Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.

Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation of antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different RNA degradation products: pocket 1 recognizes guanosine, while pocket 2 coordinates pyrimidine-rich RNA fragments. We found that the endonuclease RNase T2, along with 5' exonucleases PLD3 and PLD4, collaboratively generate the ligands for TLR7.

TLR8 Is a Sensor of RNase T2 Degradation Products.

TLR8 is among the highest-expressed pattern-recognition receptors in the human myeloid compartment, yet its mode of action is poorly understood. TLR8 engages two distinct ligand binding sites to sense RNA degradation products, although it remains unclear how these ligands are formed in cellulo in the context of complex RNA molecule sensing. Here, we identified the lysosomal endoribonuclease RNase T2 as a non-redundant upstream component of TLR8-dependent RNA recognition.

Daily repetitive sensory stimulation of the paretic hand for the treatment of sensorimotor deficits in patients with subacute stroke: RESET, a randomized, sham-controlled trial.

Background: Repetitive sensory stimulation (RSS) adapts the timing of stimulation protocols used in cellular studies to induce synaptic plasticity. In healthy subjects, RSS leads to widespread sensorimotor cortical reorganization paralleled by improved sensorimotor behavior. Here, we investigated whether RSS reduces sensorimotor upper limb impairment in patients with subacute stroke more effectively than conventional therapy.

Which clinical risk factors determine a pathological urodynamic evaluation in patients with multiple sclerosis? an analysis of 100 prospective cases.

Background: Urinary tract symptoms are an underestimated problem in multiple sclerosis (MS).

Objective: Hundred urodynamics of MS patients have been evaluated prospectively.

Design, Setting And Participants: In an inpatient rehabilitation, all persons with MS who also suffered from urinary tract symptoms received a voiding diary, post-void sonography and an urodynamic examination according to International Continence-Society-Standard.

Treatment of dysautonomia in extrapyramidal disorders.

Although extrapyramidal diseases are commonly thought to solely affect the (extrapyramidal) motor system, non-motor symptoms such as behavioural abnormalities, dysautonomia, sleep disturbances and sensory dysfunctions are also frequently observed. Autonomic dysfunction is an important clinical component of extrapyramidal disease, but it is often not formally assessed, and thus frequently misdiagnosed. Symptoms of autonomic dysfunction can impact more on quality of life than motor symptoms.

Initial experience with ropinirole PR (prolonged release).

Ropinirole is a non-ergolinic dopamine agonist, which has been used for over 10 years for the treatment of Parkinson's disease. A new formulation (PR = prolonged release) has been developed, which allows the drug to be released slowly (continuously) so that it only has to be given once daily. Switching from the previous ropinirole immediate release ( ropinirole IR) to the prolonged release (ropinirole PR) formulation at the nearest equivalent total daily dose, can take place overnight and the acceptance and tolerability are good.

Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease.

Background: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons.

Objective: To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations.

Ergoline and non-ergoline derivatives in the treatment of Parkinson's disease.

There are a large variety of dopamine agonists available. Especially de novo patients are treated with dopamine agonists to avoid dyskinesia. Dopamine agonists can be subdivided into ergoline and non-ergoline derivatives.

Restless legs syndrome--new insights into clinical characteristics, pathophysiology, and treatment options.

We summarize recent advances in the clinical definition of restless legs syndrome (RLS), in understanding the basic mechanisms, and the successful treatments of RLS. New diagnostic instruments and severity scales have been developed for better phenotyping of the individual patient. Iron metabolism related components and the dopaminergic system have been extensively investigated in respect to the pathophysiology of RLS.

[Initial status of patients and effects of rehabilitation after stroke--analysis of a patients' and a physicians' questionnaire in three neurological rehabilitation centres with a follow-up after 6 months].

Rehabilitation after stroke has to face specific problems when treating patients with more or less severe disabilities in cognition and communication. Correspondingly, stroke rehabilitation takes a special position within the larger field of rehabilitation, and relatively little is known outside the neurological scientific community about the status of patients at admission, the case mix in the centres and the short- and medium-term effects of rehabilitation. The present study describes in some detail the initial status in unselected samples of consecutive patients (n = 768) from three neurological rehabilitation centres.

Early diagnosis of Parkinson's disease.

In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection.

Breathing and locomotion in patients with Parkinson's disease.

The phase relationship between respiration and locomotion was examined in ten patients with Parkinson's disease (PD, mean age 65, range 51-79 years) and in six healthy subjects (mean age 63, range 58-68 years). Locomotion was measured by means of pressure sensors attached below the subjects' feet. Respiration was measured using respiratory inductive plethysmography.

Workshop I: Parkinson's disease and sleep--results of the group discussion.

