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At least 649 records · Page 36Linked to original sources
PubMed2000

Peripheral neuropathy associated with anti-GM2 ganglioside antibodies: clinical and immunopathological studies.

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-associated autoantibodies. However little data are available on their pathogenic effects, if any. In this study we have screened both neuropathy-associated and control sera for anti-GM2 antibodies and subsequently used high titre sera for immunohistological and complement mediated cytotoxicity studies. We identified abnormally elevated anti-GM2 antisera in the normal population, as well as in patients with peripheral neuropathies and other neurological diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antisera from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high levels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding was seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc-GDla, or with GM1a. These data indicate that although GM2 antisera can lyse neural membranes containing GM2, this antigen(s) is not detectable by standard immunohistological techniques in human or rodent peripheral nerve. This raises doubts about their pathophysiological significance in human autoimmune neuropathy.

Adolescent↗
PubMed2001

Intramural multisite recording of transmembrane potential in the heart.

Heart surface optical mapping of transmembrane potentials has been widely used in studies of normal and pathological heart rhythms and defibrillation. In these studies, three-dimensional spatio-temporal events can only be inferred from two-dimensional surface potential maps. We present a novel optical system that enables high fidelity transmural recording of transmembrane potentials. A probe constructed from optical fibers is used to deliver excitation light and collect fluorescence from seven positions, each 1 mm apart, through the left ventricle wall of the rabbit heart. Excitation is provided by the 488-nm line of a water-cooled argon-ion laser. The fluorescence of the voltage-sensitive dye di-4-ANEPPS from each tissue site is split at 600 nm and imaged onto separate photodiodes for later signal ratioing. The optics and electronics are easily expandable to accommodate multiple optical probes. The system is used to record the first simultaneous measurements of transmembrane potential at a number of sites through the intact heart wall.

Action Potentials↗
PubMed1993

Cholera toxin promotes B cell isotype switching by two different mechanisms. cAMP induction augments germ-line Ig H-chain RNA transcripts whereas membrane ganglioside GM1-receptor binding enhances later events in differentiation.

In a recent study we provided evidence that isotype switching in LPS-stimulated murine B cells was greatly enhanced by cholera toxin (CT). We found that CT acted synergistically with IL-4 to promote IgG1 differentiation at the gene transcriptional level by strongly enhancing the expression of germ-line gamma 1-RNA transcripts. In this study we ask which mechanisms are responsible for the isotype-switching effect of CT on B cells and which second messenger systems are involved in this process. We found that at least two different mechanisms are involved: 1) increased intracellular cAMP levels stimulated by the A subunit potentiates isotype switching early in differentiation by augmenting the formation of sterile germ-line gamma 1-RNA transcripts and 2) the binding of the nontoxic B subunit to the membrane GM1-ganglioside receptor promotes later stages of differentiation. Although the whole toxin gave up to a ninefold increase in IgG1 differentiation the cAMP-independent effect of rCTB gave at most a fivefold increase in IgG1 differentiation as compared to that seen with IL-4 alone. However, on a molar basis whole CT was at least a 1000-fold more efficient at promoting B cell switch-differentiation as compared to rCTB. Moreover, IL-4 did not stimulate cAMP in murine B cells and its effect on LPS-stimulated B cell differentiation was not decreased by inhibitors of cAMP-dependent protein kinases. However, CT's effect on B cell switch differentiation was blocked by inhibitors of protein kinases and could be partially mimicked by dibutyryl cAMP. In contrast to CT, the enhancing effect of rCTB on IgG1-differentiation was not affected by blocking of the protein kinases and the combination of rCTB and dBcAMP was as potent as the intact CT in promoting IL-4-stimulated IgG1 differentiation. Finally, the IL-4 pathway, but not the CT pathway, was sensitive to phorbol esters: In IL-4 plus LPS-stimulated B cell cultures IgG1 production was almost completely blocked by PMA. This inhibition was not associated with a decreased B cell proliferation or expression of germ-line gamma 1-RNA transcripts. The addition of CT, and to a significantly lesser extent rCTB, to these cultures enhanced IgG1-differentiation and expression of germ-line gamma 1-RNA transcripts to the same extent as in cultures without PMA. The existence of dual mechanisms operating together on B cell differentiation help to explain the strong adjuvant function by CT on IgG and IgA antibody responses after oral and parenteral immunizations.

