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PubMed1993

Immunocytochemical evidence for the presence of substance P-like peptide in Diphyllobothrium dendriticum.

Substance P immunoreactivity (SP-IR) was detected in the nervous system of the gull-tapeworm Diphyllobothrium dendriticum. The distribution of the SP-IR neurons in the plerocercoid differs from that of other peptidergic and aminergic neurons in the worm. As well as occurring in the ganglionic commissure and along the two main nerve cords, SP-IR neurons are located laterally to the main nerve cords but not dorsally or ventrally. The SP-IR neurons have projections extending to the surface. Bipolar SP-IR neurons with processes to the surface also occur in the tip of the scolex. A sensory function for the SP-IR neurons is suggested.

Animals↗
PubMed1993

Concerning mind.

The nature of the human mind is addressed from a neurological viewpoint. First from reported observations on subjects born blind with congenital cataract, who acquired vision after surgery, the concept of the primacy of somatosensation is developed. Therefrom some principles of the organization of higher sensory functions in the dominant parietal, occipital and temporal lobes are deduced. Sentience is traced to somatosensation. Some characteristics of the mind and of thinking are described. The non-existence of the unconscious is inferred. The question of free will is approached. Using neurological experience it is demonstrated that a good case for operation of a free will is difficult to establish. Positing the absence of a free will may be beneficial in the analysis and management of behavior. Finally the opportunity to study the nature and mechanism of the emotions in clinical neurology is outlined.

Blindness↗
PubMed2003

Aquaporin-mediated fluid regulation in the inner ear.

1. The sensory functions of the inner ear (hearing and balance) critically depend on the precise regulation of two fluid compartments of highly desparate ion composition, i.e., the endolymph and the perilymph. 2. The parameters volume, ion composition, and pH need to be held at homeostasis irrespective of the hydration status of the total organism. 3. Specific cellular water channels, aquaporins, have been shown to be essential for the fluid regulation of several organs, e.g., kidney, lung, and brain. 4. Because of functional similarities of water regulation in the kidney and inner ear this review initially summarizes some aquaporin functions in the kidney and then focuses on 6 out of 11 mammalian aquaporins that are present in the inner ear (AQP1-6). 5. Their potential role in the inner ear fluid control will be discussed on the basis of the respective expression patterns and individual pore properties. 6. Further, a working model is presented of how the endolymphatic sac may contribute to inner ear fluid regulation.

Animals↗
PubMed2004

Effects of Ca2+ -sensitizers in permeabilized cardiac myocytes from donor and end-stage failing human hearts.

During heart failure, alterations occur in contractile protein expression and phosphorylation, which may influence the effects of Ca2+ -sensitizers. To quantify the magnitude of these effects, isometric force was studied in mechanically isolated Triton-skinned myocytes from end-stage failing and non-failing donor hearts under control conditions (pH 7.2; no added inorganic phosphate (Pi)) and under mimicked ischemic conditions (pH 6.5; 10 mM Pi). Two different Ca2+ -sensitizers were used: EMD 53998 (10 microM), which exerts its influence through the actin-myosin interaction, and OR-1896 (10 microM) (the active metabolite of levosimendan), which affects the Ca2+ -sensory function of the thin filaments. The maximal force (Po) measured at saturating Ca2+ concentration and the resting force (Prest) determined in the virtual absence of Ca2+ (pCa 9) did not differ between the failing and non-failing myocytes, but the Ca2+ concentration required to induce the half-maximal force under control conditions was significantly lower in the failing than in the non-failing myocytes (DeltapCa50=0.15). This difference in Ca2+ -sensitivity, however, was abolished during mimicked ischemia. EMD 53998 increased Po and Prest by approximately 15% of Po and greatly enhanced the Ca2+ -sensitivity (DeltapCa50 > 0.25) of force production. OR-1896 did not affect Po and Prest, and provoked a small, but significant Ca2+ -sensitization (DeltapCa50 approximately 0.1). All of these effects were comparable in the donor and failing myocytes, but, in contrast with OR-1896, EMD 53998 considerably diminished the difference in the Ca2+ -sensitivities between the failing and non-failing myocytes. The action of Ca2+ -sensitizers under mimicked ischemic conditions was impaired to a similar degree in the donor and the failing myocytes. Our results indicate that the Ca2+ -activation of the myofibrillar system is altered in end-stage human heart failure. This modulates the effects of Ca2+ -sensitizers both under control and under mimicked ischemic conditions.

Acetamides↗
PubMed2003

Thermal sensation and pain in oral lichen planus and lichenoid reaction.

