Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1.

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

Paraoxonase 1: The Lectin-Like Oxidized LDL Receptor Type I and Oxidative Stress in the Blood of Men with Type II Obesity.

OBJECTIVES: Obesity has serious consequences such as the onset of metabolic syndrome, type 2 diabetes, atherosclerosis, or cardiovascular complications. The aim of this study was to evaluate the levels of paraoxonase 1 (PON1), lectin-like oxidized LDL receptor-1 (LOX-1), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and lipid peroxidation processes in the course of obesity. METHODS: 28 men took part in the experiment. Fourteen of them were obese; the control group consisted of 14 physically active men without obesity features. The concentrations of malondialdehyde (MDA), PON1, LOX-1, and tumor necrosis factor α (TNFα) as well as the activities of erythrocytic SOD, CAT, and GPx were determined in the study. RESULTS: Statistically significant higher MDA, LOX-1, and TNFα levels were observed in obese subjects. Conversely, lower concentrations of PON1 in obese men were found. CONCLUSIONS: An imbalance in oxidation-reduction processes accompanies obesity. Moreover, inflammatory cytokines and atherosclerotic complications are involved in the obesity process. The obtained results suggest that the studied parameters may be independent prognostic markers preceding the development of cardiovascular and metabolic complications in people afflicted with type II obesity.

A mechanochemical strategy for IRMOF assembly based on pre-designed oxo-zinc precursors.

We demonstrate a mechanochemical strategy that allowed the first successful mechanosynthesis of IRMOFs based on an oxo-centred secondary building unit (SBU). The presented study indicates that controlling the acid-base relationship between reagents is key to mechanochemical synthesis of IRMOFs, revealing a pre-assembled oxo-zinc amidate cluster as an efficient precursor for IRMOF mechanosynthesis.

Assessing achievement, affiliation, and power motives all at once: the Multi-Motive Grid (MMG).

In this article, we introduce the Multi-Motive Grid (MMG), a new diagnostic tool to measure motives with respect to their hope and fear components. The MMG combines features of the Thematic Apperception Test (TAT) with features of self-report questionnaires. Similar to the TAT, a set of 14 pictures representing a balanced set of achievement-arousing, affiliation-arousing, and power-arousing situations is presented together with a set of statements representing important motivational states. Six motive scores can be calculated: hope of success (HS) and fear of failure (FF) for the achievement motive, hope of affiliation (HA) and fear of rejection (FR) for the affiliation motive, and hope of power (HP) and fear of power (FP) for the power motive. Results of factor analyses suggest a 3-factor solution, with a general fear factor (FF, FR, FP), a factor combining the hope components of achievement and power (HS and HP), and a third factor representing HA, but the 6 a priori factors also reflect a sound structural model. Reliability data show that the internal consistency and retest reliability of the MMG scales satisfy traditional standards. External validity of the MMG has been established in all 3 motive domains. Three separate studies document that (a) individuals high in resultant achievement motivation perform better and report more flow experience, (b) individuals high in resultant power motivation profit more from a leadership training program, and (c) individuals high in resultant affiliation motivation recollect more highly memorable affiliative themes.

Characterization by serial deletion competition ELISAs of HIV-1 V3 loop epitopes recognized by monoclonal antibodies.

Characterization of the sites recognized by antibody on the V3 loop of the envelope glycoprotein gp120 of HIV-1 was done by competition ELISAs on a series of four mouse mAbs, a human mAb and a human Fab. The solid-phase antigen consisted of biotin-YNKRK-RIHIGPGRAFYTTKN, a sequence from the center of the V3 loop of gp120MN, applied to streptavidin-coated wells. Competing antigens were two series of peptides with the HIV-1MN sequence each serially deleted at either the N or C terminus but kept constant at the other terminus. For each series, the amino acid at the deleting end needed to give a minimum KD was identified. The epitope was defined as the sequence including both of the identified amino acids as terminal amino acids. For the six antibodies reported, the epitope length ranged from seven to 14 amino acids. Use of a cyclic peptide as competing fluid-phase antigen suggested the influence of conformational constraints on presumed "linear" epitopes. The operationally-defined epitope was longer than the contact residues in one of two instances in which the X-ray crystallographic structure had been determined. The longer estimates of epitope length in the current study based on competition ELISAs with serial deletions suggest that non-contact residues are significant both in epitope definition and in functional applications including immunogen design.

[Emotional and motivational influences in an affiliation conflict situation]. / Emotionale und motivationale Einflussfaktoren in einer anschlussthematischen Konfliktsituation.

