Scanning electron microscope observations on the muscle innervation of Oikopleura dioica fol (appendicularia,tunicata) with notes on the arrangement of connective tissue fibres

Critical point dried and fractured appendicularia of the species Oikopleura dioica have been examined in the scanning electron microscope. The dorsal nerve cord with ganglion cells and peripheral nerve fibres could easily be observed. Thick peripheral nerve fibres leave the nerve cord as bilateral pairs at constant intervals along the tail. Most of these fibres branch from the naked nerve cord, but some evidently originate in ganglion perikarya bulging out from the nerve cord itself. These paired peripheral nerves always have elaborate end-arborizations on the medial surface of the lateral muscle cells. They are accordingly interpreted as motor axons. Some thinner peripheral nerve fibres originate at irregular intervals from both the nerve cord and the ganglion cells. Due to the numerous extracellular fibrils that connect the bilateral layers of the epidermal fins and the muscle cells to each other, these thin nerve fibres can seldom be traced to their termination. A few ones can, however, be traced ventrally between the notochord and the muscle cells and seem to end in singular bulb-like expansions. Clusters of synaptic vesicles are present in transmission electron micrographs of such nerves, and they are accordingly believed to carry efferent impulses. The extracellular fibrils are arranged in a highly ordered pattern with thick bundles crossing the gap between the structures to be interconnected and with numerous radiating insertions on the surface of the tissues.     

Filament proteins in central,cranial, and peripheral mammalian nerves

Several classes of 10-nm filaments have been reported in mammalian cells and they can be distinguished by the size of their protein subunit. We have studied the distribution of these filaments in nerves from calves and other mammals. From the display on polyacrylamide electrophoretic gels of proteins in extracts from fibroblast and central, cranial and peripheral nerves, we cut the appropriate stained bands and prepared iodinated peptide maps. The similarities between the respective maps provide strong evidence for the presence of vimentin in cranial and peripheral nerves. The glial fibrillary acidic protein was found in axon preparations from the central nervous system, but was not identified in distal segments of some cranial nerves, nor in peripheral nerve.     

Status of cholinesterase activities in blood in neuropsychiatric disorders

The availability of easily accessible biochemical trait markers of central cholinergic activity would assist in the identification of homogeneous subgroups of neuropsychiatric patients within specific diagnostic categories. In addition to a refinement of nosology, these measures could also help to design specific treatment interventions. The activities of cholinesterase isoenzymes in blood have been reported to be abnormal in neuropsychiatric disorders with proven or hypothesized abnormalities of central cholinergic transmission. However, the relevance of these peripheral cholinesterase abnormalities to disordered central cholinergic transmission remains uncertain. Future studies examining specific cholinesterase isoenzymes in homogeneous diagnostic groups are needed to determine the potential utility of these measures as peripheral trait markers of central cholinergic activity.     

Exercise testing and training in patients with peripheral vascular disease and lower extremity amputation.

Patients with peripheral vascular disease have a high risk of coronary artery disease. The risk is even greater when the peripheral vascular disease leads to lower extremity amputation. Exercise testing using lower extremity exercise has been the "gold standard" for screening for coronary artery disease, but many patients with peripheral vascular disease and those with amputations have difficulty doing this type of exercise. Arm exercise ergometry has been shown to be a safe and effective alternative for the detection of coronary artery disease in patients who cannot do leg exercise. This test has also been used to determine safe exercise levels and may be able to predict the ultimate level of prosthetic use in amputees. Exercise training with arm ergometry also improves cardiovascular efficiency and upper body strength in poorly conditioned patients. Studies are needed to appreciate fully the role of exercise testing and training in the recovery of these patients after amputation.     

Index to volume 8 subject index

The purpose of this study was to determine if changes in peripheral levels of E or F series prostaglandin (PGE or PGF) during pseudopregnancy (PSP) in the rat can be correlated with the changes in peripheral levels of total progestin (Total P), and if estrogen surge on day 4 is associated with increased levels of PGE or PGF. The results indicate that an increase in the concentration of PGF on day 7 may have precipitated a gradual decline in peripheral P. However, no correlation was detected between PGE and peripheral total P. Furthermore, no preimplantation increase in PGE or PGF levels was detected, even though the concentrations of these PG's were relatively high during the first 4 days of PSP.     

