Universalosteoklast für mitten-und endständige Osteoklasie und Korrektur

Ohne Zusammenfassung Mit 3 Textabbildungen     

Acute and long-term humoral immunity following active immunization of rabbits with inacctivated spores of various Encephalitozoon species

Microsporidia of the genus Encephalitozoon are increasingly being reported as a cause of severe, often disseminated infections, mainly in patients with acquired immunodeficiency syndrome (AIDS). Immunological identification of each of the three recognized species (E. cuniculi, E. hellem, and E. intestinalis) requires the availability of specific immune sera. All sera available thus far have been generated by direct inoculation of rabbits with virulent microsporidian spores. This study demonstrates for the first time that subcutaneous immunization with inactivated spores of E. cuniculi, E. hellem, or E. intestinalis is capable of generating highly active rabbit hyperimmune sera to the homologous antigens, with maximal titers being 1:5,120, 1:1,280, and 1:2,560, respectively, as determined by the indirect immunofluorescence technique (IIF). Broad cross-reactivity of the rabbit antisera with all heterologous Encephalitozoon antigens was determined by IIF and immunogold electron microscopy; however, only the E. hellem immune serum strongly cross-reacted with spores of Enterocytozoon bieneusi. During the 35-month follow-up period the antibody titers to the homologous antigens declined to 1:640, 1:160, and 1:320, respectively. The observed decay curves for antibody titers against E. cuniculi, E. hellem, and E. intestinalis were fitted using mathematical modeling, resulting in a predicted duration for specific immune responses of about 7 years on average. Knowledge of the magnitude and duration of specific immune responses is a prerequisite for further evaluation of the concept of using inactivated microsporidian spores in the quest for vaccines against microsporidian infections. Received: 10 April 2000 / Accepted: 18 July 2000     

Polymorphism of germ-line immunoglobulin VH genes correlates with allotype and idiotype markers

The polymorphic nature of the immunoglobulin V_H genes was investigated by Southern blot analysis of liver DNA of sixteen different mouse strains and hybridization with V_H probes. Differences in restriction enzyme pattern (REP) were observed and six different patterns of restriction fragments were found for the sixteen strains analyzed. No equivalent polymorphism was observed in another multigene family, the actins. The six patterns correlate with immunoglobin constant region allotypes (Igh-1). Experiments with Igh-1-congenic strains suggest that the V_H REP is linked to immunoglobulin constant region haplotype. Mouse strains which share inherited idiotypes also share identical V_H restriction pattern. This provides a structural basis for the genetic linkage between idiotypes and allotypes. It also indicates that different strains carry different VH gene repertoires, which may be the basis for the expression of different inherited idiotypes in various strains. We propose that a V_H group is a set of linked genes that are coinherited as a cluster with the constant region genes and that V_H and C_H can be regarded as an extended haplotype.     

Physiological responses in sons of alcoholics

Researchers have differentiated sons of alcoholics (SOA's) from sons of nonalcoholics (non-SOA's) on various measures of physiological activity that appear to be related to the SOA's increased vulnerability to developing alcohol problems. This article summarizes major findings in the literature and discusses the implications of risk-related physiological characteristics for the future development of alcohol problems. SOA's tend to show signs of physiological activity associated with anxiety states, such as increased heart rate in response to stressful stimuli. Studies also demonstrate that SOA's differ greatly from non-SOA's in their response to alcohol. Drinking alcohol dramatically reduces SOAs' reactivity to both stressful and nonstressful stimuli. Additionally, SOA's appear to be less sensitive to alcohol's intoxicating and impairing effects. However, studies also suggest that some SOA's may experience more of alcohol's rewarding effects for a brief period after drinking. Increased stress-dampening and reduced responsiveness to alcohol's negative effects also appear to predict the development of future alcohol problems and may reflect important vulnerabilities in SOA's.     

Vitrectomy for macular pucker and vitreomacular traction syndrome

During the course of a so-called posterior vitreous detachment, a thin layer of the posterior vitreous cortex often remains adherent to the underlying retina. Tangential stretch of this vitreous pseudomembrane may cause vitreomacular traction syndrome, edema, and macular hole formation. The same process appears to underlie the development of true epimacular membranes (idiopathic macular pucker). Vitrectomy is generally agreed to be the most appropriate treatment for these clinical situations. We evaluated the incidence of vitreomacular adhesion and of visual improvement after vitrectomy of eyes with macular pucker (group 1; n=60) and vitreomacular traction syndrome (group 2; n=50). Vitreomacular attachment was assessed during vitrectomy under the condition of continuous air infusion. In the two groups, complete or partial vitreous attachment to the macula was observed in 57.4% and 74%, respectively. We conclude that vitreomacular adhesion is a common feature of the two clinical situations. Visual improvement was achieved in 73% of both groups. High rates of postoperative visual acuities of 20/50 or better (60.6% in group-1; 65.7% in group-2 cases) occurred only in eyes with preoperative values of 20/100 or better. It is reported that the visual outcome of vitreoretinal surgery for the two clinical conditions deteriorates with increasing duration after initial manifestation. Vitrectomy should not be postponed in patients who complain of disturbing visual symptoms such as reduced visual acuity, metamorphopsia and disturbance of binocular reading. This revised version was published online in July 2006 with corrections to the Cover Date.     

