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PubMed1979

Analgesia produced by microinjection of baclofen and morphine at brain stem sites.

Microinjection of either baclofen (1.5 microgram) or morphine (2.5 microgram), in equimolar doses (14 mM), at sites located in the caudal periaqueductal gray (PAG) resulted in a delay in tail flick latency (analgesia). The relative analgesic potency of baclofen among caudal PAG sites, however, did not correlate with that of morphine. Application of either drug into the caudal aspect of the cerebral aqueduct also produced analgesia, but neither agent caused analgesia when applied at PAG sites rostral to the interaural line. Baclofen also produced analgesia when microinjected in the lower brain stem at sites lateral to the midline in or near the nucleus gigantocellularis, but did not produce analgesia when applied on the midline at sites located within or near the raphe magnus. Conversely, morphine produced analgesia when applied locally at midline sites but not at sites located lateral to the midline. These data suggest that the analgesia produced by systemic administration of baclofen and morphine involves activation of different neuronal substrates.

Analgesics↗
PubMed1991

Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers.

Isolated rat livers were perfused for 60 min with either 0.3 or 0.5 microgram/ml (initial volume, 119 ml) of [3H]microcystin-LR at a constant flow of 10 ml/min in a recirculating system. During the 60-min exposure, toxin caused stimulation of glycogenolysis, liver engorgement, and cessation of bile flow. Electron micrographs of liver showed dilation of bile canaliculi and the space of Disse. loss of sinusoidal lining architecture, and decreased hepatocyte intercellular contacts. Although hepatocytes did not exhibit overt necrosis, mitochondria were hydropic, occasionally encircled by whorls of rough endoplasmic reticulum, and desmosomal tonofilaments were decreased on the plasma membrane lateral surface. Isolated mitochondria displayed inhibition of state 3 respiration and a 50-60% decrease in the respiratory control index, characteristic of hydropism. Distribution of radiolabel was 1.7% to bile, 79% to perfusate, and 16% to liver. Two to four percent was recovered in perfusate that leaked from the surface of the liver. Of the radiolabel found in bile and perfusate, 78 and 100% were associated with parent toxin, respectively. The radiolabel in liver, associated with the cytosolic fraction (S-100), corresponded to parent toxin (15%) and to a more-polar component(s) (85%). The elimination half-life from perfusate was 130 +/- 10 min (0.5 microgram/ml) and the hepatic extraction ratio 0.07 +/- 0.01. Although the calculated hepatic extraction ratio was low, there was a significant accumulation of microcystin in the liver. Many toxic effects of microcystin in the perfused liver mimicked those observed in the whole animal, suggesting that this model can be used as an alternative to whole animals for screening of potential therapeutic agents.

Animals↗
PubMed1992

Effects of three male reproductive toxicants on rat cauda epididymal sperm motion.

The sensitivity of the CellSoft computer-assisted sperm analysis (CASA) system to detect changes in rat sperm motion was evaluated. CASA motion endpoints were measured in cauda epididymal sperm from Long-Evans rats treated with each of three known male reproductive toxicants reported to affect the epididymis and epididymal sperm motility: alpha-chlorohydrin, ornidazole, and trimethylphosphate. Significant changes in endpoints describing sperm swimming vigor (curvilinear velocity and straight-line velocity) and pattern (linearity and amplitude of lateral head displacement) were observed for rats dosed with each agent when evaluations included mean values and other statistical parameters (i.e., percentiles and distributional shape). alpha-Chlorohydrin (ACH) treatment (10 mg/kg/day; 8 days) resulted in reductions in the mean percentage of motile sperm, curvilinear velocity (VCL), straight-line velocity (VSL), lateral head displacement (ALH), and linearity (LIN). Treatment with ornidazole (ONZ) (200 mg/kg/day/14 days) reduced the percentage of motile sperm. Mean VCL, VSL, and ALH were reduced by 400 mg ONZ/kg/day treatment. Trimethylphosphate (TMP) treatment led to (a) a reduction in the 75th and 90th percentiles for ALH (100 mg TMP/kg/day; 5 days) (P < or = 0.04), (b) a reduction in VCL, VSL, and ALH (250 mg TMP/kg/day), (c) a reduction in the percentage of motile cells and in the 10th and 25th percentiles for VSL (600 mg TMP/kg/day), and (d) increases in the 90th percentile for VSL, in the mean, 75th, and 90th percentiles for VCL, and in the 75th and 90th percentiles for ALH (600 mg TMP/kg/day). The general utility of these analytic approaches in reproductive toxicology studies was demonstrated in the observations of effects at or below dose levels previously reported.

