Lateral Tissues Research Articles

Diagnosis and treatment of elbow instability

肘关节不稳是急性骨折脱位及慢性运动劳损中常见的肘部疾患,对于急性肘关节不稳的治疗至关重要,及时治疗避免形成慢性不稳.慢性不稳治疗较为困难.本文综述了肘关节不稳的表现、诊断及治疗.肘关节不稳的治疗原则为将复杂的骨折脱位变为简单的骨折脱位,恢复解剖结构,包括关节面和软组织.肱尺关节损伤时外侧组织的修复尤为重要.肘关节复发性不稳应以手术治疗为主。

Combined Thigh Flap for Closure of Massive Trunk Defect

A massive trunk defect resulting from resection of recurrent sarcoma was reconstructed with a combined free flap incorporating medial, anterior, and lateral thigh tissues. This flap included the tensor fasciae latae, lateral thigh perforator, and rectus femoris, all based on the lateral femoral circumflex pedicle. A saphenous vein conduit enabled this flap to replace resected tissues at the lower thorax. Combining the three different commonly used thigh flaps on a single large pedicle enabled transfer of a 47.5 x 33.5-cm mega-flap.

Lymphocytes from one side of the bovine mammary gland migrate to the contra lateral gland and lymph node tissue

The four quarters of bovine mammary glands are completely separated and two quarters on each side (right or left) are connected to ipsi lateral supra mammary lymph nodes. It is not clear whether cells infused into the cistern of the mammary gland are capable of migrating to lymph nodes or the general circulation. To examine cell migration, a prescapular lymph node was removed from each of two lactating and three non-lactating dairy cows, and isolated lymphocytes were stained with Hoechst 33342. Autologous stained cells were infused into the mammary gland and then activated by intramammary infusion of zymosan-stimulated serum (source of C5a). After 17 h, Escherichia coli J5 bacterin was infused into the contra lateral mammary gland to mimic infection. After 43 h cows were euthanized and tissue samples (mammary quarters, right and left supra mammary, mesenteric, ileocecal and prescapular lymph nodes, liver and spleen) were collected for microscopic examination as well as flow cytometric analysis. Hoechst stained cells were detected not only in infused quarters, but also in contra lateral quarters as well as in both supra mammary lymph nodes. This indicates that cells infused into the mammary gland migrate to contra lateral tissues and supra mammary lymph nodes.

Jaw thrust can deteriorate upper airway patency

Upper airway obstruction is a frequent problem in spontaneously breathing children undergoing anesthesia or sedation procedures. Failure to maintain a patent airway can rapidly result in severe hypoxemia, bradycardia, or asystole, as the oxygen demand of children is high and oxygen reserve is low. We present two children with cervical masses in whom upper airway obstruction exaggerated while the jaw thrust maneuver was applied during induction of anesthesia. This deterioration in airway patency was probably caused by medial displacement of the lateral tumorous tissues which narrowed the pharyngeal airway.

Determination of select antidepressants in fish from an effluent‐dominated stream

Increasing evidence indicates widespread occurrence of pharmaceuticals and personal care products (PPCPs) in municipal effluent discharges and surface waters. Studies that characterize the fate and effects of PPCPs in aquatic systems are limited, and to our knowledge, data regarding pharmaceutical accumulation in fish of effluent-dominated ecosystems have not been previously reported. In the present study, fish populations were sampled from a reference stream and an effluent-dominated stream in north Texas, USA. Lepomis macrochirus, Ictalurus punctatus, Cyprinus carpio, and Pomoxis nigromaculatus were killed; the liver, brain, and lateral filet tissues dissected; and the tissues stored at -80 degrees C until analysis. Fish tissues were extracted using solid-phase extraction and then analyzed by gas chromatography-mass spectrometry in the negative chemical ionization mode. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and the SSRI metabolites norfluoxetine and desmethylsertraline were detected at levels greater than 0.1 ng/g in all tissues examined from fish residing in a municipal effluent-dominated stream. To our knowledge, the present study is the first report of SSRI residues in fish residing within municipal effluent-dominated systems.