四种鱼类外周血红细胞细胞周期及DNA含量

通过流式细胞仪测量了兴国红鲤（Ｃｙｐｒｉｎｕｓ ｃａｒｐｉｏ Ｖａｒ． Ｓｉｎｇｕｏｎｅｎｓｉｓ）、奥利亚罗非鱼（Ｓａｒｏｔｈｅｒｏｄｏｎ ａｕｒｅａ）、 鳙（Ａｒｉｓｔｉｃｈｔｈｙｓ ｎｏｂｉｌｉｓ Ｒ．）和团头鲂（Ｍｅｇａｌｏｂｒａｍａ ａｍｂｌｙｃｅｐｈａｌａ Ｙｉｎ．）红细胞的ＤＮＡ含量,四种鱼与鸡红细胞ＤＮＡ含量的比值分别为１·６５、０．９６、０．９１、１·１５,以鸡红细胞ＤＮＡ含量２．３ｐｇ／Ｎ计算,四种鱼二倍体体细胞的 ＤＮＡ含量分别为３．８０ ｐｇ／Ｎ, ２． ２２ｐｇ／Ｎ、２． ０８ｐｇ／Ｎ、 ２． ６６ｐｇ／Ｎ。另外,四种鱼外周血红细胞分别有２６％、 ２６％、 ２３％、 ２４％的细胞处于 ＤＮＡ合成期（Ｓ）,ＤＮＡ合成后期（Ｇ２）和分裂期（Ｍ）,这表明这四种鱼类的外周血红细胞并非失去分裂能力的特化细胞群,它们表现了较强的细胞周期现象。这有可能是这几种硬骨鱼类外周血仍具有造血功能的缘故。     

β2-Adrenergic Receptors on Peripheral Nerves

We report that peripheral nerves have a functional adenylate cyclase-coupled beta-adrenergic receptor. The pharmacological specificity of this receptor is shown to be of the beta 2 subtype. Two peripheral nerves, the sciatic from the frog and rat and the vagus from the rat, responded to beta 2-agonists with 10-50-fold increases in intracellular cyclic AMP level. This increase was inhibited by the beta-adrenergic antagonist propranolol. In contrast, a central nerve tract, the corpus callosum, responded to isoproterenol with only a minimal one- to twofold increase in cyclic AMP level. These studies demonstrate that peripheral nerves have beta 2-adrenergic receptors that are responsive to exogenously applied catecholamines and suggest a role for these ligands in the previously described modulation of axonal conduction.     

The Central and Peripheral Nervous System of Acoela (Plathelminthes). An Electron Microscopical Study

The fine structure of the nerve cells and the neuropile in the brain of acoels and the peripheral nervous system and the synapses have been studied. On the basis of the vesicle content, four nerve cell types are distinguished. The presumptive glial cell is also visualized. The synapses appear to be of the following four types: asymmetrical, ribbon, symmetrical and electrical. The peripheral nervous system consists of a subepithelial and a submuscular plexus; they present asymmetrical and symmetrical synapses. In the light of these results, the nervous system of acoels should no longer be considered as primitive.     

Well-being and affective style: neural substrates and biobehavioural correlates

One of the most salient features of emotion is the pronounced variability among individuals in their reactions to emotional incentives and in their dispositional mood. Collectively, these individual differences have been described as affective style. Recent research has begun to dissect the constituents of affective style. The search for these components is guided by the neural systems that instantiate emotion and emotion regulation. In this article, this body of research and theory is applied specifically to positive affect and well-being. The central substrates and peripheral biological correlates of well-being are described. A resilient affective style is associated with high levels of left prefrontal activation, effective modulation of activation in the amygdala and fast recovery in response to negative and stressful events. In peripheral biology, these central patterns are associated with lower levels of basal cortisol and with higher levels of antibody titres to influenza vaccine. The article concludes with a consideration of whether these patterns of central and peripheral biology can be modified by training and shifted toward a more salubrious direction.     

Rapid Communication: Human Peripheral Myelin Protein-22 Carries the L2/HNK-1 Carbohydrate Adhesion Epitope

Abstract: Molecular genetic studies have established that mutations in the gene encoding the 22-kDa peripheral myelin protein (PMP-22) are responsible for hereditary peripheral neuropathies in the trembler mouse and in a subset of humans with Charcot-Marie-Tooth disease, type 1a. The function of the PMP-22 protein remains unknown. Several studies on myelin proteins in the PNS have indicated that the L2/HNK-1 epitope, which is believed to be both a ligand for cellular adhesion and a target for autoimmune monoclonal IgM neuritis, may be found on heretofore unidentified proteins with a molecular mass of 19–28 kDa. In this report, we provide immunological evidence that at least one of these proteins is PMP-22.     