Administration, Oral↗
PubMed1982

Pulmonary veno-occlusive disease in siblings: case reports and morphometric study.

Two cases of fatal veno-occlusive disease are described: the first in a boy 14 years old and the second in his sister, who died, at age 13, only a few months later. In both, the first symptom was effort-induced dyspnea and the course of the disease was rapid. The chest radiograph of the boy showed diffuse opacities, whereas that of the girl showed Kerley lines bilaterally. In both, at autopsy, a diagnosis of severe veno-occlusive disease was confirmed, with partial or complete occlusion of much of the pulmonary venous bed by organized thrombi. The pulmonary vascular system of the girl was processed for light microscopic morphometry by injection of radiopaque medium into the veins of one lung and the arteries of the other. Although there was little filling of the venous system, much of the arterial system filled down to the capillary level. Pre-acinar and intra-acinar arteries showed medial hypertrophy and extension of smooth muscle into precapillary arteries. The concentration of patent intra-acinar arteries relative to alveoli was not significantly less than normal, whereas the concentration of veins was strikingly reduced. Possible pathogenetic mechanisms are discussed.

Adult↗
PubMed2001

Antibody to the HNK-1 glycoepitope affects fasciculation and axonal pathfinding in the developing posterior lateral line nerve of embryonic zebrafish.

The HNK-1 glycoepitope, carried by many cell recognition molecules, is present in the developing posterior lateral line nerve and on other primary axons of zebrafish. To elucidate the function of HNK-1 in vivo, the antibody 412 to HNK-1 was injected into zebrafish embryos at 16 h post fertilization (hpf). The injected antibody bound specifically to axons carrying HNK-1. This treatment selectively affected the growth of either one or both posterior lateral line nerves in 39% of the experimental cases (13 of 33 animals), which was significantly more (P<0.0002) than in uninjected, vehicle injected, and non-immune IgG injected controls (1.2% of the animals; one of 85 animals), as assessed at 27 or 33 hpf. Other HNK-1 immunoreactive nerves, such as the ventral motor nerves were unaffected, indicating that antibody binding per se did not interfere with axon growth. The primordium of the posterior lateral line was not affected in its caudal migration and in depositing differentiating neuromasts along the trunk, showing that injections did not retard development and that initial formation of lateral line organs is probably independent of contact with nerve fibers. We suggest that the HNK-1 glycoepitope is an important modulator of embryonic nerve growth.

Animals↗
PubMed2006

Interlimb transfer of grasp orientation is asymmetrical.

One the most fundamental aspects of the human motor system is the hemispheric asymmetry seen in behavioral specialization. Hemispheric dominance can be inferred by a contralateral hand preference in grasping. Few studies have considered grasp orientation in the context of manual lateralization and none has looked at grasp orientation with natural prehension. Thirty right-handed adults performed precision grasps of a cylinder using the thumb and index fingers, and the opposition axis (OA) was defined as the line connecting these two contact points on the cylinder. Subjects made ten consecutive grasps with one hand (primary hand movements) followed by ten grasps with the other hand (trailing movements). Differences between primary and trailing grasps revealed that each hemisphere is capable of programming the orientation of the OA and that primary movements with the right hand significantly influenced OA orientation of the trailing left hand. These results extend the hemispheric dominance of the left hemisphere to the final positions of fingers during prehension.

Adult↗
PubMed1996

Malignant intracranial teratoma in a juvenile Wistar rat.

