The Use of Lysostaphin in in Vitro Assays of Phagocyte Function: Adherence to and Penetration into Granulocytes

The usefulness of lysostaphin for the removal of cell-adherent and extracellular bacteria in assays performed to measure the intracellular killing of Straphylococcus aureus by granulocytes was investigated. The results showed that the adherence of lysosiaphin to the granulocyte surface is effectuated by a temperature-independent process and that bound lysostaphin is still microbicidal. Lysosiaphin also penetrates into the granulocytes by a temperature dependent process and kills ingested S. aureus intracellularly. Therefore, despite reports to the contrary in the literature, lysosiaphin is not a reliable agent for the removal of only extracellular S. aureus and should no longer be used in assays to determine the rate of intracellular killing by granulocytes.     

Evidence that alfalfa mosaic virus infection starts with three RNA-protein complexes

The tripartite genome of alfalfa mosaic virus (AMV) needs to be activated by its coat protein. To establish whether coat protein exerts its role by interacting structurally with one, two, or all three AMV-RNA species, the infectivity of mixtures of RNA-protein complexes with free RNAs were studied (Smit and Jaspars, Virology 104, 454-461, 1980). These studies were not fully conclusive since some redistribution of coat protein does occur as soon as RNAs are brought into contact with RNA-protein complexes. This problem was overcome by the use of ts mutants of AMV. Free ts coat protein subunits were not able to activate the wt genomic RNAs at 30 degrees in tobacco. Once complexed to the genomic RNAs at 0 degrees , the biological activity of the ts coat protein remained when assayed at the nonpermissive temperature. Apparently, the ts coat protein is inactivated during attempted redistribution at 30 degrees . Studies of mixtures of RNA-protein complexes and free RNA show that coat protein has to be present on at least two of the three RNA species. This result in combination with previous results (Smit and Jaspars, 1980) warrants the conclusion that the alfalfa mosaic virus infection starts with three RNA-protein complexes.     

Localization of the HST/FGFK gene with regard to 11q13 chromosomal breakpoint and fragile site

The HST/FGFK gene, a member of the fibroblast growth factor gene family and a protooncogene, is localized on chromosomal band 11q13. Genes in this region are frequently involved in hematopoietic and solid tumors. Here we show that the HST gene lies telomeric to the BCL1 gene, the t(11;14)(q13;q32) breakpoint, and the FRA11A rare fragile site.     

A coherent pattern among social behavior, blood pressure, corticosterone and catecholamine measures in individual male rats

Behavioral and physiological responses of 18 chronically cannulated male TMD-S3 rats were assessed during various social interactions with conspecifics, both with and without the possibility for physical contact (social vs. psychosocial stimulation). Response magnitudes (behavior, blood pressure, plasma catecholamines) depend upon both the social environmental requirements (offense, defense, psychosocial stimulus following defense) and individual characteristics. The more competitive males generally reacted with higher responses of blood pressure and catecholamines than more passive rats. In addition, these competitive males had higher baseline levels of noradrenaline. The present experiment shows that male rats differ in the individual sympathetic tone and reactivity in relation to their behavior in a social environment.     

Decreased anti-donor major histocompatibility complex class I and increased class II alloantibody response in allograft tolerance in adult rats

Permanent tolerance to allografts can be induced in adult rats by donor-specific transfusions (DST) prior to transplantation. We have previously reported, in a model of heart allograft, the presence of a heavy leukocyte infiltrate, in the allograft which displayed a strong allospecific cytotoxicity when tested in vitro against donor cells, and a strong accumulation of mRNA for granzyme A and perforin in vivo. In contrast, there was a major decrease in the accumulation of mRNA for interleukin-2 and interferon-γ. These results suggested that the DST-induced tolerance was associated with a decrease in type-1 T helper (Th1) cell function. The major role of preformed antibodies in xeno and allorejection is clearly established. Nevertheless, the consequences of alloantibody production in acute rejection and tolerance induction remains to be elucidated. We here analyze the alloantibody response in rejecting and DST-treated recipients. We show that, after transplantation, tolerant recipients, in contrast to rejecting ones, mount a low IgM alloresponse that switches to low IgG production. Detailed analysis of IgG alloantibodies in DST-treated recipients revealed that their production decrease was not equally distributed. Whereas rejecting animals mounted a strong anti-class I and II IgG alloantibody response, DST-treated recipients produced anti-class II and low titers of anti-class I IgG alloantibodies. Furthermore, among IgG subclasses, tolerant recipients predominantly produced IgG2a, a profile which, in the rat, is compatible with a Th2-controlled response. Finally, the passive transfer of immune serum from rejecting animals to DST-treated recipients could abrogate the tolerance. We suggest that the absence of anti-class I alloantibodies combined with preserved and/or increased anti-class II production plays a major role in graft tolerance in this model. These results reinforced the role of alloantibodies in rejection and in induction of tolerance.     

Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.     