Human immunodeficiency virus infection and cerebral malaria in children in Uganda: a case-control study

Background  

Human immunodeficiency virus (HIV)-1 infection increases the burden of malaria by increasing susceptibility to infection and decreasing the response to malarial treatment. HIV-1 has also been found to suppress the immune system and predispose to severe forms of malaria in adults. There is still a paucity of data on the association between HIV-1 infection and cerebral malaria in children. The aim of this study was to determine whether HIV-1 infection is a risk factor for cerebral malaria in children.     

Perceptions About Local ART Adherence Norms and Personal Adherence Behavior Among Adults Living with HIV in Rural Uganda

AIDS and Behavior - Although misperceived norms often drive personal health behaviors, we do not know about this phenomenon in the context of antiretroviral therapy (ART) adherence. We conducted a...     

Biological response to phorbol ester determined by alternative G1 pathways.

A plethora of extracellular signals is known to induce a common set of immediate early genes. The immediate early response, therefore, must not be sufficient to determine the biological outcome. An example of this is found with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). A potent activator of protein kinase C, TPA can either stimulate or inhibit cell proliferation, depending on the cell type. This cell context-dependent response to TPA is observed with two subclones of NIH 3T3 cells, the P- and the N-3T3 clones. TPA is a mitogen for the P-3T3 but an antimitogen for the N-3T3 cells. The immediate early pathway is activated by TPA in both cell types, indicating that this pathway alone does not activate DNA synthesis. The delayed induction of cyclin D1 expression by TPA is observed only in the P-3T3 cells, correlating with mitogenesis. N-Acetylcysteine does not affect the immediate early pathway but can inhibit the TPA-mediated induction of cyclin D1 and DNA synthesis. In the N-3T3 cells, TPA causes an inhibition of the cyclin E-associated kinase at the G1/S transition, correlating with growth inhibition. The growth-inhibitory activity of TPA is not affected by N-acetylcysteine. Thus, the two TPA-regulated G1 pathways can be distinguished by their sensitivity to N-acetylcysteine. These results demonstrate that TPA can activate alternative G1 pathways. Moreover, the selection of the alternative G1 pathways is determined by the cell context, which, in turn, dictates the biological response to TPA.     

The tyrosine kinase NPM-ALK, associated with anaplastic large cell lymphoma, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation

The heterogenous group of anaplastic large cell lymphomas (ALCLs) is characterized by expression of the Ki-1/CD30 antigen, a member of the tumor necrosis factor receptor superfamily. About 40 to 50% of cases diagnosed as ALCL contain a specific chromosomal rearrangement, t(2;5)(p23;q35), resulting in expression of the chimeric tyrosine kinase NPM-ALK. As NPM-ALK-positive lymphomas define a distinct subtype within the group of ALCL, the chimeric protein might be responsible for certain pathogenetic and clinicopathologic characteristics. To better elucidate the function of NPM-ALK, we investigated a possible mechanism for regulation of its activity. We demonstrate that NPM-ALK specifically binds to the intracellular domain of the cytokine receptor CD30. In vitro binding assays revealed that the ALK portion of NPM-ALK mediates interaction of the two proteins. Stimulation of the CD30 receptor by cross-linking with immobilized anti-CD30 antibody results in complete growth inhibition of Karpas 299, an NPM-ALK-positive ALCL cell line, but does not alter proliferation of HDLM-2, a Hodgkin's lymphoma-derived cell line lacking t(2;5). Western blot analysis of coimmunoprecipitated CD30 and NPM-ALK proteins from stimulated Karpas 299 cells showed that the interaction of the proteins is not modified by stimulation. Activation of CD30 neither enhanced NPM-ALK activity measured by autophosphorylation of the chimeric tyrosine kinase nor phosphorylation of phospholipase C-gamma, an NPM-ALK substrate. We conclude that NPM-ALK is not stimulated by CD30 activation, but exists as a constitutively hyperactivated protein. Interaction with CD30 may extend the subcellular localization of NPM-ALK to the microenvironment of membrane-associated proteins.