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Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system--I. Forebrain.

Nerve growth factor receptor, as recognized by the monoclonal antibody 192-IgG, was localized to multiple regions of the adult rat forebrain. Immunoreactive cell bodies and fibers were seen in both sensory and motor regions which are known to contain cholinergic and non-cholinergic neurons. Specifically, nerve growth factor receptor immunoreactivity was present in cells lining the olfactory ventricle, rostral portion of the lateral ventricle, in basal forebrain nuclei, caudate putamen, globus pallidus, zona incerta and hypothalamus. Immunoreactive cells which were situated subpially along the olfactory ventricle and anterior portions of the lateral ventricle, and in the arcuate nucleus resembled neuroglia but could not definitively identified at the light microscopic level. Animals pretreated with intracerebroventricular colchicine displayed significantly increased nerve growth factor receptor immunoreactivity in all previously positive neurons and particularly in the medial preoptic area and ventral premammillary nucleus of the hypothalamus. In such animals, receptor immunoreactivity also appeared in previously non-immunoreactive cells of the hippocampal CA3 region and polymorph layer of the dentate gyrus as well as in the mitral cell layer of the olfactory bulb. Nerve growth factor receptor-immunoreactive fibers and varicosities were seen in the olfactory bulb, piriform cortex, neocortex, amygdala, hippocampus, thalamus, olivary pretectal nucleus and hypothalamus. In most regions, such fiber-like immunoreactive structures likely represented axon terminals, although in some areas, neuroglial or extracellular localizations could not be excluded. In this context, diffuse, non-fibrillar receptor immunoreactivity occurred in the lateral habenular nucleus and medial terminal nucleus of the accessory optic tract. Furthermore, intense nerve growth factor receptor immunoreactivity occurred along certain regions of the pial surface on the ventral surface of the brain. The distribution of nerve growth factor receptor-immunoreactive cell bodies and fibers in multiple sensory and motor nuclei suggests wide-spread influences of nerve growth factor throughout the adult rat forebrain. There is a high degree of overlap with regions containing choline acetyltransferase immunoreactivity. However, significant disparities exist suggesting that certain nerve growth factor receptor-containing non-cholinergic neurons of the rat forebrain may also be affected by nerve growth factor.

Animals↗

[Relation between the size and eccentricity of the receptive fields of lateral suprasylvian neurons].

A linear interrelationship exists between the size of the receptive field in the middle suprasylvian area and the distance of the field center (up to 30 degrees) from the glance fixation point. The slope of the regression line describing this interrelationship was shown to be different for the receptive fields situated along either vertical or horizontal meridians. The factor of magnification of the visual system's previous level seems to underlie the dependence of changes in the receptive fields size on the eccentricity.

Animals↗

cAMP-synthesis in a medullary thyroid carcinoma cell line: response to adrenergic agents and prostaglandines.

Calcitonin secretion by C-cells is mediated through intracellular 3'5'-cyclic adenosine monophosphate (cAMP) and calcium signaling. Calcitonin release stimulation tests may take advantage of both signaling cascades in screening for medullary thyroid carcinomas (MTC). To elucidate the regulation of the adenylyl cyclase system we have determined cAMP levels of a calcitonin-expressing MTC cell line (RG) after exposure to adrenergic agents and prostaglandines. In early passages (20-30) cAMP concentrations were significantly elevated in RG cells after exposure to beta-adrenergic agents and prostaglandines E1 and E2. In advanced passages (60-80) the beta-adrenergic response was no longer detectable and adrenergic receptors were uncoupled from the adenylyl cyclase complex; while the effect of prostaglandines E1 and E2 remained unaffected. Preincubation with dexamethasone, in a process requiring protein new synthesis, re-established the adrenergic response in later passages, indicating that RG cells dedifferentiated in culture over time. Our in vitro findings suggest that MTC cell dedifferentiation may be accompanied by adrenergic receptor-uncoupling from the adenylate cyclase system and that this process may be reversed by dexamethasone incubation.

Adenylyl Cyclases↗

Neural precursor differentiation following transplantation into neocortex is dependent on intrinsic developmental state and receptor competence.

