Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.     

Percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease using a transluminal endatherectomy catheter (TEC): Initial results and angiographic follow-up

Purpose To evaluate the clinical results of percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease. Methods Rotational atherectomy was performed in 39 patients aged 39–87 years (mean 66.6 years). A total of 71 lesions (43 stenoses and 28 occlusions) were treated in 40 limbs. Additional balloon angioplasty was required in 54% of lesions. Fifteen patients (37.5%) presented in Fontaine stage II, 10 patients (25%) in Fontaine stage III and 15 patients (37.5%) in Fontaine stage IV. Rotational atherectomy at 750 rpm was carried out over a 0.014-inch guidewire with continuous aspiration into a vacuum, bottle. Follow-up angiography and color flow Doppler examinations were performed in 22 patients (23 limbs) after a mean period of 6 months (range 2–14 months) Results There was one primary technical failure. In 36 of 40 lesions there was a good angiographic result with residual stenoses in less than 30%. In 70 lesions treated by rotational atherectomy, however, 54% showed residual stenoses of 30%–50% and these cases required additional balloon angioplasty. The mean ankle-brachial index improved significantly (p<0.001), from 0.49 before the procedure to 1.01 after the procedure. A single distal embolus, related to primary recanalization, occurred and there were two large inguinal hematomas. Cumulative clinical patency after 6 months was 83.8% and cumulative angiographic patency after 6 months was 79.1%. Conclusion Percutaneous rotational atherectomy is a promising approach for the treatment of chronic peripheral vascular disease. Further prospective, randomized studies are necessary to compare percutaneous transluminal angioplasty with this new technical approach.     

Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

Background: It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions.

Methods: Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm2. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils.

Results: Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins.     

The fourth genus in the Orthomyxoviridae: sequence analyses of two Thogoto virus polymerase proteins and comparison with influenza viruses

The tick-borne Thogoto virus (THOV) is the type species of a newly recognized fourth genus, Thogotovirus, in the family Orthomyxoviridae. Because of the distant relationship of THOV with the influenza viruses, determination of its genomic information can potentially be used to identify important domains in influenza virus proteins. We have determined the complete nucleotide sequence of the second longest RNA segment of THOV. The molecule comprises 2212 nucleotides with a single large open reading frame encoding a protein of 710 amino acids, estimated M_r 81 284. The protein shares 77% amino acid similarity with the PB1-like protein of Dhori virus, a related tick-borne virus, and 50–53% with the PB1 polymerase proteins of influenza virus A, B and C. All the motifs characteristic of RNA-dependent polymerases were identified including the SSDD motif common to all RNA-dependant RNA polymerases, indicating that the THOV protein is functionally analogous to the influenza virus PB1 proteins and involved in chain elongation. We also report the corrected sequence of the third longest RNA segment of THOV, encoding a protein which shares 44–47% amino acid similarity with the PA-like polymerase proteins of influenza virus A, B and C. The biological significance of conserved domains in these orthomyxovirid proteins is discussed.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

The Significance of Histology and Morphometry in Predicting Lymph Node Metastases in Patients with Squamous Cell Carcinoma of the Vulva

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the κ coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter—mean nuclear volume—determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.     

Long-lasting modulation of synaptic input to Purkinje neurons by Bergmann glia stimulation in rat brain slices

Information processing in the nervous system is achieved primarily at chemical synapses between neurons. Recent evidence suggests that glia-neuron interactions contribute in multiple ways to the synaptic process. In the present study we used the frequency of spontaneous postsynaptic currents (sPSC) in Purkinje neurons in acute cerebellar brain slices from juvenile rats (13-19 days old) as a measure of synaptic activity. Following 50 depolarizing pulses to an adjacent Bergmann glial cell (50 mV; duration 0.5 s; 1 Hz) the sPSC frequency of the Purkinje neuron was reduced to 65 ± 7 % of control values within 10 min after glial stimulation and remained depressed for at least 40 min. Depolarizing pulses to 0 mV had a comparable effect (70 ± 5 % of control). The frequency of miniature PSCs, as recorded in 300 n m TTX, was not modulated after glial stimulation. Blockade of ionotropic glutamate receptors (iGluRs) with kynurenic acid (1 m m ) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 μ m ) suppressed the reduction of neuronal activity induced by glial depolarization, whereas the glial modulation of synaptic activity was not inhibited by a block of N -methyl- d -aspartate iGluRs, metabotropic glutamate receptors, cannabinoid receptors or GABA_B receptors. Fluorometric measurements of the intraglial Ca²⁺ concentration revealed no glial Ca²⁺ transients during the depolarization series, and glial cell stimulation reduced the neuronal sPSC frequency even after loading the glial cell with 20 m m of the Ca²⁺ chelator BAPTA. Our results indicate a glia-induced long-lasting depression of neuronal communication mediated by iGluRs.     

Frequency of deletion of short arm satellites in acrocentric chromosomes

The frequency of deletion of short arm satellites has been examined in various populations. Four out of 2509 males in psychiatric institutions and prisons had Dps- or Gps- (1·6 per 1000), and five out of 6187 persons in the general population had Dps- or Gps- (0·8 per 1000). The difference is not significant.

The segregation rate of the chromosome with lack of short arm satellite material did not deviate from unity in the few families where such calculations were possible. There was no increase in abortions or non-disjunction in the families with an acrocentric chromosome lacking short arm satellite material.

The study indicates that the frequency of Dps- and Gps- in the population is between 0·5 and 1·0 per 1000 and that the lack of short arm satellite material is without any deleterious effect on phenotype.

     

Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies

Apart from its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions in brain, retina and heart upon ischaemic injury. However, the physiological non-erythroid functions of Epo remain unclear. Here we use a transgenic mouse line (Tg21) constitutively overexpressing human Epo in brain to investigate Epo's impact on ventilation upon hypoxic exposure. Tg21 mice showed improved ventilatory response to severe acute hypoxia and moreover improved ventilatory acclimatization to chronic hypoxic exposure. Furthermore, following bilateral transection of carotid sinus nerves that uncouples the brain from the carotid body, Tg21 mice adapted their ventilation to acute severe hypoxia while chemodenervated wild-type (WT) animals developed a life-threatening apnoea. These results imply that Epo in brain modulates ventilation. Additional analysis revealed that the Epo receptor (EpoR) is expressed in the main brainstem respiratory centres and suggested that Epo stimulates breathing control by alteration of catecholaminergic metabolism in brainstem. The modulation of hypoxic pattern of ventilation after i.v. injection of recombinant human Epo in WT mice and the dense EpoR immunosignal observed in carotid bodies showed that these chemoreceptors are sensitive to plasma levels of Epo. In summary, our results suggest that Epo controls ventilation at the central (brainstem) and peripheral (carotid body) levels. These novel findings are relevant to understanding better respiratory disorders including those occurring at high altitude.