Adjuvants, Immunologic↗
PubMed1990

Texture discrimination by cells in the cat lateral geniculate nucleus.

The spontaneous segregation of texture areas is an impressive perceptual phenomenon, the neural basis of which is not yet understood. In the texton concept (Julesz and Bergen 1983; Julesz 1984, 1986) it is assumed that the visual system analyzes a stimulus for certain features ('textons') the spatial distribution of which is pre-attentively registered and may provide the percept of dissected texture areas. Supposed textons are blobs of a given size, oriented lines, line intersections and line terminators, suggesting that texture analysis is exclusively mediated by form-specific filters at higher, e.g. cortical, processing levels. This paper investigates the contribution of cells in the cat lateral geniculate nucleus (LGN) to segregation of typical texton differences. The results indicate that LGN cells, though not resembling the supposed texton filters, often distinguished textured arrangements of such features on the basis of a variety of other visual cues, such as global or local variations in mean luminance or differences in spatial frequency composition. Thus, cells responded to texture borders between areas differing in the size or the density of texture elements and often revealed differential firing rates to textures differing by the crossing or the terminator feature. For textures with differences in line orientation, however, only small variations of the firing rate were seen. In summary, the observations suggest a means of texture representation in the cat LGN which is different from recent concepts of texture segregation in man. For a given pair of textures, cells with receptive fields larger than, or similar to the texture raster respond to global and local luminance variations between areas and, in particular, to differences in their spatial frequency composition. These cells, hence, may signal the global texture difference without encoding spatial details of the pattern from which texton features could be identified. Cells with receptive fields small in comparison to texture elements transfer all the information necessary for analyzing these elements in detail, but themselves are relatively insensitive to global texture differences.

Animals↗
PubMed2004

Morphologic characteristics of the dentition and palate in cases of skeletal asymmetry.

The purpose of this study was to clarify the three-dimensional morphological characteristics of the dentition and palate in skeletal asymmetry in patients with skeletal Class III malocclusion using a newly defined palatal reference plane in a dental cast. Twenty patients (5 males and 15 females) who had skeletal Class III malocclusion with facial asymmetry were selected. Pretreatment posteroanterior cephalometric radiographs and maxillary dental casts were used. The lateral deviation of Me was measured as the distance from a line perpendicular to Lo-Lo' that passed through CG. The angle between the Lo-Lo' plane and the J-J' plane was measured. Each maxillary dental cast was measured using a three-dimensional surface-scanning system, and the newly defined palatal reference plane was calculated. The right/left difference in the radius of curvature of the palate and right/left differences in the vertical and mesiodistal positions of the first molars were analyzed. Linear correlation and regression techniques were used. Our findings demonstrate that the lateral deviation of the mandible is closely related to the morphology of the alveolar process and to the vertical height of the dentition. In this study, the three-dimensional application of a new palatal reference plane is very useful in morphological research, and the results provide detailed information on the characteristics of facial asymmetry.

Adolescent↗
PubMed1986

Hemodynamic changes after the administration of protamine.

Hemodynamic changes associated with the administration of protamine were studied in 30 dogs divided into three equal groups. Protamine (1 mg X kg-1 X min-1 for 4 min) was administered 10 min after 4 mg X hg-1 heparin was given via a left atrial (LA) line in group A, via a central vein in group B, and via a peripheral vein in group C. Protamine given through the central venous pressure (CVP) line resulted in an immediate and significant decrease in mean arterial pressure (MAP) to 60 +/- 4.5 mm Hg (P less than 0.025) from 72 +/- 7 mm Hg immediately after the protamine and to 58 +/- 5 mm Hg (P less than 0.025) 5 min later and with an increase in cardiac index (CI) to 3.7 +/- 0.3 L X min-1 X m-2 from 2.8 +/- .25 L X min-1 X m-2 immediately after the protamine (P less than 0.005), followed by a decrease back to 2.7 +/- 0.3 L X min-1 X m-2 5 min later. Mean arterial pressure and CI remained unchanged after administration of protamine via the peripheral vein or the left atrium. Systemic vascular resistance (SVR) decreased significantly only after administration of protamine via the CVP and was statistically unchanged when administered via the peripheral and LA line. Plasma histamine levels increased significantly after administration of protamine through the central line but remained unchanged after administration via a peripheral vein or the left atrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2007

Behavioural versus physiological mediation of life history under predation risk.