An intracranial malignant teratoma was identified in a 91-day-old male Wistar rat manifesting central nervous system-related clinical signs. This tumor occupied the right midbrain and portions of the right caudal cerebrum and cranioventral cerebellum. Microscopically, the tumor contained intermingled cartilage, bone (with medullary hematopoietic tissue), fibrous connective tissue, skeletal muscle, fat, pseudostratified ciliated epithelium, stratified squamous epithelium, serous and mucoserous glands, and neural tissue with ependymal and choroid plexus epithelia. Poorly differentiated cells with primitive cartilaginous matrix were present throughout the lining of lateral ventricles, in the aqueduct of Sylvius, and in meninges overlying normal cerebellar tissue indicating tumor metastasis occurred via cerebrospinal fluid. This neoplasm was not identified in extracranial sites and hence was considered a primary intracranial malignant teratoma with metastases via cerebrospinal fluid.

Animals↗
PubMed1989

Glial interactions with neurons during Drosophila embryogenesis.

A monoclonal antibody (Mab5B12) demonstrating specificity for glial cells within the central and peripheral nervous systems of Drosophila has been used in combination with neural-specific antibodies to study the early organization of the Drosophila embryo. The embryonic central nervous system of Drosophila contains cells within the ventral midline that are recognized by monoclonal antibody 5B12. These cells are not recognized by either a polyclonal antiserum to horse radish peroxidase, which recognizes several antigens on the surface of Drosophila neurons, or Mab22C10, which recognizes an antigen specific to the peripheral nervous system. Mab5B12-positive cells lie dorsal both to the developing anterior and posterior commissures in each thoracic and abdominal segment and to the supraoesophageal commissure. They ensheath these commissures in later stage embryos. Other Mab5B12-positive cells lie dorsolateral to the CNS and send processes laterally to the lateral sensilla during axonogenesis in the PNS. These cells surround the axons of the intersegmental and segmental nerves. Other cells that line the advancing ectoderm during dorsal closure and surround the anal pads also express the Mab5B12 antigen. Neuronal cell cultures derived from Drosophila gastrulae contain cells expressing the Mab5B12 antigen. These cells can be found separate or in close association with neuronal clusters and their axons.

Animals↗
PubMed1990

An investigation into the performance of an automated quality assurance and dosimetry system in diagnostic radiology.

A system has been developed to undertake automatic quality assurance and dosimetry for diagnostic radiology examinations. The accuracy and reproducibility of the measurements and calculations made by the system have been investigated in a laboratory study and compared with concurrent measurements of exposure parameters made using standard techniques. In a later set of experiments, doses measured using a RANDO phantom and thermoluminescent dosimeters were compared with those calculated by the automated system. Assessment was carried out over a wide range of exposure factors and for a number of different radiological examinations. It is deduced from the results that exposure parameters can be measured with comparable accuracy to standard techniques, and that the automated system is suitable for performing on-line dosimetry.

Humans↗
PubMed2001

Management of paracetamol overdose: current controversies.

Paracetamol (acetaminophen) is one of the most frequently used analgesics, and is the most commonly used substance in self-poisoning in the US and UK. Paracetamol toxicity is manifested primarily in the liver. Treatment with N-acetyl-cysteine (NAC), if started within 10 hours from ingestion, can prevent hepatic damage in most cases. Pharmacokinetic data relating plasma paracetamol concentration to time after ingestion have been used to generate a 'probable hepatoxicity line' to predict which cases of paracetamol overdose will result in hepatotoxicity and should be treated with NAC. However, later studies use a 25% lower line as their 'possible hepatotoxicity line'. Although adopting the original line may save considerable resources, further studies are needed to determine whether such an approach is safe. On the basis of the metabolism of paracetamol, several risk factors for paracetamol toxicity have been proposed. These risk factors include long term alcohol (ethanol) ingestion, fasting and treatment with drugs that induce the cytochrome P450 2E1 enzyme system. Although some studies have suggested that these risk factors may be associated with worse prognosis, the data are inconclusive. However, until further evidence is available, we suggest that the lower line should be used when risk factors are present. In Canada and the UK, the intravenous regimen for NAC is used almost exclusively; in the US, an oral regimen is used. Both regimens have been shown to be effective. There is no large scale study with direct comparison between these 2 therapeutic protocols and controversy still exists as to which regimen is superior. During the last few years there has been an increase in the number of reports of liver failure associated with prolonged paracetamol administration for therapeutic reasons. The true incidence of this phenomenon is not known. We suggest testing liver enzyme levels if a child has received more than 75 mg/kg/day of paracetamol for more than 24 hours during febrile illness, and to treat with NAC when transaminase levels are elevated. Paracetamol overdose during pregnancy should be treated with either oral or intravenous NAC according to the regular protocols in order to prevent maternal, and potentially fetal, toxicity. Unless severe maternal toxicity develops, paracetamol overdose does not appear to increase the risk for adverse pregnancy outcome.

