PPL
Periplakin (190 kDa paraneoplastic pemphigus antigen) (195 kDa cornified envelope precursor protein) [KIAA0568]
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The earliest generated cells of the mammalian cerebral cortex form the preplate layer (PPL). The subsequently born cortical plate (CP) cells split this layer into the superficial layer I (LI) and the deep subplate (SP). The cellular and molecular mechanisms that underlie this event are unclear. To investigate the role of the cyclin-dependent kinase 5 (Cdk5) and its activator p35 in preplate splitting, we used Nissl staining, carbocyanine dye tracing, cell birthdating, and immunohistochemistry for calretinin (CalR) in p35 and Cdk5 knockout mice. Our data demonstrated changes in early cortical lamination and aberrant thalamic axon trajectories in these mice. Specifically, LI was thicker, and cell-dense and thalamic axons did not accumulate in the SP layer before invading the CP. Instead, they grew past the SP and more superficial cortical layers and coursed obliquely toward the pial surface. This behavior has been previously observed in reeler mice and suggests a defect in PPL splitting. CalR immunohistochemistry and bromo-deoxyuridine birthdating confirmed the abnormality in position of the earliest generated cortical cells of mutants. These observations suggest that the p35/Cdk5 pathway plays a role in preplate splitting in addition to regulating layer formation.
MeSH Terms
- Aging
- Animals
- Body Patterning
- Cells, Cultured
- Cerebral Cortex
- Cyclin-Dependent Kinase 5
- Mice
- Mice, Knockout
- Nerve Net
- Organogenesis
- Phosphotransferases
- Tissue Distribution
The central and lateral lumbar canals constitute complex osteofibrous neurovascular tunnels, allowing movement and deformation of the spine without loss of their main configuration. Intervertebral discs play an important role in determining their configuration. Disc degeneration may alter or even threat the functional anatomical relationships between successive adjacent "juncturae" of the vertebral column. Shape and morphometric aspects of the bony neural canals reveal level dependency [39], inter-individual variation [11], and are particularly susceptible for changes with aging [49]. Articular tropism and other left-right differences may influence their morphology. In the epidural compartments behind the vertebral bodies, a sagittal membrane may totally or partly connect the deeper layer of the posterior longitudinal ligament (PLL) with the posterior midline of the vertebral body. This membrane is considered clinically significant in the prevention of movement of disc material from one side to the other at the level of the vertebral bodies [44]. Meningovertebral ligaments represent a heterogenous group of membranous formations, connecting the dura with the PPL and other elements of the spinal canal. They prevent the dura from moving away from the bony container. These ligaments may vary from loose areolar tissue to clearly individualised ligaments and from pure midsagittal septa to more laterally oriented attachments. A double cross vault structure between the PPL and the dura mater often extends from L3 to the end of the dural envelope [3]. A retrospective study of medial and paramedial attachments in CT- and MRT-scans confirmed the presence of a mediosagittal structure below L3 in 35% of the cases 7). It was hypothesized that meningovertebral ligaments may play a [7] role as a barrier to transverse displacement of extruded disc material [43]. The surrounding morphology renders the lateral neural canal its typical inverted teardrop shape [39]. The subpedicular notch of the upper vertebra provides the widest part and represents the neural foramen strictu sensu. The posterolateral aspect of two articulating vertebrae and the interposed intervertebral disc constitute the anterior wall. The morphology of the anteroinferior aspect of the intervertebral foramen strongly depends on the condition of the apophyseal rings and the intervertebral disc. The latter may show a slight physiological posterior bulging at lower lumbar levels. The posterior wall of the nerve root canal is represented by the ligamentum flavum, the pars interarticularis of the upper vertebra, and the superior articular facet of the vertebra below. Thickening of the ligamentum flavum must be considered in relationship to alterations of anterior components: trabecular reorganization and spreading of vertebrae in aging [49], and disc degeneration [38, 49]. Nerve root sleeves display a level dependent, variable oblique course from their emanation from the thecal sac towards the outer third of the neural canal [39]. The presence of anamalous lumbosacral nerve roots may result in considerable course alterations, originating from an abnormal high or low level emanation, conjoined nerve roots, a double set of nerve roots or anastomosis between nerve roots of adjacent levels [20]. Variation exists in the position of the dorsal root ganglia (DRG) relative to the intervertebral foramen. An intraforaminal position seems to be more common at L4 and L5 levels; an intraspinal position has to be expected for the S1 DRG. Intraspinal position of L4 and L5 DRG renders them more susceptible to compression from a superior articular facet or a bulging disc. Cases of extraforaminal