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Biomedical subjects

B Sommer

Publications and source records attributed to B Sommer.

At least 19 recordsLinked to original sources
PubMed2003

[MR imaging of prostate cancer].

PURPOSE: Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC. MATERIAL AND METHODS: Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. RESULTS: Major indications for MR imaging of patients with suspected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. CONCLUSIONS: Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS.

Biopsy↗
PubMed2003

Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo-66 receptor.

Nogo-66 receptor (NgR) has recently been identified as the neuronal receptor of the myelin-associated proteins Nogo-A, oligodendrocyte protein (OMgp) and myelin-associated glycoprotein (MAG), and mediates inhibition of axonal regeneration both in vitro and in vivo. Through database searches, we have identified two novel proteins (NgRH1 and NgRH2) that turned out to be homologous in their primary structures, biochemical properties and expression patterns to NgR. Like NgR, the homologues contain eight leucine-rich repeats (LRR) flanked by a leucine-rich repeat C-terminus (LRRCT) and a leucine-rich repeat N-terminus (LRRNT), and also have a C-terminal GPI signal sequence. Northern blot analysis showed predominant expression of NgRH1 and NgRH2 mRNA in the brain. In situ hybridization and immunohistochemistry on rat brain slices revealed neuronal expression of the genes. NgRH1 and NgRH2 were detected on the cell surface of recombinant cell lines as N-glycosylated GPI anchored proteins and, consistent with other GPI anchored proteins, were localized within the lipid rafts of cellular membranes. In addition, an N-terminal proteolytic fragment of NgR comprising the majority of the ectodomain was found to be constitutively secreted from cells. Our data indicate that NgR, NgRH1 and NgRH2 constitute a novel receptor protein family, which may play related roles within the CNS.

Amino Acid Sequence↗
PubMed2002

Dose-dependent neuroprotective effect of ciliary neurotrophic factor delivered via tetracycline-regulated lentiviral vectors in the quinolinic acid rat model of Huntington's disease.

The ability to regulate gene expression constitutes a prerequisite for the development of gene therapy strategies aimed at the treatment of neurologic disorders. In the present work, we used tetracycline (Tet)-regulated lentiviral vectors to investigate the dose-dependent neuroprotective effect of human ciliary neurotrophic factor (CNTF) in the quinolinic acid (QA) model of Huntington's disease (HD). The Tet system was split in two lentiviruses, the first one containing the CNTF or green fluorescent protein (GFP) cDNAs under the control of the Tet-response element (TRE) and a second vector encoding the transactivator (tTA). Preliminary coinfection study demonstrated that 63.8% +/- 2.0% of infected cells contain at least two viral copies. Adult rats were then injected with CNTF- and GFP-expressing viral vectors followed 3 weeks later by an intrastriatal administration of QA. A significant reduction of apomorphine-induced rotations was observed in the CNTF-on group. In contrast, GFP-treated animals or CNTF-off rats displayed an ipsilateral turning behavior in response to apomorphine. A selective sparing of DARPP-32-, choline acetyltransferase (ChAT)-, and NADPH-d-positive neurons was observed in the striatum of CNTF-on rats compared to GFP animals and CNTF-off group. Enzyme-linked immunosorbent assay (ELISA) performed on striatal samples of rats sacrificed at the same time point indicated that this neuroprotective effect was associated with the production of 15.5 +/- 4.7 ng CNTF per milligram of protein whereas the residual CNTF expression in the off state (0.54 +/- 0.02 ng/mg of protein) was not sufficient to protect against QA toxicity. These results establish the proof of principle of neurotrophic factor dosing for neurodegenerative diseases and demonstrate the feasibility of lentiviral-mediated tetracycline-regulated gene transfer in the brain.

Animals↗
PubMed2002

Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues.

Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and den deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties.

Animals↗
PubMed2001

Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice.

A microglial response is part of the inflammatory processes in Alzheimer's disease (AD). We have used APP23 transgenic mice overexpressing human amyloid precursor protein with the Swedish mutation to characterize this microglia response to amyloid deposits in aged mice. Analyses with MAC-1 and F4/80 antibodies as well as in vivo labeling with bromodeoxyuridine demonstrate that microglia in the plaque vicinity are in an activated state and that proliferation contributes to their accumulation at the plaque periphery. The amyloid-induced microglia activation may be mediated by scavenger receptor A, which is generally elevated, whereas the increased immunostaining of the receptor for advanced glycation end products is more restricted. Although components of the phagocytic machinery such as macrosialin and Fc receptors are increased in activated microglia, efficient clearance of amyloid is missing seemingly because of the lack of amyloid-bound autoantibodies. Similarly, although up-regulation of major histocompatibility complex class II (IA) points toward an intact antigen-presenting function of microglia, lack of T and B lymphocytes does not indicate a cell-mediated immune response in the brains of APP23 mice. The similar characteristics of microglia in the APP23 mice and in AD render the mouse model suitable to study the role of inflammatory processes during AD pathogenesis.