Mitochondrial Proteomic Analysis of a Cell Line Model of Familial Amyotrophic Lateral Sclerosis

Mutations in copper-zinc superoxide dismutase (SOD1) have been linked to a subset of familial amytrophic lateral sclerosis (fALS), a fatal neurodegenerative disease characterized by progressive motor neuron death. An increasing amount of evidence supports that mitochondrial dysfunction and apoptosis activation play a critical role in the fALS etiology, but little is known about the mechanisms by which SOD1 mutants cause the mitochondrial dysfunction and apoptosis. In this study, we use proteomic approaches to identify the mitochondrial proteins that are altered in the presence of a fALS-causing mutant G93A-SOD1. A comprehensive characterization of mitochondrial proteins from NSC34 cells, a motor neuron-like cell line, was achieved by two independent proteomic approaches. Four hundred seventy unique proteins were identified in the mitochondrial fraction collectively, 75 of which are newly discovered proteins that previously had only been reported at the cDNA level. Two-dimensional gel electrophoresis was subsequently used to analyze the differences between the mitochondrial proteomes of NSC34 cells expressing wild-type and G93A-SOD1. Nine and 36 protein spots displayed elevated and suppressed abundance respectively in G93A-SOD1-expressing cells. The 45 spots were identified by MS, and they include proteins involved in mitochondrial membrane transport, apoptosis, the respiratory chain, and molecular chaperones. In particular, alterations in the post-translational modifications of voltage-dependent anion channel 2 (VDAC2) were found, and its relevance to regulating mitochondrial membrane permeability and activation of apoptotic pathways is discussed. The potential role of other proteins in the mutant SOD1-mediated fALS is also discussed. This study has produced a short list of mitochondrial proteins that may hold the key to the mechanisms by which SOD1 mutants cause mitochondrial dysfunction and neuronal death. It has laid the foundation for further detailed functional studies to elucidate the role of particular mitochondrial proteins, such as VDAC2, in the pathogenesis of familial ALS.

Compressive/Tensile Stresses and Lignified Cells as Resistance Components in Joints of Opuntia ficus-indica and Opuntia parryi var. parryi (Cactaceae)

to being separated from the plant. Bending stress (due solely to the weight of the branches) was the predominant stress (mean bending stresses were 167 and 383 kPa for 0. ficus-indica and 0. parryi var. parryi, respectively) between stem segments. Axial, shear, and torsion stresses were relatively low compared with bending stresses for both species. Data of 0. ficus-indica and 0. parryi var. parryi show that 23.6 and 25.3% of tensile portions of joints were composed of lignified xylem cells, respectively, while compressive portions of the same joints had only 10.8 and 14.7% lignified xylem cells, respectively. The relative radial positions of lignified xylem cells for compressive, tensile and lateral portions of joints for 0. ficus-indica and 0. parryi var. parryi were analyzed. In general, lignified xylem cells were closer to the external surface in tensile tissues than in compressive and lateral tissues of joints. Thus, lignified xylem cells are located in a position to provide a high level of resistance to bending. Maximum bending stresses were positively related with amounts of lignified xylem cells in joints for both species. For 0. ficus-indica the best-fit line was y = 1.48 x + 24.2 (P = 0.012) with an r2 = 0.76. For 0. parryi var. parryi, the best-fit line was y = 54.0 x - 11.7 (P = 0.01) with an r2 = 0.92. The 1.48 slope value for 0. ficus-indica was low compared with the 54.0 slope value for 0. parryi var. parryi. Large slope values for a species may reflect a greater ability of lignified xylem cells to resist stress. In five Opuntia species for which data are available, there was a strong negative relationship between slope values and joint diameter. However, high slope values occurred in species with more horizontal stem segments. Overall, these results show bending stress is the main stress between stem segments, lignified xylem cells in stem joints provide the main resistance to joint stresses, and slope values of stress versus amounts of lignified xylem cells may be related to plant morphology.

