Background: Reticular basement membrane (RBM) thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD). Even if RBM thickness is similar in both diseases, its composition might still differ. Objective: To assess whether RBM thickness and composition differ between asthma and COPD. Methods: We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV 1 ] 92% predicted), and 17 nonallergic COPD patients (FEV 1 60% predicted), and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively). Snapfrozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin. RBM thickening was assessed by digital image analysis. Relative staining intensity of each matrix component was determined. Results: Mean (SD) RBM thickness was not signifi cantly different between asthma and COPD 5.5 (1.3) vs 6.0 (1.8) μm, but signifi cantly larger than in their healthy counterparts, ie, 4.7 (0.9) and 4.8 (1.2) μm, respectively. Collagen I and laminin stained signifi cantly stronger in asthma than in COPD. Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p Ͻ 0.05). Conclusion: RBM thickening occurs both in asthma and COPD. We provide supportive evidence that its composition differs in asthma and COPD.

Tumor-targeting of anticancer drugs is an interesting approach for the treatment of cancer since chemotherapies possess several adverse effects. In the present study, we propose a novel strategy to deliver anticancer drugs to the tumor cells through the mannose-6-phosphate/insulin-like growth factor receptor (M6P/IGF-IIR) which are abundantly expressed in several human tumors. We developed a drug carrier against M6P/IGF-II receptor by modifying human serum albumin (HSA) with M6P moieties. M6P-HSA specifically bound and internalized into M6P/IGF-IIR-expressing B16 melanoma cells as demonstrated with radioactive studies and anti-HSA immunostaining. In vivo, M6P-HSA rapidly accumulated in subcutaneous tumors in tumor and stromal components after an intravenous injection. To demonstrate the application of M6P-HSA as a drug carrier, we coupled doxorubicin to it. Dox-HSA-M6P conjugate could release doxorubicin at lysosomal pH and showed M6P-specific binding and uptake in tumor cells. In vitro, a short exposure with Dox-HSA-M6P induced killing of tumor cells, which could be blocked by excess M6P-HSA. In vivo, Dox-HSA-M6P distributed to tumors and some other organs while free doxorubicin distributed to all organs but slightly to tumors. In B16 tumor-bearing mice, Dox-HSA-M6P significantly inhibited the tumor growth whereas an equimolar dose of free doxorubicin did not show any anti-tumor effect. In addition, targeted doxorubicin did not show any side-effects on liver and kidney function tests, body weight and blood cell counts. In conclusion, M6P-HSA is a suitable carrier for delivery of anticancer drugs to tumors through M6P/IGF-IIR. Improved antitumor effects of the targeted doxorubicin by M6P-HSA suggest that this novel approach may be applied to improve the therapeutic efficacy of anticancer drugs.

Mast cell numbers in central airway smooth muscle apparently do not contribute importantly to bronchial hyperresponsiveness to adenosine.

Reply to Prof. Bradding and Dr. BrightlingProf. Bradding and Dr. Brightling have made several remarks concerning our report on mast cell numbers in the airway smooth muscle. 1 With respect to their methodological concerns we would like to respond as follows. First, we regret that in the Materials and methods section, at the end of the paragraph on ''bronchoscopy and processing'', an (essential) sentence is lacking, just before the last sentence. The sentence to be added is (separately sent to the editor as ''corrigendum''): ''Mast cells within and directly in juxtaposition to smooth muscle were counted''. We regret this omission, as this clearly has led to invalid interpretations. The reason we decided to count mast cells not only within but also in direct contact with the smooth muscle is that we wanted to take into account all likely mast cell effects on smooth muscle that could supposedly affect the level of hyperresponsiveness. We realise that we should have made that more clearly in the text.Further, in addition we actually also did count mast cells within the muscle area separately, with median (range) of 18 (0-53) for asthma biopsies and 17 (0-46) for controls. These numbers are in the same range as the other studies: some report lower, 2 some higher 3-5 numbers. Such differences are likely explained by differences in technique (frozen vs. paraffin vs. plastic-embedded sections) as discussed by Amin et al. 5 Nevertheless, when we performed statistical analysis on mast cell numbers within airway smooth muscle only, this led to the same results between the groups as we reported (no differences; see Table 1). We agree that our findings are different from several other reports, and therefore we have discussed these differences. However, we mainly discussed and pointed out the relation of mast cell numbers to AMP responsiveness. Although we agree that the indicated other studies are of importance

The authors regret that an essential sentence is missing in the Materials and methods section, which may lead to misunderstandings. This should be corrected as follows:''Materials and methods'', section ''Bronchoscopy and processing of the biopsies''. The last part: ''Tryptase positive cells were counted y as the number of positive cells per area smooth muscle.'' Should be replaced by: ''Tryptase positive cells were counted in two random, but representative sections of one biopsy per patient with at least an 80 mm interval. The area of smooth muscle was determined by grid counting using an eyepiece graticule (crosspoints each 100 mm at 10 Â 10). In this way, we evaluated per subject a mean (SD) area of 0.59 (0.40) mm 2 . Mast cells within and in direct juxtaposition with smooth muscle were counted. Mast cell number was expressed as the number of tryptase positive cells per area smooth muscle.''