Evidence for the presence of immunoglobulin E antibodies specific to the cell wall phosphomannoproteins of Candida albicans in patients with allergies.

To determine the major antigenic component of Candida albicans against immunoglobulin E (IgE) antibodies in the sera of patients with allergies who were positive for IgE antibodies to C. albicans crude antigen in a CAP system, phosphomannoproteins (CAMP/A or CAMP/B for serotype A or B strain, respectively) and their acid-stable portions (CAMP-S/A or CAMP-S/B) were isolated from beta-mercaptoethanol (2-ME) extracts of C. albicans cells of serotypes A and B, and IgE antibodies against these components were compared with those against protein complex and enolase (CAE) fractions isolated from C. albicans cells. The dot blot test, which was used to detect IgE antibodies to the C. albicans antigens, showed that IgE antibodies to the 2-ME extract and phosphomannoprotein fractions were present in the sera of 98.0% (2-ME extract), 96.8% (CAMP/A), 93.2% (CAMP-S/A), 97.2% (CAMP/B), and 81.5% (CAMP-S/B) of the patients, whereas IgE antibodies to the protein complex and CAE fractions were found in the sera of 73.6 and 48.8% of the patients, respectively. The extent of IgE binding to the 2-ME extract and phosphomannoproteins was well correlated with the fluorescence intensities estimated with the CAP system. Furthermore, the results obtained from the inhibition experiment with the CAP system indicated that the binding of IgE antibodies to Candida antigens is strongly inhibited by the phosphomannoprotein fraction and is an indication that the serum of the patients contained IgE antibodies specific to the cell wall phosphomannoproteins of C. albicans. Finally, an initial chemical analysis indicated that the epitopes for IgE antibodies on the phosphomannoproteins is a carbohydrate portion, since the ability of CAMP/A to inhibit the binding of IgE antibodies to the homologous CAMP/A was destroyed after oxidation by sodium periodate but not after digestion with proteinase K.     

Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases

 We identified eight patients with bronchiolitis obliterans (BO) in the autopsies of 81 bone marrow transplant (BMT) recipients. Rapidly progressive dyspnoea and cough were the main presenting symptoms in all eight patients, associated with overinflation and/or infiltrative opacity seen on chest X-ray and obstructive disorder revealed by pulmonary function tests. Early lesions were characterized by epithelial loss and an inflammatory infiltrate containing foamy histiocytes with mild luminal narrowing. Partial or total occlusion of the bronchiolar lumina by fibrous connective tissue was the feature of late lesions. Both changes were coexistent in all cases. In one case, small bronchi with cartilage were also affected by the obstructive process, showing bronchitis obliterans. All eight patients showed non-obstructive broncho-bronchiolitis characterized by denuding of respiratory epithelium, mural oedema and an inflammatory infiltrate in addition to BO, and these changes were also seen in 18 patients without BO. The submucosal glands of large bronchi and the trachea showed mucous retention and a mild inflammatory infiltrate in four of the eight patients. Coexistent infectious processes were seen in all cases, cytomegalovirus and Aspergillus being the most frequent organisms. BO probably develops as an immunopathological event related to graft-versus-host disease (GVHD) during the impaired immune status phase of the post-BMT period, possibly initiated by infection. Bronchial gland involvement in chronic GVHD is one of the factors responsible for this abnormal immune status. Received: 14 January 1997 / Accepted: 5 March 1997     

A case of eosinophilic gastroenteritis complicated with ileus and ascites collection]

A 30-year-old woman was admitted to our hospital because of ileus and ascites. Laboratory data on admission demonstrated marked eosinophilia (42.5% of WBC) but negative CRP-value. Abdominal CT showed marked ascites and diffuse thickening of intestinal walls. Ascites examination revealed eosinophilic ascites. The level of IL-5 both in the serum and in the ascites were also high. No evidence of eosinophilic infiltration was noted both gastric and colonic mucosal biopsy specimens. Oral prednisolone treatment (50 mg/day) was effective for her. We diagnosed her as a case of sub-serosal type eosinophilic gastroenteritis. It is essential to obtain eosinophilic ascites for correct diagnosis of the disease. And it is possible that serum and ascites IL-5 value would be reliable indicator of the activity of this disease.     

Long-term changes of hydroxyapatite-coated dental implants

There are many controversies about the long-term prognosis of hydroxyapatite (HA)-coated implants. Failure may be related to compositional and structural changes of the coating occurring during implantation. Two retrieved and two unused HA-coated blade-type implants were examined by stereomicroscopy, secondary electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and electron probe microanalysis. The objective was to investigate the HA morphology, composition, and structure, and to characterize the changes that occurred in the retrieved implant coatings. Retrieved implants presented partial loss of the coating, especially at the apical and mesiodistal edges. Remaining HA was thick and flattened in the cervical and central areas and gradually thinner and rougher towards the apical and mesiodistal edges. Increase of Cl and Mg, decrease of OH, and X-ray diffraction peak broadening were found in the retrieved implant coatings, in comparison with the unused implants. Morphological changes of the retrieved implants seem to depend on stress values in the surrounding bone and on implant mobility. Compositional changes and increased amount of lattice imperfections appeared in the retrieved implant coatings, as a result of ion substitutions in the apatite lattice. However, the present study could not confirm the influence of these changes on implant failure.     

