Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites.

Liver stage Plasmodium parasites reside in a parasitophorous vacuole (PV) that associates with lysosomes. It has previously been shown that these organelles can have beneficial as well as harmful effects on the parasite. Yet it is not clear how the association of lysosomes with the parasite is controlled and how interactions with these organelles lead to the antagonistic outcomes. In this study we used advanced imaging techniques to characterize lysosomal interactions with the PV. In host cells harboring successfully developing parasites we observed that these interaction events reach an equilibrium at the PV membrane (PVM). In a population of arrested parasites, this equilibrium appeared to shift towards a strongly increased lysosomal fusion with the PVM witnessed by strong PVM labeling with the lysosomal marker protein LAMP1. This was followed by acidification of the PV and elimination of the parasite. To systematically investigate elimination of arrested parasites, we generated transgenic parasites that express the photosensitizer KillerRed, which leads to parasite killing after activation. Our work provides insights in cellular details of intracellular killing and lysosomal elimination of Plasmodium parasites independent of cells of the immune system.

Morphology, testes development and behaviour of unusual triploid males in microchromosome-carrying clones of Poecilia formosa.

In a microchromosome-carrying laboratory stock of the normally all-female Amazon molly Poecilia formosa triploid individuals were obtained, all of which spontaneously developed into males. A comparison of morphology of the external and internal insemination apparatus and the gonads, sperm ploidy and behaviour, to laboratory-bred F(1) hybrids revealed that the triploid P. formosa males, though producing mostly aneuploid sperm, are partly functional males that differ mainly in sperm maturation and sexual motivation from gonochoristic P. formosa males.

Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in tumor patients before and during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a new chitin-binding mistletoe lectin (cbML) has been isolated and structurally characterized in these extracts. Aim of the present study was, therefore, to evaluate whether this cbML also affects immunocompetent cells and can for instance activate B-cells to produce anti-cbML-specific antibodies. Sera from patients with different tumors who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3, and cbML, isolated from a single mistletoe plant collected from an apple tree (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the 18 anti-cbML negative patients before therapy 54% developed these antibodies during therapy, and there was a significant increase in anti-cbML antibody titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the 25 patients being negative before therapy. These data indicate that cbML can induce immunological responses in patients treated with mistletoe extracts, although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies can be observed in a low incidence also in individuals, not having yet received mistletoe therapy.

[Cardiogenic shock due to acute mitral dysfunction after deep venous thrombosis]. / Schock durch akute Mitralklappendysfunktion mit schwerer Insuffizienz nach Beinvenenthrombose.

Open surgical embolectomy may be life-saving in massive pulmonary embolism. Up to now there are no studies concerning the question whether the foramen ovale should be examined routinely during surgery and whether an open foramen ovale should be closed routinely in the same session. Even case reports regarding this question are missing. We report on a 74-year old female patient who developed pulmonary embolism due to deep venous thrombosis. Six days after successful surgical embolectomy the patient developed cardiogenic shock due to a huge thrombus from the right atrium through the foramen ovale into the left atrium and the left ventricle. Immediate surgical embolectomy of a 40-50 cm huge thrombus was successful. Immediately after surgery upon the cardiac mass the patient showed symptoms of acute right leg ischemia. Thus a second embolectomy was necessary, the surgeon removed a 10 cm thrombus from the right external iliacal artery. There was no evidence of another pulmonary embolism timely related to the paradoxical embolism.

Primary structure, isoforms, and molecular modeling of a chitin-binding mistletoe lectin.

From mistletoe Viscum album L. extracts three chitin-binding lectin isoforms, cbML1, cbML2, and cbML3, were isolated and their primary structure determined. All three cbML isoforms are composed of two protein chains of 48 or 49 amino acid residues, linked by an intermolecular disulfide bond. The sequence of each single cbML chain is characterized by a relatively high number of cysteine and glycine residues, 9 and 6, respectively, and contains four intramolecular disulfide bridges. On the basis of the combined interpretation of sequencing and MALDI MS data, the following results for the three cbML isoforms were obtained: the first one consists of two identical truncated polypeptide chains (1--48), the second is a heterodimer, containing one truncated (1--48) and one full-length chain (1--49), and the third is composed of two full length chains (1--49). The cbML sequence shows 55% identity to hevein, a single-chain chitin-binding protein of 43 amino acids, one of the most predominant proteins in natural rubber latex. On the basis of the NMR data on hevein from Hevea brasiliensis the three-dimensional structure of cbML3 was modelled. The 26 sequence changes between cbML3 and hevein were accommodated with only little perturbation in the main chain folding. A comparison of the primary structures of cbML3 and hevein is shown and the effects of the sequence changes are discussed. Differences have been identified in the loop region of the molecule and the potential interface region of cbML3 supporting the dimer formation. The high-affinity chitin-binding site seems to be highly conserved.