The present study investigated the influence of induced mood (happy vs. sad) and the affiliation motive (hope of affiliation vs. fear of rejection) on cognitions and physiological reactions during the presentation of a social scenario. This scenario depicted the temporal approach to and finally the unexpected termination of a social interaction. Happy and sad moods were induced successfully, as indicated by self-report measures and physiological variables. Participants high in fear of rejection were more anxious and tensed immediately before the desired social interaction. In addition, they showed a higher level of physiological arousal. The unexpected termination of the social interaction at the end of the scenario had a strong negative effect on participants high in fear of rejection if they were in a happy mood. Thus, in this case an incongruence between the dominant motive and the actual emotional state led to emotional impairment. The results are discussed on the basis of motivational conflict theory and of learned helplessness.

Anti-CD11b monoclonal antibody improves myocardial function after six hours of hypothermic storage.

BACKGROUND: The shortage of pediatric heart donors often necessitates considerable travel time and, as a result, prolonged donor heart ischemia. This excessive hypothermic storage may contribute markedly to myocardial dysfunction in the recipient. METHODS: We investigated the role of leukocyte-endothelial interactions in this dysfunction in an isolated, immature (mean age, 11.8 +/- 1.6 days) swine heart model using a monoclonal antibody against a leukocyte adhesion molecule. We studied a total of 20 hearts subjected to 6 hours of cardioplegic arrest at 4 degrees C. Group M1/70 (n = 6) received at reperfusion 15 micrograms/mL of a monoclonal antibody F(ab')2 fragment to CD11b, the alpha-subunit of the leukocyte adhesion molecule Mac-1. Group MB10.6 (n = 8) received 15 micrograms/mL of the swine unreactive F(ab')2 MB10.6, and the third group received saline vehicle. RESULTS: Administration of M1/70 resulted in improved postischemic recovery of ventricular function compared with the two control groups (p < 0.05). CONCLUSIONS: These data implicate leukocyte-endothelial interactions mediated by the leukocyte adhesion molecule CD11b in myocardial dysfunction after long-term hypothermic ischemia. Specific antiadhesion strategies such as this may safely extend storage time for pediatric donor hearts.

Broadly neutralizing monoclonal antibodies to the V3 region of HIV-1 can be elicited by peptide immunization.

The third hypervariable region (V3) of the HIV-1 envelope gp120 protein contains the principal neutralizing domain. Most neutralizing antibodies directed toward this region are very type-specific. Conserved sequences do exist within this region, however, and may prove useful in developing vaccines and therapeutic monoclonal antibodies (MABs) capable of targeting diverse HIV-1 isolates. We have used synthetic peptides containing conserved V3 sequences as immunogens to produce a panel of neutralizing MABs. The characterization of these MABs is described here. In addition, a series of in vitro assays has been developed that may be useful in predicting the neutralization potential of individual antibodies.

[Unconscious induction of emotions and unintended change in behavior]. / Emotionsinduktion ohne Bewusstheit und Verhaltensänderung ohne Absicht.

The problem of most mood induction procedures in psychological laboratories is located in their demand characteristics. The subjects either have to help change their mood actively, or are at best only passively aware of the induction process. To overcome the necessity of consciousness of the mood induction procedure we developed a technique based on the involuntary tendency to imitate the expression of perceived faces ("emotional infection"). Three different mood induction conditions--operationalized by means of happy, neutral, or sad pairs of faces, which had to be compared in spite of their age--were imbedded in an experiment disguised as, research in perception'. The results show mood influences only in the behavioral measures: Happy induced subjects wrote significantly faster than neutral and sad ones. In contrast, the self description data--measured via mood adjectives--showed no typical changes due to the induction condition. The subjects seemed to be unaware of the cause and the effect of their changed mood.

The effect of isolated leukaemic blasts on platelet aggregation.

The effect of blastic cells isolated by Böyum's method from the blood of 20 nontreated patients with acute myelogenous leukaemia on normal platelet aggregation has been studied. The isolated blasts in concentration of 2,000/microliter and higher, inhibit normal platelet aggregation induced by ADP or collagen, but have no influence on aggregation initiated by epinephrine. This effect is unaffected by the presence of metabolic poisons or by the disruption of the blastic cell membrane. Our results seem to exclude interference of blastic cells with platelet prostaglandin biosynthesis. In patients with acute leukaemia and an increased leukocyte count the preparation of platelet suspension free of blastic cells is not possible, even by the albumin gradient method or by gel filtration. The leukaemic blast content in platelet-rich suspensions may account for the variations in the aggregation behaviour which are found in these patients. The influence of blastic cells may be an important factor in the bleeding tendency in myelogenous leukaemia