Reconstruction of neocortical circuitry by transplantation of neural precursors, or by manipulation of endogenous precursors, may depend critically upon both local microenvironmental control signals and the intrinsic competence of populations of precursors to appropriately respond to external molecular controls. Dependence on the developmental state of donor or endogenous precursor cells in achieving appropriate differentiation, integration, and connectivity is not clearly understood. Recent studies have demonstrated the ability to generate expandable, often clonal neural precursors at various stages of development. Transplantation of a variety of these precursors suggests that precursor differentiation and integration within the central nervous system (CNS) may depend directly on the level of cellular maturation, with less differentiated, earlier stage precursors offering more flexible but less efficient integration and more differentiated, later stage precursors offering more efficient differentiation to specific phenotypes. To further investigate this hypothesis within neocortex, we used the relatively immature HiB5 multipotent neural precursor cell line derived from embryonic day 16 hippocampus, which is less mature than precursor types that have demonstrated neuronal differentiation in adult neocortex. HiB5 cells labeled fluorescently, radioactively, and genetically were transplanted into murine neocortex under three different conditions expected to offer varying levels of instructive and permissive microenvironmental signals: (1) the developing cortex in utero; (2) regions of adult neocortex undergoing targeted pyramidal neuronal degeneration in which developmental signals are upregulated and in which later stage precursors and immature neurons undergo directed pyramidal neuron differentiation; or (3) the intact adult neocortex. Differentiation and integration of transplanted cells were examined histologically and immunocytochemically by morphology and using neuronal- and glial-specific markers. We found that these precursors underwent differentiation toward cortical neuron phenotypes with characteristic morphologies when transplanted in utero, but failed to do so under either of the adult conditions. HiB5 precursors demonstrated highly immature characteristics in vitro, consistently expressing neuroepithelial but not glial or neuronal markers. Under all conditions, donor cells survived and migrated 1-2 mm from the injection track 2 to 4 weeks after transplantation. HiB5 neural precursors transplanted into the developing cortex of embryonic mice in utero migrated within the cortex, integrated well into the host parenchyma, and differentiated toward morphologically diverse, neuronal phenotypes. HiB5 cells transplanted into the intact cortex of adult mice survived, but did not show neuronal differentiation. In contrast to slightly later stage neural precursors and embryonic neurons used in previous transplantation studies, the HiB5 cells also failed to undergo neuronal differentiation after transplantation into regions undergoing induced apoptotic neuronal degeneration in adult cortex. These results suggested that these early hippocampal-derived precursors might not be fully competent to respond to later stage differentiation and/or survival signals important in neocortex and known to be upregulated in regions undergoing targeted neuronal apoptosis, including the TrkB neurotrophin receptor ligands BDNF and NT-4/5. We investigated this hypothesis and found that undifferentiated HiB5 cells lack catalytic trkB neurotrophin receptors at the mRNA and protein levels, while confirming that they express trkC receptors under the same conditions. Taken together, these findings support a progressive sequence of neural precursor differentiation and a spectrum of competence by precursors to respond to instructive microenvironmental signals. (ABSTRACT TRUNCATED)

Animals↗

Primary malignant lymphoma of the uterine cervix: is radiotherapy the best therapeutic choice for stage IE?

The present report describes a 27-year-old woman diagnosed with Ann Arbor stage IE primary malignant lymphoma of the cervix. Radiation therapy was instituted as conventionally advocated at this early stage of the disease. Despite adequate local tumor response, central nervous system metastasis occurred a few months later. She succumbed to her condition 7 months after initial diagnosis. As occult distant foci may not be amenable to detection by available imaging techniques at the time of initial work-up, combination chemotherapy alone or in conjunction with radiation therapy may be the most appropriate first line of therapy in patients with stage IE primary malignant lymphoma of the cervix.

Adult↗

The trochlear motoneurons of lampreys (Lampetra fluviatilis): location, morphology and numbers as revealed with horseradish peroxidase.

