Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi

In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.     

Changes in the level of antioxidants in the blood from mice infected with<Emphasis Type="Italic"> Trichinella spiralis</Emphasis>

The biological reaction caused by oxygen-derived free radicals at the molecular and cellular levels involves many different biochemical components which can be directly damaged by oxidizing radicals. As such a reaction may lead to pathological processes, defence mechanisms have evolved to limit the rate of free radical production. These mechanisms employ low-molecular-weight non-enzymatic antioxidants and antioxidant enzymes which are inducible by oxidant stress. In this study, the activity of two antioxidant enzymes, superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9), and the level of non-enzymatic antioxidants (total antioxidant status) in the blood from mice infected with Trichinella spiralis was examined. We observed a statistically significant, up to above twofold increase (relative to the control value in uninfected mice) in the level of both enzymes as well as in the total antioxidant status. An intensification of antioxidant processes during trichinellosis could be related to the presence of T. spiralis larvae, which may induce phagocytes to generate free radicals. Our research shows that the maximum growth in antioxidant activity in the blood appears during the period of the greatest muscle damage caused by T. spiralis infection at 3–7 weeks post-infection.     

Sex differences in emotional and psychophysiological responses to musical stimuli.

Although it is known that men and women differ in their music preferences and emotional reactions to music, little is known about sex differences in physiological reactions to music. In our study, we therefore set out to examine the differential reactivity to two musical stimuli that elicit distinct psychological and physiological reaction patterns. Fifty-three healthy subjects (mean age: 26.13, SD: 3.97; 26 males, 27 females) were examined. Heart rate, electrodermal activity, skin temperature, salivary cortisol, salivary alpha-amylase, and psychological variables were assessed during the course of the whole study. Following baseline assessment, two musical stimuli, which were carefully selected and rated in a pre-study as relaxing and pleasant (renaissance music) and arousing and unpleasant (heavy metal), respectively, were introduced. They were presented on two different days in a randomized order. Whereas psychological variables did not differ between men and women, results of electrophysiological measures indicate significantly different reactivity patterns between men and women. Women displayed elevated response curves to the arousing and unpleasant stimulus, whereas men did not. However, no differences were found with regards to endocrine measures in saliva. Our results demonstrate sex differences in reactivity patterns to musical stimuli in psychophysiological measures. In our study, we were able to show that women tend to show hypersensitivity to aversive musical stimuli. This finding is in accordance with previous literature on sex differences in emotion research. Furthermore, our study indicates that the confounding effects of sex differences have to be considered when using musical stimuli for emotion induction.     

Experimental rat model for therapeutic retinal pigment epithelium transplantation—unequivocal microscopic identification of human donor cells by in situ hybridisation of human-specific Alu sequences

Transplantation of retinal pigment epithelial (RPE) cells is discussed as a possible therapeutic approach for retinal degeneration. Xenogeneic transplantation of human RPE cells in animal models has been studied extensively. Various methods have been used to identify the graft cells, but these methods interfere with cell behaviour so that the monitored physiological post-transplantation course may be influenced. In the present study, we applied a method for an unequivocal identification of the graft cells without interfering cell metabolism or behaviour using in situ hybridisation (ISH) of human specific Alu sequences. Visualisation of the strong extended nuclear signal of Alu sequences was much easier than that of the small nuclear signals of donor-specific sex chromosome probes. With Alu probe, even single graft cells can be identified and their development can be observed in short-term and long-term studies. With this procedure, we could prove that donor cells were injected correctly into the subretinal space by a special injection technique that we developed previously. In combination with immunohistochemistry, donor cells could be clearly discriminated from macrophages, which contained phagocytosed donor cell fragments. Application of these ISH methods for species-specific identification was valuable for follow-up-studies of RPE transplantation.     