Predator-generated variation in prey energy intake remains the dominant explanation of adaptive response to predation risk in prey life history, morphology and physiology across a wide range of taxa. This "behavioural hypothesis" suggest that chemical or visual signals of predation risk reduce prey energy intake leading to a life history characterized by a small size and late age at maturity. However, size-selective predation can induce either smaller size-early age or large size-late age life history. The alternative "physiological hypothesis" suggests that size-selective cues decouple the relationship between energy and life history, acting instead directly on development. Here we use a series of experiments in a fish-daphnid predator-prey system to ask whether size-selective predator cues induce a physiological mediation of development, overshadowing behaviourally based changes in food intake. We found fish chemical cues reduce the net energy intake in Daphnia magna, suggesting a behaviourally mediated reduction in energy. Experimental manipulation of food levels show further that reductions in food lead to later but smaller size at maturity. However, in line with the physiological hypothesis, we show that D. magna matures earlier and at a smaller size when exposed to fish predation cues. Furthermore, our data shows that they do this by increasing their development rate (earlier maturity) for a given growth rate, resulting in a smaller size at maturity. Our data, from a classic size-selective predation system, indicate that predator-induced changes in this system are driven by physiological mediation of development rather than behavioural mediation of energy intake.

Animals↗
PubMed2007

Assessment of anal sphincter function by Sengstaken-Blakemore tube anal manometry.

BACKGROUND: Anal manometry is a useful tool for testing the effectiveness of surgical treatment. However, most techniques for anal pressure measurement are not easily available because of high cost. The aim of the present study was to introduce an easy and reproducible method for measuring anal pressures in testing the effectiveness of surgical procedures. MATERIALS AND METHODS: We used a Sengstaken-Blakemore tube connected to a mercury manometer. After calibration of the system by inflating the distal (gastric) balloon and filling connection lines to the mercury manometer with 0.9% NaCl solution, resting and squeezing anal pressures were measured. The system was used on 50 human subjects (35 with anal fissure and 15 normal volunteers). Left lateral internal sphincterotomy had been performed in the anal fissure cases. Anal pressures were measured preoperatively and on postoperative days (POD) 2 and 20. RESULTS: Preoperative resting anal pressures in the group with anal fissure (83.4 +/- 1 mmHg) were significantly higher than those in the group of normal individuals (52 +/- 1.2 mmHg; p = 0.001). Resting anal pressures after the sphincterotomy (29 +/- 1 mmHg) were found to be significantly lower on POD 2, and resting anal pressure measurements (47 +/- 1 mmHg) on POD 20 were lower than the corresponding preoperative values. These values are closer to those of normal volunteers (p = 0.016). CONCLUSIONS: Anal manometry can be performed with this easily constructible and inexpensive system. This reproducible method can be used in the assessment of the results of surgical treatment in patients with anal and perianal diseases.

Anal Canal↗
PubMed2002

Activated microglia (BV-2) facilitation of TNF-alpha-mediated motor neuron death in vitro.

We have studied the interactions between activated microglia and injured motor neurons using an immortalized murine microglial cell line (BV-2) stimulated with either lipopolysaccharide (LPS) (Escherichia coli) or supernatant from serum-deprived motor neurons (NSC-34 cell line). Both stimuli induced BV-2 activation. Although both BV-2 supernatants induced a subsequent increase in NO generation in otherwise healthy NSC-34 cells, only LPS-activated microglial supernatant induced NSC-34 cell death through a TNF-alpha-dependent pathway. However, we observed a 20-fold increase in the amount of TNF-alpha required to kill NSC-34 cells in the absence of LPS-activated BV-2 cell supernatant, indicating that microglia secrete factor(s) that facilitate TNF-alpha-mediated motor neuron death in vitro.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Comparison of traditional low-dose-rate to optimized and nonoptimized high-dose-rate tandem and ovoid dosimetry.