Modulation of activator protein 1/DNA binding activity by acoustic overstimulation in the guinea-pig cochlea

Changes in gene expression are part of the homeostatic machinery with which cells respond to external stimuli or assaults. The activity of the early response transcriptional factor activator protein-1 (AP-1) can be modulated by a variety of environmental stimuli including those that alter the cellular oxidation/reduction status. This study investigates the activation of AP-1/DNA binding in the guinea-pig cochlea in response to acoustic overstimulation which produces reactive oxygen species. Electrophoretic mobility shift assays revealed that binding of AP-1 to its radiolabeled oligonucleotide probe markedly changed in nuclear extracts of inner ear tissues following intense noise exposure (4 kHz octave band, 115 dB, 5 h). AP-1/DNA binding increased in the organ of Corti and the lateral wall tissues immediately after the exposure, returning to near-baseline levels 5 h later. At 15 h after noise, a second peak of binding activity occurred in the organ of Corti whereas stria vascularis showed a lesser but more sustained activity. Binding in nuclear extracts from the spiral ganglion did not change. Incubation of nuclear extracts with antibodies against Fos/Jun family proteins prior to a supershift assay showed Fra-2 as a major component of the AP-1 complex immediately after the noise exposure. In the organ of Corti, Fra-2 immunoreactivity was localized to the middle turn, i.e. the region which is most affected by the 4-kHz octave band exposure. The results suggest the modulation of gene expression via the activation of AP-1 as a consequence of noise trauma but also demonstrate differential responses in cochlear tissues.

Hearing and hearing loss: Causes, effects, and treatments

Hearing loss can have multiple causes. The outer and middle ears are conductive pathways for acoustic energy to the inner ear (cochlea) and help shape our spectral sensitivity. Conductive hearing loss is mechanical in nature such that the energy transfer to the cochlea is impeded, often from eardrum perforations or middle ear fluid buildup. Beyond the middle ear, the cochlea comprises three interdependent systems necessary for normal hearing. The first is that of basilar-membrane micromechanics including the outer hair cells. This system forms the basis of the cochlear amplifier and is the most vulnerable to noise and drug exposure. The second system comprises the ion pumps in the lateral wall tissues of the cochlea. These highly metabolic cells provide energy to the cochlear amplifier in the form of electrochemical potentials. This second system is particularly vulnerable to the effects of aging. The third system comprises the inner hair cells and their associated sensory nerve fibers. This system is the transduction stage, changing mechanical vibrations to nerve impulses. New treatments for hearing loss are on the horizon; however, at present the best strategy is avoidance of cochlear trauma and the proper use of hearing aids. [Work supported by NIA and MUSC.]

Protection from noise-induced lipid peroxidation and hair cell loss in the cochlea

In order to delineate mechanisms of noise-induced hearing loss, we assessed noise trauma and its pharmacological modulation in the guinea pig. Auditory threshold shifts (measured by auditory brainstem responses), hair cell loss and lipid peroxidation (8-isoprostane formation) were determined in the absence or presence of agents known to influence the formation or action of reactive oxygen species (ROS): the non-specific N-methyl- d-aspartate (NMDA) receptor antagonist (+)-MK-801, its inactive isomer (−)-MK-801, the selective NR1/2B NMDA receptor antagonist PD 174494, the nitric oxide synthase (NOS) inhibitor l- N ω-Nitroarginine methyl ester ( l-NAME) and the anti-oxidant N-acetylcysteine (NAC). (+)-MK-801 and NAC attenuated threshold shifts and hair cell loss effectively while PD 174494 did so partially. l-NAME attenuated threshold shifts at 2 kHz but increased them at 20 kHz, and (−)-MK-801 was ineffective. Noise-induced elevation in 8-isoprostane in the cochlea was significantly attenuated by (+)-MK-801 and PD 174494 in the organ of Corti and modiolar core, by l-NAME in the lateral wall and modiolar core, and by NAC in all three regions. (−)-MK-801 did not influence noise-induced 8-isoprostane formation. There was a significant correlation between threshold shifts at 4 kHz, hair cell loss and the level of 8-isoprostane formed in the organ of Corti, but not in the lateral wall tissues. This finding suggests a causal relationship between ROS formation and functional and morphological damage. NMDA receptors and, to some extent, NOS may be involved in noise-induced ROS formation. The data also indicate that lipid peroxidation in the lateral wall tissues does not influence permanent threshold shifts.