Acetaminophen↗
PubMed2005

Three-dimensional kinematics of the equine distal forelimb: effects of a sharp turn at the walk.

REASONS FOR PERFORMING STUDY: Sharp turns are suspected to increase expression of several distal forelimb lamenesses even at the walk but the biomechanical consequences of such a movement remain unknown. OBJECTIVE: To quantify the effects of a sharp turn at the walk on the 3-dimensional movements of the distal segments of the forelimb. METHODS: Kinematics of the distal segments were measured in 4 healthy horses invasively with an ultrasonic system. Three-dimensional rotations of the digital joints were calculated by use of a joint coordinate system. Data obtained for a turn at the walk were compared to those obtained in a straight line. RESULTS: During the stance phase in a turn, the inside forelimb underwent an adduction that induced lateromotion and medial rotation in the distal interphalangeal joint and medial rotation in the proximal interphalangeal joint. These movements were maximal at heel-off and decreased during breakover as the hoof underwent a sudden lateral rotation. CONCLUSIONS: Walking in a sharp turn affects the kinematics of the digital joints outside the sagittal plane. POTENTIAL RELEVANCE: This knowledge offers the opportunity to derive hypotheses on biomechanical factors that could contribute to the pathogenesis of digital injuries and on consequences for rational shoeing.

Animals↗
PubMedDate not supplied

Establishment and characterization of a new human prostatic cancer cell line: DuCaP.

BACKGROUND: The lack of appropriate, clinically relevant, cell-based model systems has limited prostate cancer research and the development of new therapeutic modalities. Here we report the isolation and characterization of a new adherent prostate cancer cell line, derived from the dura mater of a cancer patient. METHODS: Prostate cancer tissue was harvested at autopsy from a metastatic lesion to the dura mater of a patient with hormone refractory prostate cancer. This tissue was xenografted into SCID mice and later harvested and plated on tissue culture dishes. For characterization, soft agar clonegenic assay, in vivo xenograft growth, in vitro doubling time, karyotype analysis, immunocytochemistry for cytokeratin-18, androgen receptor, and PAP (prostatic acid phosphatase) expression, RT PCR for PAP, PSMA (prostate specific membrane antigen), expression and northern and western blot analysis to determine expression of Rb and p53, were performed. RESULTS: DuCap grows in vitro (passage 55), forms colonies in soft agar, produces tumors in SCID mice (xenograft passage 12), and is androgen sensitive. DNA content was hypertriploid. PSA was detected in mouse serum and media. Cells were AR, PAP and cytokeratin-18 positive by immunocytochemistry. PSMA and PAP were detected by RT-PCR. AR, P53, and Rb were expressed in Northern blot analysis. P53 protein was detected in Western blot analysis but Rb protein was not. CONCLUSIONS: This cell line exhibits many phenotypic characteristics of clinical prostate carcinoma, including expression of PSA, PSMA, PAP and AR.

Androgens↗
PubMed1991

Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells.

