Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.     

One-year sequential follow-up of venous emptying rate and leg temperature profiles after acute deep vein thrombosis

In order to study the natural course of venous flow and temperature reaction in the legs after symptomatic first episode of deep vein thrombosis (DVT), 65 patients (57 with proximal DVT) without further thromboembolic complications during the observation period were followed for 1 year by repeated plethysmography (PG) and thermography (TG). Regarding the non-invasive parameters substantial individual variations was observed during the observation period. After 1 year pathologic PG and TG were still demonstrated in 39% (I mu (95%) = /0.43 +/- 0.05/) and 65% (I mu (95%) = /1.18 +/- 0.11/), respectively, of the patients after proximal DVT. Only a minority of the patients were normalized permanently in both PG and TG during the first year. The high frequency of remaining venous obstruction and especially, persistent thermoactivity is notable and may be of clinical importance.     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.

Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.     

Total-videoendoskopische Strumaresektion via“axillobilateral breast approach”

BACKGROUND: The axillobilateral breast approach (ABBA) is a procedure allowing thyroid resection without scarring at the neck. We operated on a series of 26 patients with this technique. METHOD: Via incisions at the edge of the mamilla and axilla, trocars are placed subcutaneously under the platyma. Dissection is performed bluntly and with an ultrasonographic scalpel under videoscopic control. The procedure itself corresponds to conventional surgery. The specimen is removed through the axillary trocar. RESULTS: Twenty-six female patients underwent thyroid resection using the ABBA technique. Subtotal resection was performed in 24. Mean operation times were 111 min (unilateral) and 187 min (bilateral). In none of these cases was conversion necessary. One transient recurrent laryngeal nerve palsy and one paresis of the arm plexus were found postoperatively. CONCLUSION: In selected patients the ABBA technique is feasible and safe with the mandatory radicalness. The primary aim of this method is the cosmetic result.     

Gewaltforschung zum Thema „häusliche Gewalt“ aus kriminologischer Sicht

Domestic violence continues to be a subject of public interest and media presence, especially when it involves spectacular cases ranging from abuse of children to fatal violence in the family. Although domestic violence has been the subject of scientific research for the last three decades, there is still no clear evidence of prevalence and etiology of this particular kind of violence. Since the introduction of the German Violence Protection Act which came into force in January 2002, domestic violence has been met with severe societal and legal sanctions. The consequences for culprits are not only theoretical but also include an increase in criminal proceedings and improved civil court protection. Therefore medical staff, particularly legal medicine, is more than ever confronted with the need to standardize documentation of injuries resulting from domestic violence. In addition, legal medical specialists are often confronted with the victims’ personal and social problems. This paper gives an insight into the historical background and recent law reforms which have created legal sanctions and protection against domestic violence.     

Neonatal Exposure to a Combination of N-Methyl-d-aspartate and γ-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits

Background: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

Methods: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests-spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)-were conducted on mice aged 55-70 days.

Results: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.     

Influence on the masticatory system in treatment of obstructive sleep apnea and snoring with a mandibular protruding device: A 2-year follow-up

The aim was to identify the incidence and types of possible adverse events in the masticatory system after treatment with a mandibular protruding device (MPD) during a 2-year period in patients with obstructive sleep apnea (OSA) or snoring. The subjects comprised 65 middle-aged patients (44 OSA patients, 21 snorers). A clinical examination and a questionnaire concerning signs and symptoms from the masticatory system were performed before, after 6 months, and after 2 years of MPD use. The frequencies of registered signs from the masticatory system, such as muscle and joint tenderness, palpation, and pain during mandibular movement, decreased significantly between baseline and the 2-year follow-up. There were significant changes in the mandibular range of protrusion (+0.7 mm, P < .001), overjet (-0.5 mm, P < .001), and overbite (-0.6 mm, P < .001) compared with the initial examination. Nine patients developed a lateral open bite during treatment, and 2 of them experienced subjective symptoms related to the altered occlusion but still used the MPD every night. No patient reported pain on opening the mouth wide or during jaw movements. Two reported tiredness on jaw function. The reported frequency of headaches was also significantly reduced (P < .01). The high compliance rate in MPD use showed that the therapy is well tolerated, but there is a risk of minor alterations in the occlusion during MPD treatment.     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.