PURPOSE: Few dose specification guidelines exist when attempting to perform high-dose-rate (HDR) dosimetry. The purpose of this study was to model low-dose-rate (LDR) dosimetry, using parameters common in HDR dosimetry, to achieve the "pear-shape" dose distribution achieved with LDR tandem and ovoid applications. METHODS AND MATERIALS: Radiographs of Fletcher-Suit LDR applicators and Nucletron "Fletcher-like" HDR applicators were taken with the applicators in an idealized geometry. Traditional Fletcher loadings of 3M Cs-137 sources and the Theratronics Planning System were used for LDR dosimetry. HDR dosimetry was performed using the Nucletron Microselectron HDR UPS V11.22 with an Ir-192 source. Dose optimization points were initially located along a line 2 cm lateral to the tandem, beginning at the tandem tip at 0.5-cm intervals, ending at the sail, and optimized to 100% of the point A dose. A single dose optimization point was also placed laterally from the center of each ovoid equal to the radius of the ovoid (ovoid surface dose). For purposes of comparison, dose was also calculated for points A and B, and a point located 1 cm superior to the tandem tip in the plane of the tandem, (point F). Four- and 6-cm tandem lengths and 2.0-, 2.5-, and 3.0-cm ovoid diameters were used for this study. Based on initial findings, dose optimization schemes were developed to best approximate LDR dosimetry. Finally, radiographs were obtained of HDR applications in two patients. These radiographs were used to compare the optimization schemes with "nonoptimized" treatment plans. RESULTS: Calculated doses for points A and B were similar for LDR, optimized HDR, and nonoptimized HDR. The optimization scheme that used tapered dose points at the tandem tip and optimized a single ovoid surface point on each ovoid to 170% of point A resulted in a good approximation of LDR dosimetry. Nonoptimized HDR resulted in higher doses at point F, the bladder, and at points lateral to the tandem tip than both the optimized plan or the LDR plan. CONCLUSION: Optimized HDR allows specification of dose to points of interest, can approximate LDR dosimetry, and appears superior to nonoptimized HDR treatment planning, at least at the tandem tip. An optimization scheme is presented that approximates LDR dosimetry.

Brachytherapy↗
PubMed1979

The analysis of sound by the sprat ear.

In the acoustico-lateralis systems of vertebrates the individual hair cells are usually polarised in their responses to displacements of the liquid in which they lie, and are often arranged in back-to-back pairs or groups with different polarities. A simple example to investigate, mechanically as well as electrically, is the utriculus of the sprat (Clupea sprattus L.). The acoustico-lateralis system of the sprat and other clupeids has two partly gas-filled bony bullae which transform pressure changes into liquid displacements capable of stimulating the sense organs of the ear and lateral line. With its related structures the utriculus is a very sensitive sound pressure detector which has one population of receptors that respond to the compressions and another that respond to the decompressions of a sound wave. We now give additional evidence that this type of organisation is unlike that of the mammalian cochlea in being specialised more for the detection of phase/time relationships than for frequency analysis.

Animals↗
PubMed2000

Radiation related prognostic factors in radiation oncology.

1. The outcome of a course of radiotherapy is very dependent on the dose per fraction. The smaller the dose per fraction, as a general rule, the better the sparing of the late reacting normal tissues. 2. Overall treatment time is important, especially for tumours with a rapid doubling time. In such a case, the ideal of small doses per fraction (to save late reacting tissues) as well as a short overall treatment time (to offset the effect of repopulating) can be achieved by small doses per fraction applied two to three times per day, including Saturdays or weekends. 3. The BED (biologically effective dose) is a simple to use formula indicating the effects of fractionation. The most important term in the formula is the alpha/beta ratio which is available from experimental work for many tumours and tissues and can be looked up. As a guide, an alpha/beta ratio of 10 for early (acute) reaction and for tumour effects, and an alpha/beta ratio of 2 for late effects plus normal tissue complications can be used. 4. The application of the BED demonstrates that for HDR intracavitary therapy for cervical carcinoma, the biologically relevant dose lateral to point M(A) falls very much more rapidly than the nominal dose. Line sources are shown by comparison with other published reports, not to be intrinsically inferior to tandem ring/tandem ovoid systems and may have advantages the more cumbersome systems do not have, and may have the large advantage of allowing multiple small fractions without anaesthesia. For the particular line source system under discussion, water in a 40 cm3 Foleys bulb is used as the protecting medium for the posterior bladder wall and the anterior rectum. This particular system allows fraction sizes far smaller than 9.1 Gy at point (M)A, e.g. 3 Gy, which bestows an even greater benefit in terms of the therapeutic ratio according to BED10 and BED2 calculations.