To investigate the antiviral CD4+ T cell response in coronavirus MHV-JHM-induced encephalomyelitis, spleen and thymic lymphocytes from diseased rats were stimulated in culture with virus Ag, expanded and tested for their specificity to viral proteins and nucleocapsid (N) and spike (S) proteins that had been expressed in bacteria. A strong T cell response specific for N was measurable during acute disease, whereas S-specific T cells were only detectable in rats with a later onset of disease. CD4+ T cell lines with specificity for virus and either N or S protein were established and their influence on the course of a mouse hepatitis virus-JHM infection was investigated. All lines were of the CD4+ phenotype. Both N and S protein-specific CD4+ T cells conferred protection to infected Lewis rats and reduced the amount of infectious virus in the central nervous system. After transfer of CD4+ T cells and challenge with virus, an increase in the antiviral IgM response occurred, but neutralizing antibodies were not detectable during the period of virus clearance. Previous CD8+ cell depletion did not abrogate protection mediated by CD4+ T cell line transfer.

Animals↗
PubMed1993

Hormonal control of transmitter plasticity in insect peptidergic neurons. I. Steroid regulation of the decline in cardioacceleratory peptide 2 (CAP2) expression.

Transmitter plasticity, the ability to alter transmitter expression, has been documented in several different preparations both in vivo and in vitro. One of these is the tobacco hawkmoth, Manduca sexta, whose central nervous system contains four individually identified lateral neurosecretory cells (LNCs) that undergo a postembryonic transmitter switch in vivo. In larvae, the LNCs express high levels of a myoregulatory peptide, cardioacceleratory peptide 2 (CAP2). In contrast, the predominant LNC transmitter in adult moths in bursicon, a classic insect peptide hormone responsible for cuticular tanning. Here we show that the CAP2-to-bursicon conversion by the LNCs is a multi-step process beginning with a decline in CAP2 levels midway through the final larval stage. We provide several lines of evidence that this CAP2 drop is regulated by the insect steroid hormone 20-hydroxyecdysone (20-HE). The LNCs exhibit a fall in CAP2 levels at the beginning of metamorphosis, immediately after the commitment pulse of 20-HE when steroid levels are elevated. LNCs not exposed to this 20-HE rise do not exhibit a decline in CAP2 level. The transmitter switch can also be prevented by using an analog of juvenile hormone to create a larval hormonal environment during the commitment pulse of 20-HE. The CAP2 decline in the LNCs could be directly induced by exogenous steroid application, but only under conditions where the LNCs remained connected to the brain. Thus, the first step in the transmitter switch by the LNCs, the decline in CAP2 levels, is triggered by the commitment pulse of 20-HE, which may act indirectly through a set of steroid-sensitive cells in the brain.

Animals↗
PubMed2002

Contribution of amygdala neurons containing peptides and calcium-binding proteins to fear-potentiated startle and exploration-related anxiety in inbred Roman high- and low-avoidance rats.

The purpose of this study was to investigate amygdala-related fear and anxiety in two inbred rat lines differing in emotionality (RHA/Verh and RLA/Verh), and to relate the behaviour of the animals to neuronal types in different nuclei of the amygdala. The behavioural tests used were the motility test, elevated plus-maze and fear-potentiated startle response. The neurons investigated were immunoreactive for the anxiogenic peptide corticotropin-releasing factor (CRF-ir), the anxiolytic peptide neuropeptide Y (NPY-ir), and the calcium-binding proteins parvalbumin (PARV-ir) and calbindin (CALB-ir). The NPY-ir, PARV-ir and CALB-ir neurons studied were subpopulations of GABAergic neurons. RLA/Verh rats, which showed a significant fear-potentiation of the acoustic startle response, had more CRF-ir projection neurons in the central nucleus of the amygdala. The same RLA/Verh rats were either less or equally anxious in the motility test (similar to open field) and elevated plus-maze as compared with RHA/Verh rats. In accordance with this behaviour, the RLA/Verh rats had more NPY-ir neurons in the lateral, and more PARV-ir neurons in basal nuclei of the amygdala than RHA/Verh rats, but no differences were detected in the number of CRF-ir and CALB-ir neurons of the basolateral complex. In conclusion, the RLA/Verh rats displayed an opposite behaviour in the fear-potentiated startle model and the exploratory tests measuring anxiety based on choice behaviour. Thus, the anxiogenic systems in the central nucleus and anxiolytic systems in the basolateral complex of the amygdala might be differentially involved in the fear-potentiated startle paradigm and exploratory tests in the Roman rat lines.

