B-cell activation and allosensitization after left ventricular assist device implantation is due to T-cell activation and CD40 ligand expression

Left ventricular assist device (LVAD) implantation is frequently complicated by B-cell activation and allosensitization, posing a significant risk to successful transplant outcome. This study investigated whether B-cell hyperreactivity and alloantibody production in LVAD recipients involves T-cell dependent pathways. T-cell calcium flux and nuclear translocation of NFATc were used to determine states of T-cell activation. Flow cytometry was used to assess human T- and B-cell activation after culture with LVAD-derived biomaterial particles. Sera from LVAD recipients and controls were tested for the presence of anti-HLA antibodies, and for soluble CD40 ligand. LVAD-derived biomaterial induced rapid and sustained calcium flux into normal T cells, resulting in calcineurin-dependent nuclear translocation of NFATc. This resulted in increased T-cell expression of CD40 ligand and subsequent B-cell activation, which was reduced by inhibitors of T-cell activation (CsA or anti-CD25 mAb) or by anti-CD40 ligand mAb. LVAD recipients demonstrated higher frequencies of anti-HLA antibodies and serum levels of soluble CD40 ligand compared with heart failure controls. The results indicate that exposure of human mononuclear cells to LVAD-derived biomaterial leads to T-cell dependent B-cell activation via CD40--CD40 ligand interaction, and suggest that treatment with calcineurin inhibitors or monoclonal antibodies against either CD25 or CD40 ligand could be effective at preventing B-cell hyperreactivity and allosensitization after LVAD implantation.     

Investigation of the infertile couple: when is the appropriate time to explore female infertility?

While the appropriate method for the investigation of female infertility continues to be debated, the timing of the investigation has received less attention. The current approach is time-consuming, and paradoxically may lead to overtreatment as well as undertreatment. Recent findings on fecundity and the conception window in humans have important implications for the timing of the investigation of female infertility. The findings support the view that fertility-oriented intercourse may have a major impact in reducing the time to pregnancy. Procedures for the investigation of female infertility are becoming less invasive and more accurate, while the therapies for infertility are more effective. It is proposed that under appropriate circumstances female infertility should be investigated after 6 months of fertility-oriented intercourse.     

Cotinine levels in follicular fluid and serum of IVF patients: effect on granulosa-luteal cell function in vitro

Cigarette smoking is accepted as a risk factor for pregnancybut its effect on fertility is uncertain. In this study we determinedthe concentration of cotinine, a nicotine metabolite, in follicularfluid and serum from women participating in an In-vitro fertilizationand embryo transfer (IVF-ET) programme. Cotinine was undetectableIn serum and follicular fluid of non-smokers but ranged from<5 to 371 ng/ml in follicular fluid and from 24 to 245 ng/mlin serum of smokers. Granulosa-luteal cells, obtained from IVFpatients and cultured for 4 days, secreted progesterone and,when an aromatizable androgen was added, oestradiol-17. Theaddition of cotinine or nicotine did not alter progesteroneor oestradlol-17 secretion. However, the presence of cotininein follicular fluid of women smokers provides evidence for accessof at least one component of cigarette smoke to the developinggamete and the cells of the follicle. Further work is requiredto determine whether fertllity is compromised by the presence,In follicular fluid, of contaminants derived from cigarettesmoke.     

Matched adaptations of electrophysiological, physiological, and histological properties of skeletal muscles in response to chronic hypoxia

This study tried to differentiate the consequences of chronic hypoxia on the electrophysiological and physiological properties and the histological characteristics of slow and fast muscles in rats. Animals inhaled a 10% O₂ concentration for a 1-month period. Then, slow [soleus (SOL)] and fast [extensor digitorum longus (EDL)] muscles were analyzed in vitro by physiological and electrophysiological measurements and histological analyses. The results were compared to those obtained in corresponding muscles of an age-matched normoxic group. After exposure to hypoxia: (1) in SOL, there was a tendency to elevated F_max, a significant increase in twitch force and tetanic frequency and a shortening of M-wave duration, and a reduced percentage of type I fibres, whereas the proportion of type IIa fibres doubled; (2) in EDL, F_max and tetanic frequency were lowered, the muscle became less resistant to fatigue, and the proportion of type IId/x fibres was halved. Then, after 1 month of hypoxia, in the SOL muscle, both the contractile and histological properties resemble those of a fast muscle. By contrast, the EDL became slower, despite its histology was modestly affected. Reduced muscle use in hypoxia could explain the tendency for deteriorating adaptations in EDL, and the faster properties of SOL could result from hypoxia-induced inhibition of the growth-related fast-to-slow shift in muscle fibre types.     

