Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders.

Purpose of reviewThe aim of this study was to examine the synaptic biomarker neurogranin in cerebrospinal fluid (CSF) in different stages of HIV infection and in relation to what is known about CSF neurogranin in other neurodegenerative diseases.Recent findingsCSF concentrations of neurogranin are increased in Alzheimer's disease, but not in other neurodegenerative disorder such as Parkinson's disease, frontotemporal dementia, and Lewy body dementia. Adults with HIV-associated dementia have been found to have decreased levels of neurogranin in the frontal cortex, which at least to some extent, may be mediated by the proinflammatory cytokines IL-1β and IL-8. CSF neurogranin concentrations were in the same range for all groups of HIV-infected individuals and uninfected controls. This either indicates that synaptic injury is not an important part of HIV neuropathogenesis or that CSF neurogranin is not sensitive to the type of synaptic impairment present in HIV-associated neurocognitive disorders

Indoleamine 2,3-Dioxygenase in Human Hematopoietic Stem Cell Transplantation

In recent years tryptophan metabolism and its rate limiting enzyme indoleamine 2,3-dioxygenase (IDO) have attracted increasing attention for their potential to modulate immune responses including the regulation of transplantation tolerance. The focus of this review is to discuss some features of IDO activity which particularly relate to hematopoietic stem cell transplantation (HSCT). HSCT invariably involves the establishment of some degree of a donor-derived immune system in the recipient. Thus, the outstanding feature of tolerance in HSCT is that in this type of transplantation it is not rejection, which causes the most severe problems to HSCT recipients, but the reverse, graft-versus-host (GvH) directed immune responses. We will discuss the peculiar role of IDO activity and accelerated tryptophan metabolism at the interface between immune activation and immune suppression and delineate from theoretical and experimental evidence the potential significance of IDO in mediating tolerance in HSCT. Finally, we will examine therapeutic options for exploitation of IDO activity in the generation of allo-antigen-specific tolerance, i.e. avoiding allo-reactivity while maintaining immunocompetence, in HSCT

Osseous hemangioma of the seventh cervical vertebra with osteoid formation mimicking metastasis: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of an osseous hemangioma located in the seventh cervical vertebra with reactive osteoid formation and non-typical findings in the radiological and the histopathological examination, mimicking metastasis of a malignant tumor. To our knowledge, this is the first description of such a case in the literature.</p> <p>Case presentation</p> <p>A 44-year-old otherwise healthy Caucasian German woman presented with a discrete sensorimotor loss of both upper limbs. Radiologically, an osteolysis in the seventh cervical vertebra suggestive of metastasis of a malignant neoplasm was diagnosed. After performing corporectomy and cage implantation of C7 on the patient, the histopathological examination was complicated by marked osteoid formation obscuring the true diagnosis of an osseous hemangioma with reactive osteoid formation.</p> <p>Conclusion</p> <p>Though hemangioma of the bone is a rare tumorous lesion in the cervical spine, it has to be taken into consideration as a reason for neck pain and sensomotoric loss of the upper limbs. Atypical radiological and histopathological presentations may hinder determination of the correct diagnosis. The treatment of such lesions must follow clinical guidelines but may be difficult to define in some cases when the correct diagnosis is not known at the time when therapy starts.</p

Elucidation of novel biosynthetic pathways and metabolite flux patterns by retrobiosynthetic NMR analysis

The labelling patterns of metabolites from experiments with stable isotope-labelled precursors can be determined by NMR spectroscopy. Complex isotopomer mixtures are found when general metabolites such as glucose are used as stable isotope-labelled precursors which are diverted to all branches of intermediary metabolism. The complex results can be interpreted by a pattern recognition approach based on comparison between the labelling patterns of secondary metabolites and primary metabolites such as amino acids and ribonucleosides. The isotope labelling patterns of intermediates in central metabolic pools such as carbohydrate phosphates, dicarboxylic acids, and acetyl CoA can be obtained by biosynthetic retroanalysis. Biosynthetic pathways as well as metabolite flux patterns can be determined from these data. The method is illustrated using the classical mevalonate pathway and the more recently discovered deoxyxylulose pathway of terpenoid biosynthesis as examples. Applications of the retrobiosynthetic method of the biosynthesis of molybdopterin and of riboflavin are also discussed. Stable isotope experiments monitored by NMR spectroscopy have also been shown to be a powerful tool for the elucidation of metabolic flux in microorganisms with unusual lifestyles and in fermentation processe

IDO-Mediated Tryptophan Degradation in the Pathogenesis of Malignant Tumor Disease

Immune escape is a fundamental trait of cancer in which the Th1-type cytokine interferon- γ (IFN-γ) seems to play a key role. Among other tumoricidal biochemical pathways, IFN-γ induces the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in a variety of cells including macrophages, dendritic cells (DCs) and tumor cells. IDO activity has been shown to reflect the extent and the course in a plethora of malignancies including prostate, colorectal, pancreatic, cervical, endometrial, gastric, lung, bladder, ovarian, esophageal and renal cell carcinomas, glioblastomas, mesotheliomas, and melanomas. Furthermore IDO activity during malignant tumor diseases seems to be part of the tumoricidal immune defense strategy, which in the long run is detrimental to the host, when tryptophan deprivation and production of pro-apoptotic tryptophan catabolites counteract T-cell responsiveness