Prevalence of tooth agenesis correlated with jaw relationship and dental crowding

Two groups of patients were selected from the State University Dental School in Ghent--an experimental group with tooth agenesis and a control group with complete dentitions. Skeletal anomalies were diagnosed by means of lateral cephalograms according to the Sassouni analysis. The amount of crowding was measured on standardized photographs by Little's Irregularity Index. The prevalence of Class I skeletal relationship appeared to be significantly higher in the agenesis group than in the control group. Skeletal deep- and normal-bite cases occurred more often in patients with hypodontia than in the control group. As far as crowding was concerned, it was less pronounced in the hypodontia group (lateral segments) than in the control group. This conclusion held true only when the "amount" of crowding was not taken into account.     

Inhibitory dopamine receptors on sympathetic neurons innervating the cardiovascular system of the pithed rat

Summary Additional experimental evidence was obtained for an inhibitory function of prejunctional ₂-adrenoceptors and/or dopamine receptors located on noradrenergic neurons innervating the heart and resistance vessels of the pithed normotensive rat. Mixed ₂-adrenoceptor receptor agonists, differing in selectivity towards either receptor type, i.e. N,N-di-n-propyldopamine (DPDA), 2-N, N-di-n-propylamino-6, 7-dihydroxy-1,2,3,4-tetrahydronaphthalene (DP-6,7-ADTN), B-HT 920 and B-HT 933 (azepexole) were used.In pithed normotensive rats, DPDA (30 and 100 g/kg/min) dose-dependently inhibited the electrical stimulation-induced increase in diastolic pressure, but did not significantly affect the stimulation-evoked increase in heart rate. The inhibition exerted by DPDA was blocked by haloperidol and sulpiride (0.3 mg/kg of each), but not by yohimbine (1 mg/kg), indicating the involvement of dopamine receptors. In this respect, sulpiride and haloperidol were found approximately equipotent.DP-6,7-ADTN (10 and 30 g/kg/min) impaired both tachycardic and vasoconstrictor responses in a dose-dependent manner. Sulpiride (0.3 mg/kg) only partially restored the DP-6,7-ADTN-depressed stimulation-evoked increase in diastolic pressure, whereas yohimbine (1 mg/kg) alone was without effect. The combination of both antagonists completely prevented the inhibition caused by DP-6,7-ADTN. On the other hand, yohimbine (1 mg/kg), but not sulpiride (0.3 mg/kg), selectively antagonized the DP-6,7-ADTN-induced inhibition of stimulation-evoked tachycardia.B-HT 920 (1, 3 and 10 g/kg/min) very effectively reduced the increase in diastolic pressure and heart rate caused by electrical stimulation. Inhibitory dopamine as well as ₂-adrenoceptors participated in the vascular effects of B-HT 920, whereas ₂-adrenoceptors were only involved in the cardioinhibitory response to this agonist.B-HT 933 (0.6 and 1 mg/kg/min) dose-dependently reduced the stimulation-evoked increase in arterial pressure through selective stimulation of inhibitory ₂-adrenoceptors, dopamine receptors not taking a part.The results confirm and extend the observations that in addition to ₂-adrenoceptors inhibitory dopamine receptors are located on the sympathetic neurons connected with the arterial vasculature of the pithed normotensive rat. The sympathetic nerves innervating the rat heart do not contain inhibitory dopamine receptors; their activity only can be modulated by ₂-adrenoceptor stimulation. In the pithed normotensive rat, activation of prejunctionally located ₂-adrenoceptors more effectively inhibits the sympathetic activity directed to the heart than that to the resistance vessels.     

Patient Satisfaction with AbobotulinumtoxinA for Aesthetic Use in the Upper Face: A Systematic Literature Review and Post-hoc Analysis of the APPEAL Study

BACKGROUND: AbobotulinumtoxinA (AboBoNT-A; Dysport^®; Ipsen, Boulogne-Billancourt, France/Azzalure^®; Galderma, Lausanne, Switzerland) is a botulinum neurotoxin type A approved for aesthetic use in the treatment of glabellar lines in adult patients under 65 years in Europe, the United States, and other countries. OBJECTIVE: We sought to analyze current literature on patient satisfaction with aboBoNT-A for upper facial aesthetic indications. METHODS: A systematic review of literature databases (PubMed/MEDLINE, Embase, the Cochrane Library, and Google Scholar) was performed to identify English-language publications reporting on patients with aesthetic indications (including glabellar lines and wrinkles) receiving aboBoNT-A, that assessed patient and/or physician satisfaction with treatment, with no restrictions on comparator studies. Structured data extraction was used to enable inter-study analysis. A post-hoc analysis was also performed to assess patient satisfaction by sex and age, using results from the noninterventional APPEAL study of patients’ satisfaction with aboBoNT-A for treating glabellar lines. RESULTS: Overall, 22 original research papers were identified. Patient satisfaction rates for aboBoNT-A treatment were significantly higher versus placebo from two weeks to between three and five months postinjection. At two to three weeks postinjection, patient satisfaction rates were 52% and 99% across studies. In studies with later time points, patient satisfaction rates were 85 to 87 percent at 5 months and between 25 and 100 percent at 6 months post-injection. Physician satisfaction was also high (97%–100%, across three treatments). No notable differences in patient satisfaction by sex or age were observed in the APPEAL study. CONCLUSION: High rates of patient satisfaction have been achieved with aboBoNT-A treatment for upper facial aesthetic indications. Despite the current recommended interval of ≥12 weeks, satisfaction with the aesthetic results of aboBoNT-A therapy is still evident up to 6 months post-injection in some patients.