Attachment and proliferation of fibroblast cells on polyetherurethane urea derivatives

Interactions of novel polyetherurethane urea derivatives with fibroblast cells as well as with plasma proteins were investigated. Fibronectin, which is a cell adhesion protein, was found to be very active in attaching fibroblast cells onto a heparinized polyetherurethane urea: its activity was found to be strongly dependent on the surface properties of the material. Fibronectin was easily adsorbed by the heparinized polyetherurethane urea, but the degree of its adsorption to the material in competition with other proteins was so low that cell attachment to polyetherurethane ureas was decreased by heparinization. Different degrees of cell attachment onto different materials due to different adsorptivities of plasma proteins were considered. Proliferation of fibroblast cells was suppressed on cationic polyetherurethane urea but unaffected on other derivatives of polyetherurethane urea. Since specific suppression of cell proliferation was not observed on the heparinized polyetherurethane urea, the latter material was expected to be useful as a long-term antithrombogenic material in vivo.     

Virulent influenza A viruses induce apoptosis in chickens

Virulent avian influenza A viruses produce lethal disease in chickens. Since cell death can be caused by either necrosis or apoptosis, we investigated the types of cell death that occur in natural hosts, chickens, infected with virulent avian viruses. Using biochemical methods, we demonstrate that virulent avian influenza viruses induce apoptosis of vascular endothelial cells in liver, kidney, and brain. Viral antigens were also detected in these organs, suggesting that viral replication induces apoptosis in infected chickens. These results indicate that apoptosis does occur in virulent avian influenza virus infection in a natural host, and may contribute to the lethality of the virus.     

Liquid filled nanoparticles as a drug delivery tool for protein therapeutics

In the present study, an attempt was made to study the feasibility of nanoparticulate adsorbents in the presence of an absorption enhancer, as a drug delivery tool for the administration of erythropoietin (EPO) to the small intestine. Liquid filled nano- and micro-particles (LFNPS/LFMPS) were prepared using solid adsorbents such as porous silicon dioxide (Sylysia 550), carbon nanotubes (CNTs), carbon nanohorns, fullerene, charcoal and bamboo charcoal. Surfactants such as a saturated polyglycolysed C8-C18 glyceride (Gelucire 44/14), PEG-8 capryl/caprylic acid glycerides (Labrasol) and polyoxyethylene hydrogenated castor oil derivative (HCO-60) were used as an absorption enhancer at 50mg/kg along with casein/lactoferrin as enzyme inhibitors. The absorption of EPO was studied by measuring serum EPO levels by an ELISA method after small intestinal administration of EPO-LFNPS preparation to rats at the EPO dose level of 100 IU/kg. Among the adsorbents studied, CNTs showed the highest serum EPO level of 62.7 +/- 11.6 mIU/ml. In addition, with the use of casein, EPO absorption was improved, C(max) 143.1 +/- 15.2 mIU/ml. Labrasol showed the highest absorption enhancing effect after intra-jejunum administration than Gelucire 44/14 and HCO-60, 25.6 +/- 3.2 and 22.2 +/- 3.6 mIU/ml, respectively. Jejunum was found to be the best absorption site for the absorption of EPO from LFNPS. The use of CNTs as LFNPS, improved the bioavailability of EPO to 11.5% following intra-small intestinal administration.     

Collagenase-like (CL) peptidase activity in synovial fluid from patients with rheumatoid arthritis

We found the presence of collagenase-like (CL) peptidase in synovial fluid by a highly sensitive fluorescence assay using (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide (Suc-GPLGP-MCA) as a substrate. Suc-GPLGP-MCA is hydrolyzed at the Leu-Gly bond by CL-peptidase. The CL-peptidase activity in synovial fluid was significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA) and in arthropathy-free controls. No significant difference in CL-peptidase activity in synovial fluid was found between patients with OA and arthropathy-free controls.     

Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus

The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.     

Hepatic parenchymal enhancement in the cirrhotic liver: evaluation by triple-phase dynamic MRI

Background: To evaluate the changes of liver parenchymal enhancement in the cirrhotic liver by means of triple-phase dynamic magnetic resonance (MR) imaging. Methods: Triple-phase multisection dynamic MR imaging was performed in 32 patients with liver cirrhosis. The control group consisted of 19 patients without liver cirrhosis. After precontrast images were obtained, arterial phase images were acquired 20 s after the start of intravenous bolus administration of 0.10 mmol/kg of gadopentetate dimeglumine. Portal and delayed phase images were then acquired 1 and 3 min, respectively, after the injection of contrast material. On each phase image, the signal-to-noise ratio (S/N) from the liver parenchyma was measured by operator-defined regions of interest (ROIs). The contrast-enhanced ratio (CER) on each phase was then obtained according to the following formula: [S/N(arterial or portal or delayed phase image) − S/N(precontrast image)]÷ S/N(precontrast image). The portal perfusion index (PPI) also was obtained according to the following formula: [S/N(portal phase image − S/N(arterial phase image)]÷ S/N(arterial phase image). The results were expressed as mean ± SD. Results: The CERs of arterial, portal, and delayed phase images in patients with and without liver cirrhosis were 0.256 ± 0.211, 0.640 ± 0.384, and 0.554 ± 0.318 and 0.132 ± 0.094, 0.404 ± 0.204, and 0.324 ± 0.144, respectively. The CERs were highest in the portal phase and lowest in the arterial phase in patients with and without liver cirrhosis. The CER of the cirrhotic liver was significantly higher than that of the normal liver in every phase (p < 0.05). PPIs with and without liver cirrhosis were 2.90 ± 4.03 and 3.86 ± 3.89, respectively. The PPI with liver cirrhosis was significantly lower than that without liver cirrhosis (p < 0.05). Conclusion: The enhancement of cirrhotic liver parenchyma is greater than that of the normal liver parenchyma at every phase of triple-phase dynamic MR imaging. Received: 17 August 2000/Revision accepted: 7 March 2001