Dead-ended autologous connective tissue chambers in peripheral nerve repair--early observations

The effects of the repair of nerve gap injuries are still unsatisfactory, despite the great progress in microsurgery. Until now, there is no effective method to induce the regeneration of the transected peripheral nerve when its distal stump is missing. The aim of this work was to examine whether the implantation of dead-ended connective tissue chambers can promote the outgrowth of injured peripheral neurites. This method differs from all previous nerve guides because it totally eliminates the distal part of the nerve and restricts the influence of surrounding tissues. We have also tried to establish whether some neurotrophic factors can be applied by means of these chambers. The results of this work show that dead-ended autologous connective tissue chambers can be a useful tool in peripheral nerve injuries treatment, even when the distal part of the nerve is missing.     

Inflammation and Programmed Cell Death in Alzheimer’s Disease: Comparison of the Central Nervous System and Peripheral Blood

Although the central nervous system (CNS) has been defined as a privileged site in Alzheimer’s disease (AD), periphery can be more than simply witness of events leading to neurodegeneration. The CNS and peripheral blood can mutually communicate through cells and factors trafficking from the circulation into the brain and vice versa. A number of articles have reviewed inflammatory profiles and programmed cell death (PCD) in AD, separately in the CNS and at the peripheral level. This review does not provide an exhaustive account of what has been published on inflammation and PCD in AD. Rather, the aim of this review is to focus on possible linkages between the central and the peripheral compartments during AD progression, by critically analyzing, in a comparative manner, phenomena occurring in the CNS as well as the peripheral blood. In fact, growing evidence suggests that CNS and peripheral inflammation might present common features in the disease. Microarrays and metabolomics revealed that dysfunction of the glycolytic and oxidative pathways is similar in the brain and in the periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery, both at the CNS and the peripheral level, in AD-related cell damage, has been observed. Possible implications of these observations have been discussed.     

Differential effects of human blood monocytes on the growth of human tumour cell lines in vitro

Summary Monocytes and macrophages have been shown to be cytotoxic towards tumour cells in vitro. However, although tumour-associated monocytes and macrophages are now widely accepted to contribute a relatively high proportion of the cellular infiltrate of experimental and human solid carcinomas, a cytotoxic/cytostatic effector function for these cells in vitro or in vivo has yet to be conclusively demonstrated. In the present study, we show that non-activated peripheral blood monocytes co-cultured with tumour cells across a semi-permeable membrane release soluble factors that modulate the growth of tumour cells in contrasting ways. After Nycoprep 1.068 separation, non-activated peripheral blood monocytes enhanced the in vitro proliferation of HT29 colon adenocarcinoma cells but inhibited T47D breast carcinoma cell replication; peripheral blood lymphocytes were incapable of mediating these effects. In contrast, peripheral blood monocytes activated by interferon caused a pronounced inhibition of both HT29 and T47D cell proliferation.     

Endogenous chicken nerve growth factor from sheath cells is transported in regenerating nerve

We report the presence of endogenous nerve growth factor (NGF) in chicken peripheral nerve. The molecule has been detected with antibodies to mouse salivary gland NGF, using immunohistochemical and immunoelectrophoretic techniques. Previous studies have shown that these antibodies inhibit the survival activity of extracts of chicken peripheral nerve. The NGF accumulated distal, but not proximal, to a ligature placed on a peripheral sympathetic nerve demonstrating that it was retrogradely transported. This transport was detected in intact nerve fibers as well as in nerves from which the peripheral target had been ablated 6 hr or 7 days previously. The results indicate that avian NGF is present in adult chicken peripheral nerves and that this molecule shares antigenic determinants with the mouse molecule. The results further demonstrate that regenerating neurons retrogradely transport NGF supplied by cells within the peripheral nerve (presumably Schwann). The possibility that these cells also provide NGF to intact neurons is discussed.     

