Quantitation of SF in the urine and tumor deserves further study as a possible marker of urothelial malignancy.

Background: Despite recent advances in therapy that have improved the overall disease course in multiple sclerosis (MS), the prognosis at the outset remains unpredictable. Objectives: To investigate whether cerebrospinal fluid (CSF) osteopontin levels correlate with disability or active disease in MS and to determine whether elevated CSF osteopontin levels are only seen in MS. Design: Cerebrospinal fluid osteopontin was assayed using enzyme-linked immunosorbent assay in duplicate by an observer blinded to the clinical status of the sample. Cerebrospinal fluid samples were not obtained from any patient who had received high-dose corticosteroid therapy in the month before analysis. Setting: Medical research institute. Patients: Thirty patients (18 women and 12 men; age range, 24-71 years) with clinically definite MS and 36 patients (22 women and 14 men; age range, 20-71 years) with other neurological diseases (ONDs) or nonneurological illnesses were included in the study. Main Outcome Measures: Disease activity for patients with MS was based on observations in the year preceding the study, including the number of relapses, the change in disability according to the Expanded Disability Status Scale, and increased T2-weighted or gadolinium-enhancing lesions on brain magnetic resonance imaging. Results: Higher CSF osteopontin levels were seen in patients with MS having active disease and in patients with ONDs that are actively deteriorating or inflammatory. However, CSF osteopontin levels in patients with MS did not correlate with disability status. Conclusions: Cerebrospinal fluid osteopontin levels do not correlate with disability in MS but tend to be higher in patients with active disease. Elevated CSF osteopontin levels are not a specific marker for MS, as they are found in patients with ONDs and nonneurological illnesses. In ONDs, the highest CSF osteopontin levels are seen in patients with rapidly progressive neurological dysfunction or widespread inflammation of the central nervous system.

No abstract

In an amyotrophic lateral sclerosis (ALS) patient who also had an IgA gammopathy, autopsy studies identified the IgA in the surviving motor neurons. Further, the IgA bound the surface of isolated bovine motor neurons and inhibited neuronal proliferation in culture. To determine the pathologic basis of this IgA interaction with motor neurons, a neuroblastoma cDNA library was generated and screened with the IgA monoclonal antibody. Reactive clones were identified as flavin adenine dinucleotide (FAD) synthetase. To extend this finding to ALS in general, quantitative RT-PCRs were performed on blood samples from 26 ALS and 30 control blood samples to determine mRNA expression levels of FAD synthetase and other electron transport chain proteins, specifically riboflavin kinase (RFK), cytochrome C1 (CYC1), and succinate dehydrogenase complex subunit B (SDHB). All expression levels were measured against a control enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Expression levels for a non-respiratory chain protein (beta-actin) were also measured. We found that FAD synthetase expression levels were decreased in ALS samples compared to expression levels in controls (P = 0.0151). Expression levels for RFK, CYC1, and SDHB were also significantly decreased in the ALS group (P = 0.0025, P = 0.0002, and P < 0.0001, respectively). As control, expression levels for beta-actin did not show a significant difference between ALS and control groups (P = 0.2118). Our data show that a reduction in electron transport proteins, namely FAD synthetase, RFK, CYC1, and SDHB, is seen in patients with ALS. It is possible that this may have an effect on oxygen-dependent metabolic pathways. Human motor neurons may be particularly susceptible to injury if there is sub-optimal oxidative metabolism.

We have previously demonstrated that a plasma natriuretic factor is present in Alzheimer’s disease (AD), but not in multi-infarct dementia (MID) or normal controls (C). We postulated that the natriuretic factor might induce the increased cytosolic calcium reported in AD by inhibiting the sodium-calcium antiporter, thereby activating the apoptotic pathway. To test for a factor in AD plasma that induces apoptosis, we exposed nonconfluent cultured LLC-PK1 cells to plasma from AD, MID, and C for 2 h and performed a terminal transferase-dUTP-nick-end labeling (TUNEL) assay. The plasma from AD increased apoptosis nearly fourfold compared with MID and C. The effect was dose dependent and the peak effect was attained after a 2-h exposure. Additionally, apoptotic morphology was detected by electron microscopy, and internucleosomal DNA cleavage was found. We inhibited apoptosis by removing calcium from the medium, inhibiting protein synthesis with cycloheximide, alternately boiling or freezing and thawing the plasma, and digesting a partially purified fraction with trypsin. Heating AD plasma to 56°C did not deactivate the apoptotic factor. These results demonstrate the presence of an apoptotic factor in the plasma of patients with AD.