BACKGROUND: Our previous findings in oral lichen planus (OLP) and lichenoid reactions (LR) raised the question whether the histopathological changes observed in sensory and autonomic innervation produce oral sensory disorders. METHODS: Spontaneous pain was assessed using the Visual Analogue Scale (VAS). Thermal pain thresholds were measured with a contact thermostimulator and mechanical pain thresholds with an electronic algometer. RESULTS: Patients with OLP reported a higher intensity of spontaneous pain than LR patients (P = 0.001). Even erosive LRs were relatively painless. No thermal or mechanical hyperalgesia was detected in oral lesions. Highest separate cold pain threshold was measured in lesions affected by intense Candida growth. CONCLUSION: Together with previous histological findings, the present data suggest that increased somatic innervation and sympathetic denervation do not promote clinical pain sensitivity or hyperalgesia in oral mucosa and that these sensory functions are not affected by OLP and LR. Candida growth may function as secondary irritant modulating the pain responses.

Analysis of Variance↗
PubMed1999

Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury.

Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the initial injury. The caspase family of cysteine proteases regulates the execution of the mammalian apoptotic cell death program. Caspase-3 cleaves several essential downstream substrates involved in the expression of the apoptotic phenotype in vitro, including gelsolin, PAK2, fodrin, nuclear lamins and the inhibitory subunit of DNA fragmentation factor. Caspase-3 activation in vitro can be triggered by upstream events, leading to the release of cytochrome c from the mitochondria and the subsequent transactivation of procaspase-9 by Apaf-1. We report here that these upstream and downstream components of the caspase-3 apoptotic pathway are activated after traumatic spinal cord injury in rats, and occur early in neurons in the injury site and hours to days later in oligodendroglia adjacent to and distant from the injury site. Given these findings, targeting the upstream events of the caspase-3 cascade has therapeutic potential in the treatment of acute traumatic injury to the spinal cord.

Animals↗
PubMed2002

Rapid renewal of auditory hair bundles.

Stereocilia, also known as hair bundles, are mechanosensitive organelles of the sensory hair cells of the inner ear that can detect displacements on a nanometre scale and are supported by a rigid, dense core of actin filaments. Here we show that these actin-filament arrays are continuously remodelled by the addition of actin monomers to the stereocilium tips, and that the entire core of the stereocilium is renewed every 48 hours. This unexpected dynamic feature of stereocilia will help our understanding of how auditory sensory function develops and is maintained.

Acoustic Stimulation↗
PubMed1997

A biosensor that uses ion-channel switches.

Biosensors are molecular sensors that combine a biological recognition mechanism with a physical transduction technique. They provide a new class of inexpensive, portable instrument that permit sophisticated analytical measurements to be undertaken rapidly at decentralized locations. However, the adoption of biosensors for practical applications other than the measurement of blood glucose is currently limited by the expense, insensitivity and inflexibility of the available transduction methods. Here we describe the development of a biosensing technique in which the conductance of a population of molecular ion channels is switched by the recognition event. The approach mimics biological sensory functions and can be used with most types of receptor, including antibodies and nucleotides. The technique is very flexible and even in its simplest form it is sensitive to picomolar concentrations of proteins. The sensor is essentially an impedance element whose dimensions can readily be reduced to become an integral component of a microelectronic circuit. It may be used in a wide range of applications and in complex media, including blood. These uses might include cell typing, the detection of large proteins, viruses, antibodies, DNA, electrolytes, drugs, pesticides and other low-molecular-weight compounds.

Biosensing Techniques↗
PubMed2000

Autoimmune encephalomyelitis ameliorated by AMPA antagonists.

Multiple sclerosis is an immune-mediated disorder of the central nervous system leading to progressive decline of motor and sensory functions and permanent disability. The therapy of multiple sclerosis is only partially effective, despite anti-inflammatory, immunosuppresive and immunomodulatory measures. White matter inflammation and loss of myelin, the pathological hallmarks of multiple sclerosis, are thought to determine disease severity. Experimental autoimmune encephalomyelitis reproduces the features of multiple sclerosis in rodents and in nonhuman primates. The dominant early clinical symptom of acute autoimmune encephalomyelitis is progressive ascending muscle weakness. However, demyelination may not be profound and its extent may not correlate with severity of neurological decline, indicating that targets unrelated to myelin or oligodendrocytes may contribute to the pathogenesis of acute autoimmune encephalomyelitis. Here we report that within the spinal cord in the course of autoimmune encephalomyelitis not only myelin but also neurons are subject to lymphocyte attack and may degenerate. Blockade of glutamate AMPA receptors ameliorated the neurological sequelae of autoimmune encephalomyelitis, indicating the potential for AMPA antagonists in the therapy of multiple sclerosis.

Animals↗
PubMed1988

Bowman lecture. Current concepts of infantile esotropia.