The cells of origin of the trochlear nerve of Lampetra fluviatilis have been labelled with horseradish peroxidase (HRP) in order to compare the location and morphology of trochlear motoneurons with those of other vertebrates and to gain insight into the phylogenetic changes of the trochlear system. About 126 bipolar and tripolar trochlear motoneuron perikarya are found in a dorsal tegmental position close to the trochlear root. Only approximately 16% of the labelled cells are on the ipsilateral side of the brain, i.e. they lie predominantly contralateral as in gnathostome vertebrates. Dorsally directed dendrites reach the area of lateral-line and retinofugal fibres, and may establish functional contacts. In addition, each motoneuron has a ventral dendrite that extends towards the fasciculus longitudinalis medialis and to the ventral tegmentum. The dendrites branch close to the oculomotor root. Lampreys show a low muscle fibre to motoneuron ratio (4.5:1), i.e., they resemble amniotic vertebrates more than other anamniotic vertebrates. These data demonstrate both closer resemblance and larger differences of cyclostome and gnathostome trochlear motoneurons than previously suggested.

Animals↗

[Rediscovery of thalidomide. Successful treatment of discoid lupus erythematosus].

Thalidomide, an oral drug introduced in Germany in 1953 as a mild sedative, was withdrawn from the world market when its teratogenic effect was discovered some years later. It has since been selectively reintroduced to treat a variety of autoimmune or inflammatory diseases such as erythema nodosum leprosum, prurigo nodularis, graft-versus-host disease, and discoid lupus erythematosus (DLE). We report on three patients with long-standing, severe DLE showing no response to systemic first-, second- and third-line treatments. After four weeks of therapy with thalidomide the skin lesions had improved dramatically and after three to six months all three patients responded with an almost complete remission. The side effects of thalidomide, especially somnolence and paresthesias, were minor and well tolerated by the patients. Our data confirm that thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, despite the risks of teratogenicity and polyneuropathy.

Adult↗

Enhanced production of monomeric interferon-beta by CHO cells through the control of culture conditions.

The enhancement of recombinant protein expression of a transfected cell line is essential for the development of an efficient large-scale bioprocess. The effect of various media additives and temperature conditions were studied in an attempt to optimize protein production, stability, and protein glycosylation from a Chinese hamster ovary (CHO) cell line producing human beta-interferon (Hu-beta-IFN). We observed a decrease in the ELISA response of the glycoprotein in the later stages of batch cultures, which was attributed to molecular aggregation. Cells were subjected to various concentrations of glycerol, dimethyl sulfoxide (DMSO), and sodium butyrate (NaBu) in a variety of culture systems and conditions. The addition of both NaBu and DMSO resulted in higher specific productivities but reduced growth rates that resulted in a net reduction of interferon produced. Glycerol appeared to stabilize the secreted beta-IFN, resulting in reduced aggregation, despite a decrease in cell growth rate. Glycosylation analysis of isolated beta-IFN showed a time-dependent decrease in sialylation in batch culture that was ameliorated by the presence of glycerol. Low-temperature conditions (30 degrees C) had the greatest effect on productivity with a significant increase in beta-IFN titer as well as a reduction in the degree of molecular aggregation.

Animals↗

Long term inhibition by estradiol or progesterone of melatonin secretion after administration of a mammary carcinogen, the dimethyl benz(a)anthracene, in Sprague-Dawley female rat; inhibitory effect of Melatonin on mammary carcinogenesis.