Mediolateral intercalation in planarians revealed by grafting experiments.

We investigated how planarians organize their left-right axis by using ectopic grafting. Planarians have three body axes: anteroposterior (A-P), dorsoventral (D-V), and left-right (L-R). When a small piece is implanted into an ectopic region along the A-P and D-V axes, intercalary structures are always formed to compensate for positional gaps. There are two hypotheses regarding L-R axis formation in this organism: first, that the left and right sides of the animal may be recognized as different parts, and L-R intercalation can induce midline structures (asymmetry hypothesis); second, that both sides may have symmetrical positional values, and mediolateral (M-L) intercalation creates positional values along the L-R axis (symmetry hypothesis). We performed ectopic grafting experiments in the head region of the planarian, Dugesia japonica, to examine these hypotheses. A left lateral fragment containing a left auricle was implanted into the medial region of the host. Ectopic structures were always formed only on the left side of the graft, where lateral tissues abutted onto the medial tissues. However, no morphologic change was induced on the right side of the graft, where left-sided tissues faced onto right-sided tissues. Molecular marker analyses indicated that ectopic structures formed on the left side of the graft were induced by M-L intercalation, supporting the "symmetry hypothesis." When the midline tissues were implanted into a lateral region, they induced a complete ectopic head, demonstrating that M-L intercalation may be sufficient to establish the L-R axis in planarians.

Differential regulation of the chick dorsal thoracic dermal progenitors from the medial dermomyotome.

The chick dorsal feather-forming dermis originates from the dorsomedial somite and its formation depends primarily on Wnt1 from the dorsal neural tube. We investigate further the origin and specification of dermal progenitors from the medial dermomyotome. This comprises two distinct domains: the dorsomedial lip and a more central region (or intervening zone) that derives from it. We confirm that Wnt1 induces Wnt11 expression in the dorsomedial lip as previously shown, and show using DiI injections that some of these cells, which continue to express Wnt11 migrate under the ectoderm, towards the midline, to form most of the dorsal dermis. Transplantation of left somites to the right side to reverse the mediolateral axis confirms this finding and moreover suggests the presence of an attractive or permissive environment produced by the midline tissues or/and a repellent or inadequate environment by the lateral tissues. By contrast, the dorsolateral dermal cells just delaminate from the surface of the intervening space, which expresses En1. Excision of the axial organs or the ectoderm, and grafting of Wnt1-secreting cells, shows that, although the two populations of dermal progenitors both requires Wnt1 for their survival, the signalling required for their specification differs. Indeed Wnt11 expression relies on dorsal neural tube-derived Wnt1, while En1 expression depends on the presence of the ectoderm. The dorsal feather-forming dermal progenitors thus appear to be differentially regulated by dorsal signals from the neural tube and the ectoderm, and derive directly and indirectly from the dorsomedial lip. As these two dermomyotomal populations are well known to also give rise to epaxial muscles, an isolated domain of the dermomyotome that contains only dermal precursors does not exist and none of the dermomyotomal domains can be considered uniquely as a dermatome.

Immunolocalization of vestitone reductase and isoflavone reductase, two enzymes involved in the biosynthesis of the phytoalexin medicarpin

Vestitone reductase (VR; E.C. 1.1.1._) and isoflavone reductase (IFR; E.C. 1.3.1.45) are phytoalexin-specific enzymes involved in the biosynthesis of medicarpin in alfalfa ( Medicago sativa L.). Immunoblot analysis of total soluble protein extracts indicated that these proteins constitutively accumulate in roots and nodules of alfalfa plants, and in alfalfa cell cultures. VR and IFR proteins are not present in healthy leaves but are rapidly synthesized upon fungal infection, and levels in cell cultures increase following elicitation. Immunolocalization studies in alfalfa organs at the cellular level indicated that VR accumulates in a narrow zone of leaf cells surrounding fungal lesions, in all cell types of mature and young roots, and in nodule meristem and lateral nodular tissues. Subcellular localization studies using immunogold labelling clearly indicated that VR is a cytosolic enzyme in alfalfa, with the majority of VR appearing free in cytosol. Association of VR with preserved endoplasmic reticulum (ER) membrane fragments was observed in several sections, but sucrose density gradient fractionation did not confirm the ER association. Although VR exhibits maximum activity in vitro in relatively acidic buffers (pH 6.0, approaching the pH of the vacuole), and the final product of the pathway (medicarpin-3-O-glucoside-6″-O-malonate) accumulates in the vacuole, no immunogold signal was observed in the vacuole. Subcellular analysis of CaMV35S∷IFR transgenic tobacco indicated that IFR is cytosolic as well. These results clearly indicate that the late steps of pterocarpan biosynthesis occur in the plant cytosol.