Detection of serum antibodies to bovine norovirus in veterinarians and the general population in the Netherlands

The close genetic relationship of human and animal strains of norovirus has raised the possibility of transmission of noroviruses from animals to humans and may explain the emergence of certain norovirus strains. To assess if exposure to bovine noroviruses (NoV) might result in infection in humans, an enzyme immunoassay (EIA) was designed and validated in order to detect antibodies against bovine norovirus. This and two other EIAs were used to test sera from 210 veterinarians and 630 matched population controls for IgG and IgA antibodies to recombinant capsid protein of bovine NoV (rBoV), Norwalk virus (rNV), and Lordsdale virus (rLDV). Of 840 participants, IgG reactivity to rBoV was found in 185 (22%), to rNV in 638 (76%) and to rLDV in 760 (90%). IgG reactivity to rBoV was more common in veterinarians (58/210: 28%) than in controls (127/630: 20% [P = 0.03]). IgA reactivity to rBoV was similar in both veterinarians and controls. Cross-reactivity of IgA and IgG antibodies to rBoV and rNV was seen, but 26% of all specimens positive rBoV antibodies showed high IgG reactivity to rBoV but low reactivity to rNV, suggesting a specific response to bovine antigen. No evidence of overall cross-reactivity of antibodies to rBoV and rLDV was seen. Among veterinarians, youth spent on farm (Odds Ratio [OR] = 1.8) and membership of the bovine practitioners' society (OR = 2.7) were significantly associated with IgG seroreactivity to rBoV. These data indicate that bovine strains of NoV may infect humans though less frequently than human strains.     

An ecological framework for cancer communication: implications for research

The field of cancer communication has undergone a major revolution as a result of the Internet. As recently as the early 1990s, face-to-face, print, and the telephone were the dominant methods of communication between health professionals and individuals in support of the prevention and treatment of cancer. Computer-supported interactive media existed, but this usually required sophisticated computer and video platforms that limited availability. The introduction of point-and-click interfaces for the Internet dramatically improved the ability of non-expert computer users to obtain and publish information electronically on the Web. Demand for Web access has driven computer sales for the home setting and improved the availability, capability, and affordability of desktop computers. New advances in information and computing technologies will lead to similarly dramatic changes in the affordability and accessibility of computers. Computers will move from the desktop into the environment and onto the body. Computers are becoming smaller, faster, more sophisticated, more responsive, less expensive, and--essentially--ubiquitous. Computers are evolving into much more than desktop communication devices. New computers include sensing, monitoring, geospatial tracking, just-in-time knowledge presentation, and a host of other information processes. The challenge for cancer communication researchers is to acknowledge the expanded capability of the Web and to move beyond the approaches to health promotion, behavior change, and communication that emerged during an era when language- and image-based interpersonal and mass communication strategies predominated. Ecological theory has been advanced since the early 1900s to explain the highly complex relationships among individuals, society, organizations, the built and natural environments, and personal and population health and well-being. This paper provides background on ecological theory, advances an Ecological Model of Internet-Based Cancer Communication intended to broaden the vision of potential uses of the Internet for cancer communication, and provides some examples of how such a model might inform future research and development in cancer communication.     

Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases

Polyglutamine diseases are characterized by neuronal intranuclear inclusions (NIIs) of expanded polyglutamine proteins, indicating the failure of protein degradation. UBB(+1), an aberrant form of ubiquitin, is a substrate and inhibitor of the proteasome, and was previously reported to accumulate in Alzheimer disease and other tauopathies. Here, we show accumulation of UBB(+1) in the NIIs and the cytoplasm of neurons in Huntington disease and spinocerebellar ataxia type-3, indicating inhibition of the proteasome by polyglutamine proteins in human brain. We found that UBB(+1) not only increased aggregate formation of expanded polyglutamines in neuronally differentiated cell lines, but also had a synergistic effect on apoptotic cell death due to expanded polyglutamine proteins. These findings implicate UBB(+1) as an aggravating factor in polyglutamine-induced neurodegeneration, and clearly identify an important role for the ubiquitin-proteasome system in polyglutamine diseases.     