Several forms of esotropia with a different pathophysiology that meet the criterion of an onset early in life must be distinguished from essential infantile esotropia. A hypothesis is presented, according to which a delayed development or a congenital defect of retinal disparity sensitivity (motor fusion) in an otherwise normal infant with immature sensory functions causes esotropia under the influence of various strabismogenic factors. Some of these factors are genetically determined, hence the familial occurrence of essential infantile esotropia. The absence or marked decrease of stereopsis and the asymmetry of optokinetic nystagmus are interpreted as the consequence of ocular misalignment early in life rather than of structural anomalies in the afferent visual pathways of esotropic patients. The therapeutic results after surgery are classified into four groups: subnormal binocular vision, microtropia, small angle eso- or exotropia and large angle residual or consecutive eso- or exodeviations. Analysis of data from 358 operated patients with a documented onset of esotropia prior to the sixth month of life has shown that the probability of obtaining an optimal functional result is increased when surgical alignment is completed before completion of the second year of life. However, surgery after the age of two or even four years of life does not preclude the development of binocular vision on a subnormal or anomalous basis.

Child, Preschool↗
PubMed2007

Mechanisms of disease: involvement of the urothelium in bladder dysfunction.

Although the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.

Humans↗
PubMed1993

Skin potential recordings during cystometry in spinal cord injured patients.

In order to investigate autonomic mechanisms associated with bladder filling and bladder contraction, skin potentials from the hands and the feet of 32 spinal cord injured patients were recorded during cystometry. All had a complete clinical loss of motor and sensory function below the lesion, but in 3 patients, the autonomic lesion was electrophysiologically assessed as incomplete. In patients with a complete autonomic lesion, any rise in intravesical pressure associated with bladder hyperreflexia induced SP responses below the level of the lesion. SP responses were never obtained during bladder filling, as the intravesical pressure remained low. These results tend to confirm those of Guttmann and Whitteridge, but differ in so far as SP responses at the foot were a regular finding in all paraplegic and in most tetraplegic patients. Furthermore, bladder contraction failed to elicit SP responses below the level of the lesion in patients with an incomplete autonomic lesion. This study emphasises the importance of assessing the integrity of the autonomic nervous pathways when dealing with autonomic mechanisms in spinal cord injured patients. The possible relation between SP responses and bladder neck dysfunction is further discussed.

Cystoscopy↗
PubMed2006

Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice.

There is growing evidence implicating the glutamate system in the pathophysiology and treatment of mood and anxiety disorders. Glutamatergic neurotransmission is mediated by several receptor subfamilies including multiple NMDA receptor subunits (NR2A-D). However, little is currently understood about the specific roles of NMDA subunits in the mediation of emotional behavior due to a lack of subunit-specific ligands. In the present study, we employed a mouse gene-targeting approach to examine the role of the NR2A subunit in the mediation of anxiety- and depressive-related behaviors. Results showed that NR2A knockout (KO) mice exhibit decreased anxiety-like behavior relative to wild-type littermates (WT) across multiple tests (elevated plus maze, light-dark exploration test, novel open field). NR2A KO mice showed antidepressant-like profiles in the forced swim test and tail suspension test, as compared to WT controls. Locomotor activity in the nonaversive environments of the home cage or a familiar open field were normal in the NR2A KO mice, as were gross neurological and sensory functions, including prepulse inhibition of startle. Taken together, these data demonstrate a selective and robust reduction in anxiety- and depression-related behavior in NMDA receptor NR2A subunit KO mice. Present results support a role for the NR2A subunit in the modulation of emotional behaviors in rodents and provide insight into the role of glutamate in the pathophysiology and treatment of mood and anxiety disorders.

Analysis of Variance↗
PubMed2000

Intrathecal administration of 4-aminopyridine in chronic spinal injured patients.

STUDY DESIGN: Intrathecal administration of 4-aminopyridine (4-AP) in chronic spinal cord injured (SCI) patients. OBJECTIVE: To determine the safety and effects of intrathecal administration of 4-AP in a small population of chronic SCI patients. SETTING: The post anesthesia care unit of a tertiary care hospital. METHODS: Following animal mode studies to establish dosing safety, six subjects with chronic SCI were examined. In each subject, an intrathecal catheter was placed with the tip as close to the lesion level as possible. 4-AP was infused at 5 microg/h for a period of 4-5 h. Vital signs were recorded and sensory-motor physical examinations and pain questionnaires were administered for 24 h. In two patients, samples of cerebrospinal fluid for analysis were drawn from a second intrathecal catheter. RESULTS: No adverse systemic side effects were noted. One patient showed transient improvement in sensory function; two showed transient increases in spasticity; three showed transient increases in cutaneomuscular reflexes and two showed an apparent small increase in volitional motor control. The concentration of 4-aminopyridine in the cerebrospinal fluid reached a peak of 163 ng/ml at 4 h in one subject and 122 ng/ml at 5 h in the other subject examined. CONCLUSION: Intrathecal administration of 4-aminopyridine at a rate of 5 microg/h does not appear to cause adverse effects and may modify spinal cord function. This route of administration allows local cerebrospinal fluid concentrations equivalent to those produced by maximum tolerable systemic doses, which require 1000 times more drug substance to be delivered to the subject as a whole. Intrathecal administration offers the potential to focus therapeutic effects to the lesion site while minimizing systemic side effects.