Dose Fractionation, Radiation↗
PubMed1999

Asymmetric connections, duplicate layers, and a vertically inverted map in the primary visual system.

The achiasmatic mutation is a remarkable and rare visual system mutation carried in a line of black sheepdogs. In affected animals, the optic chiasm is missing, and each retina projects entirely to the ipsilateral hemisphere. As a result of this navigational error, maps of visual space in the lateral geniculate nucleus (LGN) have a unique structure with mirror reversals of field position across the A-A1 border. Animals also have a persistent and severe congenital nystagmus. In this report we analyze a novel variant of the achiasmatic mutation, one in which retinal axons from only one eye successfully cross midline and in which the great majority of fibers from both eyes terminate in a single lateral geniculate nucleus. The dominant optic tract contains four times as many axons as the other tract. The hyperinnervated LGN has a lamination pattern consisting of duplicate and partly interwoven layers. A multiunit mapping study of visual cortex (primarily area 17 along the marginal gyrus) shows that receptive field topography and orientation selectivity are normal. The size of central binocular visual space is nearly normal and is flanked by monocular domains in the periphery. However, there is an inexplicable vertical inversion in the orientation of the cortical representation: superior fields are located rostrally, and inferior fields are located caudally. Despite a host of drastic abnormalities at all level of the visual system, from retina to cortex, this animal was behaviorally indistinguishable from normal dogs and did not have any detectable oculomotor abnormalities.

Animals↗
PubMed1996

An immunoglobulin mutator that targets G.C base pairs.

Hypermutation can be defined as an enhancement of the spontaneous mutation rate which the organism uses in certain types of differentiated cells where a high mutation rate is advantageous. At the immunoglobulin loci this process increases the mutation rate > 10(5)-fold over the normal, spontaneous rate. Its proximate cause is called the immunoglobulin mutator system. The most important function of this system is to improve antibody affinity in an ongoing response; it is turned on and off during the differentiation of B lymphocytes. We have established an in vitro system to study hypermutation by transfecting a rearranged mu gene into a cell line in which an immunoglobulin mutator has been demonstrated. A construct containing the mu gene and the 3' kappa enhancer has all the cis-acting elements necessary for hypermutation of the endogenous gene segments encoding the variable region. The activity of the mutator does not seem to depend strongly on the position of the transfected gene in the genome. The mutator is not active in transformed cells of a later differentiation stage. It is also not active on a transfected lacZ gene. These results are consistent with the specificity of the mutator system being maintained and make it possible to delineate cis and trans mutator elements in vitro. Surprisingly, the mutator preferentially targets G-C base pairs. Two hypotheses are discussed: (i) the immunoglobulin mutator system in mammals consists of several mutators, of which the mutator described here is only one; or (ii) the primary specificity of the system is biased toward mutation of G-C base pairs, but this specificity is obscured by antigenic selection.

Animals↗
PubMed2000

Immunohistochemical localization of glial cell line-derived neurotrophic factor family receptor alpha-1 in the rat brain: confirmation of expression in various neuronal systems.

The localization of glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRalpha-1) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein. For raising the antisera in rabbits, we synthesized the oligopeptide SDVFQQVEHISKGN that corresponds to residues 139 to 152 of rat GFRalpha-1. On immunospot assay, 0.5 microg/ml of an affinity-purified antibody was capable of detecting 7.8 pmol of the rat GFRalpha-1 oligopeptides. When rat brain homogenates were examined by Western blots, the antibody revealed two main bands with molecular weights of approximately 47 kDa and 53 kDa, corresponding to the known sizes of GFRalpha-1. Immunohistochemistry in rat brain demonstrated that GFRalpha-1-like immunoreactivity was present in neurons but not in glial cells. The localization of GFRalpha-1-like immunoreactivity was largely consistent with that of the corresponding GFRalpha-1 mRNA. Positive neurons were distributed widely in various brain regions, but were particularly abundant in such regions as the olfactory bulb, diagonal band, substantia innominata, zona incerta, substantia nigra, cerebellar cortex, nuclei of the cranial nerves including auditory system and spinal motoneurons. The present study showed that GFRalpha-1 in the normal central nervous system is expressed preferentially in certain multiple neuronal systems that include cholinergic system as well as dopaminergic system and motor neurons. As GFRalpha-1 protein was found in numerous brain structures, GDNF family ligands may have therapeutic application not only in degenerative diseases affecting in specific nervous systems, such as Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy, but in diffusely damaging diseases like cerebrovascular diseases.

