle.

For a better understanding of the spleen-dependent induction of the humoral immune response against thymus-independent type 2 antigens, we have studied the in vitro and in vivo localization of different capsular pneumococcal polysaccharides (PPSs) in the rat spleen. In this study, we found that in vitro binding of PPS types 3, 4, 6B, 9N/V, 14, and 23F was dependent on complement (probably a C3 fragment) and that the localization was predominantly restricted to the marginal-zone B lymphocytes and the follicular dendritic cells. In vivo, we observed with increase of time a shift of localized antigens. Shortly after injection, all PPS types localized in the marginal-zone B lymphocytes, then localized in the outer follicular mantle, and finally were found to be diffuse in the complete follicle and follicle corona. PPS types 3 and 9N/V and later also PPS type 23F localized additionally in red pulp macrophages. In particular, the localization in the marginal zone is important since the low flow in this area in combination with strongly CD21+ B cells, which are activated early, gives a maximum opportunity for the induction of a primary humoral immune response with subsequent differentiation into plasma cells or migration to the germinal center. In addition, the localization of PPSs at follicular dendritic cells should be considered important in the induction of an ongoing immune response not restricted to the spleen.

Animals↗
PubMed1995

Lymphomas with testicular localisation show a consistent BCL-2 expression without a translocation (14;18): a molecular and immunohistochemical study.

The presence of the BCL-2 protein was studied in nine non-Hodgkin's lymphomas with testicular localisation. A consistent presence of the BCL-2 protein was found. The chromosomal translocation (14;18) was seen neither by cytogenetic analysis (n = 4) nor by polymerase chain reaction amplification and Southern blotting (n = 9). Therefore, this translocation is not responsible for the presence of the BCL-2 protein in non-Hodgkin's lymphomas with testicular localisation. We suggest that the presence of the BCL-2 protein in these lymphomas is related to the differentiation stage of the B-lymphocytes or may play a role in the pathogenesis of these lymphomas. The consistent finding of the BCL-2 protein in lymphomas with testicular localisation may support the clinical observation that these lymphomas are a separate entity.

Adult↗
PubMed1995

Expression of cellular adhesion molecules in Langerhans cell histiocytosis and normal Langerhans cells.

Langerhans cell histiocytosis (LCH) is characterized by lesions with an accumulation and/or proliferation of Langerhans cells (LCs). Little is known of the etiology and pathogenesis of LCH. Although the relation between the LCH cell and normal LCs is currently uncertain, the localizations of the LCH cells is considered aberrant when compared with normal LCs. Cellular adhesion molecules (CAMs) are known to play an important role in a variety of cell functions such as migration, antigen presentation, and activation. Aberrant migration of LCs may play a role in the pathogenesis of LCH. We investigated CAMs in 27 tissue specimens of 20 patients with LCH retrieved from our files during the last 15 years. LCH cells showed strong expression of CAMs such as CD54, CD58, and the beta 1-integrin alpha 4 that are upregulated during activation of normal LCs. In contrast, CAMs not found on normal LCs could be demonstrated in a number of cases on LCH cells like CD2, CD11a, and CD11b. Also CD62L, normally expressed only by epidermal LCs, could be detected on LCH cells. The integrins alpha 5 and alpha 6, not or only weakly found on epidermal LCs and highly expressed by activated LCs, could not be demonstrated on LCH cells. Our data suggest abnormal expression of CAMs on LCH cells that may contribute to abnormal migration of LCs in LCH. The aberrant phenotype of LCH cells has characteristics of both epidermal LCs and activated LCs and may be indicative of an arrested state of activation and/or differentiation of LCs.

Adolescent↗
PubMed1994

Integrins and extracellular matrix-proteins in the different components of the Wilms' tumour.

The Wilms' tumour (WT) is composed of blastema, epithelium and mesenchyme; the epithelium and possibly also the mesenchyme develop from the blastema, parallel to embryonal development. Since interactions between cell adhesion receptors and extracellular matrix (ECM) proteins play an important role in tissue maturation, we examined the expression of the integrin subunits alpha 1-alpha 6, beta 1 and beta 4, and of the ECM proteins fibronectin, laminin and collagen I and IV, in 20 frozen WT samples and in 5 fetal and 2 adult kidneys. The integrin and ECM protein distribution in tumour epithelium and mesenchyme showed strong similarities to that in their fetal counterparts, whereas the tumour blastema differed strongly from the fetal blastema. In the WT blastema different components were recognized. Undifferentiated blastema, characterized by expression of alpha 3 and alpha 6 and the virtual absence of ECM proteins. Blastema with epithelial commitment, showing increased expression of alpha 3 and alpha 6 and the appearance of alpha 2 and, as a very early phenomenon, production of laminin. Blastema with mesenchymal commitment, with loss of alpha 3 and alpha 6 and expression of alpha 1, alpha 4 and alpha 5 and presence of ECM proteins. It is speculated that the inability of the (undifferentiated) blastema to produce ECM proteins is related to its relatively high metastatic potential when compared with epithelium and mesenchyme.