The group agreed on the facts that unwanted sleep onset has been observed after non-ergot as well as ergot dopamine agonists, that patients on these drugs need to be warned, that patients who have experienced sleepiness already must not drive a car unless the dosage is lowered and sleepiness has vanished, that a genetic predisposition for narcoleptic cataplexy has to be ruled out, that predictors of so-called sleep attacks need to be explored individually with the help of sleepiness scales and collectively in a careful study, respectively.

Effects of parkinsonian medication on sleep.

Patients suffering from Parkinson's disease (PD) often report about sleep disorders and excessive daytime sleepiness. To some extent, motor disabilities or neural degeneration of sleep modulating structures may be responsible for these effects. Depressive disorders also contribute to the occurrence of insomnia and daytime sleepiness.

[Obstructive sleep apnea syndrome caused by occupational exposure to solvents].

History And Admission Findings: A 52-year-old man working in a chemical laboratory was referred with the possible diagnosis of toxic encephalopathy. For 17 years he had been exposed to high concentrations of perchlorethylene and n-butanol vapours which every day had caused acute symptoms of organic solvent intoxication. Current complaints were autonomic nervous system symptoms, loss of concentration and memory, and fatigue in the second half of the day.

[Sleep and breathing disorders in patients with brain stem lesions].

Most information about the structures within the brain stem that modulate respiration and sleep are gathered from animal experiments. Therefore we examined 10 patients several weeks after an infarction of the brain stem by means of polysomnography and tested the chemosensitive drives of respiration. None of these patients complained about symptoms of sleep disordered breathing.

Amantadine in Parkinson's disease: pro and contra.

After almost 30 years amantadines have reached a definite position in the therapy of Parkinson's disease. Especially in akinetic crisis and in combination with L-Dops amantadine improves the major symptoms of parkinsonism if L-Dopa alone is no more sufficient. Also in cases where L-Dopa treatment is not effective there is reported of a positive reaction on amantadine (Sandyk, 1987).

[Garcin syndrome. Clinical aspects and diagnosis of a rare cranial nerve syndrome with special reference to computerized tomography and nuclear magnetic resonance image findings].

Garcin syndrome is an ipsilateral step-by-step deterioration of all 12 brain cranial nerves, first described in 1927. The underlying cause is usually a sarcoma or carcinoma of the skull base. The pathogenesis of the Garcin syndrome is chiefly determined by the slow localized growth of these tumors, rather than by their histology and primary localisation.

[Migraine and epilepsy in cerebral meningioma].

Even though the pathogenesis of migraine is entirely different from that of epilepsy, pointers towards their combined occurrence are frequent. Besides purely coincidental combinations, a variety of reasons is held responsible for this side-by-side occurrence. So far, cerebral meningiomas have been rarely reported for discussion.

[Results of modifying the standard program of insight and relaxation psychotherapy].

The inventory of methods used in insight and relaxation psychotherapy were taken as a basis for elaborating three additional psychotherapy programmes with the aim of better satisfying the needs of groups with different indications in respect of outpatient psychotherapy. The results obtained with these programmes were tested statistically, using groups of appropriate control subjects, by means of the pre- and post-test data of the MMPI, PAULI, d2 and a five-point self-estimation scale. The trend shown by the results achieved so far confirms that this differentiated therapeutic approach is correct.

[Effect of immunoglobulins on the course of therapy-resistant Klebsiella meningitis].

The case of a 28-year-old patient with refractory Klebsiella meningitis after surgical removal of an angioblastoma in the left cerebellar hemisphere (Lindau's tumour) as described in this article, shows the significance of immunoglobulin therapy in view of the synergistic efficacy increase of antibiotics and immunoglobulin. There were 4 meningitis relapses in a period of 8 months, each time 4 days after discontinuation of antibiotics, the therapy consisting of antibiotics only (penicillin G, gentamycin, lamoxactam, cefotaxim and chloramphenicol). These antibiotics, which were applied in accordance with the antibiogram, were discontinued each 16-32 days after the patient had become afebrile and CSF was free from bacteria.

Cortical bone loss and measurements of the second metacarpal bone: II. Hypodense bone in postwar Guamanian children.

Hand-wrist radiographs from 326 Guamanian children (180 boys and 146 girls) were evaluated for total width, medullary width, length, and combined cortical thickness of the second metacarpal. Bone measurements as well as standing height and weight were compared to similar published data from U.S.

On the possible involvement of ascorbic acid and copper proteins in leukemia: II. Electron spin resonance (ESR) and atomic absorption investigations on erythrocyte ghosts and plasma.

The effect of ascorbic acid on white ghosts of erythrocytes and plasma has been investigated by means of ESR spectroscopy. Since the spectra obtained are identical to the one obtained with leukemic blood it is concluded that the receptor for vitamin C has to be searched for in membrane and plasma as well. Determination of Cu and Fe by means of atomic absorption spectroscopy revealed that both of the metals are also present in the membrane.