Amyloid beta-Peptides↗
PubMed2001

[Therapeutic goals in psychological medicine--state of research and development of a standardized self-rating instrument].

From the patient's as well as from the therapist's point of view goals of therapy undoubtedly play an important role in all fields of psychological medicine (psychiatry, psychotherapy, psychosomatic medicine). On the other hand, there is a substantial lack of systematic i.e. empirical studies on this issue. Giving an overview on the available scientific literature we start by characterising therapeutic goals as a secondary psychological construction. Therapeutic goals and their multiple associations and different aspects of psychotherapy are discussed. However, a variety of definitions of therapeutic goals, often influenced by the therapeutic orientation of the authors, make it difficult to integrate concepts and to compare findings. Hence, we focus on those results which were found in relation to general concepts, i.e. beyond specific theoretical approaches. Furthermore, we discuss the pros and cons of individual measures of therapeutic goals compared with standardised self-rating instruments. Finally, we underline the lack of studies on therapeutic goals in the psychiatric sphere and report on some results of our own pilot study on the Personal Goals Questionnaire in psychiatric inpatients.

Humans↗
PubMed2001

Differences between inhaled and intravenous bronchial challenge to detect O(3)-induced hyperresponsiveness.

Ozone (O(3))-induced airway hyperresponsiveness in laboratory animals is usually demonstrated through dose-response curves with inhaled or intravenous bronchoconstrictor agonists. However, comparability of these two routes has not been well documented. Thus guinea pig airway responsiveness to ACh and histamine was evaluated 16-18 h after O(3) (3 parts/million, 1 h) or air exposure by two plethysmographic methods (spontaneously breathing and mechanically ventilated) and by two administration routes (inhalatory or intravenous). We found that O(3) caused airway hyperresponsiveness to intravenous, but not to inhaled, agonists, independent of the plethysmographic method used. Suitability of the inhalatory route to detect airway hyperresponsiveness was corroborated with inhaled ACh after an antigen challenge or extending O(3) exposure to 3 h. Acetylcholinesterase activity was not modified after O(3) exposure in lung homogenates and blood samples. Thus inhaled agonists were less effective to reveal the airway hyperresponsiveness after an acute O(3) exposure than intravenous ones, at least for the 1-h exposure to 3 parts/million, and this difference seems not to be related to an O(3)-induced inhibition of the acetylcholinesterase activity.

Acetylcholinesterase↗
PubMed2001

Psychologic distress and natural menopause: a multiethnic community study.

OBJECTIVES: This study examined the association between psychologic distress and natural menopause in a community sample of African American, White, Chinese, Hispanic, and Japanese women participating in a national women's health study. METHODS: A cohort of 16,065 women aged 40 to 55 years provided information on menstrual regularity in the previous year, psychosocial factors, health, and somatic-psychologic symptoms. Psychologic distress was defined as feeling tense, depressed, and irritable in the previous 2 weeks. RESULTS: Rates of psychologic distress were highest in early perimenopause (28.9%) and lowest in premenopause (20.9%) and postmenopause (22%). In comparison with premenopausal women, early perimenopausal women were at a greater risk of distress, with and without adjustment for vasomotor and sleep symptoms and covariates. Odds of distress were significantly higher for Whites than for the other racial/ethnic groups. CONCLUSIONS: Psychologic distress is associated with irregular menses in midlife. It is important to determine whether distress is linked to alterations in hormone levels and to what extent a mood-hormone relationship may be influenced by socioeconomic and cultural factors.

Adult↗
PubMed2000

Self-defined menopausal status in a multi-ethnic sample of midlife women.