Aged↗
PubMed1994

Partial splenectomy in children: an alternative for splenectomy in the pathological staging of Hodgkin's disease.

BACKGROUND: The more accurate staging of Hodgkin's disease in children is achieved with a staging laparotomy and splenectomy. A disadvantage of the splenectomy is the high risk for an overwhelming postsplenectomy sepsis (OPSI). Therefore, the partial splenectomy was introduced as an alternative to splenectomy in the staging of Hodgkin's diseases in children. METHODS: During the period 1982-1988, 12 children with Hodgkin's disease underwent a staging laparotomy with partial splenectomy. All patients were preoperatively vaccinated with Pneumococcus vaccine. The first three patients received 44 Gy locoregional radiotherapy, whereas nine patients received 25 Gy locoregional radiotherapy and two courses of MOPP/ABVD (mitoxin, oncovin [vincristine], procarbazine, prednisone/adriamycin, bleomycin, vinblastine, decarbazine). RESULTS: The morbidity was negligible. The pathological stage changed in three patients (25%). During a median follow-up of 6 years (range 4-10), no OPSI was diagnosed. One patient developed a secondary leukaemia. CONCLUSIONS: Staging laparotomy for Hodgkin's disease is being performed with less frequency because the majority of patients are treated with chemotherapy and low-dose radiation therapy. After splenectomy and chemotherapy regimens with alkylating agents, there is an increased risk for secondary acute leukemia. With partial splenectomy an adequate staging of the disease can be achieved, allowing a more tailored therapy so that systemic chemotherapy will not be used as frequently, resulting in a lower treatment morbidity without decreasing survival.

Adolescent↗
PubMed1994

Sweet's syndrome in myeloid malignancy: a report of two cases.

Two patients with a myeloid malignancy in whom Sweet's syndrome (acute febrile neutrophilic dermatosis) was diagnosed, are described. They suffered from fever and showed cutaneous lesions, with infiltration of the skin by mature neutrophils without signs of vasculitis. In one of them the clonal origin of the infiltrating neutrophils could be demonstrated by in situ hybridization. In this patient an association with the use of recombinant human granulocyte-colony stimulating factor was suspected. In the other patient, Sweet's syndrome was the initial symptom of haematological disease. Inadequate wound healing after surgical procedures led to the diagnosis.

Adolescent↗
PubMed1994

Surgical resection for small cell carcinoma of the lung: a retrospective study.

BACKGROUND: A retrospective review was undertaken of the survival of 21 patients with histologically proven small cell carcinoma of the lung resected between 1977 and 1991. METHODS: Twenty one patients (20 men) of median age 60 (range 44-73) years underwent surgical resection. Patients were subjected to standard clinical staging procedures. Preoperative diagnosis was small cell carcinoma of the lung in 13, non-small cell lung cancer in one, and uncertain in seven patients. Clinical staging was stage I disease in 11 and stage II in 10 patients. RESULTS: Resection included pneumonectomy in 12 cases, lobectomy in eight, and one wedge resection. Resection was complete in 16 patients. Postoperative histopathological examination confirmed small cell carcinoma of the lung in 19 specimens and mixed small cell and non-small cell carcinoma of the lung in two. Pathological staging was stage I in 11, stage II in three, and stage III in seven patients. The final pathological diagnosis of the resected specimens (n = 18) was atypical carcinoid in one, pure small cell carcinoma of the lung in 15, and mixed small cell and non-small cell carcinoma of the lung in two patients. Fourteen patients also received chemotherapy and 10 received prophylactic cranial irradiation postoperatively. Excluding the patient with a final diagnosis of atypical carcinoid, the median survival (n = 20) was 29 months (range two to 133+). Median survival for patients with pathological stage I and II disease (n = 13) was 40 months (range nine to 133+) and for patients with pathological stage III disease (n = 7) 20 months (range two to 116+). The median disease free survival was 23 months. Eleven patients relapsed between two and 101 months. There was no advantage for those patients who received postoperative chemotherapy. CONCLUSION: Curative resection offers the best chance for long term survival in patients with small cell carcinoma of the lung with very limited stage disease.

Adult↗
PubMed1994

Late recurrence of Wegener's granulomatosis presenting as solitary upper lobe pulmonary mass.

Recurrent Wegener's granulomatosis (WG) was diagnosed in a 40 year old man presenting with a solitary mass in the right lung apex and with possible lymph node enlargement in the anterior mediastinum, resembling malignancy. Eight years previously, a first episode of WG involving the upper airways and kidneys, but not the lungs, had been successfully treated with prednisolone and cyclophosphamide, which could be stopped after 2 yrs. The antineutrophil cytoplasmic antibody titres (anti-protease 3), which had been very high during the first disease episode, failed to predict the recurrence.

Adult↗
PubMed1994

Langerhans' cell histiocytosis: expression of leukocyte cellular adhesion molecules suggests abnormal homing and differentiation.

