Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II.

The extracellular matrix glycoprotein tenascin is associated with remodeling events in many embryonic and pathologic tissues. The expression of tenascin has been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was present throughout the tunica media of large and small arteries from normotensive animals; strong staining was only detectable at branching sites. In arteries from hypertensive animals, foci of strong tenascin staining were scattered throughout the tunica media. The expression of tenascin mRNA and protein by rat aortic smooth muscle cells cultured in serum-free medium was induced by the vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular smooth muscle cells attached specifically to a substratum of tenascin, but remained rounded. Thus, increased focal tenascin expression by vascular smooth muscle cells is associated with hypertension, and may mediate angiotensin II-induced changes in vascular structure in hypertension.     

JC virus granule cell neuronopathy and GCN–IRIS under natalizumab treatment

Progressive multifocal leukoencephalopathy is the most common clinical presentation of JC virus (JCV)‐associated central nervous system (CNS) disease and has emerged as a major safety concern in multiple sclerosis patients treated with the monoclonal antibody natalizumab. Here we report clinical, radiological, and histological findings of a case of cerebellar granule cell neuronopathy (GCN), a JCV‐associated CNS disease, so far unreported amongst patients treated with natalizumab. GCN should be considered as a JCV CNS manifestation in patients with newly developed, progressive cerebellar signs under natalizumab treatment, especially in cases where cerebellar atrophy can be visualized by magnetic resonance imaging. Ann Neurol 2013;74:622–626     

Myelopathy in primary Sjögren's syndrome: diagnostic and therapeutic aspects

We report a patient with a myelopathy in primary Sjögren's syndrome, proven by salviary gland biopsy and specific antibodies. Under steroid medication, the patient had a remitting and relapsing clinical course. The severity of clinical symptoms correlated with a transient contrast uptake in spinal magnetic resonance imaging. Under a treatment with azathioprine and prednisone the patient has suffered no relapse within the last 20 months. Although this is only a case report, the combination of azathioprine and prednisone may be a valuable medication in chronic cases of Sjögren's syndrome with neurologic symptoms.     

Schizophrenia, genetic retrenchment, and epidemiologic renaissance. The Sixth Biennial Winter Workshop on Schizophrenia, Badgastein, Austria, January 26-February 1, 1992.

A distinctive feature of these workshops, in addition to those noted in the introductory overview, is the selection of a relatively isolated location for a 1-week period. This, together with a rich and varied program and an ethos of informality, encourages participants to discuss not only the work presented but also their unpublished work and their intuitions based on preliminary data and analyses. Such an interchange is of inestimable value to the schizophrenia research community. In scientific terms, a panel of concluding discussants (Drs Kendell, Torrey, and Waddington) were in some measure of agreement that genetics, particularly molecular genetics, appears to be experiencing a period of retrenchment, while epidemiology is experiencing something of a renaissance. Maternal influenza was a prominent theme, although the data were far from consistent. It was argued by Dr Wessely that risk for schizophrenia putatively attributable to maternal influenza might be 5% to 10% of all cases, indicating a modest effect. Eclectically, Dr Kendell believed the effect to be "real" but slight and fragile, it being sought against large aggregates that almost inevitably result in differing findings from differing countries or from different data bases within a given country. Gender differences were also among the more prominent themes, not just in an epidemiologic context but also in a variety of other studies. This points anew to disturbances in schizophrenia of factors that regulate, or are intimately associated with, sexual dimorphism in brain development. Abnormalities in cerebral asymmetry continue to pervade a variety of research findings and point further to neurodevelopmental anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary care-based physical activity programs: effectiveness in sedentary older patients with osteoarthritis symptoms.

OBJECTIVE: This study examined, in a group of older patients, (a) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and (b) the changes in self-reported physical activity and symptoms in patients with osteoarthritis (OA). METHODS: Healthy, sedentary community-dwelling men and women aged 60 years or more were invited to participate. Following random allocation, the intervention group received individualized physical activity advice at baseline and at 3, 6, and 12 months followup. RESULTS: Of the 299 people who satisfied the study's inclusion criteria, a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline. These patients reported increases in frequency and time of walking and vigorous exercise (all P < 0.001), with no change to OA symptom scores (pain and stiffness), and a small decline in physical functioning was reported at 12 months followup in the control group only (P = 0.027). At the 12-month followup more intervention participants than control participants (P = 0.013) reported a greater intention to exercise. CONCLUSIONS: An offer of primary care-based physical activity advice, with an emphasis on the benefits for general health (rather than "treatment" for OA), will attract individuals with OA symptoms. Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes, intention to exercise did appear to be positively influenced.     

Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System

Urotensin-II (U-II) is a cyclic peptide now described as the most potent vasoconstrictor known. U-II binds to a specific G protein-coupled receptor, formerly the orphan receptor GPR14, now renamed urotensin receptor (UT receptor), and present in mammalian species. Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new potent and specific antagonist of the human UT receptor. ACT-058362 antagonizes the specific binding of (125)I-labeled U-II on natural and recombinant cells carrying the human UT receptor with a high affinity in the low nanomolar range and a competitive mode of antagonism, revealed only with prolonged incubation times. ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. The binding inhibitory potency of ACT-058362 is more than 100-fold less on the rat than on the human UT receptor, which is reflected in a pD'(2) value of 5.2 for inhibiting contraction of isolated rat aortic rings induced by U-II. In functional assays of short incubation times, ACT-058362 behaves as an apparent noncompetitive inhibitor. In vivo, intravenous ACT-058362 prevents the no-reflow phenomenon, which follows renal artery clamping in rats, without decreasing blood pressure and prevents the subsequent development of acute renal failure and the histological consequences of ischemia. In conclusion, the in vivo efficacy of the specific UT receptor antagonist ACT-058362 reveals a role of endogenous U-II in renal ischemia. As a selective renal vasodilator, ACT-058362 may be effective in other renal diseases.     

Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma.

Mouse polyclonal antisera were raised to the Mr 130,000 and Mr 115,000 cell surface glycoproteins, desmocollins, of desmosomes from bovine nasal epithelium. Immunoblotting confirmed that the antisera were specific for the desmocollins. An immunofluorescence study showed that the antisera distinguished between the basal and suprabasal layers of bovine and human epidermis. The antibodies reacted with cultured keratinocytes only after calcium-induced stratification. In epidermis, therefore, there appears to be a difference between the desmocollins of basal and suprabasal cells that may be important in relation to epidermal differentiation. Previous work has shown that polyclonal antisera raised in other animals (guinea pigs and rabbits) against desmocollins, as well as against other desmosomal components, react with all desmosome-containing epithelia. In contrast, an immunofluorescence survey of bovine, rat, and human tissues showed that the present mouse antisera stained only suprabasal skin cells and the arachnoid layer of the meninges, demonstrating that these have common determinants that distinguished their desmocollins from those of all other tissues. The antibodies also stained 11 of 12 meningiomas and, therefore, may be useful as a marker not only for the diagnosis of these tumors but also for investigation of their histogenesis.     

Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing.

Positron emission tomography was used to investigate common versus specific cortical regions for the maintenance of spatial versus phonological information in working memory (WM). Group and single-subject analyses of regional cerebral blood flow during a new 2 x 2 factorial n-back task were performed. Eight subjects had to memorize either phonological features or the location of serially presented syllables. Brain activation during phonological judgment and spatial judgment (0-back) was compared with that during two corresponding WM conditions (2-back). We observed a common network associated with the requirement of maintaining and sequencing items in WM. Seven or more subjects activated (posterior) superior frontal sulcus (pSFS, BA 6/8, global maximum) and/or adjacent gyri, posterior parietal cortex, and precuneus (BA 7). Less consistently, bilateral middle frontal gyrus (BA 9/46) was involved. Bilateral anterior (BA 39/40) and posterior (BA 7) intraparietal sulcus, as well as right pSFS, exhibited dominance for spatial WM. Although underlying stimulus processing pathways for both types of information were different, no region specific for phonological WM was found. Robust activation within the left inferior frontal gyrus (BA 44 and 45) was present, during both phonological WM and phonological judgment. We conclude that the controversial left prefrontal lateralization for verbal WM reflects more general phonological processing strategies, not necessarily required by tasks using letters. We propose a stimulus-independent role for the bilateral pSFS and its vicinity for maintenance and manipulation of different context-dependent information within working memory.