Biocompatibility correlation of polymeric materials using human osteosarcoma cells.

Metal implants are the preferred materials to generate articular prostheses, plates, or bone pegs in orthopedic surgery. Although titanium and titanium alloys show a relatively good biocompatibility, clinical experience revealed that coating of the metallic implant surface may increase the biocompatibility. In a search for optimum bone implant surfaces, we determined polarity and contact angle parameters of a variety of polymers and substances and correlated the findings in a biocompatibility assay using an in vitro bone cell model. We report that an optimum adherence of SAOS-2 cells to such surfaces and a good vitality for polymers are characterized by water-based contact angles of 80 degrees and 20 degrees for advancing and receding probes, respectively.

Veterans Affairs Multicenter Low Vision Enhancement System (LVES) study: clinical results. Report 1: effects of manual-focus LVES on visual acuity and contrast sensitivity.

PURPOSE: The Department of Veterans Affairs LVES Study is a multicenter study to determine the effectiveness of the Low Vision Enhancement System (LVES) as a visual rehabilitation device. The purpose of this study was to explore the efficacy of the Beta 1 manual-focus LVES for improving visual acuity and contrast sensitivity. METHODS: Patients whose visual acuity was 20/80 or worse in the better eye from any disease, who did not have significant visual field loss, who had previous low vision experience and were capable of working with the LVES were enrolled in a comprehensive prospective multicenter clinical evaluation. Initially, corrected spectacle visual acuities were measured using a standardized ETDRS chart. Contrast sensitivities were also measured with spectacle correction using a standardized Peli-Robson chart. These results were then compared to the acuities and contrast sensitivity obtained with the LVES at optimal magnification. Also, visual acuities were measured using an Eschenbach 3x spectacle-mounted binocular telescope, then compared to the acuities obtained using the LVES set at the lowest magnification (3x). RESULTS: All patients who completed the study demonstrated an improvement in visual acuity, with a median improvement of six lines of Snellen equivalent acuity using the LVES. Improvement in visual acuity was the same in both ARMD and non-ARMD causes of vision loss. Mean contrast sensitivity improved in 52 of 58 patients tested, with a mean improvement of 0.49 log units. CONCLUSION: The LVES significantly improves both visual acuity and contrast sensitivity in visually impaired patients who fall within the study criteria. Up to 10-fold improvement in visual acuity and up to 1.80 log units improvement in contrast sensitivity were noted in the study group when the LVES was used.

Crystal structure of mistletoe lectin I from Viscum album.

The crystal structure of the ribosome-inactivating protein (RIP) mistletoe lectin I (ML-I) from Viscum album has been solved by molecular replacement techniques. The structure has been refined to a crystallographic R-factor of 24.5% using X-ray diffraction data to 2.8 A resolution. The heterodimeric 63-kDa protein consists of a toxic A subunit which exhibits RNA-glycosidase activity and a galactose-specific lectin B subunit. The overall protein fold is similar to that of ricin from Ricinus communis; however, unlike ricin, ML-I is already medically applied as a component of a commercially available misteltoe extract with immunostimulating potency and for the treatment of human cancer. The three-dimensional structure reported here revealed structural details of this pharmaceutically important protein. The comparison to the structure of ricin gives more insights into the functional mechanism of this protein, provides structural details for further protein engineering studies, and may lead to the development of more effective therapeutic RIPs.

The strain of guardianship for men in the United States.

This study examined the extent to which control, commitment, and support influenced the strain experienced among men in the U.S. who were acting as guardians for aged adults, an atypical role for such men. A total of 146 male guardians responded to a questionnaire. Results of the study showed that control and commitment were associated with less strain, whereas the use of formal support systems was related to greater levels of strain. Additionally, strain was found to be less prevalent among older guardians.

Susceptibility to the development of pigment cell tumors in a clone of the Amazon molly, Poecilia formosa, introduced through a microchromosome.

The Amazon molly Poecilia formosa is a gynogenetic fish that reproduces through the development of ameiotic diploid eggs triggered by insemination by males of related species without following karyogamie. This leads to clonal offspring. In rare cases, however, this gynogenesis is leaky, and paternal DNA in the form of small supernumerary chromosomes is included into the maternal genome. We have obtained a clone where one such microchromosome contains a pigmentary locus, resulting in macromelanophore pigmentation of the carrier. Approximately 5% of these fish spontaneously develop exophytic nodular or papillomatous pigment cell tumors. The tumors display considerable differences with respect to growth characteristics and invasiveness, despite the genetic uniformity of the affected animals. Following transplantation to syngeneic hosts, a remarkable clonal variability was observed. Oncogenes that are involved in tumorigenesis in hereditary melanoma of the closely related fish Xiphophorus appear not to be instrumental for induction of the P. formosa pigment cell tumors. Moreover, a new genetic locus is defined that mediates susceptibility to pigment cell tumor development and leads to transformation of chromatoblasts.