Langerhans' cell histiocytosis (LCH) is characterized by an accumulation of cells with a Langerhans' cell (LC) phenotype. Most patients present with solitary skin or bone lesions, but multi-organ lesions may appear. Twenty-two LCH-tissue sections from 13 children and adolescents, with lesions at different sites, were investigated for the expression of leukocyte cellular adhesion molecules. Surprisingly, the LCH cells showed expression for CD2 in 11 lesions. Staining of LCH cells for CD11a and CD11b was positive in six and three lesions, respectively. Staining for CD11c, CD44, CD54, and CD58 was found consistently positive in all lesions. The strong reactivity for CD54 (intercellular adhesion molecule-1) and CD58 (leukocyte function antigen-3) is in contrast with the epidermal LC. LCs in culture are known to up-regulate the expression of CD54 and CD58. These changes are thought to reflect the in vivo situation during migration of activated LCs from the skin to the draining lymph node. It can be concluded that the abnormal cells in LCH not only share characteristics with the epidermal LC, but have additional characteristics of the activated LC, a cell capable of migration. The presumed immunological dysregulation in LCH may affect the expression of cellular adhesion molecules, reflected by the inconsistent expression of CD11a and CD11b and the unexpected expression of CD2. These features may contribute to migration of LCs to aberrant sites in combination with abnormal persistence and proliferation.

Adolescent↗
PubMed1994

The tumor microenvironment: possible role of integrins and the extracellular matrix in tumor biological behavior of intratubular germ cell neoplasia and testicular seminomas.

In the present study, we examined the distribution of integrin subunits and extracellular matrix proteins in normal testis, intratubular germ cell neoplasia (ITGCN), and primary and metastatic seminomas. Compared to normal testis in ITGCN, Sertoli cells showed increased expression of alpha 3, alpha 6, and beta 1 integrin subunits. Malignant intratubular germ cells stained for alpha 3, alpha 6, and beta 1 integrin subunits. Progression of ITGCN to invasive seminoma was associated with loss of alpha 3 integrin subunit expression by tumor cells. Consequent to this loss, it can be speculated that the strong expression on ITGCN may be related to the noninvasive character of the lesion as is also known from other noninvasive tumors. All tumors showed a strong expression of alpha 6 and beta 1 integrin subunits. The alpha 5 integrin subunit was weakly expressed in primary seminomas in all stages. No differences were observed in integrin expression between primary and metastatic tumors. The distribution of extracellular matrix proteins was heterogeneous and revealed clear architectural differences between seminomas that may reflect different stages of tumor stroma formation. To our knowledge, the results presented in this study provide the first information on the possible role of tumor-extracellular matrix interactions in the biological behavior of ITGCN and testicular seminomas.

Extracellular Matrix Proteins↗
PubMed1993

[Partial instead of complete splenectomy in children for the pathological staging of Hodgkin disease].

OBJECTIVE: Evaluation of partial splenectomy in children for pathological staging of Hodgkin's disease. DESIGN: Prospective clinical study. PLACE: University Hospital Groningen. METHOD: From 1982 to 1988, 12 children with Hodgkin's disease underwent partial splenectomy during laparotomy for pathological staging. A follow-up of these children was conducted up for a median of 6 years (range 4-10) postoperatively. RESULTS: The median hospital stay after the laparotomy was 7 days. There was no postoperative mortality; one patient needed a relaparotomy. During a median follow-up of 6 years, one patient died of secondary leukaemia. All the other children were well. None of the patients developed sepsis and no Howell-Jolly bodies could be found in their blood. CONCLUSION: Partial splenectomy for pathological staging of Hodgkin's disease is a safe procedure which causes hardly any underestimation of the stage of the disease and which ensures adequate spleen function, depending on the treatment used for Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Bronchial lavage and bronchoalveolar lavage in allergen-induced single early and dual asthmatic responders.

The phenotypic cellular profile of bronchial lavage (BL) and bronchoalveolar lavage (BAL) was studied in 7 single early (SR) and 10 dual asthmatic responders (DR). Lavage was performed, after previously having determined bronchial hyperresponsiveness to histamine and the response to house dust mite (HDM) challenge. The recovered lavage fluid was separated in two fractions, BL and BAL. Total fluid recovery and cell number from the BL and BAL were comparable in both patient groups. Differential cell counting and immunocytochemistry were performed. DR had a significantly higher number of eosinophils and EG2+ cells in BL but not in their BAL. No differences could be found in CD4+, CD8+, and HLA-DR+ cells. A strong correlation was found between eosinophils in the BL+ and EG2+ cells in the BL (r = 0.79, p < 0.001) and between eosinophils in the BL and peripheral blood eosinophils (r = 0.70, p < 0.0025). The number of EG2+ cells and the number of epithelial cells in both BL and BAL showed a correlation (r = 0.55, p < 0.05). Dual responders had a higher total IgE (p < 0.01), and total serum IgE correlated well with the eosinophils in the BL (r = 0.85, p < 0.0001). Our observations demonstrate cellular differences in the lung on mainly a bronchial level between single early and dual asthmatic responders. A bronchial lavage eosinophil and EG2+ cell count and higher blood total IgE level are associated with the tendency to develop a dual asthmatic response.

Adult↗