4-Aminopyridine↗
PubMed2005

Bowel management in patients with spinal cord injury -- a multicentre study of the German speaking society of paraplegia (DMGP).

STUDY DESIGN: A descriptive, cross-sectional, multicentre design was used. OBJECTIVE: To analyse bowel management in patients with spinal cord injury (SCI) especially the occurrence of unplanned bowel evacuations and duration of planned bowel evacuation. SETTING: In total, 29 rehabilitation facilities for SCI patients in Austria, Germany, the Netherlands and Switzerland, with a total of 837 hospitalized SCI patients. METHOD: Data were collected by nurses within 1 week in November 2001 using a quantitative questionnaire containing 14 questions. For data analysis, a chi (2)-test was used for differences in the outcome of bowel evacuation procedures associated with different interventions. Stepwise multiple logistic regression was used to analyse the relationship between the outcome of bowel management and the interventions as well as intervening factors. RESULTS: More unplanned bowel evacuations were associated with usage of oral laxatives (n=444, P<0.001) as well as bowel evacuation every day (n=270, P<0.05) or every second day (n=368, P<0.05). The outcome of less unplanned bowel evacuations was associated with manual removal of stool combined with digital stimulation (n=35, P<0.05) and spontaneous bowel evacuations (n=104, P<0.001). Short duration of bowel evacuation (<60 min) was associated with manual removal of stool (n=64, P<0.05), the sitting position at defecation (n=494, P<0.001) and low frequency of bowel evacuation (>or=3 days) (n=638, P<0.05). Duration >60 min was associated with the use of oral laxatives (n=444, P<0.001) and complete loss of sensory function (n=349, P<0.05). Stool of hard consistency was associated with the manual removal of stool (n=64, P<0.001), the manual removal of stool in combination with digital stimulation (n=53, P<0.001) and the sitting position at defecation (n=494, P<0.05). Stool of soft consistency (n=341) was associated with the complete motor lesion (n=443, P<0.05). CONCLUSION: Manual removal of stool was combined with low risk of unplanned bowel evacuations and short duration of evacuation time. These results are useful to improve the outcomes of bowel management in SCI patients.

Administration, Oral↗
PubMed2007

Assembly domains in TRP channels.

The large family of mammalian TRP (transient receptor potential) ion channels encompasses diverse sensory functions. TRP proteins consist of six transmembrane domains, with a pore-loop motif between the fifth and sixth domains and cytosolic N- and C-termini. The intracellular strands not only interact with various proteins and lipids, but also include essential multimerization regions. This review summarizes the current knowledge of the intrinsic assembly domains that assure tetrameric TRP channel formation.

Amino Acid Motifs↗
PubMed1984

Masked and unmasked pure-tone thresholds of infants and adults: development of auditory frequency selectivity and sensitivity.

Detection thresholds for pure tones (1000 Hz and 4000 Hz) in noise and in quiet were estimated for infants at 6 months and 12 months of age and for adults. A visually reinforced head-turn procedure under control of a PDP-11/03 minicomputer was used. An adaptive protocol with a 5-dB step size was employed for the threshold estimates. Infant thresholds were poorer than adult thresholds in each condition. In noise, infant-adult differences were 8 dB (6-month-old infants) and 6 dB (12-month-old infants) at each frequency. In quiet, infant-adult differences were 14 dB (6-month-old infants) and 12 dB (12-month-old infants) at 1000 Hz but were only 7 dB (6-month-old infants) and 5 dB (12-month-old infants) at 4000 Hz. The masking data suggest that infants are at only a slight disadvantage in detecting a target in a background of noise and are consistent with a frequency selectivity mechanism that is proportional to that of adults. The detection-in-quiet data, with greater correspondence among the groups at 4000 Hz than at 1000 Hz, support the notion that hearing sensitivity varies with frequency in a different way in infants than in adults. Data on task performance reveal significant age effects, and the possibility that such effects have biased the observed differences in the estimates of sensory function among the groups is considered.

Acoustic Impedance Tests↗