Histological Evidence of Protein Aggregation in Mutant SOD1 Transgenic Mice and in Amyotrophic Lateral Sclerosis Neural Tissues

The mechanisms leading to neurodegeneration in ALS (amyotrophic lateral sclerosis) are not well understood, but cytosolic protein aggregates appear to be common in sporadic and familial ALS as well as transgenic mouse models expressing mutant Cu/Zn superoxide dismutase (SOD1). In this study, we systematically evaluated the presence of these aggregates in three different mouse models (G93A, G85R, and G37R SOD1) and compared these aggregates to those seen in cases of sporadic and familial ALS. Inclusions and loss of motor neurons were observed in spinal cords of all of these three mutant transgenic lines. Since a copper-mediated toxicity hypothesis has been proposed to explain the cytotoxic gain-of-function of mutant SOD1, we sought to determine the involvement of the copper chaperone for SOD1 (CCS) in the formation of protein aggregates. Although all aggregates contained CCS, SOD1 was not uniformly found in the inclusions. Similarly, CCS-positive skein-like inclusions were rarely seen in ALS neurons. These studies do not provide strong evidence for a causal role of CCS in aggregate formation, but they do suggest that protein aggregation is a common event in all animal models of the disease. Selected proteins, such as the glutamate transporter GLT-1, were not typically observed within the inclusions. Most inclusions were positively stained with antibodies recognizing ubiquitin, proteasome, Hsc70 in transgenic lines, and some Hsc70-positive inclusions were detected in sporadic ALS cases. Overall, these observations suggest that inclusions might be sequestered into ubiquitin-proteasome pathway and some chaperone proteins such as Hsc70 may be involved in formation and/or degradation of these inclusions.

Localization of the auxin permease AUX1 suggests two functionally distinct hormone transport pathways operate in the Arabidopsis root apex.

Auxins represent an important class of plant hormone that regulate plant development. Plants use specialized carrier proteins to transport the auxin indole-3-acetic acid (IAA) to target tissues. To date, efflux carrier-mediated polar auxin transport has been assumed to represent the sole mode of long distance IAA movement. Localization of the auxin permease AUX1 in the Arabidopsis root apex has revealed a novel phloem-based IAA transport pathway. AUX1, asymmetrically localized to the plasma membrane of root protophloem cells, is proposed to promote the acropetal, post-phloem movement of auxin to the root apex. MS analysis shows that IAA accumulation in aux1 mutant root apices is impaired, consistent with an AUX1 phloem unloading function. AUX1 localization to columella and lateral root cap tissues of the Arabidopsis root apex reveals that the auxin permease regulates a second IAA transport pathway. Expression studies using an auxin-regulated reporter suggest that AUX1 is necessary for root gravitropism by facilitating basipetal auxin transport to distal elongation zone tissues.