A single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA) has been shown to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances, including attenuation of the preovulatory Luteinizing Hormone surge and Gonadotropin-Releasing Hormone release and amplification of the preovulatory 17beta-Estradiol (E2) surge. In this study, we examined the hypothesis that a single administration of DMBA increases the E2 and Progesterone inhibition of the spontaneous and Isoproterenol-induced Melatonin (MT) secretion from the pineal gland, during the latency phase. Also, the incidence of mammary tumors, as well as the possible preventive effect of various doses of Melatonin, were recorded up to 6 months after daily administration. For all studies, Sprague-Dawley rats, 55-60 days of age, received, on the Estrous day of the Estrous cycle, a single dose of 15 mg DMBA delivered by intragastric intubation. For the study on ovarian steroids, they were ovariectomized 5 days later and then sacrificed by decapitation at 10 a.m., one month later. Pineal glands were removed and placed in perifusion chambers containing Hanks 199 medium. The medium was saturated with O2/CO2 (95%/5%) and its pH was 7.4. Ten independent chambers were immersed in a water bath at 37 degrees C. Each pineal gland received medium (flow rate: 0.16 ml/min) through a system of input lines. The fractions were collected every 10 min, and immediately frozen at -20 degrees C until Melatonin RIA. Experiments were repeated to obtain up to five experimental points for each treatment. E2 (10(-11)-10(-9) M) and Progesterone (10(-9)-10(-7) M) were applied during the entire perifusion period (7 h). Isoproterenol (10(-6) M) was applied for 20 min after 2.5 h in perifusion. Melatonin concentrations and Areas Under the Curves were compared using two-factor ANOVA as well as parametric or nonparametric two-sample methods after testing sample normality. For the study on the possible preventive effect of Melatonin, they were daily treated, by the intragastric route, with increasing doses of Melatonin for 6 months. The percentage of female rats having at least one mammary carcinoma were compared using the Fischer exact t-test. During the latency phase, in vehicle-treated rats, E2 and Progesterone treatments lead an almost significant inhibition of the Isoproterenol-induced stimulation of Melatonin secretion. In DMBA-treated rats, E2 treatment leads to a complete blunting of the Isoproterenol-induced stimulation of Melatonin and Progesterone treatment leads to a cyclic inhibition of the Isoproterenol-induced Melatonin secretion. During the promotion phase, there was a dose-dependent inhibitory effect (up to 65% inhibition) of the daily administration of Melatonin, on mammary tumors occurrence. In conclusion, the long term inhibition of DMBA upon Melatonin secretion from the pineal gland might accelerate the promotion of mammary tumors induced by the mammary carcinogen. Inversely, the daily administration of Melatonin for 6 months induces a long lasting protective effect against the formation of mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Quality assurance growing pains: a state perspective on implementing an organizational-wide quality system in environmental laboratories.

To implement an effective and efficient quality system in a network of established environmental testing laboratories requires a committed long-term effort that is potentially fraught with multiple obstacles. This presentation discusses one state's ongoing efforts at implementing such a system. First is the need to convince management of the rationale for a quality systems-based approach versus the traditional QA/QC program. Once development of a quality system has been sanctioned, a team-based approach utilizing project planning tools is a good way to approach the effort. Resources are assigned to the development of key quality system components, and generally a phased-deployment or roll-out works best. Once implementation is underway, assuring operational utilization and compliance with the quality system are vital steps in the process. Important to successful implementation is ongoing assessment and refinement of the quality system. Fundamental and key elements of the laboratory quality system are numerous and need to work in concert with each other. Quality system elements to be discussed in the presentation range from management and QA roles and functions to the typical documentation of laboratory policies and procedures. Numerous QA assessment tools and other vital quality system practices that play an important role in making a complete quality system are addressed. In addition, efforts must be undertaken to integrate the laboratory quality system with other management systems within the organization. The bottom line is that all environmental laboratories need a quality system more now than ever. Data users need it. Customers' expectations for data quality are high. USEPA policy and/or programs call for it. Additionally, good quality systems can benefit the organization in multiple ways and help avoid the "pay-me-now or pay-me-later" syndrome. In conclusion, all environmental testing laboratories (i.e., academic, private, commercial and especially governmental) need to invest in and implement a quality system based on a recognized standard (e.g., NELAC, ISO 17025, ANSI/ASQC E-4). The author recommends pursuing NELAP laboratory accreditation with a NELAP-recognized accrediting authority.

Environmental Monitoring↗

Microsyringe-based deposition of two-dimensional and three-dimensional polymer scaffolds with a well-defined geometry for application to tissue engineering.

A technique for controlled deposition of biomaterials and cells in specific and complex architectures is described. It employs a highly accurate three-dimensional micropositioning system with a pressure-controlled syringe to deposit biopolymer structures with a lateral resolution of 5 microm. The pressure-activated microsyringe is equipped with a fine-bore exit needle and a wide variety of two- and three-dimensional patterns on which cells to be deposited can adhere. The system has been characterized in terms of deposition parameters such as applied pressure, motor speed, line width and height, and polymer viscosity, and a fluid dynamic model simulating the deposition process has been developed, allowing an accurate prediction of the topological characteristics of the polymer structures.

Biocompatible Materials↗

Optimal injection points for the neuromuscular blockade of forearm flexor muscles: a cadaveric study.