Peripheral circadian oscillators in mammals: time and food

Peripheral cells from mammalian tissues, while perfectly capable of circadian rhythm generation, are not light sensitive and thus have to be entrained by nonphotic cues. Feeding time is the dominant zeitgeber for peripheral mammalian clocks: Daytime feeding of nocturnal laboratory rodents completely inverts the phase of circadian gene expression in many tissues, including liver, heart, kidney, and pancreas, but it has no effect on the SCN pacemaker. It is thus plausible that in intact animals, the SCN synchronizes peripheral docks primarily through temporal feeding patterns that are imposed through behavioral rest-activity cycles. In addition, body temperature rhythms, which are themselves dependent on both feeding patterns and rest-activity cycles, can sustain circadian, clock gene activity in vivo and in vitro. The SCN may also influence the phase of rhythmic gene expression in peripheral tissues through direct chemical pathways. In fact, many chemical signals induce circadian gene expression in tissue culture cells. Some of these have been shown to elicit phase shifts when injected into intact animals and are thus candidates for physiologically relevant timing cues. While the response of the SCN to light is strictly gated to respond only during the night, peripheral oscillators can be chemically phase shifted throughout the day. For example, injection of dexamethasone, a glucocorticoid receptor agonist, resets the phase of circadian liver gene expression during the entire 24-h day. Given the bewildering array of agents capable of influencing peripheral clocks, the identification of physiologically relevant agents used by the SCN to synchronize peripheral clocks will clearly be an arduous undertaking. Nevertheless, we feel that experimental systems by which this enticing problem can be tackled are now at hand.     

Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice

Tight junction (TJ)-like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19-deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological "sealing" function of Schwann cells.     

Characterization of a new class of potent inhibitors of the voltage-gated sodium channel Nav1.7

Voltage-gated sodium channels (Nav1) transmit pain signals from peripheral nociceptive neurons, and blockers of these channels have been shown to ameliorate a number of pain conditions. Because these drugs can have adverse effects that limit their efficacy, more potent and selective Nav1 inhibitors are being pursued. Recent human genetic data have provided strong evidence for the involvement of the peripheral nerve sodium channel subtype, Nav1.7, in the signaling of nociceptive information, highlighting the importance of identifying selective Nav1.7 blockers for the treatment of chronic pain. Using a high-throughput functional assay, novel Nav1.7 blockers, namely, the 1-benzazepin-2-one series, have recently been identified. Further characterization of these agents indicates that, in addition to high-affinity inhibition of Nav1.7 channels, selectivity against the Nav1.5 and Nav1.8 subtypes can also be achieved within this structural class. The most potent, nonselective member of this class of Nav1.7 blockers has been radiolabeled with tritium. [3H]BNZA binds with high affinity to rat brain synaptosomal membranes (Kd = 1.5 nM) and to membranes prepared from HEK293 cells stably transfected with hNav1.5 (Kd = 0.97 nM). In addition, and for the first time, high-affinity binding of a radioligand to hNav1.7 channels (Kd = 1.6 nM) was achieved with [3H]BNZA, providing an additional means for identifying selective Nav1.7 channel inhibitors. Taken together, these data suggest that members of the novel 1-benzazepin-2-one structural class of Nav1 blockers can display selectivity toward the peripheral nerve Nav1.7 channel subtype, and with appropriate pharmacokinetic and drug metabolism properties, these compounds could be developed as analgesic agents.     

Structural bioinformatics prediction of membrane-binding proteins

Membrane-binding peripheral proteins play important roles in many biological processes, including cell signaling and membrane trafficking. Unlike integral membrane proteins, these proteins bind the membrane mostly in a reversible manner. Since peripheral proteins do not have canonical transmembrane segments, it is difficult to identify them from their amino acid sequences. As a first step toward genome-scale identification of membrane-binding peripheral proteins, we built a kernel-based machine learning protocol. Key features of known membrane-binding proteins, including electrostatic properties and amino acid composition, were calculated from their amino acid sequences and tertiary structures, which were then incorporated into the support vector machine to perform the classification. A data set of 40 membrane-binding proteins and 230 non-membrane-binding proteins was used to construct and validate the protocol. Cross-validation and holdout evaluation of the protocol showed that the accuracy of the prediction reached up to 93.7% and 91.6%, respectively. The protocol was applied to the prediction of membrane-binding properties of four C2 domains from novel protein kinases C. Although these C2 domains have 50% sequence identity, only one of them was predicted to bind the membrane, which was verified experimentally with surface plasmon resonance analysis. These results suggest that our protocol can be used for predicting membrane-binding properties of a wide variety of modular domains and may be further extended to genome-scale identification of membrane-binding peripheral proteins.