Waterlogging Tolerance Among a Diverse Range of Trifolium Accessions is Related to Root Porosity, Lateral Root Formation and ‘Aerotropic Rooting’

Waterlogging tolerance, root porosity and root anatomy were evaluated for 20 Trifolium accessions (species and sub-species, all annuals) selected from the eight Sections of the genus. Nine accessions were sensitive [relative growth rate (RGR) reduced by up to 80%] to waterlogging, nine accessions were tolerant (RGR not reduced), and in two accessions RGR increased (up to 1.9-fold), when compared to drained controls. Growth of the main (i.e. tap) root axis was severely reduced in all accessions when waterlogged. Lateral roots formed the bulk of the root system of tolerant accessions when grown in waterlogged soil. Lengths of the longest lateral roots were up to three-times longer than the main root axis. Root porosity varied from 0.7–12% among accessions when grown in aerated solution and from 1.1–15.5% in plants grown in hypoxic (0.031–0.045 mol O 2m −3) solution. In some accessions aerenchyma formed by cell lysigeny; in others it formed by schizogenous cell separation, or a combination of both processes. O 2consumption rates of expanded lateral root tissues varied by up to 1.7-fold (on a mass basis) among the six accessions tested and was reduced by an average of 24% for roots of plants grown in hypoxic solution prior to measurements. Accessions with the highest root porosity tended to have longer roots when grown in waterlogged soil. Three accessions formed ‘aerotropic roots’ and the lateral root lengths of these plants exceeded those of all other accessions, suggesting enhanced O 2movement to the submerged lateral root axis via the aerotropic roots. Waterlogging-tolerant accessions were identified in seven of the eight Sections in Trifolium, and the tolerant accessions tended to be those with extensive lateral root systems of relatively high porosity.

Functional β2-Adrenergic Receptors Are Present in Nonstrial Tissues of the Lateral Wall in the Gerbil Cochlea

Recently, we have demonstrated that functional β₁-adrenergic receptors are the dominant β-adrenergic receptor subtype in the stria vascularis and that β₁-adrenergic receptors stimulate K⁺ secretion in strial marginal cells. The goal of the present study was to determine whether nonstrial tissues in the cochlear lateral wall contain β-adrenergic receptors and if so which subtype is present. Pharmacological tools were used to identify receptors in functional studies where cAMP production was measured. Further, receptors were identified as transcripts by cloning and sequencing of reverse-transcriptase polymerase chain reaction (RT-PCR) products. Experiments were performed on gerbil nonstrial lateral wall tissues. Tissues stimulated with 10^–5M isoproterenol produced 0.42 ± 0.22 pmol cAMP per ear within 12 min (n = 14). The selective β-adrenergic receptor agonist isoproterenol stimulated cAMP production with an EC₅₀ of (2 ± 3) × 10^–7M (n = 7). Isoproterenol-stimulated cAMP production was inhibited by the β₂-adrenergic receptor antagonist ICI 118551 with an IC₅₀ of (7 ± 7) × 10^–6M, which corresponds to an affinity constant of 1 × 10^–7M (pK_DB = 6.89 ± 0.23, n = 3). Isoproterenol-stimulated cAMP production was not inhibited by the highly selective β₁-adrenergic receptor antagonist CGP 20712A. The IC₅₀ and the affinity constant for CGP 20712A were estimated to be >3 × 10^–4 and >6 × 10^–6M, respectively. RT-PCR of total RNA isolated from nonstrial lateral wall tissues using primers specific for β₁-, β₂- and β₃-adrenergic receptors revealed products of the predicted sizes for the β₁- and β₂- but not for the β₃-subtype. Sequence analysis confirmed that amplified cDNA fragments encoded gene-specific nucleotide sequences. These results demonstrate that nonstrial lateral wall tissues contain transcripts for β₁- and β₂- but not for β₃-adrenergic receptors and that the β₂-adrenergic receptor is the dominant functional receptor subtype. The cellular localization and function of the β₂-adrenergic receptors remains to be determined.

Vesicular Storage of Adenosine Triphosphate in the Guinea-pig Cochlear Lateral Wall and Concentrations of ATP in the Endolymph during Sound Exposure and Hypoxia