Botulinum toxin acts at neuromuscular junctions close to muscle motor points and is used to help manage spastic upper-limb deformities. To develop a system allowing clinicians to identify optimal injection sites by an easily reproducible technique, forearm flexor muscles were dissected in 20 formalin-preserved human limbs. Motor points for flexor carpi ulnaris, flexor carpi radialis, flexor digitorum superficialis and pronator teres were (1) identified, (2) related to a reference grid based on lines (proximal, distal, lateral, medial and diagonals) drawn between forearm anatomical landmarks, and (3) defined in terms of their percentage distances along the established grid lines.

Anti-Dyskinesia Agents↗

Acinar flow irreversibility caused by perturbations in reversible alveolar wall motion.

Mixing associated with "stretch-and-fold" convective flow patterns has recently been demonstrated to play a potentially important role in aerosol transport and deposition deep in the lung (J. P. Butler and A. Tsuda. J. Appl. Physiol. 83: 800-809, 1997), but the origin of this potent mechanism is not well characterized. In this study we hypothesized that even a small degree of asynchrony in otherwise reversible alveolar wall motion is sufficient to cause flow irreversibility and stretch-and-fold convective mixing. We tested this hypothesis using a large-scale acinar model consisting of a T-shaped junction of three short, straight, square ducts. The model was filled with silicone oil, and alveolar wall motion was simulated by pistons in two of the ducts. The pistons were driven to generate a low-Reynolds-number cyclic flow with a small amount of asynchrony in boundary motion adjusted to match the degree of geometric (as distinguished from pressure-volume) hysteresis found in rabbit lungs (H. Miki, J. P. Butler, R. A. Rogers, and J. Lehr. J. Appl. Physiol. 75: 1630-1636, 1993). Tracer dye was introduced into the system, and its motion was monitored. The results showed that even a slight asynchrony in boundary motion leads to flow irreversibility with complicated swirling tracer patterns. Importantly, the kinematic irreversibility resulted in stretching of the tracer with narrowing of the separation between adjacent tracer lines, and when the cycle-by-cycle narrowing of lateral distance reached the slowly growing diffusion distance of the tracer, mixing abruptly took place. This coupling of evolving convective flow patterns with diffusion is the essence of the stretch-and-fold mechanism. We conclude that even a small degree of boundary asynchrony can give rise to stretch-and-fold convective mixing, thereby leading to transport and deposition of fine and ultrafine aerosol particles deep in the lung.

Aerosols↗

[Ontogenetic divergence in the phytoparasitic nematodes Macroposthonia nainitalensis and M. tenuiannulata (Criconematidae, Tylenchia)].

Promorphogenesis, egg cleavage, and gastrulation proceed in Macroposthonia nainitalensis similarly to other phytonematodes of the subclass Tylenchia. Before the onset of gastrulation, the greatest similarity was observed in a descendant of the micromere 2b, which separates macromeres of the third division. Deviations from the general line of development started in this species during embryonal organogenesis with the formation of an external epithelium with a special rough surface layer, which was absent in the embryos of other phytonematodes. In addition, during this period of acceleration, the digestive system developed, while peristaltic changes in body shape appeared at the tadpole stage. Later, somatic muscle development was enhanced in the first instar larvae of M. nainitalensis, while in the second instar larvae of Macroposthonia spp. somatic muscle cells were located at an acute angle to the longitudinal body axis. In addition, denticles--microchaetae appeared in the second to fifth instar larvae of these nematodes. All these features, which have not been observed in other phytonematodes of the subclass Tylenchia, help the peristaltic crawling of Macroposthonia spp. In contrast to other Tylenchia, the musculocutaneous sac did not develop in Macroposthonia spp. However, there are similarities in the development of the digestive and genital systems.

Animals↗

Interobserver and intraobserver reliability of Lenke's new scoliosis classification system.