Proctolin-related material in the mouse brain as revealed by immunohistochemistry

By use of a specific antiserum against the insect peptide proctolin we were able to identify proctolin-immunoreactive neurons in the mouse brain. These nerve cells belong to the nuc. mesencephalicus n. trigemini. Furthermore, the antiserum stained very few nerve fibers with varicosities in the immediate neighborhood of the roof of the third ventricle. The chemical identity of the immunoreactive material with genuine proctolin remains to be elucidated.     

Angiostrongylose bei Mensch und Tier

Zusammenfassung Die vorliegende Arbeit gibt eine Übersicht über den Stand der Angiostrongylose-Forschung. Von den bisher bekannten 16 Angiostrongylus-Arten haben drei eine medizinische Bedeutung: Der Rattenparasit A. cantonensis (Chen, 1935), Dougherty 1946 ist im südostasiatisch-pazifischen Raum Erreger einer eosinophilen Meningoenzephalitis des Menschen. A. costaricensis Morera und Céspedes, 1971, eine kürzlich in Costa Rica bei Haus- und Baumwollratten festgestellte Art, kann sich in den Mesenterialgefäßen des Menschen ansiedeln und Gefäßthrombosen und Darmentzündung hervorrufen. Eine Humanpathogenität des Fleischfresserparasiten A. vasorum (Baillet, 1866) läßt sich nach den heutigen Kenntnissen nicht ausschließen; als Ursache für zentralnervöse Erkrankungen des Menschen kommt dieser Parasit jedoch höchstwahrscheinlich nicht in Betracht, da die Larven auch im spezifischen Endwirt nicht in das Zentralnervensystem einwandern. Über A. vasorum werden folgende, zum Teil unveröffentlichte Forschungsergebnisse mitgeteilt: In der Schweiz wurden Fälle autochthoner Angiostrongylose des Hundes festgestellt und die Nacktschneckenart Arion rufus als natürlicher Zwischenwirt ermittelt. Neue experimentelle Zwischenwirte sind die Landschneckenarten Deroceras agreste, D. laeve und Vitrea diaphana sowie die Süßwasserschneckenarten Anisus leucostomus und Lymnaea tomentosa. Von verschiedenen Labortierarten ist nur die Nilratte, Arvicanthis niloticus, für A. vasorum empfänglich, in der sich der Parasit bis zur Geschlechtsreife entwickelt. Hunde lassen sich nach den Untersuchungen von Neff (1971) oral, intraduodenal, intraperitoneal, intravenös, subkutan und perkutan durch die skarifizierte Haut infizieren.

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Angiostronglyosis in man and animals

Summary A review is given on the present state of angiostrongylosis research. From the 16 known Angiostrongylus species three are of medical importance: A. cantonensis (Chen, 1935), Dougherty, 1946, a parasite of rats, may produce meningoencephalitis of man in the Pacific area and South-East Asia. A second species A. costaricensis Morera and Céspedes, 1971 was recently reported from house rats and cotton rats in Costa Rica; it can parasitize the mesenteric blood vessels of man leading to thrombosis and enteritis.According to our present knowledge, the possibility of a pathogenic effect by the parasite of carnivores A. vasorum (Baillet, 1866) to humans may not be fully dismissed. However, the parasite has no cerebral migration in its normal hosts and it is unlikely that it would produce a disease of the central nervous system in man.The authors discuss their partly unpublished data on A. vasorum. The occurrence of autochthonous angiostrongylosis was established in Switzerland transmitted by the slug Arion rufus. The slugs, Deroceras agreste and D. laeve, the terrestrial snail Vitrea diaphana and freshwater snails, Anisus leucostomus and Lymnaea tomentosa were found to be suitable as new experimental intermediate hosts. From many laboratory animals only the Nilerat, Arvicanthis niloticus, was found to be susceptible to the parasite reaching sexual maturity in that host. Experiments carried out by Neff (1971) showed that dogs can be successfully infected per os, through intraduodenal, intraperitoneal, intravenous and subcutaneous injections, or through the percutaneous route by application of infective larvae to the scarified skin.

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Nach einem Vortrag an der VI. Tagung der Dtsch. Ges. für Parasitologie, am 10.–12.4. 1972 in Hannover.