Previous studies have revealed putative vesicular stores of adenosine triphosphate (ATP) in the marginal cells of the cochlear stria vascularis which may serve as a source of ATP for purinergic signalling. This study aimed to provide further evidence of ATP storage in the cochlea and to see whether ATP levels in the endolymph are affected by noise and hypoxia. Tissues from the lateral wall and organ of Corti of the guinea-pig cochlea were fractionated to obtain vesicular (VF) and mitochondrial (MF) fractions. Free and total ATP were then measured by the luciferase-luciferin reaction from which membrane-bound vesicular ATP was calculated. In the lateral wall, the VF contained 2.02+/-0.04 nmol ATP/mg protein (n = 5), significantly greater (p < 0.001; paired Student's t-test) than the concentration of ATP in the MF (0.36+/-0.05). In the organ of Corti, the VF contained 0.69+/-0.08 nmol ATP/mg protein (n = 4), significantly smaller than the amount in the VF of the lateral wall tissues (p < 0.001; non-paired Student's t-test). Small amounts of fumarase. an enzyme of the mitochondrial matrix, in the VF, excluded the possibility of mitochondrial ATP contamination. To investigate the effect of hypoxia and noise on the ATP concentrations in the endolymph, fluid samples were collected from the first (basal) cochlear turn of anaesthetized guinea-pigs. As a result of hypoxia (15 min, 13% F1O2), ATP concentrations (nM, mean +/- SEM) increased from 6.2+/-2.3 to 9.3+/-4.5 (n = 4), but the difference was not statistically significant. As a result of noise (15 min, 10 kHz, 110 dB SPL. broad band), the ATP levels increased significantly from 7.4+/-1.2 to 16.0+/-1.8 (p = 0.01; Student's t-test: n = 4). This study has demonstrated the presence of a vesicular store of ATP in the stria vascularis of the cochlea and described an increase in the ATP levels in the endolymph during noise exposure. The findings suggest that ATP is actively secreted from the vesicular store under conditions of metabolic stress. The presence of ATP under basal conditions supports a role for ATP in the sound transduction process during normal function.

Presence of human herpesvirus 6 and herpes simplex virus detected by polymerase chain reaction in surgical tissue from temporal lobe epileptic patients.

We investigated the presence of human herpesvirus 6 (HHV-6) and herpes simplex virus (HSV) in surgical tissue from temporal lobe epileptic patients. A total of 17 cases were studied, including eight males and nine females. The mean age was 24.9 +/- 11.1 years and the mean age of onset was 11.1 +/- 5.4 years. Five patients were diagnosed as encephalitis/meningitis and another three had a history of suspected encephalitis/meningitis, but no patient showed any obvious neurological symptom or mental handicap. Mesial and lateral temporal tissues were examined by polymerase chain reaction. Among six patients positive for HHV-6 (35%), the mesial temporal lobe was positive in four and the lateral temporal lobe was positive in three. Herpes simplex virus was positive in only one patient. Three of the six patients positive for HHV-6 did not show any apparent causes. Mild encephalitis/meningitis induced by HHV-6, a condition sometimes not recognized as encephalitis/meningitis, may be one of the most frequent causes of temporal lobe epilepsy.

Multiple pathways in the midline regulate concordant brain, heart and gut left-right asymmetry.

The embryonic midline in vertebrates has been implicated in left-right development, but the mechanisms by which it regulates left-right asymmetric gene expression and organ morphogenesis are unknown. Zebrafish embryos have three domains of left-right asymmetric gene expression that are useful predictors of organ situs. cyclops (nodal), lefty1 and pitx2 are expressed in the left diencephalon; cyclops, lefty2 and pitx2 are expressed in the left heart field; and cyclops and pitx2 are expressed in the left gut primordium. Distinct alterations of these expression patterns in zebrafish midline mutants identify four phenotypic classes that have different degrees of discordance among the brain, heart and gut. These classes help identify two midline domains and several genetic pathways that regulate left-right development. A cyclops-dependent midline domain, associated with the prechordal plate, regulates brain asymmetry but is dispensable for normal heart and gut left-right development. A second midline domain, associated with the anterior notochord, is dependent on no tail, floating head and momo function and is essential for restricting asymmetric gene expression to the left side. Mutants in spadetail or chordino give discordant gene expression among the brain, heart and gut. one-eyed pinhead and schmalspur are necessary for asymmetric gene expression and may mediate signaling from midline domains to lateral tissues. The different phenotypic classes help clarify the apparent disparity of mechanisms proposed to explain left-right development in different vertebrates.