OBJECTIVES: This study aimed to identify factors associated with women's perceived menopausal status and to evaluate agreement between women's self-designation and a menstrually-based classification in a multi-ethnic sample of women. METHODS: A cross-sectional survey was conducted as part of a large, seven-site, multi-ethnic study, the Study of Women's Health Across the Nation (SWAN). All variables were assessed by self-report in 13952 women aged 40-55 years. Multiple linear regression was used to assess determinants of self-defined menopausal status, stratifying by race/ethnicity within three anatomical/hormone use strata. Kappa statistics were used to evaluate agreement between the self-defined and menstrually-based classifications. RESULTS: For women with an intact uterus, at least one ovary and not using hormones, menstrual patterns explained about half the variance in self-defined menopause status with older women classifying themselves later in the transition. Disagreement between menstrually-based and self-defined menopausal status was 39, 38, 36, 32 and 29% for Hispanic, African-American, Japanese, Caucasian, and Chinese women, respectively (kappa statistics=0.46, 0.41, 0.40, 0.53 and 0.58). Women with vasomotor symptoms tended to self-designate themselves as being in transition regardless of their menstrual patterns. Age and 12 months of amenorrhea explained about 40% of the variance in self-categorization among women using hormones with an intact uterus. Bilateral oophorectomy, age and time since surgery explained about 20% of the variance among post-surgical women. CONCLUSIONS: Menstrual characteristics are strong predictors of women's self-perceived menopausal status. However, additional factors, including symptoms and cultural differences in the meaning of specific bleeding patterns, are also relevant and require further investigation.

Adult↗
PubMed2000

Neuropathology in mice expressing human alpha-synuclein.

The presynaptic protein alpha-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson's disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. alpha-Synuclein accumulates in Lewy bodies and Lewy neurites, and two missense mutations (A53T and A30P) in the alpha-synuclein gene are genetically linked to rare familial forms of Parkinson's disease. Under control of mouse Thy1 regulatory sequences, expression of A53T mutant human alpha-synuclein in the nervous system of transgenic mice generated animals with neuronal alpha-synucleinopathy, features strikingly similar to those observed in human brains with Lewy pathology, neuronal degeneration, and motor defects, despite a lack of transgene expression in dopaminergic neurons of the substantia nigra pars compacta. Neurons in brainstem and motor neurons appeared particularly vulnerable. Motor neuron pathology included axonal damage and denervation of neuromuscular junctions in several muscles examined, suggesting that alpha-synuclein interfered with a universal mechanism of synapse maintenance. Thy1 transgene expression of wild-type human alpha-synuclein resulted in similar pathological changes, thus supporting a central role for mutant and wild-type alpha-synuclein in familial and idiotypic forms of diseases with neuronal alpha-synucleinopathy and Lewy pathology. These mouse models provide a means to address fundamental aspects of alpha-synucleinopathy and test therapeutic strategies.

Animals↗
PubMed2000

Mouse models of alpha-synucleinopathy and Lewy pathology.

The discovery of two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (alphaSN) that are genetically linked to rare familial forms of Parkinson's disease and its accumulation in Lewy bodies and Lewy neurites has triggered several attempts to generate transgenic mice overexpressing human alphaSN. Analogous to a successful strategy for the production of transgenic animal models for Alzheimer's disease we generated mice expressing wildtype and the A53T mutant of human alphaSN in the nervous system under control of mouse Thy1 regulatory sequences. These animals develop neuronal alpha-synucleinopathy, striking features of Lewy pathology, neuronal degeneration and motor defects. Neurons in brainstem and motor neurons appeared particularly vulnerable. Motor neuron pathology included axonal damage and denervation of neuromuscular junctions, suggesting that alphaSN may interfere with a universal mechanism of synapse maintenance. Thy1-transgene expression of wildtype human alphaSN resulted in comparable pathological changes thus supporting a central role for mutant and wildtype alphaSN in familial and idiopathic forms of diseases with neuronal alpha-synucleinopathy and Lewy pathology. The mouse models provide means to address fundamental aspects of alpha-synucleinopathy and to test therapeutic strategies.

Amino Acid Substitution↗
PubMed2000

Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease.

Amyloid beta protein (Abeta) deposition in the brain is a hallmark of Alzheimer's disease (AD). The fibrillar form of Abeta is neurotoxic, although the mechanism of its toxicity is unknown. We showed that conversion of Abeta to the fibrillar form markedly increased binding to specific neuronal membrane proteins, including amyloid precursor protein (APP). Nanomolar concentrations of fibrillar Abeta bound cell-surface holo-APP in cortical neurons. Reduced vulnerability of cultured APP-null neurons to Abeta neurotoxicity suggested that Abeta neurotoxicity involves APP. Thus Abeta toxicity may be mediated by the interaction of fibrillar Abeta with neuronal membrane proteins, notably APP. An Abeta-APP interaction reminiscent of the pathogenic mechanism of prions may thus contribute to neuronal degeneration in AD.