A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin

Histone lysine methylation is a central modification to mark functionally distinct chromatin regions. In particular, H3-K9 trimethylation has emerged as a hallmark of pericentric heterochromatin in mammals. Here we show that H4-K20 trimethylation is also focally enriched at pericentric heterochromatin. Intriguingly, H3-K9 trimethylation by the Suv39h HMTases is required for the induction of H4-K20 trimethylation, although the H4 Lys 20 position is not an intrinsic substrate for these enzymes. By using a candidate approach, we identified Suv4-20h1 and Suv4-20h2 as two novel SET domain HMTases that localize to pericentric heterochromatin and specifically act as nucleosomal H4-K20 trimethylating enzymes. Interaction of the Suv4-20h enzymes with HP1 isoforms suggests a sequential mechanism to establish H3-K9 and H4-K20 trimethylation at pericentric heterochromatin. Heterochromatic H4-K20 trimethylation is evolutionarily conserved, and in Drosophila, the Suv4-20 homolog is a novel PEV modifier to regulate position-effect variegation. Together, our data indicate a function for H4-K20 trimethylation in gene silencing and further suggest H3-K9 and H4-K20 trimethylation as important components of a repressive pathway that can index pericentric heterochromatin.     

Human defensins

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work     

Palmitic acid metabolism in the soleus muscle in vitro in hypo- and hyperthyroid rats

The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5–1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO₂ and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T₃) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56–66% for TG, 9-14% for MG/DG and 24–32% for PL. Our results thus indicate that even short-term T₃ excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected.     

Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment,acupuncture and stabilising exercises on the pregnancy,mother, delivery and the fetus/neonate

Background  

Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone.     

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.     

Die Wirkungen von Eserin, Cholin und Glucose auf die Synthese und die Freisetzung von Acetylcholin im Darm

Zusammenfassung Die Wirkungen von Eserin, Cholin und Glucose auf die Freisetzung und die Synthese von Acetylcholin (ACh) wurden im isolierten Dünndarm des Meerschweinchens durch Bestimmungen des ACh-Gehaltes des Gewebes und der ACh-Freisetzung in die Badelösung untersucht.In Lösungen, die Eserin, Cholin und Glucose enthielten, nahm der ACh-Gehalt des Gewebes zu, und es erfolgte eine Freisetzung von ACh in die Badelösung. Die Zunahme des ACh-Gehaltes des Gewebes, welche nur in Eserin-haltigen Lösungen auftrat, konnte auf intracelluläre Anhäufung von ACh zurückgeführt werden.ACh wurde auch in Cholin-freien Lösungen synthetisiert, doch war die ACh-Synthese geringer als in Gegenwart von Cholin. Aus der ACh-Synthese in Cholinfreier Lösung und dem Anteil des Nervengewebes am Darmvolumen wurde die Cholinkonzentration im Nervengewebe berechnet. Es zeigte sich, daß die intracelluläre Cholinkonzentration viel größer als die Cholinkonzentration im Plasma war. Die Cholinaufnahme in das Nervengewebe scheint deshalb in vivo durch aktiven Transport zu erfolgen.Bei Fehlen von Glucose trat keine Synthese von ACh auf, die Freisetzung von ACh hingegen war etwa doppelt so groß wie in Glucose-haltiger Lösung. Die Erhöhung der ACh-Freisetzung nach Glucose-Entzug könnte eine Anzahl der Symptome des hypoglykämischen Schockes erklären.

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Summary The effects of eserine, choline, and glucose on the liberation and the synthesis of acetylcholine (ACh) were studied in the guinea pig's small intestine by measuring the ACh content of the tissue and the amount of ACh liberated in the bath.Incubation in solutions containing eserine, choline, and glucose caused an increase in the ACh content of the tissue and the liberation of ACh. The increase in tissue content, which was only found when eserine was present, appears to result from intracellular accumulation of ACh.ACh was also synthezised in choline free solution, but the amounts were smaller than in the presence of choline. Estimation of the choline concentration in the nervous tissue, from the ACh synthesis in choline free solution and the amount of nervous tissue in the intestine, shows that the choline concentration in nerve is much higher than in plasma. It is suggested that uptake of choline in vivo necessitates an active transport process.No synthesis of ACh was found in the absence of glucose; the liberation of ACh was increased and occured entirely on account of the initial ACh content. The increase in ACh liberation after glucose withdrawal might explain some symptoms of hypoglycemic shock.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.