Amygdala↗
PubMed1997

Second-site reversion of a dysfunctional mutation in a conserved region of the tobacco mosaic tobamovirus movement protein.

The N-terminal two-thirds of tobamovirus movement proteins (MPs) contain two well conserved regions. Within region I (amino acids 56-96) is an area predicted by computer analysis to have loop secondary structure (amino acids 76-87). A single or two double amino acid mutations were introduced into the loop in region I of the TMV MP to destabilize the structure. The three mutant MPs were defective in movement function. The single amino acid mutation resulted in a Pro81-->Ser substitution. The mutant virus, TP81S, containing the Pro81-->Ser substitution, was propagated on a transgenic line of Nicotiana tabacum that expresses the sunn-hemp mosaic tobamovirus MP. Inoculation of virus progeny from the transgenic plants onto hypersensitive N. tabacum indicated the presence of infectious virus at a low frequency. Necrotic lesions were detected at 4 days postinoculation, 2 days later than those induced by wild-type TMV. Inoculation of virus extracted from necrotic lesions onto N. tabacum resulted in a delayed and attenuated systemic infection relative to that induced by TMV, indicating that a second-site mutation restored movement function rather than a reversion of the original mutation. Sequence analysis revealed that the revertant MP gene had two additional amino acid substitutions, a Thr104-->Ile and a Arg167-->Lys. Introduction of the amino acid substitutions individually or in combination into the MP of TP81S indicated that both substitutions were required for the revertant phenotype. The data indicate that structure within region I is important in maintaining an active conformation for functional MP, that changes outside region I can compensate for alterations within the region, and suggest that region I may interact with a distal portion of the protein.

Amino Acid Sequence↗
PubMed1981

Inputs to the torus semicircularis in the electric fish Eigenmannia virescens. A horseradish-peroxidase study.

The posterior lateral-line lobe, contrary to present belief, projects bilaterally to the torus semicircularis, although the contralateral projection is considerably more extensive. The torus also receives bilateral inputs from the medial octavo-lateralis nuclear complex, the reticular formation, a sublemniscal nucleus, and the nucleus prae-eminentialis. Unilateral inputs to the torus were found originating from the ipsilateral mesencephalic tectum and the contralateral lobus caudalis of the cerebellum. Extensive commissural systems between the right and left torus are also described for the first time.

Animals↗
PubMed1981

Central connections of the posterior lateral line lobe in mormyrid fish.

Primary electroreceptor afferents terminate in the posterior lateral line lobe (PLLL) in electroreceptive teleosts. This paper examines the central connections of PLLL in fish of the family Mormyridae using horseradish peroxidase and tritiated amino acid tracing techniques. Some connections of the closely related lobus caudalis of the cerebellum are also examined. There are three zones on each side of the mormyrid PLLL cortex. Two receive input from mormyromast receptors, and one from ampullary receptors. An intrazonal projection system, intrinsic to PLLL, connects neighboring points within each zone. It also joins corresponding zones on the two sides of the body via commissural fibers. An interzonal system connects the two mormyromast zones on the same side of the midline. Central structures which project to PLLL include lobus caudalis, nucleus paratrigeminalis lateralis, and nucleus praeeminentialis. Nucleus praeeminentialis projects bilaterally and somatotopically to the lower molecular layer of PLLL. PLLL cortex projects bilaterally and somatotopically to two major mesencephalic sites: n. praeeminentialis, and n. lateralis. Somatotopically corresponding points in each zone of PLLL cortex project to the same small region of n. lateralis. Nucleus lateralis has a large and somatotopically organized projection to n. praeeminentialis. The afferent and efferent connections of lobus caudalis are similar to those of PLLL, indicating its close association with the electrosensory system. The anatomical results show that there is ample opportunity for electrosensory information arising on left and right sides of the body to interact centrally. One can suggest that comparison of afferent input from the two sides would reduce the non-significant variability which affects both of them equally. The results also show the presence of several somatotopically organized feedback lops which return the results of higher order processing of electrosensory information to earlier stages.

Afferent Pathways↗