positions of dorsal root ganglia have been reported at L4 and L5 levels [22]. On its recurrent course through the lateral canal, the sinuvertebral nerve(s) supplies the laterodorsal outer annulus of the intervertebral disc, the PLL, the anterior 2/3 of the dural sac and the anterior vascular plexus [4, 14]. Many blood vessels pass through the lateral neural canal: the anterior and posterior spinal canal branches, anterior and posterior radicular branches, and veins of the anterior and posterior internal vertebral venous plexus [9]. Per segment, one ore two thick and one to four thin sinuvertebral nerves (SVN) originate from rami communicantes close to the connection of the latter to the spinal nerve [14]. The extensive ramifications of the thin SVNs complete a thorough network at the floor of the central lumbar canal. A large part of it supplies the PLL. The PLL is assumed to play an important role in proprio- and nociception [34, 39]. It is probably one of the first structures to mediate nociceptive information from disc tissue [14]. After injection of neuronal tracers into the sympathetic trunk at L3-L4 in rats, labeled cells were found in higher DRGs as well as labeled nerve fibers in the dura mater at lower levels. These findings indicate both a segmental and a non segmental pathway of sensory innervation of the dura mater and a role of higher DRGs in mediating LBP [25]. In the neighborhood of the SVN, other small branches emanate from the rami communicantes and join the dorsal ramus and the segmental artery that enters the neural canal. The sympathetic nerve plexus inside the anterior longitudinal ligament and the SNVs provide a network of nerve fibers around the vertebral bodies and intervertebral discs. These pathways explain the sympathetic component of the innervation of a number of spinal structures. The dorsal ramus innervates the facet joints at the corresponding level and one below, before it gives off muscular and cutaneous branches.
MeSH Terms
- Aging
- Disease Progression
- Humans
- Intervertebral Disc
- Low Back Pain
- Lumbar Vertebrae
Intraepithelial lymphoid cells (IEL) obtained from the mucosa of mouse small intestine were tested for natural killer (NK) activity in a 20-h 51Cr-release assay against YAC-1 and RLfemale1 tumor cells. It was found that IEL possess a strong NK activity, higher than spleen cells, whereas lymphocytes from Peyer's patches (PPL) did not show any NK activity. The cytotoxic activity of IEL could be boosted by interferon (IFN-beta ) treatment, but no NK activity could be induced in PPL by in vitro IFN-beta treatment. The characteristics of the NK effector cells present in the mouse intestine strictly resemble those of NK cells in the spleen. In fact, intestinal NK activity is not affected by depletion of adherent cells and only partially reduced by anti-Thy-1.2 antibodies plus complement. Moreover, the age dependency of NK cytotoxicity is identical for IEL and spleen. Finally, NK-insensitive target cells are not lysed by IEL.
MeSH Terms
- Aging
- Animals
- Cell Separation
- Cytotoxicity, Immunologic
- Female
- Intestinal Mucosa
- Killer Cells, Natural
- Lymphocytes
- Lymphoma
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Inbred DBA
- Peyer's Patches
Skin testing for penicillin allergy with penicillin G (Pen G), penicilloic acid (PA), and penicilloyl poly-L-lysine (PPL) was performed on 740 subjects, and the results were assessed from epidemiologic and immunologic perspectives. Approximately 95% of these patients had histories of apparent allergic reactions to beta-lactam antibiotics, and 63% were skin-test positive. The prevalence of positive skin tests was related to the time that had elapsed between clinical reactions and skin testing. Ninety-three percent were skin-test positive 7 to 12 mo after reactions, and 22% were positive 10 yr or more after reactions. Patients under 30 yr of age had a prevalence of positive skin tests 1.7-fold higher than older patients. Testing with PPL, PA, and Pen G detected 76.3%, 55.3%, and 57.1% of the positive patients, respectively. Omission of PPL, PA, or Pen G would have led to a failure to detect 25.6%, 7.2%, and 6.2% of the positive patients, respectively. Subjects with skin tests positive to penicillin often reacted to skin tests with other beta-lactam antibiotics; 73% (41 of 56) reacted to ampicillin and 51% (38 of 74) reacted to cephalothin. No serious allergic reactions were provoked by testing. None of the 83 skin test--negative patients treated with beta-lactam antibiotics immediately after testing experienced acute allergic reactions. Two patients developed mild urticaria beginning 3 and 5 days into therapy. One skin test--negative patient experienced urticaria 3 hr after receiving oral penicillin 6 mo after skin testing. This patient's skin-test status immediately before therapy was unknown. These results support the position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients at risk, or not at risk, for allergic reactions to penicillin.
MeSH Terms
- Adolescent
- Adult
- African Continental Ancestry Group
- Aging
- Ampicillin
- Benzeneacetamides
- Carbenicillin
- Cephalothin
- Drug Hypersensitivity
- Female
- Humans
- Intradermal Tests
- Lactams
- Male
- Penicillanic Acid
- Penicillin G
- Penicillins
- Polylysine
- Skin Tests
- Time Factors