STUDY DESIGN: The assignment of idiopathic scoliosis curves to the curve types,1-6 to the lumbar spine modifier (A, B, or C), and to the sagittal thoracic modifier (-, N, +), as recently described by Lenke et al, was evaluated by five observers on two occasions. OBJECTIVE: To determine the intraobserver and interobserver reliabilities of Lenke's new system for classifying idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Lenke et al recently introduced a new system for classifying idiopathic scoliosis. METHODS: Preoperative standing long cassette coronal and sagittal radiographs as well as side-bending radiographs of 51 consecutive patients who underwent surgery for idiopathic scoliosis were labeled with the Cobb angles for all the curves. The center sacral vertical line was marked as the bisection of the proximal sacrum perpendicular to the true horizontal line. Five observers independently assigned a curve type, a lumbar spine modifier, and a sagittal thoracic modifier to each curve following the guidelines as described by Lenke et al. Assignment of the curves was repeated 3 weeks later, with the curves presented in a different order. Kappa coefficients were used to determine the interobserver and intraobserver reliabilities. RESULTS: All five reviewers agreed on the overall classification in 21 (41%) of the 51 patients. A mean kappa value of 0.62 was determined for interobserver reliability, and a mean kappa of 0.73 for intraobserver reliability. Determination of an upper thoracic curve as structural or nonstructural and assignment of a lumbar spine modifier were the main reasons for disagreement. CONCLUSIONS: Lenke's new classification system is more reliable than the older King classification, but proper classification of high thoracic and lumbar curves seems to be difficult.

Humans↗

[Atypical heparin-induced thrombocytopenia (HIT)--"heparin allergy" with thrombocytosis].

We report a truck driver with severe soft tissue contusion of both legs who developed atypical heparin-induced thrombocytopenia (HIT) after a thrombosis prophylaxis with unfractionated heparin; despite a thrombosis the patient showed a systemic allergic reaction to heparin in combination with elevation of thrombocytes and positive heparin-dependent antibodies. Six days after the initial trauma deep vein thrombosis of the left lower leg was diagnosed and fasciotomy was performed, preventing an imminent compartment syndrome. Another 5 days later the patient developed exanthema of the trunk and upper extremities and urticaria on his face, as well as severe headache. His platelet count increased from 134,000/microliter to 258,000/microliter. After exclusion of other causes for these symptoms, a reaction to heparin-dependent antibodies (heparin-platelet-factor 4 complex) was demonstrated 2 days later. Thrombosis prophylaxis was changed to hirudin (Refludan) and elevation of thrombocytes to 445,000/microliter was noted. Shortly after rinsing of an intravenous line with less than 50 IE unfractionated heparin at day 36 after trauma the patient developed an anaphylactic shock, which could be managed with cortisone. We suggest that in HIT the thrombocytopenia may represent only one form of an allergic reaction to heparin. The cause of the thromboembolic event is an antigen-antibody reaction to heparin taking place on the surface of the thrombocyte. This is similar in all forms of systemic reaction to heparin application, even though the symptoms may vary. As thrombocytopenia may not be the main symptom of a heparin-induced antibody reaction--in our hospital only 5 of 10 patients with HIT--the disease should rather be named "heparin allergy". We suggest a new classification of different pattern of heparin allergy types I-IV. The new types I and II are similar to HIT types I and II. Type III is the reaction of antibodies without decrease of thrombocytes, and type IV the reaction of antibodies associated with systemic allergic symptoms.

Anaphylaxis↗

[Semi-supervised exercise using a step machine at home after myocardial infarction].

Home exercise programs for patients with myocardial infarction effectively improve their ability to exercise as well as quality of life. However, there are no efficient methods for monitoring the patient's clinical status or conveying the physician's instructions to the home setting. To resolve these problems, we developed a computer-based, automated, telemetry system comprised of central and peripheral computers and telephone line. Five myocardial infarction patients were evaluated for peak oxygen uptake (peak VO2) and anaerobic threshold (AT) before hospital discharge. At home, the patients performed 10-min exercise using a step machine. Patient data including blood pressure, pulse rate, and electrocardiogram before and after exercise were stored in the peripheral computer, and the central computer automatically retrieved the data through the phone line. If the current heart rate was less than the heart rate at AT, extreme changes in blood pressure were noted or dangerous arrhythmias appeared, appropriate instructions were indicated on the display of the peripheral computer. Following these instructions, the patients continued home exercise programs for 6 months. Peak VO2 and AT increased significantly in all patients (peak VO2: baseline 24 +/- 3.3 ml/kg/min, 6 months later 33.3 +/- 3.7 ml/kg/min, p < 0.01, AT: baseline 15.2 +/- 2.7 ml/kg/min, 6 months later 18.5 +/- 2.8 ml/kg/min, p < 0.01). The computer-based automated telemetry system combined with a step machine facilitated effective prescription and monitoring of exercise programs at home.

Adult↗

Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications.

Animals↗