Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation.

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.     

IgE-mediated allergy to fungal allergens in Finland with special reference to Alternaria alternata and Cladosporium herbarum.

BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens.     

Predominance of a rare type of HIV-1 in Estonia

An earlier study has indicated that a complex recombinant HIV-1 strain dominates the epidemic in Estonia. The objective of this study was to further investigate the molecular epidemiology and genetic structure of HIV-1 in Estonia. Most of the investigated individuals became infected after August 2000 when HIV-1 started to spread rapidly among Estonian intravenous drug users (IDUs). Two viral DNA regions, gag/pol and gp41, were sequenced and subtyped from peripheral blood mononuclear cells or plasma from 141 individuals. Phylogenetic analysis in the gp41 region revealed that the most frequent type of the virus among IDUs was a circulating recombinant form, CRF06_cpx, whereas a few samples showed highest sequence similarity to a subtype A strain circulating in Ukraine and Russia. Likewise, in the gag/pol region, most of the samples were classified as CRF06_cpx, with a few classified as subtype A. In this region, however, 16% of the sequences turned out to be mosaic unique recombinant forms consisting of CRF06_cpx and subtype A. At least 9 mosaic forms were identified, each with distinct patterns of multiple crossover. To characterize Estonian CRF06_cpx as well as recombinant isolates in more detail, 4 near-full-length HIV-1 genomes were sequenced.     

A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte-endothelium interactions under shear stress

Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule mediating leukocyte interactions with blood vessels during leukocyte extravasation. Molecularly VAP-1 is a cell-surface-expressed ecto-enzyme belonging to the group of semicarbazide-sensitive amine oxidases (SSAO; EC 2.4.6.3), which deaminate primary amines. Here we asked whether peptides displaying a suitable free amine group could be a substrate or inhibitor of SSAO and thus regulate VAP-1-mediated leukocyte adhesion. On the basis of a molecular model of VAP-1, we designed synthetic peptides that fit to the substrate channel of VAP-1. One of these lysine-containing peptides effectively inhibits VAP-1-dependent lymphocyte rolling and firm adhesion to primary endothelial cells under physiologically relevant shear conditions. The same peptide inhibits the SSAO activity of endothelial and recombinant VAP-1 in a selective and long-lasting manner. We also show that all enzymatically active VAP-1 is displayed on the cell surface. Our results suggest that, in addition to soluble amines, specific cell-surface-bound molecules containing free NH(2) groups in a suitable position may modulate the enzymatic activity of SSAO. Moreover, the inhibitory peptide diminishes leukocyte interactions with endothelial cells under conditions of shear, and thus it may be useful to treat inflammatory conditions.     

Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and South America

For reliable classification of HIV-1 strains appropriate reference sequences are needed. The HIV-1 genetic subtype F has a wide geographic spread, causing significant epidemics in South America, Africa, and some regions of Europe. Previously only two full-length sequences of each of the HIV-1 subtype F subclusters F1 and F2 have been described. To extend the knowledge of subtype F variation on a complete genome level, three new virtually full-length F1 sequences were cloned and sequenced, two from Africa and one from South America. Comparison of the new and previously described sequences showed that monophyletic clustering of the subcluster F1 of subtype F is consistent and highly supported in all genome regions. Two additional full-length strains were shown to be mosaics of subtypes F and D. These epidemiologically unrelated F/D sequences showed similar chimeric structure, suggesting that they may represent a previously undescribed circulating recombinant form (CRF). This was supported by partial sequences from three additional unlinked F/D recombinants. Genetic distances in the phylogenetic trees suggest that the recombination event leading to the putative CRF occurred relatively long ago, close to the divergence of the F1 and F2 subclusters. Furthermore, all five F/D recombinants are linked to the Democratic Republic of Congo, suggesting that the original recombination event took place in central Africa.     

Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.     

Factors related to postmenopausal muscle performance: a cross-sectional population-based study

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm^–2 kg^–1 and N kg^–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.