Animals↗
PubMed1984

Basis for the specificity of anti-5-HT-like antisera in immunocytochemistry applied to the central nervous system.

Recently (Pecci Saavedra et al. 1982; Brusco et al. 1982, 1983) we have showed that the actual specificity of the rabbit anti-5-HT antibodies, is for the beta-carboline derivatives of 5-HT as a result of cyclization of the lateral chain. We explained this as resulting from the use of formaldehyde which acted both as a fixative in the preparation of the tissues, and as the coupling agent in the preparation of the immunogen. Following this line we have fixed several brain stem specimens with 0.5% p-benzoquinone; 3% glutaraldehyde; 4% paraformaldehyde plus 0.25% glutaraldehyde and compare the results with tissues fixed in 4% paraformaldehyde. Glutaraldehyde and p-benzoquinone do not produce cyclization of 5-HT but immobilize monoamines in situ. As expected, the antibodies applied according to the PAP technique did not stain the neuronal bodies of the raphe system, known to contain 5-HT when 3-4% glutaraldehyde or 0.5% p-benzoquinone were used. Good staining was obtained with 4% paraformaldehyde alone or with 4% paraformaldehyde plus 0.25% glutaraldehyde. A quantitative assay of the spot test of Larsson (1981) was devised for measuring in vitro the inhibitory effects of 5-HT, of the 5-HT-BSA complex and of the cyclic derivative, 6-OH-1,2,3,4-tetrahydro-beta-carboline. The results confirmed that the avidity of the antiserum is much greater for the cyclic derivatives contained in the 5-HT-BSA complex and for 6-OH-1,2,3,4-tetrahydro-beta-carboline than for 5-HT. It is concluded that the formation of a new ring by the lateral chain of 5-HT is responsible of the in-vitro and in the tissue immunoreactivity of the anti-5-HT-antibodies.

Animals↗
PubMed1995

Distribution of microsomal epoxide hydrolase and glutathione S-transferase in the rat olfactory mucosa: relevance to distribution of lesions caused by systemically-administered olfactory toxicants.

This study represents part an of ongoing effort to understand the mechanism underlying the distribution of the olfactory mucosal lesion resulting from the systemic administration of compounds such as 2,6-dichlorobenzonitrile (dichlobenil) and beta,beta'-iminodipropionitrile (IDPN). Immunohistochemistry was performed to localize the microsomal form of epoxide hydrolase (mEH) and glutathione S-transferase (GST) isozymes alpha, mu and pi in the rodent olfactory mucosa. GST-pi was found in abundance in the Bowman's glands of the mucosa lining the dorsal medial meatus (DMM) of the nasal cavity and in the nuclei of basal and sustentacular cells of the dorsal and lateral nasal cavity. Liver and olfactory mucosal levels of mEH are equivalent by Western blot analysis. mEH appeared to be localized in the apical cytoplasm of sustentacular cells in all regions of the olfactory mucosa except for the epithelium lining the DMM. These observations, coupled with the known profile of metabolites for dichlobenil, suggest that systemically-administered compounds causing site-specific lesions in the epithelium lining the DMM of the nasal cavity may do so by the in situ production of reactive epoxide metabolites which are then poorly capable of being detoxified. Thus, the distribution of metabolic enzymes, rather than the absolute level of an enzyme in a tissue, may dictate lesion distribution in the case of toxicants which are bioactivated in target tissues.

Animals↗
PubMed2000

Differential expression of the PSD-95 gene family in electrosensory neurons.

The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.

Amino Acid Sequence↗