Resident rights. Knowledge of and implementation by nursing staff in long-term care facilities.

In this study, we assessed the differences between certified nursing assistants' (CNAs) and nurses' (RNs and LPNs) level of knowledge and perceived implementation of resident rights. The CNAs and nurses responded to a series of 11 scenarios representing rights such as privacy, choice, and respect. Their responses suggested that although they knew what the appropriate response to the situation was, it was not the typical response to that type of situation within their facilities. Implications for teaching and applying resident rights are discussed.

[Polymer-supported synthesis of biopolymers--foundations and applications]. / Polymer-gestützte Synthese von Biopolymeren--Grundlagen und Anwendungen.

The application of polymer supports for the synthesis of polypeptides, oligonucleotides, and oligosaccharides is presented in this article and discussed in view of their methodology. The fundamentals of the polymer-supported synthesis are described as well as the role of the polymer supports in the synthetic cycle, and the problems associated are debated. It is focused on typical polymer supports for each substance class, and an overview is given on recent tendencies of development in the polymer-supported methods of synthesis.

Implementation of recommended guardianship practices and outcomes of hearings for older persons.

We analyzed 1,160 court records to determine whether implementation of recommended procedural safeguards and guardianship practices was associated with outcomes of hearings for older persons. The presence of the proposed ward at the hearing was not related to decisions about guardianship. Proposed wards who retained their own counsel were more likely to receive limited guardianships or have the petition denied. Wards with undefined court-appointed counsel more often received full guardianships than those without representation.

Outcomes of equity/inequity among older spouses.

The extent to which perceptions of global and specific equity/inequity were associated with dissatisfaction, disagreement between spouses, partners' regard for one another, and gender-role attitudes was investigated for eighty-two couples over age sixty. The differential influence of equity/inequity for the well-being of women and men was studied.

Guardianship reform: does revised legislation make a difference in outcomes for proposed wards?

There is a lack of critical examination of the efficacy of guardianship reform. Yet, the awarding of guardianship, especially when it is unwarranted, may deprive individuals of their most basic civil liberties. This longitudinal research investigated whether guardianship decisions differed prior to and following revision of state statutes increasing procedural safeguards. Using data from 766 petitions for guardianship of persons 60 years of age or over from Iowa and Missouri, it revealed that in most cases, a request for a full guardianship was tantamount to receiving one. Least restrictive alternatives were seldom employed, and few petitions were denied either before or after legislative changes. Reasons for the seeming discrepancy between revised statutes and guardianship decisions are suggested. No amount of statutory reform, however, will alter the tendency for society's attitudes toward aging to overshadow and shape the interpretation and implementation of legislation.

Face recognition in age-related maculopathy.

Patients with age-related maculopathy (ARM) complain frequently of difficulty with face recognition. The authors attempted to quantify the level of impairment by comparing face recognition with clinical tests of visual function, namely contrast sensitivity, grating acuity, letter-chart acuity, and word-reading acuity. For face recognition, we used 32 black-and-white photographs that had been cropped to remove the outline of hair so that identification was predominantly dependent on the facial features. The observer's distance from the screen on which the photographs were projected was varied. The angular size of the faces was indicated by the equivalent viewing distance (EVD). Four male and four female models were used, and for each model, there were four photographs with different facial expressions--happy, sad, angry, and afraid. For each photograph, the subject's task was to name the model and identify the facial expression. Threshold EVD (50%) was determined for correct identity recognition and expression recognition. For eight subjects all experimental procedures were repeated at a lower luminance level. For ARM subjects, increasing task complexity (grating/letters/words) substantially decreased resolution. Face-recognition abilities were most closely related to word-reading acuity when comparisons were made either across subjects or across luminances within subjects. Contrast sensitivity was associated poorly with face-recognition thresholds. In some subjects with more advanced ARM, identity recognition was substantially poorer than expression recognition.

What do discharge planners plan? Implications for older Medicare patients.

This research examines the discharge-planning process, specifically assessing the extent to which components critical to effective discharge planning are implemented in acute-care settings. We surveyed 16 discharge planners in rural and metropolitan hospitals. The analysis examined the degree to which discharge-planning programs incorporate client-centered planning activities, collect information about the client's care deficits, use community services to support the client on discharge, and the extent of interdepartment involvement in discharge planning. Results indicated that the majority of planners were client centered in their planning; however, a complete assessment of the client's resources and care deficits did not occur on admission. We discuss implications for discharge planning.