Alzheimer Disease↗
PubMed2000

Transgenic approaches to model Alzheimer's disease.

Two transgenic mouse lines were generated which express human APP751 containing familial Alzheimer's disease (AD) mutations in brain neurons. These mice develop pathological features reminiscent of AD. The degree of pathology depends on both expression levels and specific mutations. In mice with more advanced pathology (APP 23), typical plaques appear at six months which increase with age and are Congo Red positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. A quantitative analysis of degenerative changes by state-of-the-art unbiased stereological methods revealed a significant reduction in neuronal cell bodies of the CA1 field of the hippocampus when compared to controls. This reduction is directly related to plaque load. When subjected to analysis in the Morris water maze, 18 month old APP 23 mice show a significant increase in platform finding latency throughout the entire trial when compared to non-transgenic littermates.

Alzheimer Disease↗
PubMed2000

Liporecycling: a technique for facial rejuvenation and body contouring.

BACKGROUND: Soft tissue augmentation using autologous fat is a standard method in facial rejuvenation and in refinement of body contouring. Different procedures by different authors have been described, each with its specific advantages and disadvantages. OBJECTIVE: The purpose of this article is to describe a method of harvesting, processing, and reinjection of fat that provides new aspects and advantages compared to previously described procedures. METHODS: We report about a new method of autologous fat grafting. Fat is harvested during machine-assisted liposuction in tumescent local anesthesia with microcannulas, processed in a special open manner, and reinjected through a 24-gauge needle for intra- and subdermal augmentation. RESULTS: Short- and long-term results are equivalent to other methods of fat cell grafting. CONCLUSION: Advantages of the described method include easy harvesting during conventional machine-assisted liposuction, the possibility of removing undesired bands of fibrous tissue from the graft, and easy passage through a 24-gauge needle. Thus sub- and intradermal augmentation is possible with the same material and syringe.

Adipose Tissue↗
PubMed2000

Current concepts of fat graft survival: histology of aspirated adipose tissue and review of the literature.

BACKGROUND: Controversy remains about the longevity of correction in autologous fat grafts and its relation to adipocyte survival. Reported long-term fat graft survival rates differ widely, depending on harvesting method, means of reinjection, injection site, and evaluation methods. OBJECTIVE: To demonstrate histologic findings of aspirated adipose tissue and compare the findings to the reports in the literature. METHODS: Review of the literature and the histology of transplanted fat 7 years after subcutaneous implantation and trypan blue staining to determine the vitality of defrosted adipocytes. RESULTS: Fat cells survive aspiration with a suction machine or syringe equally well. Use of a liposuction cannula or 14-gauge needle gives comparable results. Local anesthesia or tumescent local anesthesia is recommended for the donor site, preferably with addition of epinephrine. CONCLUSION: Clinical longevity of correction after autologous fat transfer is determined by the degree of augmentation resulting from the amount of fibrosis induced and the number of viable fat cells. Survival of aspirated fat cell grafts depends mainly on the anatomic site, the mobility and vascularity of the recipient tissue, or underlying causes and diseases, and less on harvesting and reinjection methods.

Adipose Tissue↗
PubMed1999

Expression of metabotropic glutamate receptor subtype mRNA (mGluR1-8) in human cerebellum.

The expression of metabotropic glutamate receptor (mGluR) mRNAs in the human cerebellar neocortex was investigated using in situ hybridization. mGluR1, 3 and 4 mRNAs were most abundant and widely distributed, whereas mGluR2, 5 and 7 mRNA expression was circumscript. mRNAs coding for mGluR1, 3, 4 and 7 were expressed in Purkinje cells. mGluR1 and 4 mRNAs detectable in granule cells and mGluR1, 2, 3, 4 and 7 mRNAs in Golgi cells. mGluR5 mRNA was detectable in putative Bergmann glia as well as mGluR3 mRNA, which was widely expressed in glial cells. mGluR8 mRNA expression was very low in a subset of stellate/basket cells of the molecular layer whereas mGluR6 mRNA was not detectable in the cerebellar cortex.

Aged↗